DE1643948A1 - Process for the production of acetylene compounds - Google Patents

Description

Prof. Dr. Albert Eschenmoser, Küsnacht / Zurich (Switzerland)

Case EM 1-7 / E Germany

Process for the production of Aeetylenverbindungen * »

The present invention relates to a novel process for the preparation of α-0χο-α, β-ββοο-9 (γ) -acetylene » compounds of the general formula

(D

209824/1170

BATH

wherein each of the symbols R ₁ , R ^, R, and R ₂ signifies hydrogen or an organic radical and at least 2 of the radicals mentioned are bonded to one another. This process relates in particular to the production of cycloaliphatic α-oxoa, β-seco-β (7) -aetylene compounds and α-Οχο-α, β-seco "steroid-β (7) -ynes.

It has been found that the compounds characterized above can be obtained if hydrazones of α, ß-Oxido-7-carbonyl compounds of the general formula

(11)

wherein R denotes a hydrogen atom or preferably a nucleofugal group and the symbols R ₁ , Rg, R, and R ₁ ^ have the above meaning, with evolution of nitrogen. possibly fragmented under oxidative conditions.

This fragmentation of the epoxy hydrazone takes place with splitting off of molecular nitrogen, splitting of the bond between the carbon atoms α and β and formation a triple bond between the carbon atoms β and 7, and an oxo group on the carbon atom α according to FIG general formula

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(II)

(D

It has also been found that the same compounds can be obtained if hydrazones of α-hydroxyβ-R'-7-carbony compounds are used the general formula

(in)

where R denotes a hydrogen atom or a nucleofugal group, R ¹ denotes a free or preferably reactive esterified hydroxyl group and the symbols R 1, Rp, R- and Rj, which have the above meaning, are fragmented with evolution of nitrogen, optionally under oxidative conditions.

The inventive fragmentation of the hydrazone takes place with splitting off of molecular nitrogen and breaking the bond between the carbon atoms α and β and formation of a triple bond between the carbon atoms β and 7, and an oxo group on the carbon atom α

20982A / 1 170

according to the general formula

(III)

(D

It has also been found that these acetylene compounds can also be obtained by using oximes, their esters or ethers of α, ß-oxido-7-carbonyl compounds of the general formula

(IV)

wherein R ' ^{1 is} an esterified or etherified or preferably free hydroxyl group and the symbols R ,, Rp, R-. and R ₂ , which have the meaning given above, are reacted in a basic medium with a reactive ester or ether of hydroxylamine.

In this reaction, too, fragmentation occurs, with the bond between the carbon atoms α and β canceled and a triple bond between

2 0 9 8 2 kl 1 170

the carbon atoms β and 7 and an oxo group on the carbon atom α is formed according to the general formula

Further, it has been found that compounds of the acetylene mentioned can win if one oximes, their esters or ethers, from a-hydroxy-ß-R ¹ -7 ^ carbonyl compounds of the general formula

(V)

wherein R ¹ , R ¹ ', R ^, Rg, R-. and R ₁ , as defined above, is reacted in a basic medium with a reactive ester or ether of hydroxylamine.

In this reaction, too, fragmentation occurs, which proceeds analogously to the two shown above and to the general formula

ORIGINAL INSPtCTSD

2 0 9 8 2 UI 1 1 7 0

16439Λ8

(ν) (D

is equivalent to.

It was also found that the oximes and hydrazones mentioned, which are used as starting materials, are already under the conditions under which they are formed, can fragment, for example in the implementation of the corresponding 7-carbonyl compounds with a derivative of hydrazine substituted by a nucleofuge group or with a reactive one Ester or ether of hydroxylamine. This reaction also proceeds according to one of the reaction schemes shown above.

A closer look at the method described above shows that it is apparently a novel version of the (Y-C-C-C-X) fragmentation schemes where the remainder X is for

represents a diazonium group.

In all cases discussed, the original oxo group on the ^ carbon atom becomes the above general Formulas, z, B, about the intermediate stage of an oxime, hydrazone, Tosylhydrazone etc. primarily converted into a diazo or diazonium group. This process is (on any Stage) with the elimination of the substituent on the carbon atom ß, e.g. with the opening of the α, ß-oxido ring between

209824/1 170

Oxygen and the β-carbon atom or the elimination of the remainder R 'connected. The above fragmentation scheme can thus be summarized in formula A.

This means that, for example, the treatment of the epoxy oximes of the formula IV with reactive esters of hydroxylamines, as well as the oxidation of the epoxy hydrazones of the formula II (where R stands for hydrogen) or the decomposition of the tosyl hydrazones of α-hydroxy-β- H'-7-oxo compounds of the formula III lead to the intermediate formation of the same intermediate product (A) or (A ¹ ) or to its protonated form according to the abovementioned decay. This in turn breaks down into the end products with the elimination of nitrogen:

N-NH-R

N = NHM

Nf)

0-0

N-OH

R ¹ -C

N-NH-K

HO-C

In this scheme, M is a nucleofuge group,

2 0 9 8 2 UI 1 1 7 0

The diazonium compound (A) can have the corresponding Diazo compound of the type B N

β N I C

- C-

ß _τ y

Il

(B)

(A)

γ · -σ

Y-C

in which R * and Y 'can optionally together form a single group, for example an epoxy group, with splitting of the bond R'-Cβ and formation of the double bond between the carbon atoms β and 7. The fractionation step necessary for the formation of the diazonium group and the fractionation step can also take place with one another, that is to say synchronously. In A, the radical Y can represent, in addition to an oxygen anion or a free or substituted hydroxyl group, for example an alkoxy group (see formula A ¹ ), any other group, for example a nitrogen-containing group, which in the course of fragmentation or after subsequent hydrolysis into a Oxo group can be converted.

Thus, the method according to the invention is thereby

characterized in that compounds of the general formula (VI)

R ₁

(VI)

^v "3 ^R 2

209824/117 0

wherein PL, Rp, R, and Rk have the meaning given above, X represents a diazonium radical or a radical which can be converted into a diazonium radical under the decomposition conditions and Y is a radical which can be converted into an oxo group under the reaction conditions and, if appropriate, subsequent hydrolysis means decomposed with fragmentation and elimination of molecular nitrogen and the products obtained, if appropriate hydrolyzed.

It is advisable to proceed in such a way that the connection of formula VI is formed in situ. Thus, one embodiment of this method is to have compounds of the formula VI, in which X is a convertible into a diazonium radical Group and R ,, Rp, R- ,, R ^ and Y are those given above Own meanings with a means that translates

the group X can be converted into a diazonium radical, the obtained Product decomposes with fragmentation and elimination of molecular nitrogen and products obtained, if applicable hydrolyzed.

So you can from a compound of the formula R ₁

(VII)

start out, wherein R ,, Rp, R .. and R ₂ , the above meaning

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16439Λ8

own, X ^! a group that can be converted into a diazonium radical, Z denotes the radical R 'and Y denotes a radical that can be converted into an oxo group under the reaction conditions and, if appropriate, subsequent hydrolysis, or Z and Y together represent a divalent radical that can be converted into an oxo group under the decomposition conditions and, if appropriate, subsequent hydrolysis and treat them with an agent which can convert the group X '! into a diazonium radical, a double bond being formed between the carbon atoms β and 7 and the bond between the radical Z and the carbon atom β being broken and the compound obtained with fragmentation and cleavage decompose of molecular nitrogen and hydrolyze the products obtained if necessary *

There is a special embodiment of the method in that there are α, ß-unsaturated carbon compounds the formula

(VIII)

wherein R, R ', R _7, and R ^ have the above-named meaning, before or during the fragmentation, in any order, on the one hand into suitable for the fragmentation products · Additions to the olefinic double bond and on the other hand

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converted into nitrogen-containing carbony derivatives, whose nitrogen-containing residue can be split off, leaving behind the pair of electrons required for fragmentation and fragments with elimination of molecular nitrogen.

The starting materials to be used in the present process are derived from corresponding compounds of the above formulas, such as, for example, from α, β-unsaturated carbonyl compounds of the formula VIII. The symbols R ₁ , R 2, R, and Rj denote hydrogen atoms or organic radicals, at least one of these symbols preferably representing one of the following radicals:

a) a saturated or unsaturated acyclic hydrocarbon radical, which is a straight or branched, optionally carbon chain interrupted by heteroatoms and optionally has at least one functional group, or

b) a saturated or unsaturated, mononuclear or polynuclear, optionally ring-substituted, alicyclic Hydrocarbon residue, or

c) a mononuclear or polynuclear aromatic hydrocarbon residue, which may have core substituents, or

d) a mononuclear or polynuclear aralkyl or aralkenyl radical which may have core substituents, or

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e) a saturated or unsaturated, mononuclear or polynuclear heterocyclic radical, which is optionally ring-substituted,
where preferably at least two of the symbols R ,, R ₀ , R,

1 d $

and Rh together represent groups of atoms which together with the carbon atoms α and / or β and / or 7 (cf. formulas VI or VIII) saturated or unsaturated, mono- or form polynuclear, optionally ring-substituted, carboxyclic or heterocyclic ring systems.

The organic radicals listed above can carry additional functional groups.

Preferred starting materials are, for example, compounds derived from the following α, β-unsaturated ketones:

(a) α, β-Unsaturated carbony! compounds with a carbo- or heterocyclic ring, which preferably contains 5 or more ring members in which the olefinic double bond between neighboring ring carbon atoms and the Carbonyl group are arranged in a side chain in the α-position to the double bond. The ring can be attached to carbon atoms, which do not belong to the olefinic group, with a further mono- or polycyclic, carbo- and / or heterocyclic group Be condensed ring system. The ring (s) can have substituents, for example optionally carrying functional groups Hydrocarbon residues or functional groups have. The side chain carrying the carbonyl group can in particular be a hydrocarbon radical with 1 or more carbon atoms,

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which can be interrupted by heteroatoms, e.g. 0, S or N, one or more unsaturated carbon-carbon bonds have and, in addition to the carbonyl group, can optionally carry further functional groups. Which differ from the said Carbony! Compounds supply starting materials the fragmentation according to the inventive method either open-chain compounds with a carbonyl group and a triple bond or cyclic compounds in which the newly formed carbonyl group and the triple bond are arranged separately in two side chains. As examples of carbonyl compounds of this group the following compounds can be named:

l-tl-Oxo-S-äthyl-hept - ^ - en-l-ylü-cyclopent-l-en, l-propionyl-cyclohexa-l, 4-diene,
1-formyl-cyclooct-l-en and Cedrenai.

(b) α, β-Unsaturated ketones with an oarbo- or heterocyclic ring, which preferably contains 8 or more ring members, in which the keto group in the ring and the olefinic Double bond are arranged exocyclically in a side chain in the α-position to the keto group. The ring can be with a be condensed further mono- or polycyclic, carbo- and / or heterocyclic ring system. The ring or rings can be substituents, e.g. hydrocarbon radicals or functional groups optionally bearing functional groups Groups. The side chain containing the olefinic double bond can in particular have a hydrocarbon radical

'■ · Π η;, -: ι / 117 0

- l4 -

1Θ43948

1 or more carbon atoms, interrupted by heteroatoms, e.g. 0, S or N, one or more further unsaturated ones Contain carbon-carbon bonds and can carry functional groups. The different from these carbonyl compounds In the case of fragmentation according to the method according to the invention, two dissipative starting materials are obtained Cleavage products, namely a cyclic compound with a triple bond and an open-chain carbony compound. An example of a cyclic ketone of this group is 2-benzylidene-cyclopenta-decan-1-one called.

(c) α, ß-Unsaturated ketones with a carbo- or heterocyclic ring which can preferably contain 5 or more ring members in which both the keto group and the olefinic double bond are arranged in the ring. The ring may have carbon atoms other than the olefinic group still belong to the keto group, with another mono · ^ or polycyclic, carbo- and / or heterocyclic ring system be condensed. The ring (s) can contain substituents, e.g. hydrocarbon radicals or functional groups which may carry functional groups. Preferably at least one of the carbon atoms carrying the olefinic double bond is free of hydrogen. The starting materials derived from the carbonyl compounds of this group supply in the fragmentation the inventive method either open-chain compounds with a carbonyl group and a triple bond

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or cyclic compounds in which the carbonyl group and the triple bonds are arranged in a side chain.

As examples of carbony compounds of this group the following connections are mentioned!

3-Methyi-2- [pent-2-en-yl- (l)] - cyclopent-2-en-l-one (jasmine), 2,3 = dimethyl-cyclopent-2-en-l-one,

2- [4-methyl-pent-3-en-yl- (l)] - cyclopent-2-en-l-one, 2-methyl-cyclohex-2-en-l-one,

3-methyl-cyclohex-2-en-l-one,

2, .3-Dimethyl-cyclohex-2-en-l-one,

Piperiton, 2- [dee-4-en-yl- (l)] - cyclohex-2-en-l-one,

(d) α, ß-Unsaturated ketones in which the olefinic Double bond a bridge in a bicyclic, carbocyclic and / or heterocyclic ring system, the rings of which are identical or can be of different sizes, and forms the keto group in a-position is arranged to the olefinic group in one of the two rings. The rings can be attached to carbon atoms neither the olefinic group still belong to the keto group, with a further mono- or polycyclic, carbO "» - and / or heterocyclic group Be condensed ring system. The rings can have substituents, for example hydrocarbon radicals optionally carrying functional groups or functional groups. The starting materials derived from the carbony compounds of this group in the case of fragmentation by the process according to the invention, yield mono- or polycyclic compounds, in

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which the newly formed carbonyl group and the triple bond are arranged in one and the same ring. The following representatives can be mentioned as examples of carbony compounds of this group: bicyclo [10.3.0] pentadec-1 (12) -en-13-one, bicyclo [9.4.0] pentadec-l (II) -en-12 -on, bicyclo [4.4.0] dec-l (6) -en-2-one,
Bicyclo [10.3.0 "3pentadec-l (12) -en-2-one, 13-oxa-bicyclo [10.4.0] hexadec-l (12) -en-16-one, 4-isopropenyl-bicyclo [4.4. 0] dec-l (6) -en-7-one,

-ζ Ο

10,10-dimethyl-tricyclo [7.1.1.CK] undec-3 (8) -en-4-one, Bicyclo [5 x 3 x 0] dec-1 (7) -en-2-one and

6,10-dimethyl-3-isopropyl-bicyclo [5.3.0] dec-l (7) -en-2-one. (e) α, ß-Unsaturated ketones with a cyclic keto group in which the olefinic double bond is a Carbon atom that is common to both rings of a bicyclic, carbo- and / or heterocyclic ring system, with the Connects carbon atom in α-position to the keto group. In these rings can carbon atoms that are neither of the olefinic Group still belong to the keto group, with another mono- or polycyclic, carbo- and / or heterocyclic Be condensed ring system. The rings can have substituents, for example optionally carrying functional groups Hydrocarbon residues or functional groups, carry. Those derived from the carbonyl compounds of this group

2 0 9 8 2 k I 1 1 7 0

In the case of fragmentation according to the invention, starting materials are provided Process substituted cyclic compounds in which the newly formed carbonyl group is in a ring and the triple bond is arranged in a side chain of the ring. As examples of Carbony! Compounds of these The following representatives can be named in the group: 6-methyl-bicyclo [4.4.0] dec-l (2) -en-3-one and 7,7-dimethyl-bicyclo [4.4.O] dec-1 (2) -en-J-one.

(f) α, β-Unsaturated cyclic carbonyl compounds in which the carbonyl group in a side chain and the Qjepp * .lbi »dijni | They are arranged in a bio-cyclicalK; - c * | pba and / or '' heterocyclic ring system, the rings of which can be the same or different sizes, the olefinic double bond connecting a carbon atom shared by both rings with the carbon atom on which the side chain is located . The rings can be fused to carbon atoms that do not belong to the olefinic group with a further mono- or polycyclic, carbo- and / or heterocyclic ring system. The rings can have substituents, for example hydrocarbon radicals or functional groups which may carry functional groups. The starting materials derived from the carbonyl compounds of this group, when fragmented by the process according to the invention, yield cyclic ketones which contain the triple bond in a side chain located on the same ring. As an example of a carbonyl compound

2 0 9824/1170

of this group can be named 10,10-dimethyl-4-acetyl-tricyclot7.1.1.0 ^:> ] · undec-2 (4} -en.

Of the carbony compounds of groups (a), (b), (c), (d), (e) and (f) derived starting materials produce acetylene compounds according to the process according to the invention, which are mostly new substances, which are used as intermediate products for the production of technical interesting, known and new compounds are versatile. Those acetylene compounds at the same time contain a carbonyl group, for example by catalytic Jatftial ^ or total hydrogenation in either known or new fragrances or flavors are transferred.

Preferred starting materials are also those enumerate those differing from α, β-unsaturated 7-oxosterol derive whose double bond sAschwiz two neighboring Carbon atoms of the steroid ring skeleton, i.e. in positions 1-17

They particularly belong to the series of Androstane, Pregnane, Cholane, Cholestane, Spirostane, or Furostane Cardanolides or their A-nor-, Α-homo-, B-nor- and / or B-homo-derivatives, as well as their 19-nor-derivatives, e.g. Oestrane and contain the oxo group in one of the positions 1, 2, 3, 4, 6, 7, 11, 12, 15, 16, 17 or 20. Primarily, the starting materials used are those that differ from 3-oxo-4,5- or 1,2-unsaturated steroids, 4-0xo-

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5,10-unsaturated steroids or from 20-0xo-16,17-unsaturated Derive steroids of the above series.

Among the starting materials, those that are derived from compounds are particularly to be designated as being whose enone system is in a transoid configuration.

First and foremost, preferred starting materials also include those in which the radicals R, and Rp are connected to one another and / or in which the carbon atoms α and β are bridge members in a system with at least ⁵ locally host-condensed rings are. It goes without saying that the fragmentation according to the invention cannot be carried out or can only be carried out to a limited extent in the case of starting materials which would lead to extremely high-tension cyclic systems, such as, for example, a glyclobutin ring or cyclohexine ring.

In the preceding formulas, the radical X 'denotes in particular an oxo group or a nitrogen-containing group Derivative thereof, primarily the oximido group or its derivatives esterified or etherified at the oxygen atom, or a hydrazo group, its derivatives substituted by a nuoleofuge group R or an iminoaziridine group.

The radical Y is a hydrolysis into an oxo group under the reaction conditions and, if appropriate, subsequent hydrolysis convertible residue, such as a free or esterified hydroxyl

20982W117Q

group, e.g. one by a carboxylic acid or especially sulfonic acid, or a hydroxyl group esterified by hydrogen halide. But it can also be a together with the remainder of Z. Hetero atom, e.g. a nitrogen or preferably oxygen atom, including a bridge over the carbon atoms α and ß, primarily represent an epoxy group.

The radical Z also corresponds to the radical R ¹ and is then particularly a reactive esterified hydroxyl group, in particular a hydroxyl group which is acidic with a strong inorganic acid, for example hydrochloric or hydrobromic acid, with an organic sulfonic acid , such as lower alkane, for example methane or ethanesulphonic acid, or aromatic sulphonic acids, for example benzene, p-toluene or ρ-chlorobenzenesulphonic acids, or with an organic carboxylic acid, in particular aromatic carboxylic acid, such as benzoic acid, p-nitro, p-chloro or 2,4-Dinitrobenzoic acid or is esterified with monoesters of carbonic acid, for example ethoxyformic acid, The esters with methane or p-toluenesulfonic acid or with hydrogen chloride are particularly suitable.

In above. Partial formulas R means a hydrogen atom or a nucleofugal group, such as the residue of an organic sulfonic or sulfinic acid, in the first place! Line of an allphatic Sulfonic or sulfinic acid, such as a lower alkane, e.g. methane or ethanesulfonic acid or an aromatic, in particular monocyclic aromatic sulfonic acid, such as benzene, toluene, halobenzene, nitrobenzene,

209824/1170

primarily p-toluenesulfonic acid. However, R can also represent a halogen atom, such as a chlorine, bromine or iodine atom or an alkoxy, aryloxy, alkylthio or arylthio group. The attachment of the radicals Y and Z to the double bond between the carbon atoms α and β takes place in a manner known per se, as does the conversion of the oxo group on carbon atom 7 into a dlazonium radical. The ketones can thus be ^{reacted with hydrazine and the N 1} -unsubstituted hydrazones are obtained, which are then converted, for example by oxidation, into the mostly undetectable diazonium compounds.

· .; . £, - ■ © .ie -decomposition and fragmentation of the N ¹ -uhsubstitu- ■ ated hydrazones can ζ-.B. can be achieved by oxidation. In this case, it is preferable to oxidize under mild conditions, such as, for example, at low temperatures. Suitable oxidizing agents are generally those agents which are able to convert hydrazones into diazo compounds, for example metal oxides or metal peroxides such as mercuric oxide, manganese dioxide, silver oxide, lead oxide, sodium peroxide, nickel peroxide, and also molecular oxygen, halogens, hypohalites, organic peracids and diazodicarboxylic acid esters. The oxidation is preferably carried out in a solvent in which both the hydrazone and the oxidizing agent are soluble, e.g. in methanol, ethanol, acetic acid, acetone, ether, etc.

Hydrazones whose N ¹ nitrogen atom is substituted by a nucleofugal group (R), for example a Tosy group

209824/1170

is, can by means of inorganic or organic bases, for example alkali metal hydroxides, alkali metal alcoholates, such as Sodium methylate, or potassium t ^ butylate, or pyridine or Piperidine, to be fragmented. The fragmentation also succeeds when using acidic reagents such as Brönsted acids such as acetic acid, sulfuric acid or. Phosphoric acid or Lewis acids. The fragmentation can also be carried out in dimethyl sulfoxide run using sodium hydride. It can also be brought about thermally or photochemically. The reaction is two-fold in polar solvents, such as Methanol, methanol, dimethyl sulfoxide, dimethylformamide, Methylene chloride, chloroform or acetonitrile carried out. It is also possible to cause the fragmentation by having the hydrazones in a heterogeneous phase polar adsorbents, primarily those with a large surface area, e.g. silica gel at room temperature brings. For example, the hydrazone dissolved in ether can be applied to a column of silica gel soaked with hexane and elute with an ether-hexane mixture. The wished Fragmentation product can then from the eluate in the usual way Way to be won. You can also bring about the fragmentation with an ion exchanger by adding a solution of the Bringing hydrazone into contact with a hydrazone, e.g. at an elevated temperature.

In many cases, decomposition and fragmentation are extremely easy. So the initial

209824/1 170

.23- Ί643948

hydrazone often already under the conditions in which they are are formed, decompose in the desired manner, for example in the implementation of an α, ß-oxido-7-oxo compound with tosylhydrazine in a polar solvent such as a lower aliphatic alcohol, e.g. methanol, Ethanol, propanol, in dimethyl sulfoxide, dimethylformamide or in lower aliphatic carboxylic acids such as acetic acid. This variant proves to be particularly advantageous if the hydrazone is in a mixture of methylene chloride-acetic acid at temperatures between about -35 to about ^. 30 °, ^ in particular below -10 °, and the reaction mixture optionally warmed to temperatures above 0 °. In this case, is there excess hydrazine or If the starting materials are only formed at an elevated temperature, e.g. at room temperature, the formed carbonyl group in the process product, in particular an aldehyde group, at the same time in the corresponding hydrazone be transferred. If there is a highly reactive oxo group in the end product, it is therefore advantageous to use one Excess of hydrazine compound. The resulting. Hydrazo group can be, for example, by hydrolysis or by Cooking with a reactive aliphatic carbonyl compound, such as acetone or pyruvic acid, cleave to the oxo group. In the isolation of obtained aldehydes e.g. in the presence of alcohols the corresponding acetals or hemiacetals are formed very easily.

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For the conversion of the oximes, their esters or ethers in the diazonium compounds and for their decomposition and fragmentation, the oximes and their derivatives are placed in basic form Environment with a reactive ester of hydroxylamine. In particular, esters are used as such strong inorganic acids such as sulfuric acid, hydrohalic acid e.g. hydrochloric or hydrobromic acid, with organic Sulphonic acids, such as lower alkane, e.g. methane or ethanesulphonic acids, or aromatic acids, e.g. benzene, Toluene or p-chlorobenzenesulfonic acid, or with organic Carboxylic acids, especially aromatic carboxylic acids, such as benzoic acid, p-nitro, p-chloro or 2,4-dinitrobenzoic acid, or with monoesters of carbonic acid e.g. ethoxyformic acid. The esters of hydroxylamine with methane or p-toluenesulfonic acid or the chloramine in primarily the sulfuric acid ester of hydroxylamine. This inventive implementation is carried out as

already emphasized above, in a basic medium, for example in an alkali metal hydroxide solution, e.g. in aqueous Sodium or potassium hydroxide solution, if desired, with the addition of ammonia. It will preferably be in one with water at least partially miscible solvent made, such as in a lower aliphatic alcohol, e.g. methanol, ethanol or a cyclic ether such as tetrahydrofuran or dioxane. Should two phases form in the reaction mixture, ensure that the mixture is well mixed by stirring. The renkt i ^ n

2 ^ / 1170

BATH ORIGINAL

takes place at a higher temperature, but preferably when left to stand at room temperature or lower temperature. It usually ends after 2-24 hours. The reaction products can be isolated in the usual way.

The invention also relates to those embodiments this process by which the starting materials are formed under the reaction conditions. So you can e.g. the chloramine to be used as a reagent, which is composed of aqueous sodium hypochlorite and concentrated aqueous ammonia is obtainable at low temperatures, e.g. 0 °, in the presence of the oxime and the basic agent as an intermediate and perform the fragmentation by standing for 5-6 hours or gently warming.

But you can also use the oxime or its esters or ethers starting from the corresponding 7-carbonyl compounds form under the reaction conditions, for example by reaction in a basic medium with an excess of reactive Esters or ethers of hydroxylamine. The desired fragmentation can be achieved directly. The intermediate formation of the oxime, its esters or ethers and their cleavage can also be seen by reaction with a Achieve mixture of hydroxylamine and said esters or ethers of hydroxylamine in a basic medium.

Those obtainable by the process according to the invention Products are largely new compounds, which as such have interesting technical or physiological properties

209824/1170

own businesses and therefore directly for various purposes Are useful or as starting materials or intermediates for the production of known or new industrially valuable organic compounds can be used.

The method according to the invention can be applied to the various areas of the organic chemical industry are used. With the help of this new procedure succeeds it, for example, to produce disubstituted acetylene compounds that were previously difficult or impossible to obtain was. .

The method according to the invention is suitable, for example, both for the production of known odoriferous and flavors that were previously only available after cumbersome and uneconomical processes, as well as for Development of numerous new fragrances and flavors. From suitably substituted penten- (2) -one and hexen- (2) -one compounds one can use the new process numerous, partly known partly new unsaturated aliphatic Produce aldehydes and ketones with an ice double bond. A particular advantage of the invention is that the process end products have triple bonds that by partial catalytic hydrogenation easily into cis double bonds get convicted. The new process also makes it possible to produce macrocyclic fragrances, e.g. cyclopentadecanone (EXALTON) and J-methyl-cyclopentadecanone (MUSKON),

209824/1170

which are important for the fragrance industry and which have so far been very important due to the lack of economical manufacturing processes
were expensive to manufacture in a simpler and much more economical way.

The α-Οχο-α, β-seeo-steroid-ß (7) -ins obtained by the new process, especially those of the oestran, androstan, pregnan, cholan, cholestan, spirostan, purostan and cardanolide series are new and also form an object of the present invention. They represent a new class of compounds in the steroid series. They are intermediate products for the production of biologically active steroids. For example, the (5,6) - or (5,10) -enol form of 5-oxo-3-yne-4,5-seco compounds can be alkylated in the 6- or 10-position and, after hydration of the triple bond, the A ring
conclude. The well-known, highly effective 6- or 10-alkyl-3-oxo-steroids are obtained. If they are known to
effective steroids, such as testosterone, progesterone,
Cortisone etc. have essential groups, they also have interesting pharmacological effects. Thus, for example, shows 17β-hydroxy-5-oxo-4,5-seco-19-nor-androst-3-yne and its esters, especially those with lower ones
Alkanoic acids, especially with acetic acid, are an interesting one
anti-ovulatory effectiveness without concurrent other
To show hormone effects.

Of particular note are the ring-A-seco-steroids of the androstane and pregnan-

20982 4/1170

hey, like the ring-D-seco-steroids with aromatic ring A, e.g. l-oxo-l ^ -seco-androst-S-ine, l-oxo-l ^ -seco-pregn-2-ine, 5 ~ Oxo-4,5-seco-androst-3-ine, S-Oxo- ^ S-seco-pregn-3-ine and ΐ6-0χο-ΐ6,17-3βοο-Δ '-''- ^ -19-nor-pregnatrien-17 (20) -ineferner 9-0xo-9, ll-seco-steroid-ll (12) -ine of the oestran, androstan, pregnan, cholestan, cholan and spirostan series and 10-0xo-5,10-seco-steroid ~ 4 (5) - and -5 (6) -ine of the 19-nor-androstan-, pregnan-, cholestan-, cholan-, spirostan- and Cardanolld series.

The invention also relates to those embodiments of the method in which the starting materials are under forms the reaction conditions, as for example above already mentioned.

The new compounds can optionally be used in the form of pharmaceutical preparations. These contain the compounds mixed with a pharmaceutical suitable for enteral, topical or parenteral administration organic or inorganic, solid or liquid carrier material. Such substances come into being for the formation of it in question that do not react with the new compounds, such as water, gelatin, lactose, starch, stearyl alcohol, Magnesium stearate, talc, vegetable oils, benzyl alcohol, Gum, propylene glycol, polyalkylene glycols, petrolatum, cholesterol or other known excipients. The pharmaceutical preparations can be used, for example, as tablets, coated tablets, ointments, creams, Capsules or in liquid form as solutions, suspensions

20982 A / 1 1 70

or emulsions are present. If necessary, they are sterilized and / or contain auxiliary substances such as preservatives, Stabilizing, wetting or emulsifying agents, solubilizers or salts to change the osmotic pressure or buffers. You can also find other therapeutically valuable ones Contain substances. The preparations are obtained by customary methods.

The new compounds can optionally also in veterinary medicine, e.g. in one of the forms mentioned above.

The starting materials used according to the invention are known or can be obtained in a manner known per se will.

The oximes of the 7-oxoa, ß-oxido-steroids, used as starting materials, whose epoxy groups sit on two adjacent carbon atoms of the steroid ring skeleton are new. They also form an object of the present invention.

Also new are the hydrazones and oximes of the 7-oxo-a-hydroxy-ß-R'-steroids used as starting materials, the hydroxyl and R ^{1 groups of which are located} on two adjacent carbon atoms of the steroid skeleton. They also form an object of the present invention.

The invention is described in more detail in the following examples. The temperatures are in degrees Celsius specified.

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Example 1ϊ

11 g are dissolved
which has the following structural formula:

in 1 liter of methanol, add 6 ml of 6N sodium hydroxide and 25 ml 30% hydrogen peroxide is added and the solution is stirred for 24 hours at room temperature. The reaction solution is in Poured 4 liters of ice water and extracted several times with methylene chloride. The extract becomes neutral with saline washed, dried with sodium sulfate and freed from the solvent. In this way, 9.1 g of crude product, Man chromatographed 8.9 S of this product on thirty-fold Amount of silica gel {Merck; Grain size: 0.05 - 0.2 mm) using a hexane-ether mixture in a volume ratio of 9: CL. 6.32 g of pure material are isolated from the eluate 1,12-Epoxy-bicyclo [10.3.0] pentadecane-13-bn, which the following Structural formula applies;

209824/1 170

The product has the following physical properties: Kp - 120 ° C / O, O6 Torr; η "°" l, 5043i W: Ä _mSiV " 303 πιμ, £ o 45 j IRj r _Ce0 m 1742 cm" ¹ .

5.9 g of epoxy ketone are dissolved. in 20 ml of ethanol, a solution is from 5 * 0 g tosyl hydrazine in 20 ml of ethanol are added and the total solution to stand for 40 hours at room temperature. The reaction mixture is poured into water and extracted with ether. The extract is extracted twice with saline solution and then dried with sodium sulfate. Removal of the ether gives 9.8 g of a yellow oil containing the tosylhydrazone of 1,2-epoxy-bicyclo [10.3 °] pentadecan-13-one, which is processed further without further purification. 2.04 g (5 millimoles) of the crude tosylhydrazone are dissolved in 10 ml of abs. Methanol, the solution is heated to reflux temperature and 10 ml of 1 molar methanolic sodium methylate solution are added. After refluxing for 24 hours, the dark brown reaction solution is poured into water and extracted with ether. The extract is washed neutral with water and freed from the solvent. 1.25 g of crude product are obtained. By distilling twice in a bulb tube at 1O4-1O6 ° C / O5 Torr, 682 mg of pure Cyolopentadec .- ^ - is obtained. .ih-l-on,. that slowly freezes. P. = 41-42 ° C. IR spectrum:

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Example 2:

60 mg of a sodium hydride dispersion are washed in oil (50%) under nitrogen several times with pentane, 10 ml of dimethyl sulfoxide are added and the mixture is stirred for 2 hours at room temperature. A solution of ^{100 m} S of the crude tosylhydrazone prepared according to Example 1 in 4 ml of dimethyl sulfoxide is then added and the reaction mixture is stirred for 2 hours at room temperature. The dark brown reaction solution is taken up in ether and extracted several times with dilute sodium chloride solution. By removing the ether, 202 mg of crude product is obtained, which is distilled in a bulb tube. The product boiling at HO ⁰ C / 0.02 Torr consists of 75 mg of cyclopentadec-4-yn-1 ^ -one. which is identical to the product prepared according to Example 1.

The Cyclopentadec ^ -in-l-one. can be used as an intermediate in the manufacture of cyclopentadecanone, which is a well-known fragrance substance, as shown below: _#

100 mg of crystallized cyclopentadec.-4-in-l-one are in 2 ml of ethanol using a palladium-carbon catalyst hydrogenated at room temperature. After uptake of 16.7 ml of hydrogen within about 4 minutes, the hydrogenation takes place to a standstill. The catalyst is filtered off, the solvent is removed and the crude product is distilled in a bulb tube at 120-130 ° C / 0.05 torr. 77 mg of cyclopentadecanone are obtained

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with a P. of 58-63 C,

If, in Example 1, the starting ketone is replaced by 14-methyl-cyclopentadec-1 (12) -en-13-one, the corresponding 3-methyl-cyclopentadecyn- (4) -one (1) is obtained, from which, by catalytic hydrogenation 3 ~ M ^et hyl-cyclopentadeoanon- (l) is available.

Example 3:

30 g of 2 ~ ethyl-eyclopenten- (2) -one- (l) are dissolved in 25O ml of methanol and at -5 ° with 215 g of a 30 percent. aqueous hydrogen per oxide solution. Subsequently, 23 ml of 6N aqueous sodium hydroxide solution are added dropwise to this solution in accordance with the increase in temperature with vigorous stirring so slowly (approx. within 15 minutes) that 0 ° is not exceeded. Stirring is continued for two hours , worked up as described in Example 1. In this way, 27 g of a reaction product are obtained which, according to gas chromatographic analysis, consists of 85 % 2-ethyl-2,3-epoxy-cyolopentanone. Yield; 82 %. Bp = 65-67 ⁰ ZlO Torrj djf ° = 1.0536? Η ^ ⁰ »1.4558.

The epoxy ketone prepared in this way (5 g) is dissolved in 100 ml of a methylene chloride-acetic acid mixture (1: 1) with 8 g of tosylhydrazine left to stand for 5 minutes. The resulting solution of 2-ethyl-2,3-epoxy-cyolopentanon-tosyihydrazone is while stirring vigorously and at the same time passing through Air poured into 3 °° ml of 5% sulfuric acid. By evaporation

201124/1170

of the methylene chloride gives an orange precipitate. The aqueous phase is decanted off and the residue is washed again with water and heated under reflux with 50 ml of hexane for half an hour. This treatment with hexane is repeated, the hexane extracts are washed neutral with water and concentrated. The reaction product is distilled in vacuo. Pure hept-4-yn-1-al of bp ^ ₅ = 88 ° is obtained in this way; dj ⁰ = 0.9085; rip ⁰ * 1.4507, IR spectrum: · -CHO at 2720 and 173Oj ♦ '"' - CsC- at 2230 cm" ¹ .

From the heptin- (4) -al- (l) one can prepare cis-heptin- (4) -al- (l), as described below.

100 mg of the heptane (4) as- (1) obtained are dissolved in 2 ml of ethanol and, after the addition of a spatula tip (10-20 mg) of the deactivated palladium-carbon catalyst, are subjected to catalytic hydrogenation at room temperature. After the uptake of 1 mole of hydrogen, the rate of hydrogenation decreases significantly. The reaction is now interrupted, the catalyst is filtered off and the solvent is evaporated off. Distillation of the residue in a bulb tube gives 80 mg of a reaction product which, according to spectroscopic behavior, gas chromatographic analysis and physical data, consists of pure cis-heptene- (4) -al- (l). Kp = 42 ° / 10 mm Hg, ng «1.4405. IR spectrum: -CHO at 1720 cm " ¹ } -CH = CH- (cis) at 715 cm" ¹ d ^ ° = 0.8663.

Example 4:

To a solution "of 82 g jasmine (a mixture of 65 $ of the cis and 35 # of the trans compound) in 750 ml of methanol 284 g of a 28% hydrogen peroxide solution are added and the mixture is cooled

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to -5 ° and add 49 g of a 6 N aqueous sodium hydroxide solution dropwise and with stirring over the course of 45 minutes. The temperature rises to 2-4 °. It is left to stand for 18 hours, then the reaction mixture is poured into water, extra. heals and cleans the product obtained. This gives 55 6 of the epoxy jasmone, which at O ₄ OOl mm mercury pressure at 61-

64 ° passes.

4.95 g of the epoxy jasmone and 6.2 g of tosylhydrazine are dissolved at 0 in 65 ml of a 2: 1 mixture of methylene chloride and acetic acid, whereupon the temperature is slowly increased Increases by 20 °. The nitrogen evolution that begins is then accelerated by heating to reflux temperature and adding 1 g of toluenesulfonic acid. To 9 1/2 hour boiling on the reflux condenser, the reaction mixture is cooled and 100 ml of concentrated sodium bicarbonate solution are added to. The reaction mixture is steam distilled and the distillate is extracted with ether. After drying and evaporation of the ether, 2.2 g of the crude indec-8-en-5-yn-r2-one are obtained.

Ig this ketone is dissolved in 3 ml of pentane and mixed with Hydrogen hydrogenated in the presence of 0.1 g of palladium-charcoal catalyst. After the usual work-up and distillation pure undecan-2-one is obtained, which is identical to that produced by other means.

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Example 5:

40 g of 2-methyl-2,3-oxido-cyclohexan-l-one are added with stirring to an ice-cooled solution of 62 g of tosylhydrazine in 600 ml of a 2: 1 mixture of methylene chloride and acetic acid. The reaction solution immediately turns yellow-orange and evolves nitrogen. Approximately 4530 ml of nitrogen is obtained after 90 minutes. The reaction mixture is poured into 1 l of water and extracted twice with ether. The ethereal solutions are washed with 10% aqueous sodium hydrogen carbonate solution and with saturated sodium chloride solution and evaporated in vacuo. The residue is distilled with steam in the presence of 500 mg of calcium carbonate, the distillate is extracted with ether, evaporated and the residue is distilled in vacuo. One obtains' 13.5 g hept-5-al * nl Kp of _{15 mm} 65-66 ⁰

O(\ OCi

n £ = 1.4554, _dj ^y = 0.9210.

The structure of the compound obtained can be converted into the known Hepten-1-al by means of catalytic Hydrogenation can be confirmed.

The starting material can be obtained as follows: 23.5 g of 2-methyl-cyclohex-2-en-l-one (obtained according to Org.Synth. Collect. Vol IV, 162, 1963) are mixed in a mixture of 258 g of 30 # -igen hydrogen peroxide and 750 ml of methanol dissolved. Is added within 1 hour, at I5-I8 ⁰ with vigorous stirring and cooling, 76 g of a 20 # aqueous Natriumhydroxyd-

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solution to. The mixture is stirred at 20-25 ° for 3 hours, the reaction solution is poured into 2 liters of saturated sodium chloride solution and the ether is extracted in a Kutscher-Steudel extractor. The extract is evaporated and distilled in vacuo. 46 g of α-methyl-1-oxido-cyclohexan-1-one are obtained in this way, which passes over at 72 ° -78 ° under 14 mm excess pressure; djj ° «1.0830j χξ ° - 1.4649. ■

11.2 g of hept-5-in-l-al are hydrogenated in 3 ° ml of pentane and in the presence of 1 g of poisoned palladium catalyst. After adsorption of one equivalent of hydrogen (after about 8 hours), the work is carried out as usual and, after distilling the crude product, 9.1 g of cis-hept-5-en-1-al with a b.p. _{17 m} 54-55 ° are obtained; crack ⁰ - 1.4360, d ^ ° «0.8586. This compound has a strong, fresh green odor.

Example 6:

24.8 g epoxy-isophorone, prepared according to the method described in Org. Synth., Coll. Vol. IV, 552, described method,

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and 31.5 g of tosylhydrazine (= 5 # excess) were in 280 ml Stirred alcohol at room temperature for 6 hours. The reaction mixture was then poured into water and washed with ether extracted. The extract was washed twice with brine and dried with sodium sulfate. After removing the Aether remained 49.7 g of a yellow, thick oil that not crystallized and was further processed directly. 9 g of the Toeylhydrazone dea Epoxy-isophorone containing oils were dissolved in 90 ml of dimethyl sulfoxide and stirred under nitrogen for 22 hours with 3.4 g of potassium hydroxide, the solution slowly turning brown with evolution of nitrogen. To work up that was Poured reaction mixture into approx. 500 ml of water and extracted with ether. The extract became neutral with saline washed ^ After distilling off the ether, 2.45 g remained low-viscosity crude product, which was distilled in a bulb tube at 11 Torr. 971 mg of a distillate which passed over at approx. 70 ° and which was obtained from 4,4-dimethyl-heptin- (6) -one- (2)

20th
consisted (n £ - 1.4423). IR spectrum: bands at 3300, 2950,

2130 and 1715 cm " ¹ .

The 4,4-dimethyl-heptin- (6) -one- (2) can by partial catalytic hydrogenation in 4,4-Dimethyl-cis-hepten- (6) -one- (2) and by catalytic total hydrogenation in 4, 4-dimethyl-heptanone- (2) are converted.

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Example 7:

1.29 g of the tosylhydrazone obtained in Example 1 were dissolved in 12 ml of abs. Dissolved dimethyl sulfoxide and mixed with 430 mg of sodium ethylate (= 100 $ excess). The reaction mixture was stirred under nitrogen at room temperature for 20 hours. For work-up, the reaction mixture was poured into water and extracted with ether. The extract was washed neutral with water. After removal of the solvent, 967 mg of a crude product remained, which was ^{distilled in a bulb tube at 105-150 o} / 0.02 torr. 466 mg of a product were obtained which proved to be identical to the cyclopentadecin- (4) -one- (1) prepared according to Example 1. V

Example 8:

1 * 25 g of the tosylhydrazone prepared according to Example 1 were in 12 ml of abs. Dissolved dimethyl sulfoxide and treated with 685 mg of potassium tert-butoxide (= 100 $ excess). The reaction mixture was stirred for 7 hours under nitrogen at room temperature. In the process, nitrogen evolution occurred immediately while the solution turns brown. The work-up of the reaction mixture was the same as in Example 7 carried out, whereby one received 856 mg of crude product, which in the spherical

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1643348

tube was distilled at 107-125 ° / 0.03 Torr. There were 421 mg of cyclopentadec-4-in-l-one from P '. 39-41 ° obtained.

Example 9:

On a column of 135 g silica gel (Merck, grain size 0.05-0.2 mm) in hexane, 4.5 g of the tosylhydrazone prepared according to Example 1 were slowly applied in ether. Vigorous evolution of nitrogen immediately occurred. the Elution was carried out with a 2 liter ether-hexane mixture 4: 1. Cyclopentadec-4-yn-1-one was obtained in about 70% yield vom P. 40-42 °, which turned out to be identical to the comparator preparation.

Example 10:

By partial catalytic hydrogenation of the cyclopentadecin- (4) -one- (l) one arrives at the cis-Cyclopentadecen- (4) -one- (l), as this is described in the following:

220 mg of cyclopentadecin- (4) -one- (l) were in ethanol using 220 mg of palladium-carbon catalyst, the was poisoned with pyridine, hydrogenated until the theoretical amount of hydrogen was absorbed. After filtration and removal of the alcohol, 212 mg of crude product were obtained, which was distilled in a bulb tube at 80 ° / 0.01 Torr. One received

209824/1170

20th
204 mg of a colorless oil, n ^ = 1.4914, which tended to crystallize slightly on standing and which turned off. -; · cis-cyclodecen- (4) -one- (l) consisted. When tested by gas chromatography, the product had a purity of 98.5 % . IR spectrum: bands at 3020, 2925, 2880, 1713 ,. 1652 (shoulder) and 7IO cm ".

The cis-cyclopentadecen- (4) -one- (l) is a new substance that has excellent odor properties.

By partial hydrogenation of the homologous 3-methylcyclopentadecin- (4) -one- (l) 3-methyl-cis-cyclopentadecen- (4) -one- (l) is obtained in an analogous manner, which is also is a new very interesting fragrance.

Example 11:

The complete catalytic hydrogenation of the cyclopentadecin- (4) -one- (l) led to the well-known cyclopentadecanone, as described below:

1.5 g are added to a spatula tip of Raney nickel suspended in 10 ml of pure methanol and pre-hydrogenated Cyclopentadecin- (4) -one- (l) in 20 ml of methanol and then allows hydrogen to act while shaking until the Absorption of this gas has practically come to a standstill. After the ;, ΛΊ:? * Filtration of the catalyst and removal of the 1.4 g of reaction product are obtained, which spontaneously crystallizes after distillation in a bulb tube. on

209824/1170 _BAD

This produces a ⁰ at 63-65 melting cyclopentadecanone, which in admixture: shows with the authentic compound no melting point depression, but also at 63-65 ° melts (1: 1).

This hydrogenation product is in the IR spectrum no evidence of the presence of an acetylene bond or an ethylene bond. In contrast, one recognizes as in the initial connection, the strong absorption of a Carbonyl group at about 1710 cm ".

By catalytic hydrogenation of 3-methylcyclopenta-. decin- (4) -on- (l) in the manner described above, a completely saturated liquid ketone is obtained, according to IR spectrum is identical to the well-known (+) - Muscon.

The BicyclotlOO'Olpentadecrl ^ lSj-en-T ^ '- o ^ and that ^ -Methyl-bicyclo [10.3.0] pentadecTl (12) -ea * il3ron, which Compounds according to Example 1 and 2 can be used as starting materials, for example according to the method described by BÖCHI et al. described method [J.Am.Chem.Soc. 22 * 5558 (1957) 1 by condensation of cyclododecanone with succinic acid diethyl ester or methyl succinic acid diethyl ester according to STOBBE, cyclization of the condensation product by means of Polyphosphoric acid and acid hydrolysis of the resulting bicyclic ß-keto ester are produced.

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Example 12:

200 mg of tosylhydrazine are added to a solution, cooled to -20 °, of J> k6 mg of 3-oxo-4ß, 5-oxido-17ß-acetoxy-5ß-androstane in 2 ml of methylene chloride and 2 ml of glacial acetic acid. The yellow solution is stirred for a further 20 hours at -20 °, then warmed to room temperature, the tosylhydrazone formed within about 2 hours with fragmentation and release of the above. 25 ml of nitrogen decomposed. The now colorless reaction mixture is diluted with ether, washed successively twice with water, twice with saturated ice-cold sodium hydrogen carbonate solution and three times with saturated sodium chloride solution, dried and evaporated in a water jet vacuum. The oily crude product obtained is chromatographed on 20 g of silica gel (Merck). With a methylene chloride-ethyl acetate (20: 1) mixture, 318 mg of 5-0xo-17β-acetoxy-4,5-seco-androst-3-yne are eluted. After recrystallization from pentane, 276 mg of the pure compound from P. 95-96 ^{0 are obtained} . In the IR spectrum, this has bands at 3300, 2120, 1725 and. 1700 cm " ¹ .

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Example 13 =:

A solution of 684 mg Ια, 2a-0xido-3-oxo-17ß-acetoxy-5a-androstane in 4 ml of methylene chloride and 4 ml of glacial acetic acid is cooled to -20 °, treated with 400 mg of tosylhydrazine and stirred for a further 15 hours at the same temperature. With subsequent When the yellow reaction solution is warmed to room temperature, about 50 ml of nitrogen are developed while decolorizing. After the addition of ether, the reaction mixture is with Water, sodium hydrogen carbonate and washed neutral with saline, dried and evaporated in a water jet vacuum. Crystallization from ethanol or ethanol-water supplies 541 mg of pure l-0xo-17ß-acetoxy-1,2-seco-5a-androst-2-yne from P. 126-127 °. The analytically pure connection melts at 129 °.

Example 14:

5.0 g of 3-0XO-4,5-oxido-11β-hydroxy-17a, 20; 20,21-bismethylenedioxy-pregnane are suspended in 100 ml of ethanol and after adding 2.325 g of tosylhydrazine (1.05 equivalents) stirred at 25 °. After a few minutes, the reaction mixture turns yellow, the starting material goes into solution and

209824/1 1 70

nitrogen evolution begins. After a further 15 hours at constant temperature, insoluble constituents are filtered off, the piltrate is diluted with water and exhaustively extracted with ether. The organic solutions are washed with water, dilute sodium hydrogen carbonate solution and again with water, dried and evaporated in a water jet vacuum. 4.95 g of a colorless foam are obtained, which are chromatographed in toluene g \ .xöst on 50 times the amount by weight of silica gel. With toluene-ethyl acetate (95: 5) mixture, a total of 3 * 75 g is eluted by thin-layer chromatography (Systemi toluene-ethyl acetate (9: 1) mixture) of pure S-oxo-11β-hydroxy-17a, 20j 20,21-bismethylenedioxy- 4,5-seco-pregn-3-in, which in the IR spectrum includes bands at .2.78, 3.05, 4.73, 5 * 87, 8.08, 9.10, 9.20 and 10.58 μ. .

Starting from the corresponding I9-Nor connection the 5-0xo-llß-hydroxy-17a, 20: 20,21-bismethyle.ndioxy ^ S-seco - ^ - nor-pregn ^ -in is obtained in an analogous manner, that in the IR spectrum u: .a. Bands at 2.80, 3.04., 4.75, 5.85, 9 * 10 # 9 * 20 and has 10.58 μ ..

Example 15 *.

3 * 7 g S-

dioxy-4,5-seco-pregn-3-yne are dissolved in 23Ο ml of tetrahydrofuran and 700 ml of 2 _# 66-N-aqueous perchloric acid are carefully added, while cooling and stirring. After 18 hours

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'- 46 - "■

at room temperature the reaction mixture is diluted with 1 liter of water and extracted exhaustively with ether-methylene chloride (4si) mixture. The organic phases, washed neutral with sodium hydrogen carbonate solution and with water, after drying and evaporation in a water-jet vacuum yield 3.41 g of a colorless foam which, according to thin-layer chromatography, contains only traces of starting material. For the purpose of purification, the crude product obtained is dissolved in toluene and chromatographed on 50 times the amount by weight of silica gel. With toluene-ethyl acetate (9: 1) mixture, 3.05 g of a foam are eluted which, after dissolving from a very small amount of ether, 2.53 g of pure 5 » 20-dioxo which crystallizes with one mole of ether as the crystal solvent -llß, 17a, 21-trihydroxy-4,5-seco-pregn ~ 3-in from P. 82-85 °.

Example 16;

1 * 05 g of 3β-acetoxy-16a, 17-oxido-20-oxo-A -pregnen are dissolved in a mixture of 20 ml of methylene chloride and 10 ml of acetic acid, cooled to -15 °, with 1.00 g of tosy! hydrazine added and stirred at -20 ° for 20 hours. The yellow solution is then warmed to 25 °, within 2 hours develop approx. 165 ml nitrogen. The reaction mixture is diluted with ether and washed with water, ice-cold sodium hydrogen carbonate solution and neutral with saturated sodium chloride solution, it is dried and evaporated in a water-jet vacuum

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a. When mixed with ether, the residue yields 250 mg of 3β-acetoxy-16-oxo-16,17-seco-A -pregnen-17 (20) -in from P. 120 ° (indistinct). Chromatography of the mother liquors on silica gel and subsequent crystallization of the product obtained from methylene chloride-pentane gives a further 353 mg of the same compound from P. 121-124. When the aldehyde obtained above is recrystallized from ethanol-water, the oxo group is aeetalized, resulting in 3β-acetoxy-16,16-diethoxy-16,17-seco-Δ-prepregnen-17 (20) -in ^{, which melts at 132-133 0} .

Example 17:

1 * 0 g of 3-oxo-4β, 5-oxido-17β-acetoxy-19-nor-androstane are dissolved in 20 ml of alcohol and 0.625 g (= 1.05 equivalents) of tosylhydrazine are added. The solution, which soon turns yellow, is stirred for 15 hours at room temperature. Conversion and fragmentation take place within 3-4 hours with _{evolution of N 2} and discoloration. The colorless solution is washed four times with water, twice with saturated sodium hydrogen carbonate solution and then with water until neutral, dried over sodium sulfate and evaporated. The resulting crude 5-oxo-17ß-acetoxy-4,5-seco-19-nor-androst-3-yne (1.1 g) shows bands at 3300, 29OO, 2850 in the IR absorption spectrum.

20 982Λ / 1170

2100 (weak), 17 ¹ IO, 1710 cm ~. After recrystallization from chloroform-petroleum ether, the pure compound melts at 94-95 °.

Example 18:

Under the conditions given in Example I7, 3-oxo-4,5-oxido-20,20-ethylenedioxy-21-hydroxypregnane is obtained (produced from 3,21-dihydroxy-20-oxo-A -pregnen by successive ketalization of the 20-oxo group,

Oppenaueroxidation of the 3-hydroxy-Δ-en group and anil
final epoxidation of the Δ double bond) converted into 5-oxo-20,20-ethylenedioxy-21-hydroxy-4,5-seco-pregn-3-yne, which after acid hydrolysis of the ketal group at C-20, using 66 # iger acetic acid, which yields 5,20-dioxo-21-hydroxy-4,5-seco-pregn-3-yne. P. = 126-127 ° (from ether).

Example I9:

A solution of 1.95 g (5 m mol) of 3ß-acetoxy-16a, I7-

5
oxido-20-οχο-Δ -pregnen in 10 ml of methylene chloride and 5 ml of acetic acid is mixed with 2.5 g (13.5 mol) of tosylhydrazine

2 0 9 8 2 4/1 1 7 Q

and cracked at room temperature. 145 ml of nitrogen are evolved within J5 hours. The reaction mixture is then diluted with ether and washed successively twice with water, three times with saturated sodium hydrogen carbonate and three times with saturated sodium chloride solution. The washing waters are extracted with an ether-methylene chloride mixture, the organic phases are combined, dried and evaporated in a water-jet vacuum. The oily residue obtained is diluted with a little ether and then pentane is added until it becomes cloudy. 3.0 g of crystals are obtained which, after recrystallizing three times from methylene chloride-ether-pentane, 1.916 g of tosylhydrazone of "^ ß-koetoxy- 16-0x0-16,17-seco-A -pregnen-17 (20) -in from P. 148-152 ° (decomp.) (Sinters from 144 °) deliver.

Example 20:

2.0 g of 3-methoxy-16a, 17-oxido-20-oxo-A ^lj5i5 ^ ¹⁰ ^ - 19-nor-pregnatriene are reacted with tosylhydrazine in the manner described in Example 16. The work-up and chromatographic purification on silica gel yields the 3-methoxy-16-oxo-

l6,17-seco-A '3 * 5 (1) _x9_ _nor _ _pregna t _r i _en ..i7 (2o) -in. The starting material is, for example, from oestrone methyl ether via the

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17-cyanohydrin, the corresponding Lö-dehydro-rf-cyano compound and the 3-methoxy-20-oxo-A '3 * 51 ), -19-nor-pregnatetraene prepared in a manner known per se.

Example 21:

15 g of crude 3-0xo-4SS, 5-oxido-17-hydroxy-17a-ethynyl-19-nor-androstane are dissolved in a mixture of ethyl alcohol 3OO ^m l, and 20 ml of methylene chloride and treated with 9.35 g of tosyl hydrazine. The reaction solution, which turns yellow, is then stirred for 15 hours at room temperature, the tosylhydrazone initially formed being fragmented with evolution of nitrogen. The reaction mixture is then mixed with ice-water and extracted twice with ether-methylene chloride (4: 1) mixture. The organic phases, washed with ice-cold dilute hydrochloric acid, water, dilute sodium hydroxide solution and again with water, are dried and evaporated in a water-jet vacuum. By chromatography of the crude product thus obtained on silica gel and subsequent crystallization of the uniform fractions from methylene chloride-ether-petroleum ether, 8.87 g of pure 5-oxo-17a-ethinyl-17β-hydroxy-4,5 · seco-19-nor-androst-3 are obtained -in won from P. 103-104 °. [a] _D = .- ^ 3 ° · IR. spectrum: bands at 2.77, 3.00, 4.72, 5.86 and 9.52 μ, among others. The starting material is obtained in a manner known per se by epoxidizing 27α-ethynyl-19-nor «testosterone.

209824/1170

Example 22:

A solution of 3.00 g of 3-methoxy-16a, 17a ~ oxido-20-οχο-Δ 'J' ^^ '-19-nor-pregnatrien in 60 ml of methylene chloride and 20 ml of glacial acetic acid is ^{cooled to -3O 0} , with 1.96 g of tosylhydrazine were added and the mixture was stirred for 15 hours at the same temperature. The strongly yellow colored solution is then slowly warmed to approx. 20 ° and stirred for a further 6 hours. The reaction mixture is then mixed with ice water, diluted with ether and washed successively with water, ice-cold sodium bicarbonate solution and with water. The washing waters are extracted with ether and the dried organic layers are evaporated in a water jet vacuum, whereby 3.0 g of the crude 3-methoxy-16-oxo-16,17-seco-A ^J 3o (. '-19-nor-pregnatrien-17 (20) -ins are obtained in the form of a foam The compound has bands in the IR spectrum at 3.42, 3.70, 5.81, 6.20, 6.30, 6.68, 8.10 and 9.67μ.

1 * 75 g of the crude aldehyde are dissolved in 20 ml of methanol with heating, then cooled to room temperature, treated with 100 mg of p-toluenesulfonic acid and left to stand at 20 for 15 hours. The reaction solution is poured into water and worked up as usual. 1.8 g of one are obtained. Crude product, from which 1.03 g of pure, slowly crystallizing 3,16,16-trimethoxyl6,17-seco- A'5'5Ki ⁾ -19-nor-pregnatrien-17 (20) -in obtained by chromatography on silica gel

209824/1170 ORIGINAL INSPiXfSD

7643948

will. [α] _β = + 44 °; IR, »spectrum: bands at 6.20, 6.34, 6.65, 7.25, 8.10 / 8.87 and 9.50 μ, among others.

The starting material is produced by epoxidizing the well-known J-methoxy-20-οχο-Δ '^ * · * ^' -19-nor-pregnatetraens.

Example 23:

800 mg of an epoxidation from 3ß, 17ß-diacetoxy-

5
7-oxo-Δ -and residues obtained mixture of the two epimeric 3ß * 17ß-diacetoxy-5, 6-oxido-7-oxo-androstane · in positions 5 and 6 are suspended in 20 ml of ethanol and after addition of 600 mg of tosylhydrazine Room temperature stirred. The starting material only gradually goes into solution with a yellow color and after approx. 40 hours a new product begins to precipitate. After 3 days approx. 25 ml of nitrogen have evolved and the reaction mixture is then worked up as follows. The precipitated product (320 mg) is filtered off and washed with ethanol - it represents undecomposed tosylhydrazone of 3ß, 17ß-diacetoxy-5 ^, 6-oxido-7-oxo-androstane and has bands at 3 in the IR spectrum, 16, 5.76, 6.25, 8.07, 8.40, 8.50, 9.15, 9.65 and 12.20 µ. (M.p. = 100 ° dec.). The filtrate is diluted with water, extracted with an ether-methylene chloride mixture, the organic layers are washed neutral, dried and evaporated in a water-jet vacuum. The crude product obtained (600 mg) ceases

209824/1170 v ^ iq ^ al ^ -

.Mixture, from which, by chromatography, 3IO mg of amorphous 3β, 17β-diacetoxy-5-0x0-5, ö-seco-androst-ö-in can be obtained. The compound has bands at 3.02, 4.75, 5.76, 8.08 and 9.70 μ in the IR spectrum.

Example 24:

2.30 g 3 _i 17-dioxo-4SS, 5-oxido-estrane and 1.60 g tosyl hydrazine are suspended in 50 ml of ethanol and stirred at room temperature. Approx. 190 ml of nitrogen develop within 2 1/2 hours and the almost colorless solution is worked up as usual. This gives 2.30 g of a yellowish ÖIS that after Dünnschichtchr-omatogramm represents a substantially pure 5,17-dioxo-4,5-seco-estr ^ 3 ~ i ^r i and crystallized slowly. The compound has bands at 3.05, 4.75, 5.75, 5.85, 8.05 and 9.20 μ in the IR spectrum.

Example 25:

5 g of hydroxylamine hydrochloride and 15 g of crystallized Sodium acetate is used until a paste is formed

rubbed and then mixed with 100 ml of alcohol. 5 g of the 17,20j20,21-bismethylenedioxy derivative are added to the filtered solution des 3,20-Dioxo-4ß, 5ß-epoxy-11ß, 17cty21-trihydroxy-pregnans and lets cook for one hour in a stream of nitrogen. then

20982 4/1170 original u \ * r2. ^ TcD

■: ■■ - ■ ■■; '■' * - 54 -

wird.mit water, extracted with .Methylene chloride, with Washed water, dried and evaporated in vacuo. Man receives 5.26 g of the 17.20; 20,21-bismethylenedioxy derivative of the 3-0ximino-4ß, 5ß-epoxy-11ß, 17a, 21-trihydroxy-20-oxo-pregnans in the form of a pale colored foam.

To a solution of the above obtained crude oxime 9OO mg in 60 ml of alcohol is added 15 ml n.Natronlauge stirring under ice cooling Wk and 700 mg of hydroxylamine-O-sulfonic acid. '. After stirring for 4 1/2 hours at room temperature, it is diluted with water and extracted with methylene chloride. The residue of the organic solutions washed with water, dried and evaporated in vacuo is added to 40 g of SiIi-

cagel, containing 15 % water, chromatograph! From the fractions eluted with toluene-ethyl acetate (19: 1) mixture, 425 mg of pure S-oxo-11ß-hydroxy-α, 20; 20,21-bismethylenedioxy-4,5-seGo-pregn-3 are obtained. -in, which after long standing is crystalline

ψ siert and 'after dissolving from a little ether melts at 124-127.

The same connection is obtained when one

• Instead of hydroxylamine-0-sulfonic acid, an alkaline ' Solution of chloramine used.

. Example 26: "

5 g of the 17,20, '20, 21 ~ Bismethylendioxyderivates of 3ί20-dioxo-4α, 5α-epoxy-LLSs, 17a-trihydroxy-21-pregnane be with 80 ml of an as prepared in Example 25 alcohol: '<■ ^f * ' : - ■ + ■ 2 0 9 8 2 4/1170 original inspsctso

. ■. :. ■ 1-6 * 3948

holic hydroxylamine acetate solution for 3 hours Boiled reflux in a stream of nitrogen. After cooling, it is suction filtered and washed with cold methanol and ether. 2.1 g of the 17,20j20 / 21-bismethylenedioxyderlvates are obtained 3-oximino ^ a, 5a-epoxy-llß, · 17a-21 -trihydroxy-20 -oxo -pregnans in the form of a colorless powder with a decomposition point of 272-275 °

900 mg of the oxime and 60 ml of alcohol are added under stirring and cooling with ice, 15 ml n.Natronlauge and 700 _m g hydroxylamino-Q-sulfonic acid shifted After l6 hours stirring at room temperature is worked up as described in Example 26 and containing at * 40 g silica gel 15 $ water, chromatographed. First, it is eluted with 460 ml of toluene. From the following fraction obtained with 1.2 l of toluene-ethyl acetate (19: 1) mixture, 730 mg of the 5-oxo-11ß-hydroxy-17a, 20; 20,21-bisraethylenedioxy described in Example 25 are obtained » 4,5-seco-pregn-3-ins, which melts at 124-127 ° after dissolving from ether-petroleum ether. .

Example 27:.

2.0 g of 3-oxo-4β, 5-oxido-17β-acetoxy-19-nor-androstane are dissolved in 75 ml of alcohol, 3 * 0S hydroxylamine hydrochloride and 10.0 g of sodium acetate are added and the mixture is refluxed for 2 hours . Customary work-up gives 2.05 S of crude 3-0x; Lmino-4β, 5-oxido-17β-acetoxy-19-norandrostane. This is dissolved in 100 ml of alcohol, under .lais- /.

- ■■ 209824/1170

cooling with 30 ml 1N sodium hydroxide solution and 1.5 g hydroxylamine-0-sulfonic acid added and stirred for 5 hours at room temperature. The reaction mixture is then diluted with water, extracted with ether-methylene chloride (4: 1) mixture, the organic phase was washed neutral with water, dried and evaporated in a water jet vacuum. The crude product obtained is acetylXert and chromatographed on silica gel for purification, 1.25 g of pure 5-0xo-17β-acetoxy-4,5-seco-19-norandrost-3-in received from the F. 93-95 °.

Example 28:

In an analogous manner, 1.5 g of 3-oximino-4a, 5 »oxido-17ß-acetoxy-5a- ^; androstane, which was produced from the corresponding 3-oxo compound by the action of hydroxylamine, when treated with hydroxylamine-0-sulfonic acid, or with hydroxylamine-0-p-toluenesulfonate, and after acetylating 850 or »7 ^ 0 mg S -Oxo-rrß-acetoxy- ^ S'-secö-androst-3 * in obtained, which melts after recrystallization from ether / petroleum ether at 94-96 °. ·

Example 29s

A solution of, 800 mg lo, 2a-oxido-3-oxo-17ß-jacetoxy 5a-androstane in 20 ml of methanol is mixed with 50 ml of one as in Example 25. hydroxylamine acetate solution in alcohol described

2 0 9 8 2 4/1170 V

added and refluxed for 2 hours. Work-up yields the crude oxime, which is dissolved in 50 ml of methanol, mixed with 15 ml of 1N sodium hydroxide solution and 700 mg of hydroxylamine-0-sulfonic acid while cooling and then stirred for 4 hours at room temperature. After adding water and ether, the reaction mixture is washed neutral with water, hydrochloric acid and with sodium chloride solution / dried and evaporated in a water jet vacuum. The crude product obtained is post-acetylated and crystallized from ethanol-water? <.- r ^v iv., where pure l-0xo-17ß-acetoxy-l _J 2-seco-5a-androst-2-yne precipitates. The analytically pure compound melts at 129 °.

Example 30:

I ₁ Og of 3.beta.-acetoxy-L6A, 17-oxido-20-oximino-A -pregnen ^ (prepared from the corresponding 20-Öxoverbindung according to Example 25) are dissolved in 60 ml of tetrahydrofuran, cooled to 0 °, with vigorous stirring with 15 ml of a 1N sodium hydroxide solution and 750 mg of hydroxylaniine-O-sulfonic acid and then stirred for 5 hours at room temperature. Work-up yields 920 mg of a crude product from which, after acetylation and chromatography, pure 3β-acetoxy-16-oxo-16,17-seco-pregnen-17 (20) -in from P. 121-124 are obtained.

209 8 24/1170

example

2.5 g of 3-methoxy-16a, 17-oxido-20-oximino-A ¹ ' ⁵ⁱ⁵ ( ¹⁰ ) -19-nor-pregnatriene (prepared in a manner known per se from 3-methoxy-20-oxo-A' 3 * 5 (1;, -19-nor-pregnatetraen via the corresponding Ιβα, 17-oxido compound) is reacted with 2.2 g of hydroxylamine-O-sulfonic acid under the conditions given in Example 25. The usual work-up and subsequent chromatography on silica gel yields 3-methoxy-16-oxO-16,17-seco-A * 3 * 5 { / -19-nor-pregnatrien-17 (20) -in »

Example 32:

To a solution of 3OO mg of 3,7,20; 20,21-Bismethylenedioxyderivates des 3,20-Dioxo-4ß, 5'ß-epoxy-11ß, 17a * 21-t3? I-- ■ Hydroxy-pregnans in 60 ml of alcohol are added with stirring 15 ml of sodium hydroxide solution and 800 mg hydroxylamine-0-sulfonic acid. After 5 1/2 hours it is poured onto water and extracted three times with methylene chloride. The residue of the organic solutions, washed with water, dried and evaporated in vacuo, is chromatographed on 40 g of silica gel containing 15 % water. After a preliminary fraction of 450 ml of toluene, 100 mg of 5-oxo-llß- are mixed with 600 ml of toluene-ethyl acetate (19: 1) mixture

2 0 9 8 2 A / 117 0

eluted, which crystallizes after standing for a long time and after Dissolve from a little ether. Melts at 124-127 °.

Example 33:

To a solution of the βΟΟ mg] 7,20j20> 21-Bismethylendioxyderivates of ^3,20-dioxo-1 J-, 5.11 .SS, 17a, 21-pentahydroxy-pregnan in β ml absolute pyridine are added under cooling with an ice-methanol mixture 0.6 ml methanesulfonyl chloride. After leaving to stand for 3 days at -10, the mixture is poured onto 15 ml of saturated sodium hydrogen carbonate solution and ice, stirred for minutes and then extracted several times with ether. The ethereal solutions are washed with dilute hydrochloric acid, dilute sodium hydrogen carbonate solution and water, dried and evaporated in vacuo at 30 ° with the addition of methylene chloride.

The resulting _21-i 17,20i20 Bismethylendioxyderivat of 3.20 »dioxo-4-mesyloxy-5, ILSS, 17a _A 21-tetrahydroxy-pregnan is dissolved in 10 ml of alcohol and, while stirring, 270 mg of p-toluenesulfonylhydrazine. 5 hours later, the reaction solution is poured into dilute sodium hydrogen carbonate solution and extracted with methylene chloride. The residue of the organic solutions washed with water, dried and evaporated in vacuo is chromatographed on

30 g silica gel containing 15 % water. The end. the fractions eluted with toluene / ethyl acetate (19: 1) mixture are obtained . . 2Q9 8 2 4/1170 '"_ _Λ

ORIGINAL IMSPEOTSD

- ..: - 1843948

-'6O -

300 mg S-seco-pregn ^ -in, which in the IR spectrum has bands at 2.78 * 3 * 05, 4.73 * 5 * 87 * 8.08, 9 * 10, 9.20 and 10.58 μ, F. « 124-127 °.

The 17a, 20; 20,21-bismethylenedioxy derivative used as the starting material of 3,2Q-Dioxo-4,5, llß, 17a, 21-pentahydroxy-pregnane is produced as follows? To a mixture of 5 g of the 17,20; 20,21-bismethylenedioxy derivative of hydrocortisone and 200 ml of t-butanol are added to 10 ml with stirring 30 # hydrogen peroxide and ISO mg osmium tetroxide. 22 hours later another 10 ml of 30% hydrogen peroxide and 150 mg of osmium tetroxide are added. Do a total response time from 90 hours you pour carefully on one Solution of 50 g of potassium iodide in 500 ml of water and ice and extracted several times with ether. The essential solutions will be washed with sodium thiosulphate solution and water, dried and evaporated in vacuo. To the boiling solution of the residue 600 mg of animal charcoal are added to a chloroform-methanol mixture, whereupon suction filtered and washed with methanol will. The piltrate is concentrated until crystallization begins. 1.15 g of the 17.20; 20.21-bismethylenedioxy derivative are obtained of 3,20-dioxo-4,5, llß, 17a, 21-pentahydroxypregnan, which after dissolving from ether-petroleum ether at 244-248 ° melts.

-20 9 8 ZA / 1170

. Example -5cl

2 g of 3,20-dioxo-4,5-oxido-pregnane are dissolved in 100 ml of ethanol (heat up briefly and cool again) and 1.2 g of p-tosylhydrazine (= 1.05 mol) are added. An intense yellow coloration occurs within a few minutes of the reaction solution stirred at room temperature. After about 15 minutes, the Np development begins. 140 ml of nitrogen are separated out within 2 hours, and at the same time the reaction solution is also discolored again. It is taken up in.Aether-Chloroform- ^ Jl) mixture and worked up as usual. On crystallization from methylene chloride ether, 1.12 g of 5 * 20-DiOXo- ¹ , 5-secopregn-3-yne, mp 153-156 °, Ca] | ° = 118 are obtained from the 2.12 g of crude product ° + 1 °.

Example 35 ^:

Starting from the 3- ⁰ xo-4-chloro-5-hydroxy-17-acetoxy-19-nor-androstane obtained by the procedures described in Example 33, the ^{5-oxo-17-acetoxy-l-i,} 5-s .eeo-19-nor-androst-

20Ö824 / 1 "17-0

4 The starting material is obtained by adding Δ - $

Oxo-17ß-acetoxy-19-nor-androstane accumulates hypochlorous acid.

Example 36:

Under the conditions given in Example 33, the 3-0xo-4-mesyloxy-5 ~ hydroxy-2O, 20-ethylenedioxy-21- * acetoxy-pregnane (made from 3 * 21-dihydroxy-20-oxo-A pregnen by successive ketalization of the 20-oxo group, Subsequent Oppenauer oxidation of the "3 ^ Hydroxy-A - grouping, Acetylation of the 21-hydroxy groups hydroxylation

4th
the Δ double bond and mesylation of the 4-hydroxy group) is converted into the 5-0x0-20,20-ethylenedioxy-21-acetoxy-4,5-seco-pregn-3-yne after acid hydrolysis of the ketal group at C-20 , by means of 66% acetic acid, which delivers 5i20-dioxo-21-acetoxy-4, S-seco-pregn ^ -in ...

Example 37: ^

To a solution of 750 mg of the 17.20; 20.21-Βΐ3-methylenedioxy derivative des 3,20-ϋϊοχο-4,5,11β, 17α, 21-pentahydroxy-pregnans in 12 ml of pyridine is added with cooling an ice-methanol mixture 1.2 ml methanesulfonyl chloride.

209824/1170 original ws

-63- ■■■ - .:

The mixture is left to stand for 20 hours at -10 ° and then poured onto 30 ml of saturated sodium hydrogen carbonate solution and ice, while stirring. dried and evaporated at a bath temperature of 3 ° in vacuo. The residue is chromatographed on 35 S silica gel. From the fractions eluted with acetone-hexane (1; 2) mixture one receives the 17 * 20) 20,21-bismethylenedioxy derivative of 3,20-dioxo- = 4-. methanesulfonyl-oxy-5illßil7s _J) 21 ~ tetrahydroxypregnans in the form of a colorless, crystalline residue.

600 mg of hydroxylamine hydrochloride and 1.8 S crystallized Sodium acetate is triturated and mixed with 12 ml of alcohol added, whereupon it is suction filtered and the filtrate is added to the mesylate obtained above. Let stand overnight and cool down is filtered off from the crystals obtained and with washed in cold methanol. 53 ° mg of a crystallizate are obtained after redissolving from a methylene chloride alcohol -Aether -mixture melts at 272-273 ° with decomposition.

150 mg of the crystals obtained above and 10 ml Alcohol is mixed with 2.5 ml of sodium hydroxide solution while stirring and cooling with ice and 120 mg of hydroxylamine-0-sulfonic acid added «According to 3 hours of stirring at room temperature is poured into water. .Empty and extracted with methylene chloride. The residue of the washed with water, dried and in a vacuum

2 09824/1170

Vaporized organic solutions are chromatographed on 7 * 5 g of silica gel containing 15 % water. 84 mg of 5-oxo-11β-hydroxy-17α, 20; 20,21-bismethylenedioxy-4,5-secopregn.3-yne, which crystallizes after standing for a long time and melts at 124-127 ° after dissolving from a little ether.

, . Example 38:

2.0 g of 3-0xo-4-mesyloxy-5-hydroxy-17β-acetoxy-19-norandrostane are dissolved in 75 ml of alcohol, with 3.0 g of hydroxylamine hydrochloride and 10.0 g of sodium acetate added and during

209 8 2 4/1 170

Boiled under reflux for 2 hours. The usual work-up provides 2.0 g of a still impure product. This is dissolved in 100 ml of alcohol, while cooling with ice, with 30 ml of 1N sodium hydroxide solution and 1.5 g of hydroxylamine-O-sulfonic acid are added and 5 hours stirred at room temperature. The reaction mixture is then diluted with water, extracted with ether-methylene-chloride (4: 1) mixture, the organic phase washes neutral with water, dried and evaporated in a water jet vacuum The crude product obtained is acetylated and used for purification Chromatographed silica gel, whereby one.reines 5-0xo-lTß-acetoxy-4,5 ~ seco-19-nQr-androst-3-yn obtained from the F. 93-95 ° * The starting material is analogous to that of Example 37 starting from Δ -S-Oxo-lTß-acetoxy-ig-nor-androsten produced

Example 39ι.

In an analogous manner, 1 * 0 g of 3-0xo-4-mesyloxy-5-hydroxy-17β-acetoxy-5a-androstane _5, which is prepared from the corresponding Δ -3-oxo compound by successive hydroxylation and selective mesylation, is used in the treatment with hydroxylamine and hydroxylamine-0-sulfonic acid, or with Hydroxyiarniri-0-p - to.luolsulfo.nat, and post-acetylation 700 or 620 mg 5-0xo-17ß-acetoxy-4 _i 5 "seco-androst-3- obtained in, which melts after recrystallization from ether / petroleum ether at 94-96 °.

20982471 170

Example 40:

1.0 g crude oxime of 14,15-oxido-bicyclo [10.3.0] pentadecanone- (l), this in turn by epoxidation using hydrogen peroxide sodium hydroxide solution and subsequent oximation from bicyclo [10.3,0] pentadecen- (l4) -one- (l) is obtainable dissolved in 60 ml of methanol, cooled to 0 and with stirring with 20 ml of 1N sodium hydroxide solution and 1.0 g of hydroxylamine-Q-sulfonic acid offset. After 15 hours at room temperature, the reaction mixture is diluted with water and extracted with ether. The neutral washed and dried essential solution provides after evaporation of the solvent 800 mg of an oil, which after again distilling in the bulb tube pure cyclopentadec-4-in-l-one from the F. 40-42 ° delivers. The compound is easily converted into the melting point at 58-63 ° by catalytic hydrogenation Cyclopentadecanone converted.

Example 4l:

18.4 g of 3β-acetoxy-9a, ll-oxido-12-oximino-5aspirostane are suspended in 1.25 l of ethanol. After adding 10 ml of 1N sodium hydroxide solution, the solution is placed in an ice bath

cooled with stirring to 0 ° and with 15 * 3 S hydroxylamine-0-sulfonic acid offset. After 5 minutes, the ice bath is removed and the reaction mixture for a further 16 hours at room temperature stirred. In a vacuum at 30-40 ° to approx. 5OO ml

2 0 9 8 2 4/1170

/ T643S48 - β? -

concentrated reaction solution / is mixed with ether-chloroform (3: 1) extracted »The extracts become neutral with · water washed, dried and evaporated to dryness. From the 19 g of crude product are obtained after crystallization from chloroform-methanol 8.1 g Jß-Hydroxy-9-0x0-9, ll-seco- ^ a-spriost-ll-in,

P. 219-220 °, [a] ^ ° = 104 ° +, 1 °,

yy -

Example 42:

10 * 0 g of cis-jasmone is converted into the corresponding α, β-epoxy ketone by reacting with iger hydrogen peroxide solution and sodium hydroxide solution and then oxidized pa in a manner known per se. The crude OxIm (10.2 g) is dissolved in 500 ml of ethanol and 15Ο ml of 2N sodium hydroxide solution, cooled down, mixed with 15 g of hydroxylamine-07sulfonic acid and stirred for 10 hours at room temperature. The work-up and subsequent distillation yields the cis-Undec-8 ~ en-5-in-2-onKp. 96-98 ° /! mm Hg.

In an analogous manner, trans-undec-8-en-5-yn-2-one, boiling at 86-89 ° / 0.3 mm Hg, is obtained from trans-jasmone.

Example kj>:

5.0 g of oxime of epoxy isophorone under the condition specified in Example 40 with I5 g of hydroxylamine-0-sulfonic acid reacted, wherein the at 7O ⁰ (11 mm / Hg) boiling

20982Λ / 1170

- 68 -:. ■ "■ '■■

ΡΩ

4,4'-dimethyl-heptyne - (6) -ori- (2), (ng = 1.4423) is obtained,

Example 44:

5.0 g of 2-mesyloxy-3-hydroxy-3,5 _i 5-trimethyl-cyclo- • hexanone- (l) (prepared by reacting isophorone with hydrogen peroxide and osmium tetroxide and reacting the product obtained with methanesulfonyl chloride in counter- . War of absolute pyridine) are dissolved in 150 ml of ethanol, 3.8 g of tosylhydrazine are added while stirring and the mixture is heated to 30 °. 5 hours later, the reaction solution is poured into dilute sodium hydrogen carbonate solution and extracted with ether. After evaporation of the solvent and distillation of the thin residue, 4,4-dimethyl-heptin- boiling at 70 ° (11 mm / Hg) is obtained from the extract. (6) -on- (2), (n ^ ° = 1.4423). /

r '■■. ■■ - ■ ;.' - :: -

Example 45i - '- ^: - -.

5g hydroxylamine hydrochloride and 15 g crystallized Sodium acetate was triturated to form a paste and then 100 ml of alcohol was added. To the filtered 5 g of the ^ -Mesyloxy ^ -hydroxy ^^ S-trimethy! - are added to the solution. cyclohexanone- (l) and leaves for one hour in a stream of nitrogen Cook. Then it is diluted with water, with methylene chloride

- ■■■; 20 98 21/1170

'"' ■ '■ BAD ORIGINAL

extracted, washed with water, dried and evaporated.

To a solution of 1 g of the product obtained in 60 ml of ethanol, J> 0 ml of η-sodium hydroxide solution and 1.5 g of hydroxylamine-Q-sulfonic acid are added with stirring and while cooling with ice. After stirring for 4 1/2 hours at room temperature, it is diluted with water and extracted with methylene chloride. The residue of the washed, dried with water and evaporated in vacuo organic solutions obtained after the distilling at 70 ° (11 mm / Hg) boiling 4, _{4-dimethyl-heptyne} - '(6) -Qn- (2), ( τξ ° = 1.4423). · ' ^: Ζ

Example 46: - ^

A solution of 720 mg of 3-0xo-4a-methyl'4ß / 5-oxido-17ß-acetoxy-androstane in 4 ml of methylene chloride and 4 ml of acetic acid is cooled to -18, treated with 400 mg of tosylhydrazine and stirred for 18 hours at constant temperature. The mixture is warmed to room temperature, releasing nitrogen the yellow solution is discolored. The reaction mixture is diluted with ether, the organic phase separated, three times each with water, sodium bicarbonate and saturated saline washed, dried and evaporated in a yakuum, The oily residue is adsorbed on 40 g of silica gel and the Column with a methylene chloride-ethyl acetate (20: 1) mixture eluted. After evaporation of the fractions, 579 mg are obtained of the crude 4-methyl-5-oxo-l7ß-acetoxy-4,5-secQ-androst-3-yne,

2 0982 ^ / 117 0 " ^J.

which after recrystallization from pentane at 93-95 ° melts (yield 53 ° ^m s) ·

Example 47:. ■

1 * 15.8 g of 3β-acetoxy-16β-methyl-16a, 17-oxido-20-οχο-Δ -pregnen (from P. 175-176 °) are in 12 ml of a

Fe mixture of methylene chloride-glacial acetic acid (1: 1) dissolved, to -18 ° cooled and mixed with 650 mg of tosylhydrazine with stirring. The mixture is left to stand for 18 hours at the specified temperature, slowly warmed to 20, with 30 ml of nitrogen being split off will. The reaction mixture diluted with ether is worked up analogously to the preceding example. By repeated Crystallization of the crude product obtained in ether-pentane gives 1.180 g of the tosylhydrazone of 3ß-acetoxy-16ßmethyl-16a, 17-oxido-20-oxo-A -pregnens from P. 124-125 °.

"480 mg of this compound are attached to 40 g of silica gel

(Merck) adsorbed, with nitrogen being split off. The column is eluted with methylene chloride-ethyl acetate mixtures and, after evaporation, 27Ο mg of crude 3β-acetoxy-16-oxol6-methyl-16 _# 17- "Seco-A -pregn-17 (20) -in, which after dissolving out a little ether-pentane melts at 125-127 °.

Example 48:

173 mg 1-Oxo -Pa, 3 -ox i do-17 [^ - aoot οχ.γ- ^ α-ίχηά roatan im ;. ί

209 82Λ / 1 170

BAD OBiGiNAL

100 mg of tosyhydrazine are dissolved in 10 ml of a methylene chloride-glacial acetic acid (l: l) mixture dissolved and stirred for 4 days at 20 °. The subsequent work-up and chromatography of the obtained The crude product on silica gel yields 40 mg of 3-oxo-17β-acetoxy ~ 2.3 = seco-5a-androst-1-yne from 110 °.

Example 49:

To a solution of 11 g
l (12) -en-2-one in one liter of methanol is added slowly and with stirring 6 ml of a 6-n. Sodium hydroxide solution and then 25 ml of 30 show hydrogen peroxide. The mixture is stirred at room temperature for 24 hours, then poured into 4 liters of ice water and extracted several times with ether. The ethereal particles are combined and washed several times with dilute sodium thiosulphate and sodium chloride solution, dried over magnesium sulphate and evaporated. The residue crystallizes on standing and consists of practically pure epoxy ketone, mp 40-42 °, which is processed further without further purification.

3 g of this epoxide and 2.5 g of tosylhydrazine are used dissolved in 25 ml of methanol at room temperature and stand left .. After 3 days, the crystals formed are filtered off away. 2.6 g of cyclopentad.ec-S-in-l-one are obtained in this way from P. 51 - 52 °. -

2 09824/1170

: 1643348

One arrives at the same product with comparable ones Yields if you use bicyclo ^. ^. Olpentädec-ldlJ-en- ^ -one epoxidized in an analogous manner and treated with tosylhydrazine in methanol.

Example 50:

To a solution of 21 g cedrenal in one liter

Methanol is added slowly and with stirring at room temperature 8 ml of a 6-n. Sodium hydroxide solution and 50 ml of 30 # strength Hydrogen peroxide. After stirring for 24 hours at room temperature the reaction solution is poured into 4.1 ice water and extracted several times with methylene chloride. The extracts are washed several times with saline and with water, dried over .. sodium sulfate and evaporated in vacuo. The residue is distilled at 110 ° and 0.005 mercury pressure. - ·

>, ■: ■■

14.2 g of the epoxyaldehyde obtained are dissolved in 21 ml of a 3: 5 mixture of acetic acid and methylene chloride and 17.25 g of tosylhydrazine in 21 ml of the same solvent mixture are added while cooling to below 10.degree. One lets. Stand for 11/2 days at room temperature, add water and work up as usual. Crude 1- (pormylmethyl) -3-ethinyl-4,4,8-trimethyl-bicyclo [3.3.0] octane is obtained in this way. ..

20982 /, / 1 170

IM 3948

Example 51s

Add 20 ml of ~ $ 0 hydrogen peroxide and 8 ml of a 6-n. aqueous sodium hydroxide solution at room temperature to a solution of 1J g of 10,10-dimethyl-tricyclo- [7.1.1,0 ⁵ * ⁸ ] undec ~ 3 (8) -en-4-one in 600 ml of methanol, add more after 20 hours 10 ml of hydrogen peroxide (30 $ ig) and leave to stand for 24 hours. Then another 10 ml of 30% hydrogen peroxide are added, the reaction solution is left to stand for a further 2 days, concentrated in vacuo, diluted with water and extracted again with ether. After washing the extracts with water, drying over magnesium sulfate, evaporating the solvent and distilling the residue, 11.9 S of pure epoxy ketone [bp. 82-85 ° / 0.05 Torr., Χξ ° = 1.5071, [<^ ° = -126 _s 4 °, d ²⁰ = 1.091, V _{G = o} = 17.5 cm " ¹ ].

5 g of this epoxy ketonswerden in 50 ml of methylene chloride and 50 ml of acetic acid, cooled to -30 ⁰ and treated with a solution of 5 * 0 g tosyl hydrazine in 50 mL of methylene chloride and 30 ml of acetic acid. The reaction solution is warmed to room temperature, with the evolution of nitrogen, diluted with water, the organic layer is separated off, washed with dilute sodium carbonate solution and then with water and dried as usual. After evaporating the solvent in vacuo, 4.9 g of a solid product are obtained which can be purified by sublimation. That

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thus obtained I0 _J .10 - DiTnethyi "-bicycXo [7.1.'l] undec-6-in-2-onschmilzt at 83 ⁰ C.

The 10,10-Dimethy1- used as starting material

-τ Q

Trioyclo [7.1 «l« Cr] undec-3 (8) -en-4-one can be prepared as follows will:

A mixture of 15 g of nopadiene (oc = + 46.44 °), 12 g of acetoxyacrylonitrile and 100 ml of xylene is heated at 150 for 7 hours, whereupon the solvent is distilled off and the residue is extracted with ether. Evaporation of the solvent gives 12 g of crude product which is recrystallized from petroleum ether. 4-Acetoxy-4-cyano-10,10-dimethyl-triCyClo [JI ^ LO *} uncec-7-ene is obtained, which has the following constants: bp ". = 110-115 ° / 0.01 torr; P . = 103-104 °; [a] ^ ° = -1.8 °, 10 ^ in CHCl ₃ .

A mixture of 11 g of 4-acetoxy-4-cyano ^ 10 _J 10--. dimethyl-tricyclo [7 »1.1.0 ^} undec-7-en, 10 g of potassium hydroxide and 150 ml of ethanol .wird is heated for 24 hours at reflux temperature, after which the alcohol is distilled off. The residue is diluted with water and extracted 5 times with ether. The ether extracts are washed neutral, dried and evaporated. By distilling the residue - in a high vacuum, 5 ^ 0 g of 10,10-dimethyl-tricyclo- are obtained.

-z Q

[7.1.1.0 ^ "] undec-3 (8) -en-4-on, which has the following constants

° / 05 torr; [aj ^ ° 544 °; n ^ °

has: b.p. = 95-100 ° / 0.5 torr; [aj ^ ° = -54.4 °; n ^ ° = 1.5268;

d | ° = 1.023.

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Example 52:

170 g of 30% hydrogen peroxide are added to a solution of 76 S piperitone in 450 ml of methanol at 15 ° and with stirring, and 40 g of 6-n is added over the course of one hour. aqueous sodium hydroxide solution and the mixture is stirred for a further 3 hours. It is diluted with water, extracted with ether, the ethereal solution is neutralized and washed as usual. After evaporation of the ether and distillation of the crude product, 61.1 g of the pure epoxy-ketone with a bp _mm 106-109 ° are obtained. [A] _D = + 43.9 °.

27 g of the product obtained are in a solution of 31.2 g of tosylhydrazine in 400 ml of methylene chloride / acetic acid (2: l) given and the mixture is stirred for 14 hours at 2 ° - one warms slowly to 20 ° and gives after 1 l / 4 hours, 2 g of p-toluenesulfonic acid are added. The nitrogen release is accelerated and after an hour can hold approximately 3550 ml of nitrogen gas.

The reaction mixture is worked up as usual, with

PO

PO , 13.9 g of 3-isopropyl-hept-1-yn-6-one are obtained, n ^ - 0, d ²⁰ = 1.4462; = 2250 cm " ¹ ,» ^ _n = 17IO cm " ¹ , [α] ² , ³ = + 4.48?

5.3 g of the product obtained are dissolved in 60 ml of pentane and in the presence of 0.25 g of a 10 ^ igen Palla

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hydrogenated dium animal charcoal catalyst. After 6 hours are two equivalents of hydrogen and the 3-isopropyl-heptan-6-one is isolated in the usual way. It distills under 13 mm of mercury pressure at 86 C and has

'ΡΩ ΡΩ

a strong fruity odor. n ^ = 1.4327; d = 0.8440.

Example 53 ^:

304 S 2-n-pentyl-cyclopent-2-en ~ l-one are dissolved in a mixture of 25ΟΟ ml of methanol and 1700 g of hydrogen peroxide (30 ^ ig), then 164 g of a 6-n. aqueous sodium hydroxyl solution is slowly added at -5 ° and with thorough stirring. After 20 minutes, the addition is complete, whereupon the mixture is stirred for a further 90 minutes at -5 °. 0.001 mm passes.

2.5 g of the epoxy ketone described above will be slowly at 0 in a solution of 3 g of tosylhydrazine in 40 ml Dissolved methylene chloride / acetic acid (2: 1) and added dropwise with vigorous stirring to 25Ο ml of 5% aqueous sulfuric acid. After the evolution of nitrogen has ended, hexane is used to ex-

2 0 9 8? KI 1 1 7 0

soaked and the extract neutralized, dried and distilled as usual. This gives 0.5 g-Dec-4-in-1-al ^vomK P-0.001 ^ - 42 °.

Example 54:

4.0 g of 3-methyl-2,3-oxido-cyclohexan-l-one are added at 2 ° to a solution of 6.2 g (0.033 mol) of tosylhydrazine in 60 ml of a mixture of methylene chloride and acetic acid (2: 1) admitted. The solution turns yellow instantly. It is left to stand at 2 ° for 14 hours, evolving about 400 ml of nitrogen. The reaction mixture is then slowly warmed to 27 ° while stirring. After about 3 hours you will develop an additional 370 ml of nitrogen. The reaction mixture is treated in the manner described in Example 53 'are thus obtained 2.2 g of hept-6-in-2-on, having the following physical constants:.. B.p. 53-54 ⁰ Ao mm Hg, n ^ ° = 1.4389, d ^ ° »0.8969.

Catalytic hydrogenation of a sample of hept-6-in-2-one in the presence of a deactivated palladium catalyst gives hept-6-en-2-one which has the following physical properties: 'Sdp. = 4γ ^ο / ΐ5 mm Hg, - ΐξ ° = 1.4255, ^ ⁰ = 0.8475.

By catalytic hydrogenation of another sample of heptin- (6) -one- (2) in the presence of platinum oxide becomes pure Obtain heptan-2-one. -

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The oxido-ketone used in this example can be prepared as follows;

22 g of 20% sodium hydroxide solution are added dropwise at 15-17 ° C a solution of 24.5 g (0.22 mol) of 3-methyl-cyclohex-2-en-l-one and.76 ml (0.67 mol) 30 tiger hydrogen per- • oxide·. added in 220 ml of methanol. The reaction mixture is worked up in the manner described in Example 53. 3-Methyl-2,3-oxido-cyclo- ™ is obtained in 50% yield hexan-1-one * that passes at 79 - 80 ° / l2 mm Hg.

Example 55 ^:

8.2 g (0.05 mol) 6-methyl-bicyclo · [4.4.0] deG-l-en-3-one are at 15 in a mixture of 9 * 3 ml (0 ^ 15 mol) 55 #igem hydrogen peroxide and 50 ml of methanol dissolved. Of the obtained solution are stirred within 10 minutes 8 ml of 10 # sodium hydroxide solution were added dropwise, the Temperature of the mixture is kept below 17 °. The reaction mixture is stirred for a further 4 hours at room temperature and then extracted twice with ether. The United Extracts are washed neutral with water; dried over anhydrous sodium sulfate and concentrated. Durbh Distillation of the residue gives 6 g of pure 1,2-epoxy-6-methyl-bicyclo [4.4.03decan-3-one, that boils at 76 -..- 78 ° / 0.001 ram Hg.

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- Dissolve 5.8 g (0.032 mol) of the epoxy ketone in a solution, cooled to 0 °, of 6.4 g (0.032 mol) of tosylhydrazine in a mixture of methylene chloride and acetic acid (2: 1; 35 ml) and the reaction mixture is stirred for 45 minutes at 0 °, the solution becoming discolored and thicker will. The solution is allowed to warm to room temperature, whereupon nitrogen evolution begins. Within one hour at room temperature, approx. 800 ml of nitrogen develop. The reaction mixture is extracted with ether and washes the extract several times with conc. Natr iujnbi ear bonat solution and then with water. The extract is dried and concentrated. Distillation of the residue is obtained 3 * 5 g of pure 2-methyl-2- [butyn- (3) -yl- (l)] -cyclohexanone- (l), that boils at 124% 0 mm Hg.

• Example 56:

140 mg, tosylhydrazine are added at 0 to a solution of 100 ml of 1,2-epoxy-l-propionyl-cyclohexene (4) in 6 ml a mixture of glacial acetic acid and methylene chloride (2: 1) given * One leaves the reaction mixture for 1/4 hour Stand at 0 ° C, then pour it into a buffer solution (pH 6.5) and extract with ether. The essential extract becomes neutral washed and concentrated. The raw, the tosylhydrazone of L, 2-epoxy-l-propionyl-cyelohex-4-en containing product is on a silica gel column using a mixture of hexane and

2 0 9 8 2/47 117 0 ORIGINAL

- 8ο -

Ether chromatographed. The epoxytosylhydrazone decomposes with evolution of nitrogen. The eluate becomes 20 mg cis-non-(3) -in- (6) -al- (l) isolated.

By catalytic hydrogenation of this compound in the presence of a deactivated palladium catalyst, ice-cis-Nona-3,6-dien-1-al obtained at 76 - 80 ° / 10 mm Hg boils and its 2,4-dinitrophenylhydrazone melts at 69 - 70,

The epoxy ketone used in this example can be obtained as follows:

4g ethynyl-ethyl-ketone (. Prepared as described in Soc 1952 ».1437 method), 8 g of butadiene and a trace ·, hydroquinone .in- a-.Autoklaven'Während" ·· · -. "·. - Heated to 120-130 ^° C. for 3 hours. The reaction mixture is distilled in vacuo. 4.1 g of l-propynyl-cyclohexadiene (1.4) are obtained, which passes over at 85-87 ° / 10 mm Hg.

A solution of 500 ml of 1-propionyl-cycrlphexä-1,4-diene in 4 ml of methanol and 1.06 ml of 30% water per oxide 0.31 ml of 6N sodium hydroxide solution is added while cooling with ice, the reaction mixture is left to stand overnight at 4 °, it is then poured into ice water and extracted with ether. The essential extract is washed 3 times with ice water and dried over sodium sulfate. After removing the aether the residue is distilled in vacuo. 401 mg / l, 2-epoxy-l-propionyl "-cyclohex-4-ene, which is between 90 and 100 passes at 11-mm Hg. '.

■■ "20 9 8 2 /, / 11-7 0

Example 57;

3> 50 g of 3,3,17,17-bis-ethylenedioxy-5-β, 10-oxido-6-oxoöstran is dissolved in 30 ml of ethyl alcohol and, after the addition of 1.70 g of TdKy / hydrazine, stirred for 24 hours at room temperature. The reaction proceeds with the elimination of approx. 195 ml of nitrogen. The reaction mixture is diluted with ether and methylene chloride, mixed with water and worked up as usual. 3.17 of its crystalline mixture is obtained, which is chromatographed on silica gel for separation. The more apolar fractions (74l mg) represent pure 3.3, i7 _? 17-bisäthylenedioxy-10-oxo-5,10-seco'-estr-5 (6) ~ ^{iri , which melts at 182-183 0} after being redissolved once from methylene chloride ether. The more polar fractions (375 mg) consist of one Mixture followed in the chromatogram by 1.353 g of pure 3,3-ethylenedioxy-10,17-dioxo-5, 10-secO-oestr-5 (6) -in. The last-mentioned compound melts after recrystallization once from methylene chloride-ether at 213-214 °.

Example 58:

1 * 75 g of the 3-methoxy_i6-oxo-16,17-seeο-Δ ^J ^ '5k -'_ 19_ _rlor -.p _r egnatrien-17 (20) -lns obtained in Example 20 are dissolved in 20 ml of methanol with warming , cooled to room temperature, treated with 100 mg of p-Tolüoistilfonsäure and 15 hours

Ζ09824 / Ί T7Ö

"6433.-48

left standing. The yellow reaction mixture is Poured ice-cold saturated sodium bicarbonate solution, and extracted twice with ether. The organic phases will washed neutral with water, dried and evaporated in vacuo. The resulting oil (1.8 g) is purified by chromatography on Sillcagel, or by preparative thin-layer chromatography of weakly polar by-products (approx. 160 mgX severed. The 3 * 16,16-trimethoxy-16,17-sec.o-

in (1.03 g) crystallizes after spraying with ether and melts at 55 "57 ° ·

Example 59 *

24.7 / g of 3,17-dioxo-4β, 5-oxido-estran are dissolved in 500 ml of ethanol and, after the addition of 17.2 g of tosylhydrazine, stirred at t · room temperature. Approx. 19-00 ml of nitrogen develop within 8 hours and the temporarily yellow colored reaction solution is discolored. Customary work-up (dilution with ether, washing neutral with sodium bicarbonate solution and water, drying and evaporation) gives an amorphous crude product (approx. 25 g) which is purified by chromatography on silica gel. After recrystallization of the combined chromatogram ⁼ crude fractions from methylene chloride / ether, 14.7 g of pure 5,17-ΟΙοχο-4,5-3βοο-03ΪΓ ~ 3-1η of F. 107 are obtained -109 ⁰ J [a] ^ ⁵ = + 72 ° (c = 1.032).

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Example 60:

A solution of 800 mg of 3β, 17β-diacetoxy-5,6-oxido-7-oxo-androstane and 600 mg of tosylhydrazine in 20 ml of ethanol is stirred for 100 hours at 25 °. The precipitated crystals {310 mg) are suction filtered, washed with alcohol and dried. The tosylhydrazone of the starting compound, which melts at approx. 180 ° with decomposition, is present. The Piltrat is then diluted with water and extracted with ether. Customary work-up gives 64o mg of an amorphous crude product, the chromatography of which on silica gel 3β / 17β-diacetoxy ^ -oxo ^ ö-seco-androst-o-yne supplies. In the IR spectrum, the compound has bands at 3.10, 4.75, 5.75, 5.80, 5.85, 8 ^ .10, 8.17, 8.55, 9.20 and 9.70 μ.

Example 6l:

3.0 g of 3-methoxy-16a, 17-oxido-20-oxo- ^A1i5i5 ^ ¹⁰ ^ -19-nor-pregnatriene are dissolved in a mixture of 60 ml of methylene chloride and 20 ml of glacial acetic acid and stirred at about -30 1.96 g of tosylhydrazine were added. After 15 hours at -30, the yellow reaction solution is slowly warmed to room temperature and stirred for a further 6 1/2 hours. The mixture is then poured onto ice / water and extracted three times with ether-methylene chloride (4: 1) mixture. the

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organic phases are washed neutral with ice-cold sodium bicarbonate solution and with water, dried and evaporated in vacuo. 3 * 15 g of a yellowish foam are obtained which. is chromatographed on 50 times the amount by weight of silica gel for purification, 3-methoxy-16-oxo-16,17-seco-Δ ^lj 3o ( ¹⁰ ^ -i9-nor-pregnatrien-17 (20) -in being obtained. The compound lies as an oil that is difficult to crystallize and has bands at approx. 3 * 70, 5 * 83, 6.2%, 6.69, 8.13 and 12.25 μ in the IR spectrum.

Example 62:

A solution of about 100 mg of cyclohexylaminoaziridine in 20 ml of ether was admixed with 200 mg of 3-oxo-4ß, 5-oxido-17ß-acetoxy-androstane and a drop of glacial acetic acid and stirred for 20 minutes at room temperature. The ethereal solution was extracted once with 10 ml of 10 % potassium hydroxide solution, twice with 10 ml of water each time, dried with sodium sulfate and freed from ether. Crude product: 245 mg · 12 mg of this crude hydrazone were heated to 200 ° in a bulb tube at 0.03 torr for about 15 minutes, the cleavage product distilling. This was distilled once more, then rinsed out with ether and the ether evaporated. Crystallization from pentane yielded a crystalline compound with a melting point of 94 °, which according to the IR spectrum, melting point and mixed sample, thin-layer chromatogram (silica gel G, benzene / vinegar

'*? 098? H / 11: ii

ester 7: 2) with 5-oxo-17ß-acetoxy-4,5-seco-androst-3-yne was identical

Example 63:

4.88 g of 3-0x0-4, S-are dissolved in 250 ml of ethanol and 20 ml of methylene chloride, mixed with 2.90 g of p-toluenesulfonylhydrazine and 18 hours stirred at room temperature. The usual work-up of the colorless reaction solution gives 5 * 00 g of a crude product from which by chromatography on silica gel 2.95 g of 5-0xo-17β-carbomethoxy-4,5-seco ~ androst-3-in be won. The pure, recrystallized from a methylene chloride-ether mixture Compound melts at 96-98 °. The raw material used

4 is androsten in a manner known per se from 3- ° xo-17ß * -carbomethoxy-A won.

Example 64:

A solution of 2.45 g of 3,20-dioxo-4,5-oxido-21-hydroxy-pregnane and 1.45 g of p-tosylhydrazine in 100 ml of ethanol and 5 ml of methylene chloride is 5 hours at room temperature touched. The amount of nitrogen evolved during this time is about 160 ml. Work-up yields 2.5 g of one Crude product from which by chromatography and subsequent

ORIGINAL

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7643948

Crystallization from methylene chloride ether 1.60 g of pure 5,20-Dloxo-21-hydroxy-4,5-seco-pregn-3-in from P. 126-127 L · = +106.

Example 65:

5.00 g of cholestenone epoxide are dissolved in 50 ml of a 1: 1 mixture of methylene chloride-glacial acetic acid and, after addition of 2.50 g of p-tosylhydrazine, stirred for 12 hours at room temperature. The work-up and subsequent filtration of a solution of the crude product obtained in benzene through 10 times the amount by weight of aluminum oxide gives pure 5-oxo-4,5-secocholest-3-yne. The compound has bands at 3315, 2120 and 1705 cm " ¹ in the IR spectrum.

Example 66:

A mixture of 468 mg of l ^ -Methyl-bicycloClO ^ .Olpentadec-l (l2) -en-13-one, 4-00 mg of tosylhydrazine and 5 ml of ethanol are refluxed for 48 hours. When cooling down I85 mg of tosylhydrazone of the bicyclic ketone from P. 135-138 ° crystallize out of the reaction mixture.

121 mg of the tosylhydrazone are dissolved in 4.5 ml of chloroform and add 110 mg of p-nitroperbenzoic acid to the solution at 0. The reaction mixture is left to stand in the refrigerator for 3 days

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1643348

and then takes it up in aether. The ethereal solution is successively mixed with potassium,) odide solution, sodium thiosulfate solution, Soda solution and water shaken out. After drying with sodium sulfate, the solvent is evaporated off. The raw product (92 mg) is chromatographed on 60 times the amount of silica gel (Merck »0.05-0.2 mm). By eluting with a hexane-ether mixture (9: 1) gives 17 mg of product, which is purified by distillation. 3-Methylcyclopentadec-4-yn-1-one is obtained from F, 41-42 °.

200 mg of 3-methyleyclopentadec-4-yn-1-one are hydrogenated in 10 ml of ethanol using a lO. ^ Igem palladium-carbon catalyst. 40 ml of hydrogen are consumed within 11 minutes. The hydrogenation mixture is filtered off, the solvent is evaporated and the residue is distilled at 90 ° / 0.01 torr. 199 mg of pure chemical 3-methyl-cyclopentadecane ^{ion (ng 0} = 1.479 *) are obtained.

200 mg of 3-methyl-eyelopentadec-4-in-ion are hydrogenated in ethanol using 200 mg of palladium-carbon catalyst poisoned with 40 ml of pyridine. After using 22.2 ml Hydrogen, the hydrogenation is terminated. The hydrogenation mixture is filtered and the filtrate is concentrated. By Distillation of the residue at 95 ° / 0.01 Torr is obtained

20 194 mg cis-S-methyl-cyclopentadec ^ -en-l-one (η _β = 1.4880). The IR spectrum of this compound shows characteristic bands at 1710, 73Ο and cm. UV spectrum in ethanol: λ _mav = 286 and 242 ΐημ (£ = 52 and 100, respectively).

2098 2 /./ 1170 ORIGINAL INSPSCTSD

example

A mixture of 3OO mg of l4-methyl-l, 12-epoxybicyclo [10.3.0] pentadecan-13-one, 276 mg acetone-tosylhydrazone and β ml of a methanol-phosphoric acid mixture (weight ratio 10: 1) is refluxed for 23 hours. The reaction mixture is poured into ice water and shaken out with ether. The essential extract is washed with soda solution and water and dried with sodium sulfate. The crude product remaining after removal of the ether is chromatographed on silica gel (Merckj 0.05-0.2 mm). Elution with a hexane-ether mixture (9s 1) gives 212 mg of 3-methyl-cyclopentadec-4-yn-1-one.

This product can be used for analytical purposes by chromatography on basic aluminum oxide (activity II) and subsequent distillation at about 100 ° / 0j005 Torr, getting cleaned. The pure product is identical to the product produced according to Example 66.

Example 68:

A solution of 15 g of bicyclo [5.3.0] dec-l (7) -en-2-one [Liebigs Ann. 505, 274 (1933)] in 650 ml of ethanol and 10 ml 6N sodium hydroxide solution is added to 28 ml of hydrogen peroxide at 10 ° and leaves the reaction mixture for 14 hours at room temperature

2 0 9 8 2 A IA 1 7 0

stand. After evaporation of the ethanol, the residue is diluted with water and extracted four times with ether. The ether extracts are washed neutral, dried and concentrated. Distillation of the residue in a high vacuum gives 14.5 g of pure 1,7-epoxy-bicyclo [5.3 "0l-decan-2-one _J which has the following constants: b.p. = 40-4l ° / 0.02 Torr;

or) on I

dj = 1.092; n ^ = 1.4950. The IR spectrum at 1695 cm ^x shows the absorption characteristic of the carbonyl.

A solution of 1.1 g of tosylhydrazine in 10 ml of methanol, 15 ml of glacial acetic acid and 1.5 ml of 85% phosphoric acid 1.0 g of 1,7-epoxy-bicyclo [5 «3« 0] -decan-2-one are added at room temperature to. The reaction mixture immediately turns deep yellow and then quickly discolors with evolution of gas. To half an hour the reaction mixture is poured into water and extracted four times with ether. The ether extracts are washed neutral with aqueous sodium bicarbonate and then with water, dried and evaporated. The yellow viscous residue is washed with petroleum ether extracted. The residue that remains after the petroleum ether has been evaporated off is distilled in a high vacuum. You get in 78 # yield cyclodec-5-in-l-one, which has the following Has constants; B.p. = 53 ~ 55 ° / O, O2 torr; d ^ ° =

20 -]

1.073; «J = 1.5139 · The IR spectrum shows at 1710 cm the absorption characteristic of the carbonyl.

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Example 69:

A suspension of 0.5 g of Raney-Niekel in 200 ml of methanol is shaken in a shaking vessel under hydrogen at room temperature until the suspension no longer absorbs hydrogen. Are then added to the g-IO I5 ⁰ cooled suspension 22 Cyclopentadec - ^ - in-l-one and shakes the Hydrierungsgemisoh under hydrogen. After 4980 ml of hydrogen has been consumed, the hydrogenation comes to a standstill. The hydrogenation mixture is filtered and the solvent is distilled off in a rotary evaporator. 22 g of pure cyclopentadecanone are obtained. P. = 62-63 °) Kp. = 96-98 ° / 0.02 Torr.

Example 7O:

A solution of 15 g of bicyclo [4.4.0] dec-l (6) -en-2-one in 650 ml of methanol and 10 ml of 6 N sodium hydroxide solution ~ are added at 0 ° was added dropwise 25 ml of 30 #iges to hydrogen peroxide. The reaction mixture is left to stand at 15 for 14 hours and then another 10 ml of 30% hydrogen peroxide are added. After a further 24 hours, the methanol is distilled off in a rotary evaporator. The residue is diluted with 100 ml of water and extracted four times with ether. The ether extracts are washed neutral, dried and evaporated. Distillation of the residue in a high vacuum gives in

2 0 9 8 2 4/1170 original inspsctsd

80% yield 1 _J 6-epoxy-bicyclo [4.4.0] decan-2-one, which has the following constants: b.p. = 61-62 ° / Torrjj d ^, = 1.101; rip = 1.4982.

1 g of the epoxy ketone obtained is added to a solution of 1.1 g of tosylhydrazine in 20 ml of glacial acetic acid and this is left Stand the reaction mixture for one hour at room temperature. The solution, which initially turns deep yellow, quickly discolors under nitrogen evolution. The reaction mixture is poured into 30 ml of water and extracted 4 times with ether. The ether extracts are washed neutral with aqueous sodium bicarbonate and water, dried and evaporated. The yellow viscous residue is extracted with petroleum ether. The one remaining after the solvent has evaporated The residue is distilled in a high vacuum. Cyclodec-5-in-l-one, which is obtained in 75% yield has the following constants: bp 53-55 ° / 0.2 Torr; d ^ = 1.073; n | ° = 1.5139.

Example 71:

236 g of l, 12-epoxy-bicyclo [10.3.0] pentadecan · 13-one are dissolved in 500 ml of a methanol-glacial acetic acid mixture (1: 1) and 50 ml of 85 # phosphoric acid and give the cooled to 0 ° Solution with constant stirring within 10 minutes a solution of 210 g of tosylhydrazine in 800 ml of a methanol-glacial acetic acid mixture (1: 1) too. The reaction mixture, which is an orange

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assumes red color, stirring is continued at 0 for 3 ° minutes. After cooling is interrupted, nitrogen begins to develop, the temperature of the reaction mixture gradually rising to 35 °. Nitrogen evolution ceases in about 2 hours after 23.8 liters of nitrogen have been collected. The reaction mixture is diluted with 5 liters of water and extracted 3 times with 2 liters of ether each time. The combined ether extracts are washed with 3 % strength sodium hydroxide solution and then once with 2 liters of water. The ethereal phase is dried with sodium sulfate and evaporated. The residue is heated to 120 for 1 hour in an oil bath, then cooled to room temperature and taken up in 2 liters of ether. The ethereal solution is washed twice with 200 ml of 5% aqueous sodium carbonate each time, then dried with sodium sulfate and evaporated. The residue is boiled twice with 1 liter of petroleum ether (30-50 °) each time,. The combined petroleum ether extracts are boiled with activated charcoal and then filtered. After the petroleum ether has evaporated, the residue is distilled in vacuo. 192 g of cyclopentadec-4-yn-1-one are obtained. P. = 38-40 °.

Example 72:

A solution of 7 * 0 g of crude 7j7-dimethyl-bicyclo- [4.4.0] dec-1-en-3-one 6 ml of 6-n are added to 400 ml of methanol.

209824/1 170 ORDINAL inspected

Sodium hydroxide solution and then 15 ml dropwise at room temperature 30 # hydrogen peroxide added. The reaction mixture is left Stand at room temperature for 24 hours and then add another 10 ml of hydrogen peroxide. The reaction mixture is left Stand at room temperature for 70 hours and then work it up in the usual way. 2.3 S of liquid is obtained 7,7-dimethyl-1,2-epoxy-bicyclo [4.4.0] decan-3-one, which the

20 20

has the following constants: d ^ = 1, O358j n ^ - 1.4928. The IR spectrum shows a sharp carbonyl band, but no band for a carbon-carbon double bond. A solution of 2.3 g of 7,7-dimethyll, 2-epoxy-bicyclo [4.4.0] decan-3-one in 20 ml of methylene chloride and 15 ml of glacial acetic acid is mixed at -35 ° with a solution of 2.4 g Tosylhydrazine in 25 ml of methylene chloride and 20 ml of glacial acetic acid. The reaction mixture is left to stand at -35 ° for 40 hours, then warmed to room temperature and then stirred at 40 ° for one hour. Working up the reaction mixture by customary methods gives 4.1 g of a yellow viscous product which is extracted with petroleum ether. By evaporating off the petroleum ether, 0.9 g of residue is obtained from the extract, which is distilled in a high vacuum. 0.6 g of 3,3-dimethyl-2- (but-3-ln-l-yl) -cyclohexan-1-one is obtained, which has the following constants: b.p. = 45-48 ° /

ΡΩ ΡΩ

0.02 torr; dj = 0.9432; ri £ ^w = 1.4769- The IR spectrum shows sharp bands at 3300 cm ", 2120 cm (terminal triple bond) and 1710 cm" (carbonyl).

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The 7, 7-dimethylbicyclo [4.4.0] dec-l-en-3-one used as starting material can be prepared as follows;

Dihydro-7-ionone is converted into 3 * 3- ^ 1-methyl-2- (3-oxo-but-l-yl) -hexan-l-one by ozonolysis (see HeIv. Chim. Aota 21, 831 [1948]) transferred that of an aldol condensation is subjected. In this way, 7,7-dimethyll-hydroxy-bicyclo [4.4.0] decan-3-one is obtained (see HeIv. Chim. Acta 4_2, 2557 [I959]).

20 g of the crude bicyolic hydroxyketone are subjected to steam distillation over potassium hydroxide. The distillate is obtained by working up in a customary manner Methods 7 g of 7,7-dimethyl-bicyclo [4.4.0] dec-l-en-3-one.

Example 73:

A solution of 300 mg of 14-methyl-1,12-epoxy-bicyclo [10.3.0] pentadeoan-13-one is left and 495 mg of toluenesulfonylhydrazine in 15 ml of methanol stand at 4 ° for 20 hours and the reaction mixture is then allowed to warm to room temperature. The reaction mixture is then in poured ice-cold sodium carbonate solution and shaken out with ether. The essential extract is washed with ice water and dried with sodium sulfate. That after evaporation of the ether remaining crude product (61 mg) is refluxed together with 60 ml of acetone for 50 hours. The through Evaporation of the acetone obtained residue is 60 times

209824/1170

Amount of silica gel (Merck; 0.05-0.2 mm) chromatographed. By eluting with a hexane-ether mixture (9 ^ 1), 206 mg of crude product is obtained, which is distilled at 10O ⁰ A), 008 Torr. 196 mg of 3-methyl-cyclopentadec-4-yn-1-one, which is identical to the product prepared according to Example 66, are obtained.

Example 74: '' - ' ^l " ^

60 g of bicyclo [10.3.0] pentadec-l (12) -en-15-one are dissolved in a mixture of 9 ° 0 ml isopropanol, 180 ml water and 15 grams of sodium hydroxide. One drips into the solution Stir in 90 ml of 30% hydrogen peroxide at 15-20 °. The reaction mixture is stirred for 24 hours at room temperature. The excess hydrogen peroxide is at room temperature (External cooling) reduced with aqueous sodium sulfite. The water and the isopropanol are distilled off in the vacuum of the water jet pump. The residue is with Aether extracted. The extract is washed with water and dried over sodium sulfate. By evaporating the Aether, 63 g of crude 1,2-epoxy-bicyclo [10.3.0] pentadecan-13-one are obtained, which is purified by distillation.

09824/1170

Example 75:

2-Benzylidenecyclopentadecan-l-one (manufactured after the in HeIv. Chim. Acta £, 246 [1942] Way) is refluxed for 6 hours in ether together with lithium aluminum hydride. By working up after customary methods give 2-benzylidene-cyclopentadecan-lol, that melts at 65. This alcohol is made through treatment with peracetic acid at 0-10 in methylene chloride in practically quantitative yield in the corresponding Transferred to epoxy alcohol. The epoxy alcohol is in a mixture of dimethyl sulfoxide and acetic anhydride for 24 Left to stand for hours at room temperature. The epoxy of is obtained by working up by customary methods 2-benzylidene-cyclopentadecan-l-one.

A solution of 350 mg of the epoxide is left and 37O mg of tosylhydrazine in 15 ml of a methylene chloride-acetic acid mixture (2: 1) stand at room temperature for 24 hours. The reaction mixture is then heated for 6 Hours at 40 ° and then let it stand for 12 hours at room temperature. There will be a total of about 20 ml of nitrogen caught. By working up the reaction mixture after customary methods one receives 460 mg of a yellow oil, the strong smell of benzaldehyde. The oil is chromatographed on 30 times the amount of silica gel. As an eluent a hexane-benzene mixture (9: 1) was used. From the eluate

209824/1170

Cyclopentadecine, which has the following spectroscopic properties, is obtained in 52% yield: MS molecular peak 206 (G ₁₅ H ₂₅ ); NMR: -CH ₂ - (1.4 ppm) -22 H, -CH ₂ -C = C-CH ₂ (2.16 ppm) 4. H.

The experiment described above is repeated, but the crude yellow oil obtained is left to stand in the cold. In this way, white crystals are obtained which, after recrystallization from a mixture of methylene chloride, methanol and pentane melt at 126-127. The crystals consist of the Tosylhydrazone of benzaldehyde. A mixture of this substance with an authentic sample of benzaldehyde tosylhydrazone shows no melting point depression.

Example 76:

A solution of 21.3 S 1,11-epoxybicyclo [9.4.0] pentadecan-12-one in J> 0 ml of methanol is mixed with a solution of 17 * 5 g of tosylhydrazine in 100 ml of methanol and the reaction mixture is left for 3 days Stand room temperature. The reaction mixture, which was initially pale yellow, decolorized completely with evolution of sticest off. The reaction mixture is evaporated and the residue is extracted several times with hot petroleum ether. 11.7 g of cyclopentadec-5-in-l-one from P. 52 are obtained from the extracts. IR: max. At 1715 cm "(carbonyl stretching oscillation). The semicarbazone of this ketone melts at 181-182 °.

209824/1170

A solution of 3 * 3 S cyclopentadec-S-in-l-one 0.5 g of palladium-carbon catalyst is added to 120 ml of methanol and the mixture is shaken in a hydrogen atmosphere, until 380 ml of hydrogen are consumed. Filtration and removal of the solvent in vacuo gives 3 * 2 g of cis-cyclopentadec-5-en-l-one, whose semioarbazone melts at 177-179.

A solution of 440 mg of cis-Cyclopentadec-

™ 5-en-l-one in 20 ml of ethanol to 500 mg of Raney nickel and shake the mixture in a hydrogen atmosphere until 48 ml of hydrogen is consumed. By working up in the usual way 410 mg of cyclopentadecanone with a melting point of 60-61 ° are obtained.

In an exposure apparatus made of "Pyrex" glass with a centrally arranged, water-cooled lamp shaft, 3 * 2 g of cis-cyclopentadec-5-en-l-one are exposed together with 1 g of diphenyl disulfide in 250 ml of benzene under argon for 15 hours using a mercury High pressure burner (Phiips HPK 125 W). The solvent is removed in vacuo and the residue is treated with semi-carbide hydrochloride. 3.8 g of semicarbazone with a melting point of 173-175 ^{0 are obtained} , which is cleaved by stirring with 3 ° ml of 85% phosphoric acid for 3 hours at room temperature. The reaction product is diluted with water and extracted with ether. Evaporation of the ether and distillation of the residue gives 1.4 g of trans-cyclppentadec-5-en-l-one with a boiling point of 85 ° / 0.02 Torr; F. =

209824/1170

30-33 ° IR spectrum: Max. At 972 cm "(trans double bond) and 1715 cm "(carbonyl stretching vibration).

The 1,11-epoxybicyclo [9.4.0] pentadecan-12-one used as starting material can be made as follows:

A mixture of 120 g of "cyclopentadecane-l ^ -dione [prepared according to the method described in HeIv. Chim. Acta £ 0_, 705 (1967)], 1500 ml of 90% ethanol and 50 g of potassium hydroxide is heated at reflux temperature for 10 hours The ethanol is then evaporated off in vacuo, the residue is diluted with 300 ml of water and the separated organic phase is separated off by extraction with ether ] pentadecl (II) -en-12-one. The constants of this substance are as follows: Bp = 112-115 ° / 1CT ² Torr; n ^ ° =

on

1.5301; d £ ^u = 1.014.

A solution of 20 g of bicyclo [9.4.0] pentadec-l (II) -en-12-one and 16 ml of 6-n. Sodium hydroxide solution in 1200 ml of methanol is slowly added to 48 ml of 30% hydrogen peroxide at room temperature with stirring, and the reaction mixture is stirred for a further 24 hours. The reaction mixture is evaporated in vacuo, the residue is taken up in 200 ml of ether and the ether extract is washed successively with aqueous sodium sulfite solution and water. 21.3 g of crystalline l, ll-epoxy-bicyclo [9.4.0] pentadecan-12-one of F. = 38-39 ^{0 are obtained} from the ethereal phase.

209824/1170 original

Example 77:

A solution of 15 g of ll-epoxy-14-methylbicyclo [9.4.0] pentadecan-12-one in 200 ml of glacial acetic acid and 20 ml of 85% phosphoric acid is added to a solution of 13 g of tosylhydrazine in 100 ml of glacial acetic acid at room temperature while stirring and the mixture is stirred for 24 hours. The reaction solution, which was initially yellow-orange in color, gradually discolored with simultaneous evolution of nitrogen. After adding 30 g of sodium acetate, the reaction mixture is concentrated to about 100 ml by distillation in vacuo. Then 200 ml of water are added and the separated organic phase is taken up in petroleum ether. Evaporation of the petroleum ether gives 15 g of residue, from which by distillation at 10-5-107 / 0.01 Torr. 11.8 g of an oil are obtained which consists of about 90% 3-methyl-cyclopentadec-5-in-1-one. A sample of this substance purified by gas chromatography

PO ΡΩ

shows the following constants: n ^ = 1.4943; dj «0.9607.

2.4 g of 3-methyl-cyclopentadec-5-yn-1-one are dissolved in 100 ml of methanol, and 0.5 g of palladium-carbon catalyst is added to the solution and shake the mixture in a hydrogen atmosphere until 220 ml of hydrogen are absorbed. By working up of the hydrogenation mixture by customary methods gives 2.4 g of cis ^ -Methyl-cyclopentadec ^ -en-l-one in the form of an oil which, after distillation, has the following constants

20? O

has: η _β = 1.4905; d = 0.9378 .. The semicarbazone des

^209824/1170 OH ₁ Q ₁ NAL INSPICTSD

unsaturated cyclic ketone melts at I36.

2.34 S I-methyl-cyclopentadec ^ -in-l-one is dissolved in 50 ml of methanol, 0.5 g of Raney nickel is added to the solution and shake the mixture in a hydrogen atmosphere until 450 ml of hydrogen is absorbed. By processing the The hydrogenation mixture obtained by customary methods gives 2.4 g of 3-methyl-cyclopentadecan-1-one.

The raw material used in this example can be obtained, for example, as follows: "

A mixture of 234.3 g of 14-methylbicyclo [10.3.0] -pentadec-1 (12) -en-13-one [manufactured according to HeIv. Chim. Acta 50, - 707 (1967)], 2000 ml of methanol, 100 g of Raney nickel and 10 ml 10 # sodium hydroxide solution is shaken in a hydrogen atmosphere until 50 liters of hydrogen are absorbed. Man the hydrogenation mixture is filtered and the methanol is distilled off from the filtrate under reduced pressure. The residue is diluted with ether and twice with 10% sodium

1 carbonate solution and then washed neutral with water. To after drying over sodium sulphate, the solvent is evaporated off under reduced pressure. Most of 240 g are obtained consisting of ^ -Methyl-bicyclotlO ^ .olpentadecan - ^ - ol Raw product.

The crude product (240 g) together with 2000 ml of toluene and 40 g of a 70 # strength Benzdisulfonsäurelösung 4 l / 2 Heated for hours with stirring at reflux temperature. To the

20982 4/1170

After the reaction mixture has cooled to 50 °, 1000 ml of 10% sodium bicarbonate solution are added and the mixture is stirred for a further 15 minutes. The organic phase is separated off and washed again with 10 # sodium bicarbonate solution. After drying over Sodium sulfate, the solvent is distilled off under reduced pressure. Obtained by distilling the residue 198g of 14-methyl-bicyclo [10.3.0] pentadec-l (12) -en from Bp = 100-10 ° / 0.2 Torr.

P In a solution of 110.2 g of 14-methyl-bicyclo [10.3.0] -

Pentadec-l (l2) - 'en in 1000 ml of methylene chloride is added -10 ozone on for 7 hours. Then the temperature of the reaction mixture is allowed to rise to +10 while stirring ozone continues to be introduced. 3 g of 10% palladium-carbon catalyst are added to the reaction mixture and the mixture is hydrogenated it for 20 hours. 10 liters of hydrogen are absorbed in the process. The hydrogenation mixture is filtered and distilled the solvent from under reduced pressure. By distilling the residue, 99 g of 3-methyl-eyeIopentadecan-1,5-dione are obtained of bp = 125-155 ° / 0.2 Torr. By recrystallizing this product from petroleum ether (boiling range 80-100 °) one receives 87.5 g of pure 3-methyl-eyeIopentadecan-1,5-dione from P. 48-49 °.

A mixture of 50 g of 3-methyl-cyclopentadeoan-l, 5-dione, 1000 ml of ethanol and 40 g of potassium hydroxide are heated at reflux temperature for 8 hours. After removing the solution

20 9 824/1170

the residue is taken up in petroleum ether by means of a vacuum and the solution is washed neutral. By evaporating the solvent and distillation of the residue gives 38 g of 13-methyl-bicyclo [9.4.0] pentadec-l (II) -en-12-one with a melting point of 38 °. IR spectrum: maxima at 1610 cm "and 1660 cm". To a solution of 32 g of 13-methyl ~ bicyclo [9.4.0] -

pentadec-l (ll) -en-12-one and 18 ml 6-n. Sodium hydroxide solution in 2000 ml Methanol is slowly added to 75 ml of 30% hydrogen peroxide and stir the mixture for 24 hours at room temperature. Then the solvent is evaporated off in vacuo and the poured Residue in 400 ml of cold 10 # strength sodium sulfite solution. Extraction with methylene chloride and working up the extract by customary methods gives 34 g of 1,11-epoxyl-4-methyl-bicyclo [9.4.0] pentadecan-12-one from P. 40-44 ° (from petroleum ether).

Example 78:

3 ml of 6-n are added to a solution of 6 g of bicyclo [10.3.0] pentadec-l (l2) -en-2-one in 50 ml of methanol at room temperature. Potassium hydroxide and 50 ml of 30% hydrogen peroxide and the mixture is stirred for 24 hours. After adding a further 25 ml of hydrogen peroxide, the reaction mixture is stirred again for 24 hours. The excess hydrogen peroxide is removed by slowly adding aqueous sodium

20982A / 1170

sulfite solution destroyed '·. The reaction mixture is concentrated in vacuo and the residue is extracted with ether. 4.8 g of crude product are obtained from the ether extract, from which 3.8 g of 12-epoxy-bicyclo [10.3 · ⁰ ] · pentadecan-2-one are obtained in the form of crystals melting at 71-73 ° by recrystallization from petroleum ether ,

A solution of 2 g of tosylhydrazine in 15 ml of ice

^ vinegar and 3 ml of 85% phosphoric acid are added with stirring at room temperature to a solution of 2.36 g of 1,12-epoxy-bicyclo- [10.3-0] pentadecan-2-one in 20 ml of glacial acetic acid. The reaction mixture is left to stand for 36 hours, it is then poured into 200 ml of water and the oil which has separated out is extracted with petroleum ether. Evaporation of the solvent gives 2.8 g of crude product which is distilled. This gives 1.5 g of an oily liquid, melting at 104-106 ° / l0 ~ ² torr., Which comprises about 82% of Cyclopentadec ^ -in-l-one.

fc The bicyclo used as starting material [10.3.0] -

Pentadec-l (12) -en-2-one can be made as follows: A mixture of 120 g of cyclopentadecane-1,5-dione [F. = 59-60 °; manufactured according to the in HeIv. Chim. Acta ^ 0, (1967) described method], 1500 ml of 90% ethanol and 50 g of potassium hydroxide is heated at reflux temperature for 10 hours. The ethanol is evaporated in vacuo, whereupon the The residue is diluted with 3 ° 0 ml of water and extracted with ether By evaporating the ether, 105 g of crude product are obtained,

209824/1170

from the 86 g of bicyclo [9.4.0] pentadec-l (ll) -en-12-one by distillation can be obtained. This product has the following

Constants. Bp = 112-115 ⁰ / l0 ^"2 Torr; n ²⁰ = 1.5301;

20th
U ₁ , = 1.014. The tosylhydrazone of the ketone obtained melts

at 164 ° with decomposition,

A mixture of 22 g of bicyclo [9.4.Q] pentacec-l (II) -en-12-one, 150 ml of ethanol, 5 ml of 1-n. Sodium hydroxide and 3 g of Raney nickel are shaken in a hydrogen atmosphere until 4480 ml of hydrogen are absorbed. The hydrogenation mixture is filtered and the solvent is evaporated from the piltrate. The residue is washed neutral with water and then distilled. This gives 20 g of a partially crystallizing stereoisomer of bicyclo [9.4.0] pentadecan-12-ol, which has the following constants: Kp = II5-II8 / 10 ^"2 Torr; ²⁰ n"1.5131; ^ = ^20. 0.9909-

A solution of 20 g of bicyclo [9 «4.0] pentadecan-12-ol and 1 g of toluenesulfonic acid in 350 ml of toluene is heated at boiling temperature for 18 hours on a water separator. After 3 S sodium carbonate has been added, the toluene is distilled off. The residue is then distilled at 10 torr. This gives 15.8 g of bicyclo [9.4.0] pentadec-l (ll) -en from Kp. = 89-90 ° / l0 ~ ² torr. A sample of this purified by gas chromatography

20 substance has the following constants: n _ß = 1.5125;

d'f - 0.9396.

A mixture of 20.6 g of Bieyelo [9.4.0] pentadec-l (ll) -e ^ n, 80 ml of benzene, 50 ml of methanol and 200 mg of rose bengal will be used

0 9 8 2 4/1170 ^{0 Hiöi} '^<AL

with bubbling oxygen at 15 in a usual Exposure apparatus exposed to a high pressure mercury burner (Philips HPK 125 watt). At the beginning of the exposure the rate of oxygen uptake is 42 ml of Op per minute. The reaction comes to a standstill after 2010 ml of op have been taken. The solvent is in vacuo evaporated. The residue is dissolved in 100 ml of absolute ether and the solution is added dropwise to 150 rol while cooling a 50 # essential solution of boron trifluoride. That The reaction mixture is stirred overnight, whereupon the boron fluorine id-etherate by adding aqueous bicarbonate solution gets destroyed. Evaporation of the ethereal phase gives 18 g of crude product which recrystallizes from a little petroleum ether at -3 ° will. 14.2 g of pure 1,6-cyclopentadecane-dione are obtained from P. =? 79 °,

45 g of cyclopentadecane-ljö-dione and 3 ° g of solid

^ Sodium hydroxide is added to 150 ml of ethanol for 12 hours Heated to reflux temperature. The reaction solution is concentrated, the residue is mixed with 30 ° ml of water and the separated organic phase by extraction with ether. By evaporation of the ether and distillation of the residue 34 g of bicyclo [10.3.0] pentadec-l (12) -en-2-one are obtained, which has the following constants: Kp. = 108-111 / 10

20 20

Torr j np. = 1.5169; du = 0.9890. The semicarbazone of the unsaturated ketone obtained melts at 202 °.

209824/117 0

- 107 Example 79:

Bicyclo [10.4.0] hexadec-l (l2) -en (obtainable by the method described in HeIv, Chim. Acta 22 * 1883 [1947]) is closer to the method described in Example 78 in bicyclo- [10.4.0] hexadec-l (12) -en-13-one (P. = 115-117 ° / O, O1 torr; ' IR spectrum: maxima at 160 cm "[C = C-valence oscillation] and 1670 cm "[C = O-valence oscillation]).

A solution of 18.8 g Bicycle [10.4.0] hexadec-1 (12) ~ en-13-one in 1200 ml of methanol and 16 ml of 6-n. There is caustic soda slowly add 48 ml of 30% hydrogen peroxide at 20 with stirring to. After 24 hours the reaction mixture is prepared according to the methods described in the preceding examples worked up. 20 g of one for crystallization are obtained tending distilled reaction product (F. = 124-126 / 0.2 Torr.) * That according to the IR spectrum (C == 0-valence oscillation at 1700 cm "; missing bands in the area of the C = C stretching oscillation) consists of l, 12-epoxy-bicyclo [10.4.0] hexadecan-13-one. A solution of 17.5 g of tosylhydrazine in 100 ml is added at 20 ° to a solution of this product in 30 ml of methanol Methanol is added. The reaction mixture is left to stand at room temperature for 24 hours and then operated in the customary manner on. This gives 12 g of cyclohexadec-5-in-1-one. By catalytic hydrogenation of this substance by means of Raney nickel in the manner described in Example 7-7 gives the

20982A / 1 170

known cyclohexadecanone from F. 56. By catalytic Hydrogenation of cyclohexadec - ^ - in-l-one using a palladium-carbon catalyst up to the absorption of 1 mol of hydrogen, a product is obtained which, according to the IR spectrum, (C = O stretching oscillation at 1715 cm ') and NMR spectrum from cis-cyclohexadec-5-en-1-one consists.

From bicyclo [12.3.0] heptadec-l. (L4) -en-15-one, bicyclo [11.4.0] heptadec-l (13) -en-l4-one and bicyclo [10.5.0] heptadecl (12) -en-13-one (which compounds are accessible by methods known per se) can be obtained according to the invention Method Cycloheptadec-4-in-l-one, Cycloheptadec-5-in-l-one or produce cycloheptadec-6-in-l-one. From these cycloheptadecinones can by catalytic hydrogenation the corresponding cis-cycloheptadecenones by means of a palladium-carbon catalyst that have civet-like smells.

Example 80:

A solution of 14 g of tosylhydrazine in 200 ml of a mixture of methylene chloride and glacial acetic acid (2: 1) is added 12.7 g of 3-methyl-2-pentyl-2,3-oxido-cyclopentan-1-one are added at 0 °. The reaction mixture is left? J> Stand at room temperature for hours. The nitrogen developed during this time The amount is 1120 ml. The reaction mixture is in the

209 82 4/1 1 70

in Example 53 worked up manner. Fractional distillation of the crude product gives 6.5 g Undec-5-in-2-one, which has the following constants: b.p. = 43-44 ° / 0.001 Torr; d ^ ° »0.8728; n ^ ° = 1.4517.

1.4 g of ündec "5-in-2-one are in 5 ml of hexane in the presence hydrogenated by 150 mg of palladium-carbon catalyst. After 1 hour and uptake of 1 molar equivalent of hydrogen comes the reduction to a standstill. Working up in a customary manner and distilling the crude product gives 1 g cis-undec-5-en-2-one, which has the following constants: b.p. = 39-39.5 ° / 0.001 Torr; d ^ ° «0.8476; n ^ ° - 1.4454. This Ketone has a green, fruity odor.

Example 81:

65 g of 2-hexyl-cyolopent-2-en-l-one are converted in the manner described in Example 53 into 2,3-epoxide, which has the following constants: b.p. = 84-85 ° / 0.01 Torr ; d ^ m 0.9835; η _β ■ »1.4566.

In the manner described in Example 3, 10 g of 2-hexyl-2,3-epoxy-cyclopentan-l-one are treated with tosylhydrazine implemented and decomposed the tosylhydrazone obtained. After working up the reaction mixture and distilling the crude product 1 g of Undec-4-in-1-al is obtained, which is at 105 ° / 10 Torr, boiling. This aldehyde has a green odor.

20982 k / 1170

1 g of Undec-4-in-l-al is in 20 ml of hexane in the presence hydrogenated by 200 mg of palladium-carbon catalyst. The hydrogen uptake stops after about 1 hour. By working up the hydrogenation mixture and distilling the crude product, 0.7 g of cis-undec-4-en-l-al, the has a green odor.

Example 82:

In a solution, cooled to -5 °, of 90 g of 2-butylcyclopent-2-en-l-one in 800 ml of methanol, 537 g of 30% hydrogen peroxide are added dropwise within 20 minutes while stirring. Then with stirring at -5 ° 5 ^, 8 g of aqueous 6-n. Sodium hydroxide solution was added dropwise. The reaction mixture is stirred for a total of 2 / k hours at -5 °. The reaction mixture is poured into 2 liters of water and extracted twice with ether. The ether extracts are washed with saturated sodium chloride solution until they are neutral. After drying the extracts over sodium sulfate and evaporating the solvent, the crude product is distilled. 77.5 g of 2-butyl-2,3-epoxy-cyelopentan-1-one, which boils at 92-93 ° / ll Torr, are obtained.

10 g of the epoxy ketone are at 0 ° a solution of 12 g of tosylhydrazine in 150 ml of a mixture of methylene chloride and glacial acetic acid (1: 1) were added. After a reaction time of 5 minutes, the reaction solution is vigorously Stirring and introducing air into 500 ml of aqueous 5 ml

2098 2 4/1170 original insfe

Poured sulfuric acid. An orange-colored one forms Precipitate, which is washed out several times with water after the liquid has been poured off and then twice with 50 ml of hexane each time heated on the water bath. The hexane extracts are washed neutral with water and concentrated. By distillation of the residue is obtained 2.4 g of non-4-in-l-al, which at 8l ~ 82 ° / 10 Torn is boiling.

2.3 g non-4-yn-l-al is hydrogenated in 3 ^m ° l hexane mg in the presence of 250 palladium-carbon catalyst. After the uptake of 1 equivalent of hydrogen, the hydrogenation comes to a standstill. Customary work-up and distillation of the residue gives cis-non-4-en-1-al of P. 72 ° / 10 Torr.

Example 83:

In a cooled to -8 solution of 119 * 3 g of 2-heptyl-cyclopent-2-en-l-one in 700 ml of methanol are under Stir within 3 ° minutes 150 ml 9 ° hydrogen peroxide dripped in. Then at -10 ° within 30 minutes 66 ml of 20% aqueous sodium hydroxide was added dropwise. That The reaction mixture will then stand at 0 ° for 25 hours calmly. The reaction mixture is poured into twice the volume of water and extracted 3 times with ether. The ether extracts are washed 2 times with saturated sodium chloride solution and then 4 times with 20% aqueous

209824/1170

Perrosulfate solution shaken out. The organic phase is then washed neutral with saturated sodium chloride solution, dried over sodium sulfate and evaporated. Distillation of the residue gives 60.3 g of 2-heptyl-2,3-epoxy-cyclopentan-1-one, which has the following constants: b.p. 139/14 torr; n ^ ^u «1.4576; dj = 0.9656.

11.8 g of the epoxy ketone are at 0 a solution of 11.2 g of tosylhydrazine in 14o ml of a mixture of Methylene chloride and glacial acetic acid (2: 1) were added. After a reaction time of 10 minutes, the reaction solution is under vigorous stirring and introduction of air into 1000 ml of an aqueous 5 # sulfuric acid solution cooled to 3, the Contains 7 g of 30% hydrogen peroxide, poured in. the further work-up is carried out in the manner described in Example 81. By distilling the crude product 1.8 g of dodec-4-yn-1-al are obtained, which has the following constants: bp 56 ° / 0.1 Torrj n ^ ° = 1.4548; d ^ ° = 0.8824.

1 * 3 g of Dodec-4-in-l-al are in 6 ml of hexane in Hydrogenated in the presence of 70 mg palladium-carbon catalyst. After the uptake of 1 equivalent of hydrogen, the hydrogenation comes to a standstill. By customary work-up and distillation the residue gives 1 g of cis-dodec-4-en-l-al of bp. 63-64 ° / E, OOl Torr.

209824/1170

Example 84:

In a solution of 77, cooled to -8 °. » 8 S 2-decyl-Oyclopent-2-en-l-one in 350 ml of methanol are added dropwise within 1/4 hour with stirring 64 ml of 90% hydrogen peroxide. 35 ml of 20% aqueous sodium hydroxide solution are then added dropwise at -10 within 30 minutes. The reaction mixture is stirred for 25 hours at 0 ° and then worked up in the manner described in Example 83. Distillation of the crude product gives 2-decyl-2,3-epoxy-cyclopentan-1-one, which has the following constants: Kp ¹ . 97 ° / E, QQl Torr; n ^ ° = 1.4603; df ⁰ * 0.9412.

26.0 g of the epoxy ketone are at 0 ° a solution of 24.4 g of toxylhydrazine in 370 ml of a mixture of diglyme and glacial acetic acid (2: 1) were added. After a reaction time of 10 minutes, the reaction solution is stirred vigorously and introducing air into 1.3 liters of an aqueous 5 # sulfuric acid solution cooled to 3 °. It educates A yellow precipitate immediately forms, which is worked up in the manner described in Example 82. By distillation of the crude product, 4.9 g of pentadec-4-yn-1-al with a boiling point of 88 ° / 0.001 Torr are obtained.

1.0 g of pentadec-4-in-l-al is dissolved in 3 nil hexane in Hydrogenated in the presence of 55 mg of palladium-carbon catalyst. After 1 equivalent of hydrogen has been taken up, the hydrogenation takes place

209824/1170

to a standstill. Customary work-up and subsequent distillation of the crude product gives 0.8 g of cis-pentadec-4-en-1-al of 85 ° / 0.001 torr.

Example 85:

A solution, cooled to -5 °, of 30 g of 2-ethylcyelopent-2-en-l-one in 250 ml of methanol is added, with stirring, to 215 S of 3 ° hydrogen peroxide. Then with stirring at -5 ° 23 g of 6-n. aqueous sodium hydroxide was added dropwise within 15 minutes. The reaction mixture is stirred for a further 90 minutes. Then the reaction mixture is poured into twice the volume of saturated sodium chloride solution and extracted twice with ether. The ether extracts are washed neutral with saturated sodium chloride solution, dried and evaporated. Distillation of the residue gives 27 g of 2,3-epoxy-2-ethyl-cyclopentan-1-one, which has the following constants: b.p. 65-67 ° / 10 Torr; djp = 1.0536; n £ ^u = 1.4558.

5 S 2,3-epoxy-2-ethyl-cyclopentan-l-one are added at 0 ° to a solution of 8 g of calcium hydrazine in 100 ml of a mixture of methylene chloride and glacial acetic acid (1: 1). After a reaction time of 5 minutes, the reaction solution in 3 ⁰⁰ 5 rol #ige sulfuric acid is poured. During the pouring it is vigorously stirred and at the same time

209824/1 170

Air sucked through. An orange-colored appears. Precipitation, which is separated from the liquid phase by decanting. The precipitate is washed several times with water and then twice with 50 ml of hexane each time for 1/2 hour Heated to reflux temperature. The hexane extracts become neutral washed and evaporated. Distillation of the crude product (1.1 g) gives hept-4-yn-1-al, which has the following constants has: bp 88 ° / 45 torr; d ^ ° = 0.9085-

Example 86:

4 g of undec-8-en-5-yn-2-one (prepared according to Example 4) are dissolved in 20 ml of pentane in the presence of 1.0 g Hydrogenated palladium-carbon catalyst. After taking 1 Equivalent to hydrogen, the hydrogenation comes to a standstill. By customary work-up and distillation of the crude product you get 3.5 g cis-cis-undeca-5,8-diene-2-oh, the one has a green fruity odor and has the following constants: b.p. 32 ° / 0.001 torr; d ^ ° «0.8955; n ^ ° - 1.46X8.

Example 87 *.

5 g of 2-pentyl-2,3-epoxy-cyclopent-2-en-l-one (prepared according to Example 53; dj ^v = 0.9912; n £ = 1.4560) are added to a solution of 6 g of tosylhydrazine in 70 ml

209824/1170

a mixture of methylene chloride and glacial acetic acid (.2: 1) was added. The reaction mixture is allowed to come to room temperature heat and let it stand for 1/2 hour. The amount of nitrogen evolved in the reaction is 460 ml. The reaction mixture is then in 2 times the volume Poured water and extracted 2 times with ether. The ether extract is with 10 $ aqueous sodium carbonate solution and washed once with water. After the Aether ™ has evaporated, the residue is subjected to steam distillation. The distillate is extracted with ether. Dec-4-in-1-al, the

PO PO

has the following constants: άξ ^ν = 0.8877; n £ = 1.4549. This aldehyde has a vegetable-like odor.

4 g of dec-4-in-l-al are hydrogenated in 50 ml of hexane in the presence of 50 ° mg of deactivated palladium-carbon catalyst. After the uptake of 1 equivalent of hydrogen, the hydrogenation comes to a standstill. Customary work-up of the hydrogenation mixture and distillation of the crude product gives cis-dec-4-en-l-al, which has an intense fruity odor and the following constants: b.p. 78-80 ° / 10 torr; djf ° = 0.8569; τξ ° = 1.4472.

209824/1 170

Example 88:

If one uses ljS-epoxy-l-propionyl-cyclopentane analogously in the manner described in Example 56 with tosylhydrazine, this gives the hept-5-in-1-al, a colorless oil with a pleasant, vegetable-like smell.

The starting material is processed in the usual way

Oxidation with hydrogen peroxide from the known 1-propionylcyclopent-1-en obtain,

209824/1170

Claims (1)

Patent claims: 1. Process for the production of α-Οχο-α, ß-seco-ß (7) acetylene compounds of the general formula (D wherein each of the symbols R _{1 , R 2} , R, and R 1 denotes hydrogen or an organic radical and at least 2 of the radicals mentioned are linked to one another, characterized in that compounds of the general formula (VI) where R- ,, Rg * Rz ^{and R} 4 ^d * ^e have the meaning given above, X represents a diazonium radical or a radical convertible into a diazonium radical under the decomposition conditions and Y a radical convertible into an oxo group under the reaction conditions and, if appropriate, subsequent hydrolysis means under fragmentation and splitting off 2 0 9 8 2 4/1170 1643348 decomposed molecular nitrogen and optionally obtained products hydrolyzed. 2. The method according to claim 1, characterized in that the compound of formula VI is formed in situ. 3. The method according to claim 1, characterized in that that compounds of the formula VI in which X is a group which can be converted into a diazonium radical and R ,, R R ,, Rj, and Y have the meaning given above, with converts an agent that can convert the group X into a diazonium radical, the product obtained with fragmentation and splitting off of molecular nitrogen and the products obtained are optionally hydrolyzed. 4. The method according to claim 3, characterized in that that one of a compound of the formula where R ₁ , Rg, R- ,, R ^ and Y have the abovementioned meaning, X 'denotes a group which can be converted into a diazonium radical, Z a reactive esterified hydroxyl group 209 824/1170 or Z and Y together form a divalent one under the decomposition conditions and optionally subsequent hydrolysis is a radical convertible into an oxo group, with treated an agent that converts the group X 'into a diazo radical can convert, with a double bond formed between the carbon atoms β and 7 and the bond between the radical Z and the carbon atom β is dissolved and the resulting compound with fragmentation and cleavage decomposed by molecular nitrogen and optionally hydrolyzed products obtained. 5. Process according to one of Claims 1-4, characterized in that α, ß-unsaturated carbonyl compounds the formula where R ₁ , Rg * ^R -z and R ^ have the abovementioned meaning, before or in the course of the fragmentation in any order, on the one hand, into addition products to the olefinic double bond that are suitable for fragmentation and, on the other hand, into nitrogen-containing carbonyl derivatives, their nitrogen-containing radicals below Leaving the for the 209824/1 170 ORIGINAL INSPiO 1643348 Fragmentation required electron pair can be split off is and fragments with elimination of molecular nitrogen, 6. The method according to any one of claims 1-5 *, characterized in that that one hydrazones of α, ß-oxido-'Y-carbonyl compounds the general formula wherein R is a nucleofugic group and the symbols R., R ₂ , R_ and R ^ have the above meaning, fragments with evolution of nitrogen. 7. The method according to any one of claims 1-5, characterized in that hydrazones of α, β-oxo-7-carbonyl compounds the general formula wherein the symbols R ,, Rp * R- * and Rn have the above meaning own, under oxidative conditions and under nitrogen 209 824/1170 development fragmented. 8. The method according to any one of claims 1-5 *, characterized in that hydrazones of α-hydroxy-ß-R ¹ carbonyl compounds of the general formula where R is a nucleofugal group, R ^{1 is} a reactive esterified hydroxyl group and the symbols R ₁ , Rg, R-, and Ru have the above meaning, fragmented with nitrogen development. 9 «The method according to any one of claims 1-5, characterized in that hydrazones of α-hydroxy-ß-R ¹ carbonyl compounds of the general formula wherein R ^{1 stands} for a reactive esterified hydroxyl group and the symbols R ,, Rg, R- * and R ₁ , the above-mentioned 20 9 824/117 0 ORtQJNAL have meaning, under oxidative conditions and under Nitrogen winding is fragmented. 10. The method according to any one of claims 1-5, characterized in that oximes, their esters or ethers of β, β-oxido ⁷ Y-carbony! Compounds of the general formula where R ¹ 'stands for a free, esterified or etherified hydroxyl group and the symbols R ,, Rp, R, and R ^ have the meaning given above, in a basic medium with a reactive ester or ether of hydroxylamine. 11. The method according to any one of claims 1-5, characterized in that oximes, their esters or ethers of α-hydroxy-β-R ¹ -carbony! Compounds of the general formula wherein R, R, R ₁ , R, and R ₁ . the significance given above 20982 Λ / 1170 own device, reacts in a basic medium with a reactive ester or ether of hydroxylamine. 12. The method according to any one of claims 6-9, characterized characterized in that starting materials are used in which the radical R denotes the R, est of an organic sulfonic or sulfinic acid, represents a halogen atom, an alkoxy, aryloxy, alkylthio or arylthio group. 13. The method according to claim 12, characterized in that starting materials are used in which the radical R denotes Represents the residue of a lower alkanesulfonic acid. 14. The method according to claim 12, characterized in that that starting materials are used in which the radical R represents the radical of a monocyclic aromatic sulfonic acid. 15. The method according to claim 12, characterized in that starting materials are used in which the radical R denotes Represents the remainder of the toluenesulfonic acid. 16. The method according to any one of claims 7 or 9, characterized characterized in that the fragmentation of N'-unsubstituted hydrazones by treatment with an oxidation * medium causes. 209824/1170 original inspsctbd 17. The method according to claim 1β, characterized in, that the oxidizing agent used is one capable of converting hydrazones into diazo compounds. 18. The method according to any one of claims 6, 8 and 12-15 »characterized in that the fragmentation of N ¹ -substituted hydrazones is effected by means of inorganic or organic bases. 19. The method according to any one of claims 6, 8 and 12-15, characterized in that the fragmentation of N ¹ -substituted hydrazones is effected by means of acidic agents. 2O ^- . Process according to one of Claims 6, 8 and 12-15 », characterized in that the fragmentation is effected thermally or photochemically. 21. The method according to any one of claims 6, 8 and 12-15, characterized in that the fragmentation is effected with polar adsorbents. 22. The method according to any one of claims 6, 8 and 12, characterized in that one of the fragmentation subjecting hydrazones forms under the reaction conditions. 209824/1 170 23 »Method according to one of claims 10 and 11, characterized characterized in that the reactive ester of hydroxylamine is an ester with a strong inorganic Acid, used with an organic sulfonic acid or organic carboxylic acid. 24. The method according to claim 23, characterized in that that one uses an ester of hydroxylamine with methane or p-toluenesulfonic acid. 25. The method according to claim 23, characterized in that that chloramine is used. 26. The method according to claim 23, characterized in that the sulfuric acid ester of hydroxylamine is used . 27. The method according to any one of claims 8, 9 and 11-26, characterized in that starting materials are used in which R ^{1 is} a hydroxyl group esterified with a strong inorganic acid, with an organic sulfonic acid or organic carboxylic acid. 28 *. Process according to Claim 27, characterized in that starting materials are used in which R ^{1 represents} a hydroxyl group esterified with methane or ρ-toluenesulphonic acid. 209824/1170 29 · The method according to claim 27, characterized in that that starting materials are used in which R 'represents a chlorine atom. 30. The method according to any one of claims 6 and 8, characterized characterized in that the hydrazones to be subjected to fragmentation are formed under the reaction conditions. 31. The method according to any one of claims 10 and 11, characterized in that the ester of hydroxylamine forms under the reaction conditions. 32. The method according to any one of claims 10 and 11, characterized in that the oximes and their esters under the reaction conditions. 33. The method according to claim 32, characterized in that that one corresponding α, ß-substituted carbonyl compounds reacted in a basic medium with an excess of reactive ester or ether of hydroxylamine. 3 ^ · · Method according to claim 33, characterized in that that one corresponding α, ß-substituted carbonyl compounds reacted in a basic medium with a mixture of hydroxylamine and an ester or ether of hydroxylamine. • "209824/1170 35 · Method according to one of claims 1-3 ^ -j thereby characterized in that compounds of the formulas shown are used as starting materials, in which each of the symbols R ,, Rp, R, and R ^ are hydrogen or one of the following radicals designatedί a) a saturated or unsaturated acyclic hydrocarbon radical, which is a straight or branched, optionally carbon interrupted by heteroatoms ^ chain and optionally at least one functional group has, or b) a saturated or unsaturated, mononuclear or polynuclear, optionally ring-substituted, alicyclic Hydrocarbon residue, or c) a mono- or polynuclear aromatic hydrocarbon radical, which optionally carries core substituents, or d) a mononuclear or polynuclear aralkyl or aralkenyl radical which may have core substituents, or e) a saturated or unsaturated, mononuclear or polynuclear heterocyclic radical which is optionally ring-substituted is, where optionally at least two of the symbols R _{1, R p} , R and R ^ together represent atomic groups which, together with the carbon atoms α and / or β and / or 7, are saturated or unsaturated, mononuclear or polynuclear, optionally 2 0 9 8 2 h I 1 1 7 0 ORIGINAL INSPECTED ring-substituted, carbocyclic or heterocyclic ring systems form. 36. The method according to any one of claims 1-35 * thereby characterized in that starting materials are used which are derived from α, ß-unsaturated 7-oxosteroids, their Double bond sits between two adjacent carbon atoms of the steroid ring skeleton. 37. The method according to claim 36, characterized in that starting materials are used which differ from β, ßunsaturated 7-Oxosteroids are derived from the series of Androstane, Pregnane, Cholane, Cholestane, Spirostane, Purostane or cardanolides, or their A-nor-, Α-homo-, B-nor- and / or B-homo-derivatives or their 19-nor derivatives. 38. The method according to claim 36, characterized in that that hydrazones of 7-oxo-a, ß-oxido-sterciden, the series of androstanes, Pregnane, Cholane, Cholestane, Spirostane, Purostane or Cardanolide belong, or their A-nor-, Α-homo-, B-nor- and / or B-homo derivatives or their 19-nor derivatives are used . 39. The method according to claim 38, characterized in that a hydrazone of 3- 2 0 9 8 2 A / 1 1 7 0 original iNS oxido-17ß-acetoxy-5 <* - androstane is used. 40. The method according to claim 38, characterized in that that the starting material is a hydrazone of la, 2a-oxido-3-oxo-17ß-acetoxy-5a-androstane used. 41. The method according to claim 38 *, characterized in that that the starting material is a hydrazone of 3-oxo-4,5-oxido-11ß-hydroxy-17a, 20j20,21-bismethylenedioxypregnane used. 42. The method according to claim 38, characterized in that a hydrazone of 3ß-Acetoxyl6a, 17-OxIdO ^ O-OXO-A- ⁵ -pregnen is used as the starting material. 43. The method according to claim 38, characterized in that a hydrazone of 3 ° ^x ° -4a, 5-oxido-17ß-acetoxy-19-nor-androstane is used as the starting material. 44. The method according to claim 38, characterized in that that the starting material is a hydrazone of Δ -3-Οχο-4,5-oxldo-17ß-acetoxy-19-nor-androstane used. 45. The method according to claim 38, characterized in that that the starting material is a hydrazone of 3-oxo- ORIGSNAL INSP10T2D 209824/1 170 4,5-oxido-20,20 ~ ethylenedioxy-21-hydroxy-pregnane is used. 46. The method according to claim 38, characterized in that a hydrazone of 3-methoxy-ΐβα, 17-oxido-20 ~ oxo-A '^' - ³ ^ ^ -19-nor-pregnatriene is used as the starting material. 47. The method according to claim 38, characterized in that that one as a starting material. a hydrazone of 3ß-acetoxy- 9a, ll-oxido-12-oxo-5a-spirostane used. ™ 48. The method according to claim 37, characterized in that hydrazones of 7-oxo-ahydroxy-β-R ¹ steroids, in which R ^{1 is} a reactive esterified hydroxyl group, and those of the series of androstanes, pregnanes, cholanes, cholestanes, are used as starting materials , Spirostane, Furostane or Cardanolide belong, or their A-nor-, A-homo-, B-nor- and / or B-homo-descendants or their I9- nor derivatives, or their N-substituted by a nucleofugal group Derivatives used. 49. 'The method according to claim 48, characterized in that the starting material, a hydrazone of 3-oxo-4-R ¹ -5-oxy-11ß-hydroxy-17a, 20; 20,21-bismethylenedioxy-pregnane, where R ¹ denotes a reactive substituted hydroxyl group, or its ^{derivatives substituted by a nucleofuge group N 1} -substituted. 2 0 9 8 2 kl 1 1 7 0 50. The method according to claim 48, characterized in that a hydrazone of 3-0xo-4_r '^ - hydroxy-lTß-acetoxy-ip-nor-androstane, wherein R' denotes a reactive esterified hydroxyl group, or its by a nucleofuge group N ¹ -substituted derivatives are used. 51. The method according to claim 48, characterized in that the starting material is a hydrazone of 3 ~ 0xo-4-R'-5-hydroxy-20,20-ethylenedioxy-21-acetoxy-pregnane, in which R ^{1 is} a reactive denotes esterified hydroxyl group, or its derivatives N'-substituted by a nucleofugal group. 52. The method according to claim 48, characterized in that a hydrazone of 3ß ~ acetoxy » 9a-hydroxy-II-R "-12-oxo-5a-spirostane, where R * is a reactive W denotes a capably esterified hydroxyl group, or its derivatives N'-substituted by a nucleofuge group are used. 53 · The method according to claim 37, characterized in that that the starting materials oximes or their esters of 7-oxo-a, ß-oxido-steroids, the series of androstanes, Pregnane, Cholane, Cholestane, Spirostane, Purostane or Cardanolide belong, or their A-nor-, Α-homo-, B-nori r-d / or B = homo-derivatives or their 19-nor-derivatives are used. - · ■ · "'j O -T / -ι - ^r 7 A - u Cf ü · _'."-; / 1 i (U ORIGINAL IMSPiCTSO 54. The method of claim 53 * characterized in that a Oxitn or its ester of 3-oxo-4a, 5-oxido-17-acetoxy-5 uses ^a androstane. 55. The method according to claim 53j, characterized in that that an Oxitn or its ester of la, 2a-0xido-3-oxo-17ß-'acetoxy-5o> androstane used. 56. The method according to claim 53 » characterized in that an oxime or its ester of 3-oxido-11ß-hydroxy-ΐγα, 20; 20,21-bismethylenedioxy-pregnane is used. 57. The method according to claim 53 > characterized in that an oxime or its ester of 3ß-acetoxyl6,17-oxldo-20-oxo-A -pregnen is used. 58. The method according to claim 53 * characterized thereby net that an oxime or its ester of 3-oxo-4ß, 5-oxido-17ß-acetoxy-19-nor-andrastan used. 59 · The method according to claim 53 *, characterized in that an oxime or its ester of Δ -3-oxo-4,5-oxido-17ß-acetoxy-19-nor-androstene used. 20982A / 1170 60. The method according to claim 53, characterized in that an Oxitn or its ester of 3-0xo-4,5-oxido-20,20-ethylenedioxy-21-hydroxy-pregnane used. 61. The method according to claim 53, characterized in that an oxime or its ester of 3- ^M ethoxy-16a, 17-oxido-20-οχο-Δ '^' - ^ -19-nor-pregnatriene is used. 62. The method according to claim 53 *, characterized in that that one is an oxime or its ester of 3ß-acetoxy-9a, 10-oxido-12-oxo-5a-spirostane used. 63. The method according to claim 27, characterized in that; Oximes or their esters of 7-oxo-a-hydroxy-ß-R ¹ steroids, where R 'is a reactive esterified hydroxyl group and which belong to the series of androstanes, pregnans, cholanes, cholestanes, spirostanes, furostanes or cardanolides, are used as starting materials , or their A-nor-, A-homo-, B-nor- and / or B-hornο derivatives or their 19-nor derivatives, are used. 64. The method according to claim 63, characterized in that an oxime or its ester of 3 ~ 0 ^χ ° - ^ - ^ '- 5- hydroxy-17ß-acetoxy-5a-androstane, wherein R ^{1 is} a reactive esterified hydroxyl group , used. 209824/1 1 70 65. The method according to claim 63, characterized in that an oxime or its ester of Jt-Oxo-kB. ¹ - 5,11β-dihydroxy-17a, 20j 20,21-bismethylendloxy-pregnan, wherein R 'represents a reactive esterified hydroxy group, is used. 66. The method according to claim 63, characterized in that an oxime or its ester of 3-0x ° - ^ - R '-5-hydroxy-17ß-aoetoxy-19-nor-androstane, where R 'stands for a "reactively esterified hydroxyl group" is used. 67. The method according to claim 63, characterized in that an oxime or its ester of 30 ° acetoxy-9a-hydroxy-II-R'-12-OXo-Ja-SpIrOStEn, in which R ^{1 is} a reactive esterified hydroxyl group, is used. 68. The method according to claim 35, characterized in that that one uses starting materials that differ from α, ßunsaturated carbony compounds with a mono- or polycyclic, Derive carbo- and / or heterocyclic ring system in which the olefinic double bond in one Ring and the carbonyl group in the α-position to the double bond are arranged in a side chain. 09. The method according to claim 35, characterized in that starting materials are used which differ from a ^ ß « 20982 ^ / 1170 - 13ο - unsaturated carbony compounds with a mono- or
Derive polycyclic, carbocyclic ring system in which the olefinic double bond in a ring and the
Carbonyl group are arranged in a side chain in the α-position to the double bond. 70. The method according to claim 35 > characterized in that the starting material used is a compound of the formula VI in which R, the ^ -Aethyl-hex ^ -en-l-yl radical, R_ hydrogen and R- and R ₂ , together represent the propenyl radical. 71. The method according to claim 35, characterized in that the starting material used is a compound of the formula VI in which R _{1 is} the ethyl radical, Rp is hydrogen and R, and R ^ together is the but-2-en-ylene-l, 4- represent rest. 72. The method according to claim 35 *, characterized in that that a starting material of the formula VI is used, which is derived from cedrenal. 73 · The method according to claim 35, characterized in that starting materials are used which differ from α, β-unsaturated carbonyl compounds with a mono- or
polycyclic, carbo- and / or heterocyclic ring system sliding, in which the carbonyl group in a ring and 2 0 9 8 2 U 1 1 1 7 0 ORIGINAL MSPSCTED - 157 - the olefinic double bond is exocyclic in the α-position are arranged in the Carbony! group. 74. The method according to claim 35 *, characterized in that that one uses starting materials that differ from α, ßunsaturated carbonyl compounds with a mono- or Derive polycyclic, carbocyclic ring system, in which the carbonyl group in a ring and the olefinic Double bond are arranged exocyclically in the α-position to the carbonyl group, the one containing the carbonyl group and the ring carrying the olefinic double bond has at least 8 ring members, 75. The method according to claim 35 *, characterized in that the starting material used is a compound of the formula VI in which R ₁ and R ₂ together represent the tridecylene radical, R _{2 represent} hydrogen and R represents the phenyl radical. 76. The method according to claim 35 *, characterized in that that one uses starting materials that differ from α, β-unsaturated Carbonyl compounds with a mono- or polycyclic, carbo- and / or heterocyclic ring system derive in which the olefinic double bond and the carbonyl group in the α-position to the olefinic double bond are arranged in the same ring. ORIGINAL! NöPfc 209824/117 0 .138- '16 ^ 3948 77 · The method according to claim 35 * characterized in that that one uses starting materials that differ from α, β-unsaturated compounds with a mono- or polycyclic Derive ring system in which the olefinic double bond and the carbonyl group are in the α-position to the double bond are arranged in the same ring, the latter containing at least 5 ring members. 78. The method according to any one of claims 35, 76 and 77, characterized in that a starting material of the formula VI is used in which R, and R_ together represent the ethylene radical, R, hydrogen and R ₁ ^ represent the ethyl radical. 79. The method according to any one of claims 35, 76 and 77, characterized in that a starting material of the formula VI is used in which R ₁ and R 2 together represent the ethylene radical, R represents hydrogen and R _{2 represents} the butyl radical. 80. The method according to any one of claims 35, 76 and 77, characterized in that a starting material of the formula VI is used in which R ₁ and Rp together represent the ethylene radical, R, hydrogen and R ₁ ^ the pentyl radical. 81. The method according to any one of claims 35, 76 and 77, characterized in that a starting material is the Formula VI used, in which R, and Rp together the 209824/1170 original inspected Ethylene radical, R, the methyl radical and R ₁ ^ represent the pentyl radical. 82. The method according to any one of claims 35, 76 and 77, characterized in that a starting material of the formula VI is used, in which R, and Rp together the ethylene radical, R, the methyl radical and R ₂ , the pent-2-ene represent l-yl radical. 83. The method according to any one of claims 35, 16 and 77, characterized in that a starting material of the formula VI is used in which R ₁ and R 2 together represent the ethylene radical, R hydrogen and R ^ the hexyl radical. 84. The method according to any one of claims 35, 76 and 77, characterized in that a starting material of the formula VI is used in which R ₁ and R 0 together Ethylene radical, R represents hydrogen and R _{2 represents} the heptyl radical. 85. The method according to any one of claims 35, 76 and 77, characterized in that a starting material of the formula VI is used in which R ₁ and R ₂ together represent the ethylene radical, R_ hydrogen and R ^ the decyl radical. 86. The method according to any one of claims 35, 76 and 77, äaduroh marked ,, that one is a starting material of the J09824 / 1170 - l40 - Formula VI used, in which R ₁ and R _g together represent the propylene radical, R, hydrogen and R ^ represent the methyl radical. 87. The method according to any one of claims 35 * 76 and 77 *, characterized in that a starting material of the formula VI is used in which R, and Rp together represent the propylene radical, R represents the methyl radical and R ₂ ^ hydrogen. 88. The method according to any one of claims 35, 76 and 77, characterized in that a starting material of the formula VI is used in which R, and Rp together the 2,2-dimethylpropylene-1,3-radical, R, the methyl radical and R ₂ represent hydrogen .. 89. The method according to any one of claims 35 * 76 and 77 *, characterized in that a starting material of the formula VI is used in which R 1 and R "together are a propylene radical which bears an isopropyl group on the carbon atom adjacent to the = CX group, R represents the methyl radical and R ₂ represents hydrogen. 90. The method according to claim 35, characterized in that that one uses starting materials that differ from α, ßunsaturated Derive ketones in which the olefinic double bond forms a bridge in an at least bicyclic, ORIGINAL INoPiCiH 20982W1170 carbo- and / or heterocyclic ring system and the carboxyl group in α-position to the double bond in one of the Rings is arranged. 91. The method according to any one of claims 35 and 90, characterized characterized in that starting materials are used which are derived from α, β-unsaturated ketones in which the olefinic double bond forms a bridge in an at least bicyclic, carbocyclic ring system and the Carbonyl group is arranged in the α-position to the double bond in one of the rings, the ring containing the carbonyl group at least. Contains 5 ring links. 92. Method according to one of claims 35 * 9 ° and 9I * characterized in that a starting material of the formula VI is used in which R. and Rp together represent the propylene radical and R ^ and R ^ together represent the butylene radical. 93. The method according to any one of claims 35 * 90 and 91, characterized in that a starting material of the formula VI is used in which R, and Rp together represent the butylene radical and R, and R ^, together represent the propylene radical. 94. The method according to any one of claims 35j 90 and 91> characterized in that a starting material of the formula VI is used in which R ₁ and R 2 together represent the ethylene 20982 4/1170 rest and R, and R ₂ . together represent the decylene radical. 95. The method according to any one of claims 35 * 9 ° and 91 *, characterized in that a starting material of the formula VI is used in which R ₁ and R 2 together are the nonylene radical and R ₇ . and R ₂ . together represent the propylene radical. 96. The method according to any one of claims 35 * 90 and 91 »characterized in that a starting material of the formula VI is used in which R ₁ and R _? together the propylene radical and R, and R ₂ . together represent the nonylene radical. 97. The method according to any one of claims 35 * 90 ^and 91 *, characterized in that a starting material of the formula VI is used in which R ₁ and R _p together represent the radical -CH (CRV) -CHp- and R-, and R ₂ , together represent the decylene radical. 98. The method according to any one of claims 35 * 90 ^and 91 *, characterized in that ma, n uses a starting material of the formula VI, in which R 1 and R _ together are the 2-methylpropylene-1,2-radical and R 1 and R 2 ₂ . together represent the nonylene radical. 99. Procedure according to one of claims 35 * 90 and 91 * characterized in that a starting material is used 20982A / 117Ö Formula VI used, in which R ₁ and R ₂ together represent the propylene _{radical and R 1} and R 1 together represent the desylene radical. 100. The method according to any one of claims 35 * 9 ° ^and 91 *, characterized in that a starting material of the formula VI is used in which R ₁ and R p together represent the ethylene radical and R 1 and R 1 together represent the dodecylene radical. 101. The method according to any one of claims 35 »9 ^Ö and 91 *, characterized in that a starting material of the formula VI is used in which R- and R_ together represent the propylene radical and R ₁ and R 1 together represent the undecylene radical. 102. The method according to any one of claims 35 »90 and 91 *, characterized in that a starting material of the formula VI is used in which R _{1 and R p} together are the butylene radical and R and R ₂ . together represent the decylene radical. 103. Method according to one of Claims 35 »90 and 91, characterized in that a starting material of the formula VI is used which is different from 10,10-dimethyl-tricyclo- -Z Q [7.1.1.0- ⁵ *] undec-3 (8) -en-4-one derives. 2098? I / 117 0 104 · The method according to claim 35, characterized in that that one uses starting materials that differ from α, ßunsaturated Derive ketones with an at least bicyclic, carbo- and / or heterocyclic ring system, in which the olefinic double bond and the carbonyl group are arranged in the same ring and the olefinic double bond a. two rings connecting the carbon atom in common with the carbon atom in the α-position to the carbonyl group. 105. The method according to any one of claims 35 and 104, characterized in that starting materials are used which are derived from α-, β-unsaturated ketones with an at least bicyclic, carbocyclic ring system in which the olefinic double bond and the carbonyl group are arranged in the same ring un the olefinic double bond is connected by a carbon atom shared by two rings with the carbon atom in the α-position to the carbonyl group. 106. The method according to any one of claims 35, 104 and 105, characterized in that a starting material of the formula VI is used which is different from 6 ~ methyl-bicyclo [4.4.0] decl (2) -en-3-one derives. 107. The method according to any one of claims 35, 104 and IO5, characterized in that a starting material is used ? 0 9 Β '.: -Ι / 1 1' '0 BATH ORIGINAL Formula VI used, which is different from 7 * 7-dimethyl-bloyclo [4.4.0] -dec-l (2) -en-3-one derives. 108. A method according to any one of claims 1-34, characterized in that as starting materials which are derived from α, ßungesättigten yl-carbonylamino! Derived compounds, used in the description of compounds shown. 109. The method according to any one of claims 1-34j characterized in that the starting materials derived from α, β-unsaturated 7-carbony compounds are used in compounds shown in the examples. 110. α-0χο-α, ß-seco-steroid-ß (7) -ins and their derivatives. 111. α-0χο-α, ß-seco-steroid-ß (7) -ine, the series of which Oestrane, Androstane, Pregnane, Cholane, Cholestane, Spirostane, Purostane or Cardanolide belong, or their A-nor-, Α-homo-, B-nor- and / or B-homo-descendants or their 19-nor derivatives. 112. l-0xo-l, 2-seco-steroid-2-ine, which belong to the androstane and pregnane series or their 19-nor derivatives. 113 5-OXO-4,5-seco-steroid-3 ~ ine, which the androstane and Pregnan series or their 19-nor derivatives. ' ¹ O 9 8? A / 1 1 7 0 114. 9-0x ° -9ill-seco-steroid-ll (l2) -ine those of the Oestran, Androstan, Pregnan, Cholestan, Cholan and Spirpstan series. 115. 10-oxo-5,10-seco-steroid-ine der 19-nor-androstan-, pregnan-, cholestan-, cholan-, spirostan- and cardanolide series, which have the triple bond in 4 (5) "or in 5 (6) position exhibit. 116. 16-Oxo-16,17-seco-steroid-17 (20) -ine of the Pregnan- and 19-nor-pregnane series. 117. 16-0x0-16,17-seco-steroid-17 (20) -ine of the 19-norpregnan series with aromatic ring A. 118. 5-Oxo-5 * 6-seco-steroid-: o-ine those of the androstan- and Pregnan series or their 19-nor derivatives. 119. 5-Oxo-17β-acetoxy-4,5-seco-androst-3-yne. 120. l-0xo-17β-acetoxy-1,2-seco-5a-androst-2-in. 121. 5-0xo-11ß-hydroxy-17a, 20; 20,21-bismethylenedioxy-4,5-seco-pregn-3-yne. 209824/1170 122, 5j20-dioxo-11ß, 17a, 21-trihydroxy-4 _i 5-seco-pregn-3-yn. 123.3ß-Acetoxy-16-oxo-16,17-seco-A -pregnen-17 (20) - 124. 3β-Acetoxy-16 _i lo-diethoxy-ΐβ, 17-seco-A -pregnen-17 (20) -in. 125. 5-Oxo-17β-acetoxy-4 _i 5-seco-19-nor-androst-3-yne. 126. 5-Oxo-17β-acetoxy-4,5-seco-19-nor-androst-1-en-3-yne. 127. 5,20-dioxo-21-hydroxy »4 _i 5" seco-pregn-3-in. 128. 5-0x0-20,20-ethylenedioxy-21-hydroxy-4,5-secopregn-3-in. 129. 3-Methoxy-16-oxo-16,17-SeCO-A ¹ '^{5> 5} ^ ¹⁰ ^ - 19-norpregnatrien-17 (20) -in. 130. 3β-acetoxy-9-oxo-9, ll-seco-5a-spriost-ll-in. 131. 17β-Hydroxy-5-oxo-4,5-seco-19-nor-androst-3-yne and its ester. 2 0 9 8 2 /. / 117 0 - 148 132.3β- ^Acetox y "'9-oxo-9, ll-seco-5a-spirost-ll-in. 133 5-oxo-17a-ethinyl-17ß-hydroxy-4,5-seco-19-nor- androst-3-in. 134. 3,17-diacetoxy-5-oxo-5j6-seoo-androst-6-yn. 136. 4-methyl-5-oxo-17β-acetoxy-4,5-seco-androst-3-yne. 137. 3ß- ^Ac etoxy-l6-oxo-l6-methyl-l6,17-seco-A ^ pregn-17 (2O) -In. 138. 3-Oxo-17β-acetoxy-2,3-seco-5a-androst-1-yne. 139 · Cyclopentadecine. l40. Cycloaliphatic -5-oxo-l-ines of the formula (CH ₀ ) where η 10-14 and R denotes hydrogen or a lower alkyl radical. 2Ö8824 / 1 170 141. Cycloaliphatic 5-oxo-l-ine of claim l40 given formula, where η for 10 and 14 and R for H or CE, stands.
3 142. Cycloaliphatic β-ο-1-yne of the formula ο ^R where η is 4 to 12 and R is hydrogen or a lower alkyl radical. 143. Cycloaliphatic 6-oxo-l-ines of claim 142 given formula, where η is 4 or 9-H and R is hydrogen or CR. 144. Hexadec-7-on-1-in. 145. 2- [But-3-yn-l-yl] -cyclohexan-l-one, which is in the 2-position one or in the 3-position one or 2 lower alkyl radicals wearing. 146. Aliphatic aldehydes of the formula R-CSC-CH ₂ CH ₂ -CHO wherein R is an alkyl radical having 1 to 10 carbon atoms. 209824/1 170 147 · Aliphatic aldehydes of those given in claim l46 Formula in which R denotes the methyl, pentyl, hexyl, heptyl or represents a decyl radical. 148. Hept-l-al-5-in. 149. Non-1-al-3-en-6-in. 150. 151. Undec-2-one-5-yne, which has 2 hydrogen atoms in the 4-position or 2 lower alkyl, especially methyl radicals, 152. Hept-2-one-6-yne, which has two hydrogen atoms in the 5 position or a hydrogen atom together with a lower alkyl, in particular the isopropyl radical. w 153. The new acetylene compounds described in the examples. 154. The groups of new connections. 155 · The new connections shown in the description. 209824/1170