DE1287577B - Process for the production of lactones - Google Patents

Description

The invention relates to a new process for the production of lactones.

In synthetic organic chemistry it is often advantageous to introduce a lactone grouping into a molecule to produce either industrial products, such as lactonic fragrances or antimicrobial agents containing lactones, special ones To give properties or to produce an intermediate product with which Lactone group then a further reaction can be carried out. Normally however, in the production of a lactone, it is necessary that a carboxyl group or a functional derivative, such as an acid halide group, positionally or conformationally adjacent to a hydroxyl group, a halogen atom, etc. is, so that the reaction between the two substituents leads to the desired ring closure causes. If there is no hydroxyl group, halogen atom, etc. in the adjacent position, as is the case, for example, in the y or δ position in an aliphatic carboxylic acid is the case, such an atom or such a group must be introduced beforehand it is often difficult to find the substitution in the desired position to undertake.

A process for the preparation of lactones has now been found, which is characterized in that a carboxylic acid N-halo amide which has a hydrogen atom which is conformationally adjacent to the nitrogen atom of the amide group on the carbon atom in y- or δ-position to the carboxamide group has been found is able to conformationally adjoin this nitrogen atom, or a mixture of the corresponding carboxamide and a substance that yields positive halogen ions is homolysed and the homolysis product is hydrolysed. The carboxylic acid N-halogenamide used is preferably one which contains the group in which R is a hydrogen atom or an aliphatic, araliphatic or aromatic substituent and X is a methylene, methylidene, methylidine or an imino group or a nitrogen, oxygen or sulfur atom and »Halt is a halogen atom. The process is also characterized in that an N-haloamide of a steroid carboxylic acid or an aliphatic carboxylic acid is used as the starting material, that the hornolytic cleavage is carried out by photolysis, the radiation from a mercury vapor lamp being used as the radiation source, and that an alkali hydroxide is used to hydrolyze the homolysis product , carbonate or alcoholate is used and that the reaction mixture obtained in the homolytic cleavage is hydrolyzed under neutral or acidic conditions, an iodine-reducing agent being present.

The reaction intermediates that arise during the Be radiation, have not yet been identified but are believed to be haloamides contain, wherein the halogen atom of the N-haloamide group with a hydrogen atom has exchanged that in a positionally adjacent position to the nitrogen atom sits or is capable of positionally adjacent to the nitrogen atom to kick. So contain z. B. the raw irradiation products bound iodine and in many cases when reacted with zinc and acetic acid provide with removal the parent amide of halogen. This reaction is with the desired rearranged haloamides expected.

It is believed that the treatment of the raw irradiation product with aqueous alkali, the hydrolysis of the halogen atom bonded to the carbon atom causes and the ring closure provides the desired lactone. However, it is likely that other irradiation products also suffer hydrolysis and lactones at the same time result.

In the process according to the invention for the preparation of lactones of the formula: in which X has the aforementioned meanings, an N-halocarboxamide with a hydrogen atom bonded to a carbon, which is positionally adjacent to the nitrogen atom of the N-halo amide group or is capable of being positionally adjacent to this nitrogen atom, is the homolytic cleavage its nitrogen is subjected to halogen formation, whereby either by itself or after reaction with an alkaline substance, a lactone ring is formed in which the carbonyl group of the amide group initially present is connected via a further oxygen atom to the carbon atom to which the hydrogen atom in the adjacent position was initially connected; the nitrogen atom of the N-haloamide group bears a hydrogen atom or an aliphatic, araliphatic or aryl substituent.

By the designation »positionally adjacent atoms or groups should be expressed that these atoms or groups are in such Positions are in which they are without significant molecular tension on the Can approach the range of distances required for an interatomic bond is. So is z. B. in the steroids a hydroxyl group in the 6ß-position positionally adjacent to a hydrogen atom in the 19-position, while a hydroxyl group in the l3-position position-wise adjacent to a hydrogen atom in the lla-position is.

From the above examples it can be seen that the positionally adjacent Atoms or groups through a chain of four intervening carbon atoms are separated and thereby the positionally adjacent atoms or groups Formation of part of a six-membered structure enable, which, as is well known, is normally essentially stress-free. Form the intervening carbon atoms form part of a structure in which the rotatability and mobility of the bond are limited, as in polycyclic structures, As for example steroids, it must of course be the arrangement of all bonds enable the associated atoms or groups to move into neighboring positions.

In general it is not necessary that all of the between the CO group of the amide and the carbon with which the positionally adjacent hydrogen atom connected, lying atoms are carbon, it is also possible that at least one of the intervening atoms is oxygen, sulfur or nitrogen, provided that that the compound is chemically stable.

The N-haloamide starting compound can thus have the general formula have, in which Hal and R have the meanings given above and the groups R1, which can be identical or different, are hydrogen atoms or aliphatic, cycloaliphatic, araliphatic or aromatic groups or represent two or more together aliphatic or araliphatic groups which are formed by a double bond are connected or form a cycloaliphatic, aromatic or heterocyclic ring structure. The groups R1 can, if desired, have substituents, for example fluorine atoms or hydroxy, alkoxy, aralkoxy; Aryloxy, keto, acyloxy or acyl groups. The compounds in which Hai means iodine have not yet been described and constitute a further feature of the invention.

In this way, the reaction can be used, for example, to produce Steroid lactones are used, for example from the lactone of 3ß-acetoxy-16ß-hydroxy-ll-oxo-5oc-pregnane-20-carboxylic acid, which is used as an anti-aldosterone agent, it is also used in the fragrance industry for the production of a number of lactonic fragrances, such as undecanoic acid-y-lactone, suitable. A number of antimicrobial agents are also lactones, for example Acetomycin and α-methylenebutyrolactone.

The parent amide is derived from an aliphatic carboxylic acid, such as for example stearic acid, both y- and 8-lactones are likely to be used are formed because the hydrogen atoms in the y- and 8-position with respect to the CO group both are easily able to be positionally adjacent to the To kick nitrogen atom.

The substituents that can sit on the nitrogen atom are aliphatic, araliphatic and aryl groups, such as methyl, ethyl, Propyl, cyclohexyl, benzyl, phenyl groups, etc. However, it is preferred to unsubstituted N-Halogena mi * de to use in the implementation of C, as this is special in many cases deliver good results. The homolytic cleavage of the nitrogen-halogen bond is preferably made by irradiating the N-halamide with rays of one wavelength which is absorbed by the bond, for example by radiation from a mercury vapor or tungsten lamp. In such a case, it is preferable a solvent is present, which is of course essentially opposite to that used Radiation should be translucent. Aromatic hydrocarbon solvents, such as benzene or toluene, halogenated hydrocarbons such as Chloroform or methylene dichloride, and ether solvents such as diethyl ether, Dioxane and tetrahydrofuran are suitable. The choice of solvent depends however, largely depends on the relative solubility of the starting material. Hydroxylic however, unsaturated aliphatic hydrocarbon solvents should be avoided will.

The hydrolysis of the split products with an alkaline substance can for example be carried out with an alkali hydroxide, carbonate or alkoxide will. The hydrolysis can also be carried out using neutral or acidic media are performed, and according to one embodiment of the invention, the Products of homolytic cleavage hydrolyzed under acidic or neutral conditions, whereby a lactone is formed. The acidic conditions can be avoided by using a Mineral acid are prepared, preferably an agent should be present that Reduced iodine, such as an alkali bisulfite.

The N-haloamide starting material, if the halogen is bromine or Chlorine is produced by conventional methods of nitrogen halogenation of amides for example by reacting the parent amide with an alkali hypobromite or hypochlorite.

The N-iodamides can be obtained from the corresponding amides by reaction with a substance that provides positive iodine ions. These connections, which generate positive iodine ions are, for example, N-iodosuccinimide, iodine cyan, iodine monochloride, Iodine monobromide or a hypojodite, which in situ by reacting iodine and a Heavy metal oxide or acylate, such as lead tetraacetate, lead tetrapropionate, Mercury (II) oxide or silver oxide, can be produced. The preferred mix of reagents however, iodine and a hypochlorite, hypobromite or nitrite ester of a tertiary Alcohol, especially tertiary butyl alcohol.

The nitrogen iodination is advantageously in the presence of a Carried out hydrogen halide acceptor, for example an inorganic weak Base such as calcium carbonate. As an inert solvent, it is more advantageous Way a hydrocarbon is used. As it is usually the practice to have radiation of the N-iodamide without isolation, the solvent used should preferably be transparent to the radiation or under the irradiation conditions become responsive.

The generation of positive halogen ions is also in the process of being manufactured the N-chloro- or N-bromamides are expedient. A tertiary alkyl hypochlorite or hypobromite is suitable as a halogenating agent, especially when free halogen is used as a catalyst is present. This is how tert-butyl hypochlorite, for example, reacts and Bromine in the dark with octadecanamide to form N-chlorooctadecanamide.

As mentioned above, the preferred method is to be used in, the reaction mixture used for the preparation of the N-halamide directly; -to .-: irradiate, without isolating the N-halogen compounds. However, the nitrogen halogenation reaction will carried out in the absence of radiation that. the homolytic cleavage of the nitrogen-halogen bond causes e.g. B. in complete darkness, it is usually possible to use the N-haloamide to isolate, if so desired.

. @: It is also generally convenient to use the rearranged, halogenamide to react after irradiation with the base, the lactonization without isolation takes place in situ. Most preferred method of making lactones consists in the starting amide with iodine and a tertiary butyl hypochlorite or similar reagent with simultaneous irradiation, e.g. B. with a mercury vapor lamp, implement, whereupon aqueous alkali such as alkali hydroxide or carbonate is added, and the desired lactone, for example by chromatography is isolated. In general, it has been found that a high yield of lactone is obtained when the oxidizing agent, such as tertiary butyl hypochlorite, is used in excess.

Some interesting features of the overall response when looking at it of the reaction mechanism are important. the following: a) iodine comes first absorbed quickly but is regenerated during the reaction. Will be a little one molar excess of lead tetraacetate is used, some lead iodide is formed, b) The absorption maximum at 1765 cm- ', which indicates the presence of γ-lactone, is absent from the crude product but occurs after hydrolysis. However, the crude products of some reactions, especially those of the higher ones Temperatures were carried out, a sharp absorption maximum at 2300 cm- ', possibly indicating the presence of isocyanate.

c) The lactone yields are greatest when there is a high molar excess of lead tetraacetate or tert-butyl hypochlorite and iodine is used. Became stearamide irradiated together with lead tetraacetate, both y- and d-stearlactone became obtained in excellent yield. The structure of the δ-stearlactone was determined by its infrared spectrum and its conversion into 5-hydroxystearic acid and N-benzyl-5-hydroxystearamide confirmedL o-Toluamide was similarly converted to phthalide.

Became stearamide in methylene dichloride with tert-butyl hypochlorite / iodine Treated in the dark, the precipitate exhibited properties that were im Consistent with its formation as isomer (I) of N-iodostearamide. In the Treatment with iodine ion in acetic acid yielded stearamide in quantitative yield and iodine. This isomer of N-iodostearamide was also in benzene at <5 ° C formed, but another isomer (II) was obtained at room temperature. This was also formed when the isomer (I) was obtained from acetone or ethyl acetate crystallized. However, both isomers crystallize unchanged from chloroform off even if the saturated solutions contain the crystals of the other isomer be vaccinated. The infrared spectra of the two forms appear in chloroform solution however, being identical are very different in Nujol. It therefore appears that the two isomers are chemically different and not just mesomorphic forms represent.

The isomer (I) of N-iodostearamide started in the irradiation Benzene gave iodine and stearamide free, and the crude product gave after hydrolysis y-stearolactone. However, the isomer (II) was after a similar treatment in recovered essentially unchanged. The reason for this obvious difference between the two compounds may be in their different solubilities in benzene be sought, as both compounds in dilute chloroform solution on the semi-microscale suffered rapid photolysis when exposed to ultraviolet radiation, as from the change of Infrared spectra emerged.

The photolysis of certain amides with tert-butyl hypochlorite / iodine or Comparable irradiation of N-iodamides itself resulted in solutions that did not contain a γ-lactone band exhibited in the infrared. There was, however, a sharp band at about 1680 cm ', which is declared as belonging to an amide or to the (C = N) band of an iminolactone can be. When washing with aqueous sodium hydrogen sulfite then the expected one emerged y-lactone band. This behavior is consistent with the presence of either a y-iodamide, which cyclizes very easily, or an iminolactone, which hydrolyzed with water. In the case of 4-phenylbutyramide, photolysis gave the N-iodine compound in the presence of an excess of tert-butyl hypochlorite and iodine a compound that appears to be an N-iodine-4-phenylbutyroaminolactone iodine chloride complex appears. This complex can be converted into the desired lactone by hydrolysis be e.g. B. with mineral acid, preferably after treatment with bisulfite.

The following examples illustrate the invention. The melting points were, unless otherwise stated, determined on the Koflerbank. The infrared spectra were recorded with the Unicam SP.200 spectrophotometer. The tert-butyl hypochlorite was stored over calcium chloride at 0 ° C in the dark. The lead tetraacetate consisted of a commercial sample that was dried in vacuo and placed in a desiccator was kept over phosphorus pentoxide and potassium hydroxide chips. The chloroform was passed through an aluminum column to remove ethanol and over calcium chloride kept. Methylene dichloride and carbon tetrachloride were replaced by calcium chloride, Benzene and ether dried over a sodium wire. The irradiation was carried out in dry, oxygen-free nitrogen with a 150 watt tungsten lamp or a 125 watt mercury lamp carried out. The Pyrex reaction flask was partially used for irradiation in the cold immersed in circulating cold water in a Pyrex crystallizing dish and The lamp is hung 5 cm above it. The determination of the halogen in the N-haloamides was obtained by dissolving a weighed sample in a mixture of glacial acetic acid (3 up to 4 ml) and potassium iodide (approx. 100 mg) in the minimum amount of water and titration of the released iodine against an aqueous standard thiosulphate solution (approx 0.04 normal). Example 1 Irradiation of 3 [beta] -acetoxy-11-oxo-5 "-pregnen-20-carboxamide with lead tetraacetate and iodine a) A suspension of 1 g of amide, 3 g of iodine and 2 g of lead tetraacetate in 35 ml of chloroform was stirred at 15 ° C and meanwhile with a mercury lamp irradiated. Another portion (1.6 g) of the lead tetraacetate was added after 1 hour and then irradiating the mixture for an additional 5 hours. A thick precipitate Lead tetraacetate formed after the addition of the second portion, but dissolved later on again. The reaction mixture was filtered and the residue copious washed, first with hot chloroform, then with hot ethyl acetate. The chloroform and ethyl acetate solutions were shaken separately with aqueous sodium bisulfite, then combined and evaporated in vacuo. The residue (1.3 g) was refluxed heated with 2.5 g of potassium hydroxide in 40 ml of ethanol and 10 ml of water for 24 hours. Most of the solvent was removed in vacuo, the residue with water diluted and extracted with ethyl acetate. The ethyl acetate solution was diluted with Washed sulfuric acid, which removed a crude basic material (33 mg), and evaporated to leave a neutral residue (35 mg). After acidification the aqueous phase was extracted with ethyl acetate and the extract for 2- 'hours refluxed. Extraction of the ethyl acetate solution with aqueous potassium carbonate gave 0.12 of a solid acid. Evaporation of the organic phase in vacuo provided 0.58 - of a crude hydroxylactone [vmdz (in CHCl3) at 1700 (ketone) and 1765 (j-lactone)], that with 4 ml acetic anhydride and 4 ml pyridine on the steam bath for 15 minutes was acetylated. The crude acetoxy compound (0.64 g) was chromatographed over alumina (W o e 1 m, sour, activity level IV). Elution of the column with benzene gave the lactone of 313 - acetoxy - 16ß - hydroxy - 11 - oxo - 5a - pregnane-20-carboxylic acid, which crystallized from benzene-cyclohexane in flakes (0.55 g), mp 265 to 267 ° C (Phase change at about 240 ° C), [ec] D -23 ° (c = 1.16 in CHC13), vmdz (in CHCI,) 1710 to 1720 (broad, ketone C = 0 and acetate), 1765 (Z-lactone), identical to one authentic sample.

b) 2.0 g of amide and 3.2 g of lead tetraacetate suspended in 25 ml of chloroform and refluxing were irradiated with a tungsten lamp, while 1.1 g of iodine in 40 ml of chloroform was added dropwise with a Rate at which the iodine color was maintained in the mixture. After one hour (after 0.7 g of iodine had been added) a persistent iodine color had set in. The irradiation was then continued for a further 3 hours, during which time the iodine color became more intense and a yellow solid substance precipitated. The cooled mixture was then filtered. The residue (2.1 g) appeared to be a mixture of lead diacetate and lead iodide. A portion (0.6 g) of the crude product (1.9 g), which had been separated as above, was chromatographed over aluminum oxide (neutral, activity level III). The lactone (30 mg), mp 264 ° C. of the 3β-acetoxy-16β-hydroxy-11-oxo-5ca-pregnane-20-carboxylic acid was eluted with benzene. A second crystalline compound (6 mg), which formed from acetone-cyclohexane prisms with a melting point of 330'C (decomposition), was eluted with methylene dichloride. Other chromatographic fractions were difficult to handle oils.

The residue (1.3 g) of the crude reaction product gave after it had been worked up as described under a), basic (96 mg), neutral (0.35 g), acidic (0.30 g) and lactonic (0.30 g) fractions. The lactonic compound could not be crystallized directly. A portion (0.22 g) was acetylated and the product is chromatographed over aluminum oxide. The only identifiable connection which was obtained was the desired lactone acetate (0.11g).

c) A suspension of 2.4 g of amide, 2.4 g of lead tetraacetate and 1 g of dried Calcium carbonate in 30 ml of chloroform was combined with 0.7 g of iodine as described under b) treated and irradiated with a tungsten lamp for 3 hours. About 3 g of the raw Product were worked up as described under b) and resulted in 0.106 a, acidic, 1.50 g neutral and 0.263 g lactonic fractions. The neutral component crystallized from methylene dichloride in prisms of 3 @ - hydroxy - 11 - oxo - 5x - pregnane - 20 - carboxamide from, F. and mixed F. 272'C. The lactonic fraction yielded after acetylation and crystallization from ether, the pure acetoxylactone (117 mg).

d) Iodine in carbon tetrachloride was added dropwise while stirring a Suspension of the amide (1.2 g), 2.0 g calcium carbonate and 3.2 g lead tetraacetate in 25 ml of carbon tetrachloride were added, the mixture boiling under reflux and irradiated with a tungsten lamp. After 45 minutes (after adding 0.9 g of iodine a persistent iodine color developed. The mixture was whole Irradiated for 3 hours, then cooled and diluted with chloroform. The mix was Shaken with dilute hydrochloric acid, and the precipitate of lead chloride (1.7 g) was collected and washed with chloroform. The chloroform solution was with washed aqueous sodium bisulfite and water and evaporated in vacuo. The sticky one Residue (1.55 g) had vmaz at 1710, 1720 and 2300 (probably isocyanate) cm-'.

A portion (0.86 g) of the crude product was added with 0.6 g of potassium hydroxide mixed in 4 ml of water and 5 ml of dioxane and placed on the steam bath for 30 minutes occasional shaking heated. Then it was diluted with methanol, whereby a homogeneous Solution was obtained and refluxed for an additional 30 minutes. The mixture was then concentrated in vacuo, acidified with dilute sulfuric acid and with Ethyl acetate extracted. The ethyl acetate extraction was washed with 6N hydrochloric acid. Upon dilution of the acidic solution with water, a precipitate was formed which was extracted with ethyl acetate. The fraction thus obtained (0.162 g) had vmaz at 1765 cm- 'and resulted in the work-up according to the usual Way the lactone you want. A separate experiment showed that the authentic Hydroxylactone extracted from the ethyl acetate solution with strong, aqueous hydrochloric acid became. The original aqueous acidic extract gave on treatment with sodium bicarbonate solution a basic fraction (0.158 g), v (in CHCI,) at 1605, 1680, 1700 and 3500 cm- ', which was acetylated with acetic anhydride-pyridine. The acetylated material could cannot be cleaned. The residue of the reaction product was obtained after work-up usually neutral (0.175 g), acidic (0.145 g) and lactonic (0.163 g) Factions.

A second portion (0.69 g) of the crude reaction product was mixed with 2 ml of concentrated hydrochloric acid in 10 ml of ethanol heated on the steam bath for 30 minutes. Another amount of acid (5 ml) was then added and heating for 30 minutes continued. The mixture was then left to stand at room temperature overnight, then diluted with water and extracted with chloroform and ethyl acetate. The products obtained in the usual way were neutral (0.119g), basic (0.092 '), acidic (0.117g) and lactonic (0.180g) fractions. The combined yield of the pure lactone acetate from both hydrolyses was 0.25 @.

e) A stirred suspension of the amide (1.5 g), 5.0 g of lead acetate and 3.0 g of iodine in 40 ml of benzene was irradiated with a mercury lamp at 15 ° C. It a precipitate formed and the mixture turned brown. After 5 hours the mixture was filtered and the residue washed with hot chloroform. When the filtrate was shaken with aqueous sodium bisulfite, an oily one settled Precipitate from the hydrochloric acid diluted with ethyl acetate-acetone on shaking dissolved again. The combined organic phases were evaporated in vacuo. The crude product (1.52 g) had v, Raz (in CH Cl,) at 1710, 1720, 1755 and 2300 cm- '. The usual hydrolysis of the crude product gave acidic (0.157 g), lactonic (0.440 g), neutral (0.198 g) and basic (0.105 g) fractions. The basic fraction [v. "2 (in CHCI,) at 1670, 1700 and 3400 cm- '] was through Dissolution and precipitation from dilute sulfuric acid and then purified acetylated with pyridine-acetic anhydride. After chromatography of the product over an aluminum column (W o e 1 m, acidic, activity level IV) was crystalline Lactone acetate (36 mg). Washing the insoluble residue from the photolysis reaction with hot ethyl acetate-acetone gave a further amount of crude product (0.25 g) which after working up in the usual manner, the desired lactone (0.193 g) was obtained. The combined yield of the lactone acetate was 0.485%. Example 2 irradiation of 3ß-acetoxy-11-oxo-5x-pregnane-20-carboxamide in the presence of tert-butyl hypochlorite / iodine a) 0.54 g of tert-butyl hypochlorite was added to a stirred suspension of the amide (1.5 g) and 3.0 g of iodine in benzene were added, whereupon the mixture with a mercury lamp irradiated at 15 ° C for 7 hours. Additional hypochlorite amounts (3 - 0.36 g) were added after the 1st, 2nd and 3rd hour. The mixture was then added with 100 ml Ethyl acetate diluted and worked up in the usual way, acid (230 mg), neutral (640 mg) and lactonic (422 mg) fractions were isolated. The Lactohian Fraction gave pure lactone acetate (329 mg) after acetylation and chromatography over aluminum oxide, The neutral fraction showed pyridine after acetylation with acetic anhydride a weak lactonic absorption band at 1760 cm- '.

b) 0.90 g of amide, 2 g of iodine and 0.54 g of tert-butyl hypochlorite were stirred in 30 ml of chloroform at 15 ° C. for 10 minutes. The infrared spectrum showed a new absorption peak at 1640 cm- '. The mixture was then irradiated with a mercury lamp for 5 hours. Additional amounts of hypochlorite (3 0.27 g) were added after the 1st, 2nd and 3rd hours. The infrared absorption peak at 1640 cm "disappeared during the irradiation, but formed again after each new addition of tert-butyl hypochlorite. The reaction mixture was then sufficiently diluted with methylene dichloride and washed successively with aqueous sodium acetate, aqueous sodium thiosulfate and water. The crude product, obtained by evaporation of the organic phase, was a yellow solid (1.18 g) [vmax 1600 (weak), 1710 to 1720 (broad) cm- '] (found: I, 9.12 ° / a; corresponds to 39% of a stable C-iodine amide in crude products). Various attempts to crystallize the crude product were unsuccessful. Chromatography of a 0.125 g sample eluted a series of yellow oils which formed amorphous solids on treatment with solvents. One of these fractions contained iodine and, after treatment with ethanolic potassium hydroxide and then with dilute sulfuric acid, had a lactone absorption band at 1760 cm- '.

Another part (120 mg) of the crude product was made with zinc powder and Treated acetic acid on the steam bath for 5 minutes. The hot mixture was filtered, the residue washed with acetic acid, the filtrate diluted with water and washed with Ethyl acetate extracted. The extract was washed with an aqueous sodium bicarbonate solution and evaporated. Chromatography over aluminum oxide gave the residue the starting amide (29 mg) as the only identifiable compound.

A sample (85 mg) of the crude product was mixed with 3 ml of benzene and 2 drops Pyridine boiled for 10 minutes and then evaporated. The crude product had a faint lactonic absorption band at 1760 cm- 'which appears after shaking the sample was reinforced with dilute sulfuric acid.

The residue (0.666 g) of the crude product was treated with 0.8 g of potassium hydroxide refluxed in 5 ml of ethanol and 2 ml of water for 5 minutes. The chilled Mixture was diluted with water and extracted with ethyl acetate, then the ethyl acetate solution was washed with aqueous sulfuric acid. Try that basic fraction (0.141 g) obtained by treating the acid phase with aqueous sodium bicarbonate obtained to clean were unsuccessful. The neutral fraction (0.203 g), which was obtained by evaporating the ethyl acetate solution, was then with Potassium hydroxide hydrolyzed in aqueous ethanol for 2 hours and the solution combined with the aqueous alkali solution previously obtained. the Work-up in the usual Manner gave acidic (76 mg), neutral (0.109 g) and lactonic (0.143 g) fractions.

Example 3 Irradiation of 3β-acetoxy-11-oxo-5a-pregnane-20-carboxylic acid-N-methylamide with lead tetraacetate / iodine a) 2.0 g of the methylamide and 2.8 g of tetraacetate, the were suspended in 50 ml of chloroform, were stirred and refluxed, while 0.8 g of iodine in 25 ml of chloroform was added dropwise. The mixture was irradiated with a tungsten lamp. The iodine was used up quickly at first, however later (about 1 hour) the color reappeared. After 1.5 hours it was the mixture filtered, the filtrate washed with aqueous sodium bisulfite and evaporated. A sample (150 mg) of the crude product (2.1 g) was hydrolyzed in the usual manner. The only identifiable product was 3ß - hydroxy - 11 - oxo - 5a - pregnane - 20 - carboxylic acid-N-methylamide, which crystallized from acetone in prisms, F. 283 to 284'C (evacuated melting point tube), [-1p = -1-54 '(c = 1.24 in 1 : 1 CHChjEthanol), v, na, x (in CHCl3) at 1665 (amide C = 0), 1700 (ketone C = 0), 3450 (O - H) and 3500 (Amide N - H) cm- '.

Analysis for C ._, H3; 03N: Calculated ... C 73.6, H 9.9, N 3.7 ° / a; Found ... C 7 3.7, H 9.8, N 3.7 ° / o.

b) The residue of the crude product (2.0 g) from the previous one The experiment was carried out in 40 ml of chloroform with 3.5 g of lead tetraacetate, 2.5 g of iodine and 2 g of calcium carbonate irradiated with a Wo (frame lamp for 4 hours at the boiling point of the mixture. A sample (150 mg) of the crude product (2.0 g) resulted in the hydrolysis, which is conventional Manner was carried out, the 3ß-hydroxy compound (80 mg) and an acidic fraction (25 mg), which had a weak lactonic absorption band at 1765 cm- '.

c) The crude product (1.9 g) of the residue from b), 5.2 g of lead tetraacetate and 1.3 g of iodine were dissolved in 40 ml of chloroform at the boiling point of the mixture. Irradiated with a tungsten lamp for 6 hours - when heated in vacuo, the crude product yielded a sublimate of hexachloroethane (about 50 mg), which crystallized from ether-ethanol in needles, mp 186 to 187 ° C. (literature melting point 186.8 to 187.4 'C). The hydrolysis of the crude product gave a sticky lactonic fraction (67 mg) which was not purified-Example: Irradiation of 3β-AcetoKy-11-oxo-5a-pregnane-20 = carboxylic acid-N-phenylamide with lead tetraacetate / iodine A suspension of the phenylamide (2.5 g) and 4.0 g of lead tetraacetate in 40 ml of boiling chloroform were stirred and irradiated with a tungsten lamp while 1.0 g of iodine in 25 ml of chloroform was added dropwise over 30 minutes. Initially, the iodine was completely consumed, but its color reappeared 10 minutes after it was completely added. After 4 hours of irradiation, the cooled mixture was washed successively with dilute hydrochloric acid, aqueous sodium bisulfite and water and then evaporated in vacuo. The dark, solid residue (3.13 g) had no lactonic absorption band in the infrared. If part (1.31 g) of the crude product was hydrolyzed in the usual way, a lactonic fraction (0.168 g) was obtained which, after acetylation with pyridine-acetic anhydride and crystallization from methylene dichloride ether, gave the lactone of 3ß-acetoxy - 16ß - hydroxy-11-oxo-5cc-pregnane-20-carboxylic acid (116 g). A crude neutral fraction (2.0 g) was also isolated. The residue (1.54 g) of the crude reaction product was chromatographed over aluminum oxide. The chromatographic fractions were dark oils and amorphous solids, no crystalline compounds were obtained.

Example s Irradiation of o-toluamide with lead tetraacetate and iodine o-Toluamide (92% yield) was obtained from o-tolyl chloride and concentrated aqueous Ammonia produced at 0 ° C. It crystallized from ethanol-benzene in flakes, M.p. 144'C (literature melting point 144-145'C).

o-Toluamide (1.0 g) and 4.0 g of lead tetraacetate in 50 ml of chloroform were stirred at room temperature while powdered iodine was slowly added. The iodine color quickly disappeared and a white precipitate formed. When the iodine color persisted (after about 1 g of the iodine had been added) the mixture was irradiated with a tungsten lamp at the boiling point of the mixture under reflux for 2.5 hours, then cooled and filtered. The residue (1.9 g) from lead diacetate was washed with i \, ethylene chloride and the filtrate was evaporated in vacuo after being combined with the washing solution. The residue had v, "" (in CHCIa) at 1590 and 1680 (primary amide), 1710 and 1720 (?) Cm- '. When the crude product (1.16 g) was hydrolyzed in the usual manner, the products contained an acidic fraction (0.054 g) and a neutral fraction (0.35 g), the infrared spectrum being almost identical to that of the o-toluamide, and a crude lactone (0.25 g), v ", ax 1765 cm- ', which gave phthalide on crystallization from non-ethylene dichloride-light petroleum. Example 6 Irradiation of o-toluamide with tert-butyl hypochlorite and iodine tert-butyl hypochlorite (1 , 45 ml, 1.3 g) was added to a stirred suspension of 1.35 g of o-toluamide and 3.5 iodine in 40 ml of carbon tetrachloride at room temperature. The mixture turned slightly brownish and then darkened rapidly. After 15 minutes the mixture became diluted with 50 ml light petroleum, and the liquid was decanted from the oil which ausfiel- When evaporation in vacuo gave the liquid, a sticky mass (0.91 g), dieeinescharfeAbsorptionsbandebei2300cm-i (isocyanate) had. the oil was treated with light petroleum ( lewaschen and a Then stirred with 30 ml of tetrachloride under reflux, while irradiating with mercury light for 1 hour, during which time an intense iodine coloration occurred. If the crude product (0.7 g) was worked up in the usual way, the fractions obtained consisted of crude phthalide (0.23 g) and crude o-toluamide (0.38 g). The crude irradiation product had v max at 1600 and 1680 (primary amide), 1720 (iminolactone?), 1765 (γ-lactone), 3460 and 3580 (primary amide) cm- '.

Example ? Irradiation of octadecanamide with lead tetraacetate and iodine Octadecanamide was made by adding octadecanoyl chloride to concentrated aqueous Ammonia produced at 0 ° C. It crystallized out in flakes from benzene, F.109 ° C (literature melting point 109 ° C).

A suspension of 2.0 g of octadecanamide, 9.4 g of lead tetraacetate and 3 g of iodine in 40 ml of benzene was stirred at 30 ° C. and irradiated with a mercury lamp. After 2 hours the iodine was completely consumed and an additional 2 g was therefore admitted. The irradiation was continued for an additional 3 hours and the solution then filtered. The residue was washed with ethyl acetate and the filtrate shaken with aqueous sodium bisulfite after combining with the wash solutions and evaporated in vacuo. The crude product (2.67 g) had vmax (in CHCl3) at 1595 and 1680 (primary amide), 1725 (d-lactone?), 1765 (γ-lactone), 2346 and 2356 (amid N-H) cm- '. It was refluxed for 2 hours with 2 g of potassium hydroxide in 20 ml Hydrolyzed methanol and 5 ml of water. 15 ml of water was added to the cooled mixture added, which was then extracted with light petroleum. The extract was Washed with 500/0 strength aqueous ethanol and evaporated in vacuo, with a neutral sticky mass (0.209 g) was obtained, which after crystallization octadecanamide revealed. The aqueous ethanol solution was acidified with dilute sulfuric acid, Refluxed for 2 hours and concentrated by evaporation. The extraction with ethyl acetate gave a yellow sticky mass (1.93 g) with vmax at 1720 (d-lactone) and 1765 (y-lactone) cm- ', which after crystallization from aqueous methanol 1,2 g y-stearolactone with a melting point of 49 to 50 ° C (literature melting point 50 ° C), vmax (in CHCI,) at 1765 (γ-lactone) cm-. The aqueous methanolic mother liquor was in vacuo evaporated and the residue (0.675 g) was heated on the steam bath for 1 hour. It was then dissolved in light petroleum and chromatographed over silica gel. Methylene dichloride eluted γ-stearolactone (0.34 g) from light petroleum (boiling point 40 ° C) at -40 ° C in needles with a temperature of 38 to 39 ° C, vmax (in CHCl3) at 1720 (b-lactone) cm- 'crystallized. The analysis sample was further processed by molecular distillation at 100 ° C / 10-5 mm cleaned.

Analysis for C18H3402 Calculated .... C 76; 5, H 12.1, O 11.3 0/0; found . . . . . C 76.0, H 11.95, O 11.50 / 0. When γ-stearolactone (0.497 g) was heated on the steam bath with 0.8 g of potassium hydroxide in 25 ml of water for 1 hour and the resulting solution was cooled in ice and carefully acidified, a precipitate of 4-hydroxyoctadecanoic acid was formed. It crystallized from methylene dichloride in leaflets (0.323 mg), m.p. 86 to 87 ° C (literature melting point 87 ° C), vmax (in CHCI,) 1705 (COOH) cm- '. γ-Stearolactone (80 mg) gave, when heated for 1 hour with 0.2 ml of benzylamine in a closed tube at 100 ° C., N-benzyl-4-hydroxyoctadecanamide, which crystallized from methanol in flakes (70 mg), mp 96 ° to 97 ° C, vmax (in CHCI,) at 1660 and 3480 (secondary amide), cm- '.

Analysis for C22H43N02: Calculated .... C 77.1, H 11.1, O 8.2%; found ..... C 77.0, H 11.0, O 8.2 ° / o; δ-Stearolactone was similarly in 5-hydroxyoctadecanoic acid, m.p. 81'C (literature melting point 82 ° C), vmax (in CHCI,) at 1710 (COOH) cm- ', analysis for C18H3003: Calculated .... C 71 , 95, H 12.10 / 0; found ..... C 72.2, H 12.0%; and in N-benzyl-5-hydroxy-octadecanamide, m.p. 90 to 92 ° C, vmax (in CHC13) at 1660 and 3480) (secondary amide) cm- ', analysis for C. "H" NO: Calculated .. .. C 77.1, H 1l, 10/0; found ..... C 76.9, H 11.0 ° / 0; converted.

Example 8 Irradiation of octadecanamide with tert-butyl hypochlorite and iodine. Became tert-butyl hypochlorite (1.8 mL, 1.6 g) with stirring to give 2.3 g of octadecanamide and 5 g of iodine in 50 ml of benzene were added, the color changed to light brown. After 15 minutes the mixture was with a mercury lamp at <30 ° C for 7 hours long irradiated. Further amounts of tert-butyl hypochlorite (3-0.8 ml) were after dei 1st, 2nd and 3rd hour added. At the end of the irradiation time, the reaction mixture became washed with water. The aqueous phase was acidic, and after treatment with sodium bicarbonate solution a thick iodine precipitate settled down. The organic phase was washed with ethyl acetate diluted, washed with aqueous sodium bisulfite and with water and evaporated in vacuo. The crude product (3.22 g) was a light brown substance with sharp absorption maxima at 1720 (d-lactone) and 1765 (γ-lactone) cm- '. It was refluxed for 2 hours hydrolyzed with 2 g of potassium hydroxide in 20 ml of ethanol and 5 ml of water. The chilled The hydrolysis mixture was diluted with 15 ml of water and extracted with light petroleum. The ethanolic solution was acidified with dilute sulfuric acid and under Boiled to reflux for 1.5 hours. After concentration by evaporation, the Mixture diluted with water and extracted with ethyl acetate. The acid and the lactone (2.31 g) obtained by evaporating the extract were combined, dissolved in light petroleum and mixed with 2 g of potassium carbonate in 25 ml of water and 25 ml of methanol shaken. Evaporation of the petroleum solution gave a lactone fraction (1.60 g), vmax (in CHCl3) at 1720 (δ-lactone) and 1765 (γ-lactone) cm-1. The watery one Methanol solution was acidified and extracted with ethyl acetate. The residue (0.8 g) obtained by evaporation of the extract had vmax (in CHCl3) at 1705 (CO._H), 1720 (δ-lactone) and 1765 (γ-lactone) cm- '. The crystallization of the Lactone fraction from aqueous methanol gave γ-stearolactone, mp 49 ° C. (0.96 g). the Chromatography of the residue from the mother liquor over silica gel gave a additional amount (0.35 g) of γ-stearolactone and some δ-stearolactone (0.12 g). The chromatography the acidic fraction gave γ-stearolactone (0.08 g) and δ-stearolactone (0.39 g). the The total of the products obtained would therefore be: γ-stearolactone (1.40 g) and δ-stearolactone (0.51 g).

Irradiation of octadecanamide with tert-butyl hypochlorite and iodine was repeated a few times under conditions similar to those in the previous one Example are similar. The results are shown in Table II, two particular ones Embodiments of the work-up process are shown below: Trial IV The crude product of the reaction was not hydrolyzed, but in light petroleum dissolved and chromatographed over silica gel. The only identifiable links which were eluted were δ- and γ-stearolactone.

Experiment VII After the irradiation, the reaction mixture was covered with zinc dust and tert-butanol heated on the water bath for 1 hour. The mixture was then filtered, evaporated and hydrolyzed in the usual way.

In spiel9 irradiation of hexanamide with tert-butyl hypochlorite / iodine 2.5 g of hexanamide in 50 ml of benzene were mixed with 8 g of iodine and 3.0 ml of tert-butyl hypochlorite and irradiated at <30 ° C for 6 hours. Additional amounts of hypochlorite (2.5 ml, 1.5 ml) were added after the 1st and 2nd hour. The mixture, after diluting with ethyl acetate, washing with aqueous sodium bisulfite and evaporating, gave a crude liquid product (3.45 g) which, after conventional hydrolysis, was neutral (0.376 g), acidic (0.525 g) and lactonic ( 1.212 g) fractions yielded. The lactone fraction was an oil with vmax (film at 1700, 1730 and 1765 cm-1).

Example 10 Irradiation of N-iodohexanamide 29.0 mg of the iodamide were dissolved in 5 ml of dry, 3thanol-free chloroform. The infrared spectrum had vmdx at 1675 (amide C = O) and 3430 (N-H) cm- '. The solution was kept in the dark at room temperature for 30 minutes. The infrared spectrum was then unchanged. The solution was then irradiated with a mercury lamp through Pyrex glass at 15 ° C. After 10 minutes the infrared spectrum shows new absorption maxima at 1595, 1640, 1765, 1800 and 3540 cm- '. After 25 minutes of irradiation, the maximum at 1800 cm- 'had disappeared, a new shoulder appeared at 1720 cm-', and the intensities of the maxima at 1595, 1640, 1765 and 3540 cm- 'had increased. The mixture was then shaken with a drop of acidified, saturated potassium iodide solution and dried. The solution now had vmaz at 1600 and 1675 (primary amide C = O), 1720 (δ-lactone?), 1765 (γ-lactone), 3430 and 3540 (primary amide N - H) cm- '. The results indicate the formation of an unstable intermediate with vmax at 1640 cm- '.

Example 11 Irradiation of N-iodoctadecanamide a) The lower-melting form (I) of iodamide (2.84 g), suspended in 50 ml of benzene with stirring, was irradiated with a mercury lamp at 20 ° C. for 5 hours. Filtration of the mixture gave a solid (1.35 g) whose infrared spectrum in Nujol was identical to that of the pure octadecanamide. The filtrate was washed with aqueous sodium bisulfite and evaporated in vacuo. The residue (0.73 g) on hydrolysis in the usual way gave a clear yellow sticky product (0.586 g), vmax (in CHCl3) at 1700 (CO: H) and 1765 (γ-lactone) cm-i.

b) Became the less soluble, higher melting form (II) of iodamide (1.54g) irradiated as in the example described above, it was insoluble Material (1.25 g) unchanged iodamide (1I). The soluble product (232 mg) yielded on hydrolysis in a conventional manner a sticky product (104 mg) with vmax (in CHCl,) at 1700 and 1765 cm- '.

c) A solution of the iodamide (I) (53 mg) in 7 ml of ethanol-free chloroform was stable in the dark at about 30 ° C. She had vma2 at 1605 (weak) and 1680 cm- '. The solution was irradiated with a mercury lamp. Within An intense iodine coloration occurred for 10 minutes and the solution now had vmax 1600 (medium), 1680 and 1770 cm- '. Similar results were obtained with the same treatment obtained a sample of the higher melting point form.

Example 12 Reaction of octadecanamide with tert-butyl hypochlorite / iodine without irradiation 2.0 g of amide, 5 g of iodine and 1.6 ml of tert-butyl hypochlorite in 40 ml of benzene were removed at 20 ° C. without irradiation (the flask was covered with a foil covered) stirred for 5 hours. Further amounts of tert-butyl hypochlorite (3-0.6 ml) were added after the 1st, 2nd and 3rd hour. The mixture was then filtered. The residue (2.334 g) which was washed with benzene and light gasoline was an isomer (1I) of N-iodoctadecanamide. The filtrate (after washing with aqueous sodium bisulfite) and the residue (0. -497 g ), which was obtained after evaporation of the solution, were hydrolyzed in the usual manner. No lactonic fraction could be isolated. Example 13 Potassium tert-butoxide (prepared by dissolving potassium [800 mg] in excess tert-butyl alcohol and removing the excess by azeotropic distillation with benzene) in 100 ml of benzene was treated with 8.17 g of iodine and the precipitated Potassium iodide removed by filtration (with exclusion of moisture). 940 mg of octadecanamide was added to the filtrate and the solution was stirred for 30 minutes at room temperature. Removal of an aliquot and dilution with light petroleum gave a precipitate which, after crystallization from acetone, gave an isomer B of N-iodoctadecanamide. The reaction solution was photolyzed with a mercury arc lamp at room temperature for 7 hours. Working up according to Example 7 gave y-stearolactone (180 mg) and h-stearolactone (20 mg).

Example 14 Lactonization of 4-phenylbutyramide 1.60 g of 4-phenylbutyramide and 7.40 g of iodine in 50 ml of benzene were treated with 2.4 ml of tert-butyl hypochlorite with stirring for 15 minutes at room temperature. The stirred reaction mixture was photolyzed with a 125 watt mercury arc lamp at < 30 ° C. for 7 hours and further tert-butyl hypochlorite (3-0.8 ml) was added after the first three consecutive hours. The crystalline precipitate was filtered (2.34 g) and quickly crystallized from ethylene dichloride, an N-iodo-4-phenylbutyroiminolactone iodochloride complex having a melting point of 110 to 112 ° C., max. 224 mp. (e 2800 in tetrahydrofuran), v. " 1." 1600, 260 and 210 cm- 'was obtained. Analysis for C1oHioCIJ.N0: Calculated. . . C 26.7, H 2.25, Cl 7.9, J 56.5%; found . . . C 26.7, H 2.55, Cl 8.75, J 56.7%. This complex (300 mg) was heated with 2 ml of saturated aqueous sodium hydrogen sulfite and 5 ml of 2N aqueous sulfuric acid on the steam bath for 10 minutes. Extraction in ethyl acetate gave 4-phenylbutyrolactone (69 mg) which was identical to an authentic sample. This lactone (30 mg) in 2 ml of ethanol was saturated with ammonia gas at O 'C and allowed to stand for 12 hours. Removal of the solvent in vacuo and crystallization from ether gave 4-hydroxy-4-phenylbutyramide, mp 84 to 85.degree.

The iodine chloride complex (465 mg) in 5 ml of benzene was combined with 103 mg of pyridine treated and the precipitate removed. After adding light petroleum, continued the pyridine iodine chloride complex (identified by F., mixed F., UV- and IR spectra).

The iodine chloride complex (130 mg) in 3 ml of tetrahydrofuran was with 1 ml of triethylamine treated, the precipitate filtered and fractionally crystallized, whereby triethylamine hydrochloride (identified by F., mixed F.) and triethylamine hydroiodide (identified by F. and mixed F.) was obtained.

The iodine chloride complex (200 mg) in 25 ml of tetrahydrofuran was shaken with 2 g of Raney nickel for 12 hours. Filtration, removal of the solvent in vacuo and crystallization from benzene-light petroleum gave 4-plienylbutyiamide (40 mg), mp 81 to 82.degree. Example 15 Production and lactonization of 4-methylhexanamide a) 25 (+) - Citronellol were treated with excess toluene-p-sulfonyl chloride in pyridine at room temperature overnight and the toluene-p-sulfonate obtained was purified by filtration in light petroleum through aluminum oxide (activity level V), whereby a colorless oil (27 g) was obtained, [oc] D - + 1 ° (c = 1.07). This toluene p-sulfonate (15 g) in 150 ml of methylene dichloride was ozonated at 0 ° C. for 16 hours. After removing the solvent in vacuo, the ozonide was reduced with an excess of essential lithium aluminum hydride. Work-up gave 4-methylhexan-l-ol (3 g), bp 80 to 84 ° C./22 mm, ND = -1-2.6 ° (c = 1.50). 3.0 g of this alcohol in 22.5 ml of acetone were added to 5.1 g of chromium trioxide in 8.1 g of concentrated sulfuric acid and 25.5 ml of water and the mixture was left to stand for 11/2 hours. Work-up gave 4-methylhexanoic acid (1.75 g), bp 114 to 117 ° C / 15 mm, [a] D = + 5 ° (c = 1.02). 1.75 g of this acid was treated with an excess of thionyl chloride and the excess removed in vacuo. The acid chloride obtained was added to concentrated aqueous ammonia in dry ether with stirring. Removal of the ether in vacuo gave 4-methylhexanamide (1.3 g), F. (from light petroleum) 97 to 98 ° C [Iz] D = + 11 ° (c = 0.85).

b) 1.0 g of 4-Vlethylhexanamid and 5.3 g of iodine in 40 ml of benzene were with Treated 1.8 ml of tert-butyl hypochlorite and stirred for 15 minutes. The reaction mixture was then with a 125 watt mercury arc lamp at <30 ° C for 7 hours photolyzed. More tert-butyl hypochlorite (3-0.6 ml) was added after the first added for three consecutive hours. After cooling to 0 ° C, a portion became the crystalline precipitate (1.11 g) was filtered off. The residue of the precipitate and the filtrate were combined and the solvent removed in vacuo. The residue was hydrolyzed in the usual manner to give (-) - 4-methyl-4-ethylbutyrolactone (360 mg), b.p. 75 to 78 ° C / 6 mm, [@X] D = -0 '(c = 1.06), rotation 0 ° for all Available wavelengths.

Analysis for C, Hi202: Calculated ... C 65.6, H 9.4 ° / 0; found ... C 65.7, H 9.5 ° / a.

The above-mentioned crystalline precipitate was crystallized from methylene dichloride and gave an N-iodo-4-methyl-4-ethylbutyroiminolactone iodine chloride complex, mp 113 to 115 ° C, vm ;; ° '1610 cm-'. Analysis for C, H "CIJ, N0: Calculated ... C 20.25, H 2.9, J 61.1 ° / o; found ... C 20.05, H 2.6, I 61.5 ° / o.

This compound (280 mg) was dissolved with 2 ml of saturated aqueous sodium hydrogen sulfite and heated 5 ml of 1 normal aqueous sulfuric acid on the steam bath for 10 minutes. Extraction in ethyl acetate gave 4-methyl-4-äthylbutyrolacton, which with the above described material was identical.

The following tables show the experimental conditions under which the irradiations of two amides were carried out, together with the yields of the products obtained. Example 16 500 mg of the N-iodoctadecanamide prepared in Example 13 were dissolved in 100 ml of toluene and heated under reflux. Samples were taken at certain time intervals. After the samples essentially ceased to be oxidizable (after 60 minutes), heating was stopped. The solution was washed with ethyl acetate. The filtrate combined with the washing solutions was shaken with an aqueous sodium bisulfite solution and evaporated in vacuo. When working up according to the example? a mixture of γ-stearolactone and δ-stearolactone was obtained.

Claims (6)

Claims: 1. Process for the production of lactones, thereby characterized in that one has a carboxylic acid-N-halogenamide which is in the y- or 8-position the carbon atom located to the carboxamide group is a hydrogen atom, which is conformationally adjacent to the nitrogen atom of the amide group or in the Is able to be conformationally adjacent to this nitrogen atom, possesses, or a mixture of the corresponding carboxamide and a positive one The substance supplying halogen ions is homolyzed and the homolysis product is hydrolyzed. 2. The method according to claim 1, characterized in that the carboxylic acid-N-halogenamide used is one which has the grouping in which R is a hydrogen atom or an aliphatic, araliphatic or aromatic substituent and X is a methylene, methylidene, methylidine or an amino group or a nitrogen, oxygen or sulfur atom and "Hal" is a halogen atom. 3. The method according to claim 1 and 2, characterized in that that the starting material is an N-halogenamide of a steroid carboxylic acid or a aliphatic carboxylic acid used. 4. The method according to claim 1, characterized in that that the homolytic cleavage is carried out by photolysis, using as a radiation source uses the radiation of a mercury vapor lamp. 5. The method according to claim 1 to 3, characterized in that one for hydrolysis of the homolysis product Alkali hydroxide, carbonate or alcoholate is used. 6. The method according to claim 1, characterized in that one obtained in the homolytic cleavage Reaction mixture hydrolyzed under neutral or acidic conditions, with a Iodine reducing agent is present.