DE1964964A1 - Process for the preparation of alicyclic alpha-nitro ketones - Google Patents

Description

New Haven, Connecticut, V.St..Ac

"Process for the preparation of alicyclic tf-nitro ketones"

Priority: December 31, 1968, V, St.A., No. 788 330

The invention relates to a new method for the production of ^ alicyclic tf-nitroketones.

There have already been produced numerous alioycl is before iV Nitrcketoiie and = described in the literature The ■ "Verwsniur-g these substituted alicyclic ketones is generally -bekaxmt example, are used as intermediates in the production of Of y ω-dicarboxylic acids and u). - Aminocarboxylic acids, which in turn are starting compounds for polymers.

Dicarboxylic acids which are important for tea can be easily produced by treating aXiejclisehen α-nitroketones with mineral acids. "A typical example of this reaction is the production of mipiric acid by reacting α-nitrocyclohexanone with mineral acid""" as described by Simmons and Kreuz, Journ "Org, ehern" 33 (1968), since © 836 _f

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Valuable aminocarboxylic acids are also obtained from alicyclic nitro ketones. For example, it is known that alicyplic (Y-lfitroketones can be cleaved with aqueous bases to form ω- nitrocarboxylic acids, which in turn are then converted into the corresponding aminocarboxylic acids by catalytic reduction with hydrogen. This process is used to produce G-aminocaproic acid from 2 -Nitrocyclohexanone applied.

Further processes for the production of alicyclic öf-kitroketones from alicyclic ketones are e.g. by Feuer and Pivawer, Journ. Org. Chem. 31 (1966), page 3152 and in Dutch patent application 6712714. Lots of for this Processes required alicyclic ketones as starting compounds are easily accessible. Other allyelic ketones, on the other hand, are expensive or not commercially available.

Cyclohexene serves as the starting material for the production of 2-ki-trocyclohexanone _e (cf. Stevens, Ghesa * and Ind. ”, 1960, page 499V, whereby the cyclohexene is reacted with dinitrogen tetroxide and oxygen in a non-polar solvent however, only very low yields of 2-KitrocyclohexeriOn _i! and the process is not commercially applicable.

It has now been found that alicyclic oc-nitroketones can be obtained in very high, sometimes almost quantitative yields if 2-nitrocycloalkylperoxiniti. ^a a, te treated with certain dipolar aprptic solvents under carefully selected reaction conditions.

The conversion is described by the following equation, in which, for example, dimethylformamide is converted to 2-nitrocyolohexyl- • QQ9836 / 2211

g £ D LOCAL

lets peroxinitrate act.

Dimethylformamide

Laehowicz and Kreuz, Joürn. Org. Chenu 32 (1967), page 3885, have described a similar reaction of! -Nitrododecyl-Z-peroxy nitrate with dimethylformamide, where "1-nitro-2-dodecanone and nitric acid are obtained. However, it is known that alicyclic nitroketones under these circumstances in a strongly acidic medium are much more easily subject to cleavage than aliphatic nitro ketones. It is unexpected that in the process of the invention the alicyclic C (nitro ketones, which are formed simultaneously with nitric acid, are not degraded found that the desired alicyclic M -nitroketones can be isolated in very high yields in the presence of equimolecular amounts of nitric acid under the conditions described for this process .. *.,

The 2-nitrocycloalkyl peroxynitrates provided as starting compounds for the present process can be prepared by reacting various alicyclic olefins (which are listed in detail here) with nitrous oxide and oxygen in an inert organic non-polar solvent. At the end of this conversion, the peroxyl nitrates are isolated from the reaction mixture by filtration and / or evaporation at low temperatures. This procedure is explained in Example 1 of the test description. Suitable non-polar LÖsungsmiiit'ei that ^ jL production of the starting compounds "dienenderi ^Ä ¥ efMlrii-

00 9836/2211 ^Λ - ^

ORIGINAL

would be used are aliphatic hydrocarbons, such as hexane and heptane, cycloaliphatic hydrocarbons such as; Cyelohexane, aromatic hydrocarbons such as benzene, toluene and the xylenes, as well as ethers such as diethyl ether. \

It has also been found that within the scope of this invention the implementation of alicyclic olefins with dinitrogen tetroxide and oxygen in the first reaction stage from the beginning also in Can carry out the presence of a dipolar aprotic solvent, then in the second reaction stage the alicyclischen.oirNitroketone obtained directly in very high yields in an economical manner. The intermediate 2-nitrocycloalkylperoxynitrates, which are also unstable under certain conditions. need in this integrated new process not to be isolated, and a possible formation of peroxy- nitrate, which could interfere with the implementation avoided this procedure. This new one-step process represents the preferred embodiment of the invention.

The feasibility of this process and the very high yields of alicyclic Gf-nitroketones in the one-step process are very surprising and unexpected in the context of this invention. For example, the nitro-oxidation of olefins has hitherto always been carried out in non-polar solvents, in contrast to the dipolar aprotic solvents as used here. The nitric acid, which is formed during the production of "the nitro ketone, surprisingly does not have any hindering or other disruptive effect on the nitro oxidation, and ν, as already stated, is the alicyclic o ( -nitro ketone under the conditions according to the invention in the presence of nitric acid -> 009836 / 221 1

1964904

re unexpectedly stable. ■ '■ "" ""'

The preferred embodiment is given by the following equation, after which cyclododecene is converted into Z-nitrocyclododecanone, " explained. ; '0 - NO

dipolar aprotic ν .

, Solvents.

V -. -

+
ENT.

In the method of the invention, only specially selected dipolar aprotic solvents can be used with success. Sat For example, one can use dipolar aprotic solvents such as ketones, e.g. acetone, nitriles such as acetonitrile, sulfones such as dimethyl sulfone and do not use nitroalkanes in the context of this invention, if you use the process while achieving high yields and wants to carry out economically,

It has been found that only those dipolar and aprotic solvents which are not olefinically or acetylenically unsaturated and which have a negative charge on a free oxygen atom can be used for the preparation of alicyclic γ-nitroketones described here. Solvents of this type are a., B. in Quarterly Reviews, Vol. XVI (1962), page 165 and by Zaugg _s Jeura, Atter, Ohem *. So-called 82 (1960), page 2903 described «

Pormel *. - ■ -

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in which R and R 'each represent an alkyl radical, preferably a lower one Alkyl radical with 1 "to 4 carbon atoms, and R" denotes a hydrogen atom or an alkyl radical, preferably a lower alkyl radical, are useful as dipolar aprotic solvents in the process of the invention. Specific examples are dimethylformamide, Diethylformamide and dirnethylacetamide.

Further suitable dipolar aprotic solvents are sulfur dioxide, dialkyl sulfoxides, such as dimethyl sulfoxide, N, N'-tetraalkylureas, such as N, N ¹ -etramethylurea, hexaalkylphosphoramides, such as hexamethylphosphoramide and certain phosphonic and phosphinic esters.

N-AlkyllactaEia are preferably used. So. Are N-alkyl- £ - caprolactams and N-alky! pyrrolidones, such as N-methylpyrrolidone, im Method of the invention particularly "effective dipolar aprotic Solvent.

Furthermore, amine-N-oxides, such as pyridine-N-oxide, and trialkylphosphine oxides, such as trimethyl, triethyl and tributylphc: ^ j . Such as triethyl phosphate, heterocyclic amides such as N-Pormylpiperidin ,, N-Acetyl, N-FormyJ.-morpholine, N-acetyl morpholine, N-Porraylpyrrolidin and N-acetylpyrrolidine be leveraged ^J .n · oxide, trialkyl.

.Obgleich the purpose employed dipolar-aprotic solvent to provide the desired nitro ketones also when used in small amounts, one obtains the best Ergeteie-s, when using a molar excess of these complementary and -u _t, d, h. So more than 1 mole of solvent per mole of peroxynitrate or more than 1 mole of solvent per mole of dee olefin when a

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OBtGlNAL

step process

In the one-step process described above or in the production of the. 2-Nitrocycloalkylperoxiniträte can be alicyclic
Use olefins quite generally as starting compounds. However, alicyclic olefins having 6 to 16 carbon atoms in the ring are preferred. These starting compounds can also have substituents in the ring which are inert to the reaction system, such as alkyl and / or alkoxy radicals.

The term "alicyclic olefin" as used in the description and in the claims includes mono-, di-,
Tri- and tetraolefins, such as cyclohexene, cycloheptene, cyclooctene, cyclonones, cyclodecene, cycloundecene, cyclododecene and
Cyclotridecene; also 1,3-cyclooctadiene, 1,5-cyclooctadiene,
1,4-cyclodecadiene, 1,5-cyclodecadiene, 1,5-cyclododecadiene,
1,3,5-Cycloheptatriene, '·'. ■

⁷ !, I ^ -cyclododecatriene, 1,3,5,7-cyclooctatetraene and
1.5 »9,13-cyclohexadeeatetraene.

When considering alicyclic olefins that have more than one C = C bond
have, used as starting compounds, are obtained as
Main products are alicyclic c (-nitroketones, which have residual olefinic bonds. These compounds can be cleaved in aqueous basic solutions and then the double bonds and the nitro group are hydrogenated, U) -aminocarboxylic acids being obtained. To explain the use of such alicyclic olefins as starting compounds, reference is made to Example 10, in which 1,5 »9-cyclododecatriene is used as starting compound.

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An embodiment for the preparation of an alicyclic - (V-nitroketone according to the process of the invention consists in the action of one of the dipolar aprotic solvents mentioned on isolated 2-Nitrocycloalkylperoxiniträte at temperatures

ο · ο
between about -15 and +50 C, and preferably between about -15 and +25 G. This reaction is highly exothermic and therefore this process is generally not used, although it leads to excellent yields of nitroketone (see Example 2 below).

A more convenient method for making alicyclic «-Nitroketone from 2-Nitrocycloalkylperoxinitraten consists of that one prepares a solution of the peroxynitrate in a non-polar organic solvent and then this solution with one of the dipolar aprotic solvents is added in the temperature range mentioned.

One can convert the isolated peroxynitrate to a non-polar solvent give so as to obtain a solution of this type, or you can optionally also the peroxynitrate by nitrooxidation preparing an alicyclic olefin in situ in a suitable non-polar solvent. By using this One can see the exothermic reaction in the formation of the process Nitroketone is massive, but you need two solvents.

The introduction of nitrous tetroxide and molecular Oxygen in the reaction mixture containing the olefin can. done in different ways. You can, if necessary, pure Use oxygen, but you can also use different gas mixtures,

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that contain free oxygen. One can for example use the oxygen mixed with various inert gases such as nitrogen, methane or carbon dioxide. Preferably you can use air here.

One can use the nitrous oxide and the oxygen the das Olefin-containing reaction mixture both separately and ge. feed together. In one embodiment, an oxygen The gas stream containing the gas is passed over liquid dinitrogen tetroxide and then the gas mixture obtained in this way is then passed introduced into the reaction mixture containing the olefin. On the other hand, you can also use the nitrous oxide and the Introduce oxygen-containing gas mixture separately into the reaction mixture. According to a further form of carrion one can dinitrogen tetroxide is also more fluid in the reaction mixture Add form. Finally, you can also do the whole thing Add oxygen under pressure before the nitrous oxide is added to the mixture.

The desired nitro-oxidation of the alicyclic olefin. Takes place even when using equimolecular amounts of oxygen and nitrous oxide, however, the best results are obtained using a molar ratio of oxygen: dinitrogen tetroxide much 15 s 1

The reaction mixture to the desired # -nitroketones is easy to carry out. For example, the nitroketone can be obtained as a substance off by pouring the reaction mixture into water , which is then filtered off and carried on in the usual way processed »but sometimes you get the nitro ketone

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also as an oil, which can then be mixed with suitable organic solvents absorbs and then by distillation or crystallization isolated.

The examples illustrate the invention. Parts and percentages relate to weight.

example 1

Passing a stream of oxygen over "1.6 ml of liquid dinitrogen tetroxide at a rate of 250 ml / min, and makes the oxygen-nitrogen mixture through a solution of 4.4 g of cyclododecene (91 i" purity by VPC analysis ) in 175 ml of hexane in a three-necked flask. This reaction is carried out for 4: 5 hours. The molar ratio of oxygen / dinitrogen tetroxide is 200/1. The reaction temperature is controlled by means of an ice-coarse salt bath at 0 ° to - held for 5 ° C. After completion of the addition of dinitrogen tetroxide a considerable amount of solid precipitated from the hexane solution. the solid is filtered at 0 ° to -5 ⁰ Q afc, washed with cold hexane and dried. It wera ^ i 2, 0 g (28 96) 2-nitrocyclododecyl peroxynitrate obtained from P. 38 to 46 ⁰ C (decomp.); Λ * ίΐ HO ₉ (6.4 μ); 00NO ₅ (5.8, 7.8 and 12.8 μ ).

G ₁₂ H ₂₂ N ₂ O ₆ ;

49 C. 7th H ü f ber. i 49 , 66; 7th , 591 9, 66 found .; / 49 .71; 7th .82; 9, 24. .695 .79; 9, 26th

Example 2

1.0 g (0.0034 mol) of 2-nitrocyclododecyl peroxynitrate are mixed with 25 ml of dimethylformamide at 5 ^{° C.} The temperature is rising

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BATH ORIGINAL

to 12 C, the resulting solution is stirred for 30 minutes and added then with 100 ml of cold water. The resulting precipitate is filtered off and dried. 0.78 g (100 # der Theory) 2-nitrocyclododecanone, F. 71 "to 76 C. The IR spectrum of the solid is identical to that of an authentic sample of 2-nitrocyclododecanone

Example 3

A stream of oxygen is more than 4.0 ml of liquid dinitrogen tetroxide at a rate of 350 ml / min passed, and the oxygen-nitrogen mixture is then formed into a stirred solution of 8.8 g of cyclododecene (91 $>'purity by VPC Analysis) introduced into 350 ml of hexane. This reaction is carried out for 4 hours. The molar ratio of oxygen / dinitrogen tetroxide is 97/1. The reaction temperature is kept at 0 ° to -5 ° C. by means of an ice-salt bath.

50 ml of dimethylformamide are added to the hexane solution, the temperature rising to 20 ° C.

The reaction mixture is poured into cold water, the precipitate formed is filtered off and dried. This gives 5.6 g (50 io of theory) of 2-Nitroeyclododecanon mp 73 to 76 ⁰ C.

The two-phase filtrate from hexane-water is poured into a separatory funnel transferred, the hexane layer separated, washed with water, dried over magnesium sulfate and filtered. After this Evaporation of the hexane gives 6.1 g of an oil. The VPC-Analyzer shows that the oil at 4.8 $, is made from 2-nitrocyclododecanone

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\ ^': BAD ORIGINAL

stands, which corresponds to a total yield of 8.5 g ( $ 75 of theory).

After recrystallization of the oil from hexane, 1.8 g of 2-nitrocyclododecanone, P. 75 to 78 ⁰ C; after recrystallization from isopropanol F. 78-79 ° C (Literatürangabe F. 78-79.5 ⁰ C).

Example 4

8.8 g of cyclododecene (91 $> purity according to VPC analysis) are dissolved in a mixture of 200 ml of benzene and 50 ml of toluene. Oxygen is passed at a rate of 250 ml / min over 3.4 ml of liquid dinitrogen tetroxide and the resulting mixture is passed through the cyclododecene solution at ⁰ ° C. for 4 hours with stirring. Then 50 ml of dimethylformamide are quickly added to the reaction mixture, the temperature rising ^{to 10 ° C.} The reaction mixture is shaken out five times with 100 ml of water each time, the organic layer is dried over magnesium sulfate and filtered, the solvent is evaporated off and a solid residue is obtained. After recrystallization from hexane, this yields 6.4 g (57 % of theory) of 2-nitrocyclododecanone, mp 72 to 75 ^° C. The IR spectrum is identical to that of an authentic sample of 2-nitrocyclododecanone.

Example 5

The hexane filtrate from Example 1 is added with stirring solid dimethylsulfoxide at 10 ⁰ C, with the temperature at 15 ⁰ C increases. This reaction mixture is then poured into water, a precipitate being formed which is filtered off, washed with hexane and dried. 1.2 g (21 j6 of theory, calculated on the starting olefin) of 2-nitrocyclododecanone from F.

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ßAD ORIGINAL

75 to 76 ⁰ C.

Example 6

150 ml of dimethylformamide are mixed with 27.4 g (0.15 mol) of cyclododecene (91 % purity) and the heterogeneous solution is cooled to ⁰ ° C. Oxygen is then passed over 10.4 ml (0.15 mol) of liquid dinitrogen tetroxide and passes the resulting mixture through the dimethylformamide solution for 5 hours (the Op / NpO, ratio is 30/1). The temperature is maintained between 0 ° and 5 ⁰ C.

The reaction mixture is then poured into ice water. The resulting solid precipitate is filtered off, washed with water to remove residual acid and then dried. This gives 35, Og Peststoff, P. 65 Mi 68 ⁰ C. The ¥ PC analysis gives a degree of purity of 89.9 #, which corresponds to a total amount of nitrile ketone of 31.5 g (92% of theory) · '.:'. "The precipitate is washed with hexane, you get 29.4 i 8.5 $ of theory) pure product from P. 74 to 75 ⁰ C (literati: ^. & Gabe P, 78 to 79 ⁰ C). The IR spectrum is identical to that of an authentic sample of 2-nitrocyclododecanone.

Example 7

Give 4.4 g. Cyclododecene ( $ 91> purity according to VPC analysis) to 50 ml of dimethylformamide. Oxygen is then passed in (300 ml / min.) T.'ST 3 _D * nl fU ^ sigea dinitrogen tetroxide and the gas mixture obtained is introduced into the cyclododecene solution for 4 hours. The reaction / ftiuäui't exothermic with the temperature rising to 4ü ° Cj durwii feel with water for the remainder of the reaction, the temperature is kept at 30 to 40 ⁰ C. Bann it is poured

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8AD ORiGlNAt

Reaction mixture in ice water, a mixture of an oil and a pesticide separating out. Separating the solids from the oil by washing the Peststoffs with a small amount of cold hexane, and 2.1 g (18 # of theory) Peststoff from P. 75-76 ⁰ C. The IR spectrum is identical with that of an authentic sample of 2-nitrocyclododecanone.

Example 8

16.5 g (0.15 mol) of cyclooctene are dissolved in 150 ml of dimethylformamide and the solution is cooled to ⁰ ° C. A mixture of dinitrogen tetroxide and oxygen (molar ratio 1/40) is introduced into the solution for 2 hours, with the gas flow is regulated with a rotometer. The reaction mixture is then poured into water and the upper oily layer is extracted twice with 50 ml of ether each time. The combined oil extracts are washed twice with 50 ml of water each time, dried over magnesium sulfate, filtered and the ether is evaporated. away. The oil obtained is distilled off at G ₃ I mm pressure and 13.1 g (58% of theory) of 2-nitrocycloctanone from P. 75 to 92% are obtained. The IR spectrum is identical to that of an authentic sample of 2-nitrocyclooctanone.

Example 9

8.8 g of cyclododecene Priority (91 ί> purity by VPC analysis) to 150 ml of dimethylacetamide, "then passes to oxygen with 6.4 ml of liquid dinitrogen tetruidd and the resulting gas mixture passes for 5 hours at 5 to 8 ⁰ C in di . Cyclododecene solution a. The reaction mixture is poured into biswater, the solid precipitate formed is filtered off, treated with cold hexane and dried. 2-Mätrocy, loi non, whose IR spectrum matches that of an authentic sample of, are obtained in good yield

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2-nitrocyclododecanone is identical.

Example 10

Dissolve 16,4- g (0.1 mol) of 1,5,9-cyclododecatriene in 150 ml of dimethylformamide and the solution is cooled to 0 ⁰ C. Then it passes oxygen through 6.5 ml (0.11 mole) dinitrogen tetroxide and the gas mixture obtained is introduced into the 1,5,9-cyclododecatriene solution for 4 hours. The molar ratio of N ₂ O * to oxygen is 1/30. After all the dinitrogen tetroxide has been fed in, the solution is poured into cold water. It is extracted twice with ether, the combined ether extracts are washed twice with 100 ml of water each time, dried over magnesium sulfate, filtered and the ether is evaporated. The distillation of the oil obtained gives 3.4 g of cyclododecatriene of bp _Q γ.67 ° 0, and 7.7 g (33 ί> of theory) of a product of bp _Q - ,, -. 120 to 145 ⁰ C A repeated distillation of this fraction gives 5.1 g of 2-nitro-5,9-cyclo ~ dodecadien-on from kpq, .108 to 112 ⁰ C. The IR spectrum shows. strong absorption at 5.8 μ (C = O), 64 μ (NO ₂ ) and 10.2 yes. (C = C).

C HN; calc .: - 64.57; 7.62; 6.28.

found x 64.64; 7.81; 6.09. 64.36; 7.83; 6.14.

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Claims (1)

Claims 1. Process for the production of alicyclic c / nitro ketones, characterized in that one a) an alicyclic olefin at a temperature of about -15 to + 5O ⁰ C with ' b) Dinitrogen tetroxide and oxygen or a free oxygen containing gas in the presence c) a dipolar aprotic! solvent which has a negative Has charge on a free oxygen atom and does not contain any olefinic or acetylenic bonds and the alicyclic o (-liitroketone from the reaction mixture separates. 2. The method according to claim 1, characterized in that that one uses alicyclic olefins with 6 to 16 carbon atoms in the ring as starting compounds. 3. The method according to claim 2, characterized in that cyclododecene is used as the starting compound used. 4. The method according to claim 2, characterized in that that one uses cyclooctene as the starting compound. 5. The method according to claim 2, dadurchgekennz ei without t that you have cyclohexene as the starting compound used. 009836/2211 6. The method according to claim 2, characterized in that that one has 1,5,9-cyclododecatriene as the starting compound used, 7. The method according to claim 2, characterized in that that one has a molar ratio of oxygen / dinitrogen apply troxid of at least 15/1. 8. The method according to claim 2, characterized in that temperatures in the interval from -15 ° to +25 ⁰ C are used. 9. The method according to claim 2, characterized in that the dipolar aprotic solvent used is an N ₁ N'-dialkylcarboxamide in which each alkyl radical has 1 to 4 carbon atoms. 10. The method according to claim 9 »characterized in that that dimethylformamide is used 11 .. The method according to claim 9 »characterized in that that-one uses dirnethylacetamide. 12, method according to claim 2, characterized that a molar excess of the dipolar aprotic solvent over the alicyclic olefin is used 2-Ni tr0-5 _§ 3- ^ yc1ododecadien-on. 149 Process for the production of alicyclic «y-nitro ketones, ü a G u ι j h marked that one 009836/221 1 BATH ORIGINAL a) a 2-nitrocycloalkyl peroxynitrate at a temperature of about -15 to +50 C converts with b) a dipolar aprotic solvent, which has a negative charge on a free oxygen atom, and not an olefinic one or acetylenic bonds, and the alicyclic «-Nitroketone separated from the reaction mixture. 15. The method according to claim 14, characterized in that that you can use 2-Nitrocycloalkylperoxiniträte up to 16 carbon atoms in the ring are used as starting compounds. 16. The method according to claim 15 »characterized in that that temperatures in the range from -15 ° to +25 ° C are used. 17. The method according to claim 15 »marked thereby I think that 2-nitrocyclododecyl percxinitrate is called Starting compound used. 18. The method according to claim 15 »characterized in that the dipolar aprotic solution; -; * An N, N ¹ -dialkylcarboxamide is used in which each alkyl radical has 1 to 4 carbon atoms. 19. The method according to claim 18, characterized in that dimethylformamide is used. 20. The method according to claim 15, characterized in that the starting compound is one in one organic non-polar solvent dissolved * «2-Iitroo.ye.l>» alkylpero% initrate used 009836/2211 bad o _mwNAL 21. The method according to claim 15, characterized in that the dipolar aprotic solvent in a molar excess over that as the starting compound used peroxynitrate. applied. 22. 2-nitrocyclododecyl peroxynitrate. 009836/2211