DE1068710B - Process for the preparation of compounds of the beta-ionylidene ethylidene series - Google Patents

Description

^ 4ε (»(, ξ

GERMAN

INTERNAT. KL. C 07 β

PATENT OFFICE

EXPLOITATION PAPER 1068 710

■ '-ffrf B 49852 IVb / 12 ο

L DAY: AUGUST 6th

NOTICE THE REGISTRATION AND ISSUE OF THE EDITORIAL:

NOVEMBER 12, 1959

For the synthesis of compounds containing the /? - ionylidenethylidene radical (I), numerous processes have become known, because this remainder is a component many important natural substances, such as B. many carotenoids, such as des / J-carotene and vitamin A.

HX _n

XH ₃

Method of manufacture

of connections
the ß-Ionylidenäthyliden series

H, C

X - CH = CH - C = CH - CH =

CH ₃

XH _a

H,

In the known processes (compare e.g. BOIsler, Chinüa, Vol. 4, 1950, pp. 116ff .; HH Inhoffen and F. Bohlmann, Fortschr. Former Research, Vol. 1, 1949, pp. 175 to 210; F. Bohlmann, Angew. Chem., Vol. 62, 1950, pp. 4 to 7; E. Vogel and H. Knobloch, "Chemistry and Technology of Vitamins", 3rd Edition, Vol. 1, 1950, pp. 18 to 150 ; JSU Jones, Chem. Prod. Chem. News, Vol. 13, 1950, p. 266; JGBaxter, progress of chemistry org.Natural substances, Springer-Verlag, Vienna, Vol. 2, 1952, p. 78, and HH Inhoffen and H. Siemer, pp. 1 to 77; HO Huisman et al., Rec. des Trav. Chim. des Pays-Bas, Vol. 71, 1952, p. 911; NA Milas in "The Vitamins", Vol. 1, Academic Press Inc. Publishers, New York, 1954, pp. 4 to 58; O. Isler, Angew. Chem., Vol. 68, 1956, pp. 547 to 553, and O. Isler and M. Montavon, Chimia, Vol . 12, 1958, p. 1; cf. also, for example, German patents 818 942, 818 943, 850 745, 855 399, 858095, 857963, 873 240, 894 691, 918 987, 950551, 950 552, 951212, 957 942 , 954 247, 1008 731,

1 001 256, 1 001 258; French patents 1098 615 and 1108113; the USA patents 1789131, 2 680 755, 2 674621, 2 676 988, 2676 989,

2 676 990, 2 676 991, 2 676 992, 2 676 993, 2 676 994 and 2,766,290) become either the / 3-isomer of cyclocitral (II) or des /? - Ionons (III) or compounds of the general Constitution IV or V as starting materials for the synthesis of compounds of the / J-ionylidene ethylidene series used:

Applicant:

Aniline & Soda Factory in Baden

Corporation,

Ludwigshafen / Rhine

Dr. Horst Pommer and Dr. Wilhelm Sarnecki,

Ludwigshafen / Rhine,
have been named as inventors

H ₃ C,

H ₂ C, CH

C ^X CH ₃
H ₂

IV

Hj- ¹ / "* DD

«T. . V_ * JtIq

\ / ⁸
C.

H ₂ CX = CH.

I I

H ₂ C, CH

^X C ^XX CH ₈

HX _S

H ₂ C

H ₂ C,

XH ₅₁

HX _n

C-CHO HX '

HX _n

CH _S

H ₂
II

H ₂ III

, CH.

X-CH = CH-CO

XH,

Experience has shown that /? Xyclocitral is not a economically useful starting material for the synthesis of compounds of the /? - Ionylidenäthyliden series is. Syntheses of compounds of type IV and V are also frequently described; they are, however, for technical Procedure too cumbersome and therefore not used in practice.

CH ₃ 50 After a careful study of the literature, one can therefore conclude that until today the technically readily available and as a fragrance produced in large quantities jS-ionone (III) is preferred for the synthesis of compounds of the jö-ionylidene ethylidene series

909 648/433

3 4

The starting material is (compare, for example, the technical synthesis of 4-methylpentadiene- (2,4) -al- (l), S-methoxy-4-methylpen-

of vitamin A and des / 3-carotene, in summary tadiene- (2,4) -al- (l), 4-methylhexadiene- (2,4) -al- (l), 7-carb-

Lecture by O. Isler in the journal ifür Angew. oxy-2,6-dimethylheptatriene- (2,4,6) -al- (l), 7-carbalkoxy-

Chemie, Vol. 68, 1956, p. 547). 2,6-dimethylheptatriene- (2,4,6) -al- (1), 8-alkoxy-2,6-di-

Compared to this prior art, it has been found that 5 methyloctatriene- (2,4,6) -al- (1), ll-carboxy-2,5,10-tri-

that one compounds of the /? - Ionylidenäthyliden series methylundecapentaen- (2,4,6,8,10) -al- (l) as well as the ethers

obtained in a very advantageous manner when the / J-ionyl and ester of jö-formylcrotyl alcohol.

idenäthylalkohol (VI) or S-P'.o'.o'-trimethylcyclo- The esters of formic acid can also be classified according to this

hexen- (r) -yl- (l ')] ~ 6-methyloctatrien- (3,5,7) -ol- (2) (VII) implement invention with excellent yields and

either with a triarylphosphine and a proton i *> are also used here under the term oxo compounds

donator or a hydro salt of a triaryl phosphine and to be understood.

with an oxo compound by means of a proton acceptor Suitable proton acceptors are acid-binding ones

implements. Means, e.g. B. alkali hydroxides, alkaline earth hydroxides,

Alkali and alkaline earth amides, alkali and alkaline earth enolates

15 of ketones, ammonia, strongly basic amines, alkali i

\ / ^ ** ^{3 un (} i alkaline earth alcoholates and in some cases also

C organometallic compounds, ζ. Β. Lithium methyl,

/ \ Sodium methyl, phenyl sodium, phenyllithium, butyl

H ₂ CC - CH = CH - C = CH - CH ₂ - OH lithium, sodium acetate, indene potassium and Grignard

i Il 1 ao compounds, such as ethyl magnesium bromide.

H ₈ ¹ C., C _x CH ₃ VI The reactions are preferably carried out in solution

\ λ / CH averaged out. The choice of solvent is up

τι ^s largely on the choice of the oxo component and the

² used proton donors and acceptors

as pending.

Examples of solvents include e.g.

\ / Ethers, such as tetrahydrofuran, dimethyltetrahydrofuran,

Q dioxane, hydrocarbons such as benzene, toluene, xylene,

/ N _n cyclohexane, cyclooctane, isooctane; Alcohols like

H ₂ C C-CH = CH-C = CH-CH = CH-CH-OH 30 methanol, ethanol, isopropanol, propanol, butanol and

I II I benzyl alcohol. Strongly polar solutions are preferred

H ₂ C _x -Cs CH ₃ CH ₃ medium, such as dimethylformamide, acetonitrile and N-methyl

\ p / CH pyrrolidone.

JT ³ VII The temperatures can be within wide limits, approximately

² 35 from -50 to -J-100 ⁰ C, and are under

others depending on the melting or boiling point of the

Solvents are primarily suitable as proton donors. In general, it is advantageous to work with organic acids, especially the hydrogen halide, at temperatures around ⁰ ° C.

acids and the oxo acids of sulfur. In addition, the quantitative ratio of the starting materials, in particular

In addition, all acids are suitable which, with triaryl- 40 des / 5-ionylidene ethanol (VI) and the / JC ₁₈ alcohol (VII) phosphine salts of the triarylphosphine type and the proton donor or

for the hydrosalt of a triarylphosphine, it is advantageous to choose approximately stoichiometrically and also the one to be converted Oxo compound, although an excess of this

R- ^ PH

45 does not interfere with the course of the reaction, in special cases fd Wi bd

even promotes. However, if you want to convert dioxo compounds on both sides, a deficit is often an advantage. The proton acceptors are also mostly equi-

(R stands for identical or different aromatic radicals) valent amounts are used, but can often also be a form. X® stands for the remainder of an inorganic or 50 multiple of the equivalent may be advantageous, e.g. B. then, strong organic acid, e.g. B. trichloroacetic acid or if you have oxocarboxylic acids as the one reaction benzenesulfonic acid. partner or if the proton donor is in the

, As examples of the excess was used for the implementation.

The following aldehydes and oxo compounds are suitable. In some cases, the yields are still lower

Called ketones: formaldehyde, acetaldehyde, propion- 55 improve if you pass the reaction mixture through a Aldehyde, butyraldehyde, isobutyraldehyde, acrolein, inert or inert gas protects against the ingress of air. a-methacrolein, crotonaldehyde, hexadienal, octatrienal, some characteristic an-benzaldehyde, Cinnamaldehyde, phenylacetaldehyde, phenyl- twists of the new reaction schematically repentadienal, Acetone, butyron, methyl ethyl ketone, citral, given. For the sake of simplicity, the formulaic Cyclocitral, glyoxy acid, glyoxylic acid ester, glyoxal, 60 rendering always triphenylphosphine as triarylphos-G-glycolaldehyde, etherified and esterified glycol alde- phine, hydrochloric acid as proton donor and sodium hyde, Acetoacetic ester, oxomalone ester, oxaloacetic ester, methylate as proton acceptor and dimethylformamide / J-alkoxyacrolein, such as pVethoxyacrolein and α-methyl- chosen as solvents.

j8-ethoxyacrolein, a-methyl - ^ - acetoxyacrolein, α-methyl- So by reacting trans- / J-ionylidene-

/ 3-chloracrolein, vinyl methyl ketone, p ^ -Chlorvinylmethyl- 65 ethanol with formic acid ethyl ester the enol ether of ketone, ^ -Methoxyvinyknethylketon, chloroacetaldehyde, so-called / 3-C ₁₆ -aldehyde, an important intermediate / S-formylacrylic acid, tetradinone, propargylic acid - product of the / 3-carotene synthesis according to O. Isler (cf. aldehyde, maleindialdehyde, 2 _J 7-dimethyloctadiene- (2,6) -in- Angew. Chem., Vol. 68, 1956, p. 547), the 6- [2 ', 6', 6'-tri- (4) -dial- (1,8), 2,7-dimethyloctatriene- (2,4,6) -dial- (1,8), methylcyclohexene - (l ') - yl- (l')] - 4-methyl-l-ethoxyhexa-5-carboxy-4-methylpentadiene- (2,4) -al- (l), 5-carbalkoxy-70 triene- ( l, 3.5) (VIII).

H ₃ C,

HoC, / CH,

H ₂ C X-CH = CH-C = CH-CH ₂ -OH + (C ₆ H ₅ ) ₃ P + HCl +; C-OC ₂ H ₅

H ₂ CC

H,

CH,

CH ₃

VI

, CH,

(Dimethylformamide)
+ After ₃

H ₂ C '

C-CH = CH-C = CH-Ch = CH-OC ₂ H ₅ + NaCl + CH ₃ -OH

CH,

VIII

+ (C ₆ Hs) ₃ PO + H ₂ O

The / 3-carotene (X) itself is obtained from one mole of octatriene- (2,4,6) -dial- (1,8) (IX) in excellent purity of the compound of the formula VI and ¹ Z ₂ moles of 2.7 -Dimethyl- and yield.

H ₃ C., -CH ₃
C.

2 χ H ₂ C

H ₂ C.

X-CH = CH-C = CH-CH ₂ -OH + CH0-C = CH-CH = CH-CH = C-CHO

Il I I /

XH ₃

VI

+ (C ₆ H ₅ ) ₃ P + HCl + NaOCH ₃ IX

+ (C ₆ H _B ) ₃ P + HCl + NaOCH ₃

/ CH ₃ H ₃ C.

C C

H ₂ C ^X C-CH = CH-C = CH-CH = CH-C = CH-CH = CH-CH = C-Ch = CH-CH = C-CH = CH-C CH ₂

H ₂ C. C _n

H ₂

CH,

CH,

CH,

CH ₃

H ₂

+ 2 (C ₆ H ₅ ) ₃ PO + 2NaCl + 2CH ₃ OH + 2H ₈ O

If compounds of the trans configuration are used as starting materials, one generally obtains also compounds of the all-trans-ß-Ionylidenäthyliden series. However, if one uses the relatively stable compounds of the 9-cis series as starting material and if one avoids all isomerizing influences, such as light, acids or halogens, during the work-up one can also isolate cis compounds.

The great economic and technical importance of the ^ -IonylidenäthyHden connections lies on the Hand, if one takes into account that under this generic term, apart from many pharmaceutically significant Compounds containing vitamin A, / 5-carotene and other isoprenoid food colors with vitamin A activity fall.

The new process enriches the technology because it is possible to convert alcohols with oxo compounds in a simple manner with the aid of triarylphosphines and to obtain vinylogous compounds. The advantage of the new ηο process becomes particularly clear when it is compared with the process described in German patent application 954 247 or in German Auslegeschrift 1 025 869 in terms of yields and degrees of purity. It is also of particular advantage that compounds of the undesirable retro series which, for. B. when using /? - ionone as a starting material almost always occur as by-products, do not arise. Furthermore, when using 9-cis or 9-trans starting compounds, the synthesis proceeds without any changes in configuration in the 9-position and therefore allows the construction of pure 9-cis or 9-trans carotenoid compounds.

The parts mentioned in the exemplary embodiments are parts by weight.

\ f Example 1

150 parts of triphenylphosphine hydrochloride, 110 parts of trans - /? - ionylidene ethanol and 200 parts by volume of dimethyl

7 8

formamide become methanol for 12 hours at room temperature and sucks off. 46 parts of vitamin A are obtained

touched. The yellow solution is cooled to -1O ⁰ C and acid, which after recrystallizing once from metha-

then simultaneously leaves separate storage vessels nol a temperature of 178 to 179 ° C, X _max 351 to 352 ηαμ,

40 parts of tighnaldehyde and 87 parts of a 30% ε = 40,000 (methanol) shows,

methanol Natriumrnethylatlösung gradually increasing S.

flow. The mixture is stirred for a further 2 hours at ', / Example 4

Room temperature and uses 110 parts of 10% sulfur - 220 parts of trans - /? - ionylidene ethanol are mixed with 300 parts

acid too. The reaction product is with petroleum ether len triphenylphosphine hydrochloride in 400 parts of di-

extracted. The petroleum ether extracts are: Stirred with water methyl formamide for 12 hours at + 10 ° C. the end

washed, with sodium sulfate at - + - 5 ⁰ C for 12 hours io two separate storage vessels are now simultaneously

dried and nitrided. The filtrate is a 174 parts of a 30 ° / ₀ methanolic Natriummethy-

Column with aluminum oxide (activity 2 according to Brocklate solution and a solution of 160 parts of y-acetoxy-

Mann) filtered, from petroleum ether by distillation of α-methylcrotonaldehyde (bp ₁₅ 95 to 97 ° C) in 110 parts

freed and the residue distilled in a high vacuum. Dimethylformamide dripped. By cooling the

At _{boiling point 0> 005} 135 to 14O ⁰ C, 75 parts of Axe-15 reaction solution distilled at -10 ⁰ C. One stirs that

rophlthen (Desoxyvitarnin A) (predominantly in the all- mixture 5 hours at 0 ° C and acidifies it with

tran $ form), which on standing at a low temperature produces thinned phosphoric acid. The light yellow oily suspension

slowly crystallize and after recrystallization is now extracted with petroleum ether. The petroleum ether

from acetonitrile an F, from 75 to 76 ⁰ C show, λ _max extract is washed with water, dried with sodium

325 ηιμ, ε = 50,000 (methanol). ao sulfate, filtered and the filtrate is concentrated to one volume

_t . . . of about 400 parts. This petroleum ether extract

Example Z is nitrated through an aluminum oxide column (activity

110 parts of cis-jö-ionylidenethanol and 180 parts of tri-2 to 3 according to Brockmann). The filtrate is under Stickpheiiyiphospninhydrobromid be in 200 parts by volume of substance in a vacuum from petroleum ether and in a short-path dimethylformamide 6 hours at room temperature 25 distillation system at 70 ° C and 0.0001 Torr from Niedergerü'hrt. The mixture is cooled to ⁰ C -1O and adds boiling shares freed. 80 parts / S-formylcrotonic acid ethyl ester are added to the remaining residue. Below is 135 parts and shows X _max 324 to 325 πιμ, good cooling (the temperature must remain below 0 ° C) ε = 36,000 (isopropanol). The thus obtained vitamin A is allowed to 87 Teüe a 30 ° / ₀ methanolic sodium acetate concentrate can run by chromatographic Adnmmethylatlösung. The mixture is stirred for a further 1 hour 3 ° sorption can be further purified,
at -t-5 ° C and pour the reaction mixture onto ice and \ _B. .
10% phosphoric acid. After extraction with petroleum ether ^X ' ^ßei sP ^{iel 5}
the extract is washed neutral with water, 110 parts of trans - /? - ionylidene ethanol are dried in 300 parts with sodium sulfate and the petroleum ether is evaporated in dimethylformamide and, after addition of 115 parts, vacuum. The residue is treated with 300 Volum- 35 len triphenylphosphine hydrobromide 24 hours at parts of a 25 _^0/0 methanolic potassium hydroxide solution and boiled room temperature and stirred. 55 parts of α-methyl are refluxed under nitrogen for 60 minutes. Acrolein is distilled in and the clear solution is cooled to -5 ° C. Under the methanol, evaporate and acidify the vigorous stirring ° / ₀ aqueous methanolic reaction on. A thick crystal slurry is obtained, which can be seen in sodium methylate solution. The mixture is stirred, filtered off with suction, washed with methanol and dried in vacuo for a further 3 hours at room temperature, dried by volume. The crystals consist largely of 9-cis parts of a 10 ° / _o by weight phosphoric acid are added and extracted Vitamin Α acid, yield 92 parts. By recrystalline with petroleum ether. The combined petroleum ether solutions sieren from methanol one obtains the 9-cis-vitamin Α-acid one washes several times well with water and dries them pure. F. 189 ⁰ C, X _max (methanol) 343πιμ, ε = 37000, pale 45 at -5 ⁰ C for 12 hours over sodium sulfate. After FiI-yellow, fine needles united in tufts. tration is distilled. 82 parts of 8- [2 ', 6', 6'-tri-

. . methylcyclohexen- (l ') - yl- (l')] - 2,6-dimethyloctatetraen-

Example 3 \ (1,3,5,7) from bp _{0> 05} 135 to 138 ° C, X _max (hexane)

110 parts of trans- / 5-ionylidene ethanol with 319 ηιμ, ε = 44,000 are a light yellow, very autoxidizable oil. 150 parts of triphenylphosphine hydrochloride in 200 volumes of 5 ° ._.
share acetonitrile until the solution is clear. Then \ example 0
The acetonitrile is distilled off in vacuo and 220 parts of trans-β-ionylidene ethanol and 265 parts of the foamy residue are dissolved in 200 parts by volume of methanol. phenylphosphine in 500 parts of dimethylformamide. 60 parts of S-formylcrotonic acid (obtained by dissolving and 36 parts of hydrogen chloride, dissolved in 150 parts of alkaline saponification of the diethyl acetal of yS-formyl methanol (HCl content determined by titration), added crotonic acid ethyl ester and acidic stirred hydrolysis of re and 3 hours. It forms a clear solution, action product) and allowed to under cooling on after the addition of 80 parts of ethyl formate -15 ⁰ C a solution of 64 parts of potassium hydroxide cooled to 0 ° C and quickly with run 200 Volumteüen a 300 Volumteüen methanol. the mixture is stirred 30 ⁰ /, strength methanolic sodium methylate solution verGemisch for 1 hour at room temperature and poured 60 is suspended. the mixture is stirred for 12 hours it on ice, and 10 ⁰ / o phosphoric acid. the mixture is extracted with Room temperature and works in the same way as described under with ether, washes the red-yellow ethereal solution described in Example 5.

Water and shake out with 5% ammonia. The obtained 100 Teüe 6- [2 ', 6', 6'-Trimethylcyclohexen-

pale brown ammoniacal solution is repeatedly with (l ') - yl- (r)] - l-ethoxy-4-methylhexatriene- (l, 3.5) from

_{Ether shaken} out and then under ice cooling with 65 Kp. 0l05 110 to 113 ° C.

10% sulfuric acid acidified, with the vitamin A- _. . _

acid is partially crystalline. The precipitated acid becomes _% Example 7

taken up in ether, the yellow ether solution with water 110 parts of trans- / I-ionylidene ethanol are mixed with 170 parts

washed, dried over sodium sulfate and the ether len tritolylphosphine hydrochloride added and after

distilled off. The residue is digested with ice-cold addition of 300 parts by volume of acetonitrile for 12 hours

Stirred at room temperature. The solvent is extracted and exhaustively with petroleum ether. After it has then been distilled off under reduced pressure and worked up, 48 parts of vitamin A acid residue, dissolved in 250 parts by volume of methanol, are obtained. One methyl ester.
adds 60 parts of α-methyl-jö-ethoxyacrolein, cools the \, ^^^ _e i _S r, iel 11

Mixture to ^{0 0} C and quickly drips a solution of 5 \

28 parts of sodium methylate in 90 parts by volume of methanol 110 parts of trans-j8-ionylidene ethanol are mixed with 115 parts

to. The mixture is stirred for a further 10 hours at Zimmerlen triphenylphosphine hydrobromide and mixed at temperature, it is poured onto ice and extracted with the addition of 250 parts of methanol for 36 hours with petroleum ether. The light yellow petroleum ether extract is stirred at room temperature. 90 parts of water are then added, washed for 12 hours at ⁰ ° C. over sodium io 7-carboxy-2,6-dimethylheptatriene- (2,4,6) -al- (l) (obtained sulfate and dried after filtration through a small, by saponification of the column filled with aluminum oxide according to the British patent in vacuo from the ethyl ester 784 628, mp 193 to 194 ° C) freed to solvent. The residue is high and stirred until the solution is clear. One then cools the vacuum distilled. 91 parts of 8- [2 ', 6', 6'-tri mixture are obtained at -20 ° C. and methylcyclohexen- (r) -yl- (r)] - 2,6-dimethyl-1- ethoxy- 15 and with cooling quickly a solution of 40 parts octatetraen- (l, 3.5.7) of boiling point _{0) 001} 135 to 140 ° C. Sodium hydroxide in 200 parts of methanol. It takes place

a violent exothermic reaction, and the temperature 8 rises to + 30 ° C. The dark solution is stirred

further 15 minutes at room temperature, cooled again, 110 parts of trans - / -? Ionylidenäthanol be in 250Vo- 20 to -10 ° C, and neutralized with 10 ° / ₀ hydrochloric dissolved Schwefellumteilen dimethylformamide and, after addition of acid to congo acidic reaction. Fine, 150 parts of triphenylphosphine hydrochloride formed, light orange crystals of 13- [2 ', 6', 6'-trimethylcyclohexene, stirred at room temperature for 8 hours. Cool the mixture (R) -yl (r)] - 3,7, ll-trimethyltridecanhexaen- _(2,4,6) 8.10 to 0 ⁰ C and added dropwise at the same time, but from separate 12) -säure- (l) i (homoisoprenovitaminic acid). A solution of 60 parts of 25 is filtered off, washed with water and recrystallized from tertiary potassium butoxide dissolved in 450 parts of tertiary isopropanol. This gives 105 parts Homoisopreno-butanol, and 60 parts JOE Formylcrotonsäurebutylester vitamin Α-acid in the form of orange-red needles, mp 187 (bp. ₁₅ 110 ⁰ C) dissolved in 130 parts of dimethylformamide, to 188 ° C, X _max (cyclohexane ) 408 πιμ, «= 65,000.
to. The mixture is stirred for 10 hours at room temperature , -, \ s .

temperature. The reaction mixture is then poured onto ice 30 \ Example 12

and lO ^ o phosphoric acid and with petroleum ether 110 parts of trans- / 5-ion3didenethanol and 150 parts of tri

extracted. The extract is washed with water and phenylphosphine hydrochloride in 250 parts by volume, dried over sodium sulfate. Acetonitrile is then distilled until the solution is clear. The petroleum ether and the tertiary butanol are then distilled off in vacuo, the acetonitrile is distilled off in vacuo and the residue is redissolved in petroleum ether. The 35 was dissolved in 250 parts by volume of dimethylformamide. Petroleum ether solution is filtered through a column filled with 500 parts, 24 parts of sodium acetylide are added and aluminum oxide (according to Brockmann) is stirred for 48 hours. This at -5 ° C. A solution of 28 parts of the filtrate is then added dropwise and distilled. 82 parts of vitamin A-all-trans-2,7-DHnethyloctatriene- (2,4,6) -dial- (1,8) in 300Vo-acid butyl ester, _{boiling point O1001} 165 to 170 ° C., X _max 351 to luminescent dimethylformamide are obtained quickly to and warmed up

352 ιημ, ε = 35,000. 4o the reaction solution for 20 minutes at 50 ° C. One is neutral / _R. . . sized by adding a few drops of glacial acetic acid, adds 500

^ Example y lumteüe ethanol and stir the mixture for 12 hours

55 parts of trans-jS-ionylidene ethanol and 60 parts of tri- at room temperature. One sucks the bright red

phenylphosphine are precipitated at + 5 ° C with stirring and crystallized from benzene-alcohol

180 parts by volume of a 1.4 η methanolic sulfuric 45 um. 37 parts of all-trans-jS-carotene, F. 179 bis

acid added. The mixture is 24 hours at room 180 ° C, X _max (hexane) 442 πιμ (e = 148,000) and 481 ιημ

temperature stirred. Then one sets after cooling (ε = 136,000).

to 0 ° C 35 parts of ß-formylcrotonic acid methyl ester to \ ^ ß _e i _sp j _e i 13
and drops 240 parts by volume of a 3 η methanolic

Add ammonia solution. The mixture is stirred for a further 50 136 parts of triphenylphosphine hydrobromide, 88 parts

20 hours at room temperature and extracted the trans-ß-Ionylidenethanol and 300 Teüe Dimethylform-

Reaction product with petroleum ether. The petroleum ether amide are 3 hours at 0 ° C and 12 hours at

extract is washed with water, stirred over sodium sulfate room temperature. After adding 25 teas

dried and the solvent abde- 2,7-dimethyloctadiene- (2,6) -in- (4) -dial- (1,8) is added

put on. The residue (47 parts) shows l _max 352 to 55 with vigorous stirring quickly 110 parts by volume

353 ιημ, ε = 21,000 and consists of raw vitamin A 30% methanolic sodium methylate solution, acid methyl ester. / After the exothermic reaction has subsided, stir

VV / ß _e j _s - _e | If you keep the mixture for 2 hours, add a few drops

^ Add glacial acetic acid and leave it after adding a mixture

110 parts of trans-β-ionylidene ethanol are dissolved in 12 parts by volume of alcohol — methanol (1: 3) (500 parts by volume) for 5 hours

Dissolved lumteüen of methanol and, after adding 102 Teüen, stand at 0 ° C. The precipitate which has separated out is sucked off

Triphenylphosphine is removed for 5 hours at room temperature and recrystallized from benzene-methanol. Man

stirs. 300 parts by volume are then added dropwise at -flO ^{13 C.}

1.3 η methanolic solution of p-toluenesulfonic acid red leaflets with a melting point of 154 ° C, X _max (hexane) 433 to

to. The mixture is stirred for a further 16 hours at room temperature 65,434 ταμ, ε = 113,000;> 457 to 458 πιμ, ε = 92,000.

temperature, adds 48 Teüe / J-Forrnylcrotonsäuremethyl- / /. .

ester and mixed with 35 parts of piperidine. It ^ example 14

exothermic reaction occurs, and after 26 parts it is stirred S-ß ^ o'.o'-trimethylcyclohexen-irj-yl-il ')] -

Decay for another 8 hours at room temperature. The 6-methyloctatriene- (3,5,7) -ol- (2) (H. H. Inhoffen, F. und

90 parts of water are added to the reaction solution. 70 M. Bohlmann, Liebigs Ann. Chem., Vol. 565, 1949, p.35)

are stirred with 27 parts of triphenylphosphine hydrochloride in 100 Vohimteüen acetonitrile for 2 hours at room temperature. The acetonitrile is then distilled off, 100 parts by volume of dimethylformamide are added to the mixture, and 14 parts of 4-methyl-1-alhexadienoic (2,4) acid (6), dissolved in 30 parts by volume of isopropanol, are added. A solution of 17 parts of sodium ethylate in 80 parts by volume of ethanol is added to the mixture while stirring vigorously. The mixture is stirred for a further 1 hour "and puts it at 10 ^0; cent sulfuric bi-i to congo acidic reaction. After standing overnight, the product is filtered off with suction, the precipitate is washed with water and recrystallized from isopropanol. 14 parts of 13-Γ2 ', 6', 6'-trimethylcyclohexen- (1 ') -yl- (l')] - 3.7, l 1 -trimethyltridecahexaen- (2,4,6,8,10, 12) acid (l) (homoisoprenovitamin A acid) in the form of fine orange-red needles (after recrystallization from isopropanol); F. 188 to 189 ° C, λ _ηαχ (hexane) 400 ταμ, ε = 65000.

Claims (7)

Claims: 20 1. A process for the preparation of compounds of the jö-Ionylidenäthyliden series by reacting / J-Ionylidenäthylverbindungen with triarylphosphines and an oxo compound in the presence of a proton acceptor and a solvent, characterized in that as ß-Ionylidenäthylverbindungen / 5-Ionyiidenäthanol or that one the / I-ionylidene ethylidene compound 8-f2 ', 6', 6'-trimethylcyclohexen- (l ') -yl- (l')] - 6-methy] octatriene- (3,5,7) -ol- (2) ' _{and that} Triarylphosphine used together with a proton donor or as a hydro salt. 2. The method according to claim 1, characterized in that the reactions in dimethylformamide executes. 3. The method according to claim 1 and 2, characterized in that one triarylphosphine hydrohalides or hydrohalic acid is used as a proton donor. 4. The method according to claim 1, 2 and 3, characterized in that the proton or alkali or Alkaline earth alcoholates or hydroxides used. 5. The method according to claim 1 to 4, characterized in that the oxo compound is the ester Formic acid used. 6. The method according to claim 1 to 5, characterized in that the oxo compound is glycolaldehyde, ester or ether of glycolaldehyde, ester or ether of / J-formycrotyl alcohol, a-methyl / S-alkoxyacroleine, 7-carboxy or 7- Carbalkoxy-2,6-dimethylheptatriene- (2,4,6) -al - (1), 2,7 - dimethyloctadiene- (2 ₎ 6) -in- (4) -dial- (1,8) or 2, 7-dimethyloctatriene- (2,4,6) -dial- (1,8) is used. 7. The method according to claim 1 to 6, characterized in that the reactions are carried out in the presence an inert or inert gas. Considered publications:
German interpretative document No. 1 025 869. @ .09 648/433 11:59