DE2117597A1 - Phthalimido alkyl mercapto carboxylic acids and their prepn - as anabolic agents - Google Patents

Abstract

Novel cpds (I) and their salts with acids or bases where m is 0-4, n is 1-5, R' is H or 1-5C alkyl; R2 and R3 are CN, COOH, CONR' CONR4R5, 1-15C carbalkoxy or NR4 R5; R4 and R5 are H, 1-6C alkyl or NR4R5 is a 5- or 6-membered heterocyclic ring; or R2 and R3 are together CO-O-CO or CO-N(R4)-CO are prepd by methods in involving formation of a thioether, formation of the chain-(CH2)n-by condensation or addition across a double bond, ester, amide anhydrate and cyclic amide formation or formation of the phthalimido residue.

Description

Derivatives of mercaptocarboxylic acids.

In the main patent no ..... (patent application P 20 25 996.5) it was described that -Phthalimido-thiacarboxylic acids and the derivatives of the general formula where n denotes the numbers 1 to 5, R1 denotes a hydrogen atom or a straight-chain or branched alkyl radical having 1 to 5 carbon atoms and R2 and 113 are identical or different and denote cyano, carboxy, carbamido or carbalkoxy groups with 1 to 6 carbon atoms are in the alkyl radical, and if R2 and 11 are carboxy groups, 3 acyclic acid anhydrides and imides derived therefrom and, if R2 and / or 113 are a carboxy group, rollers of the compounds of the general formula I with organic or inorganic bases have valuable pharmaceutical properties as well as intermediate products for the production of pharmaceuticals.

In the further processing of the field on which the invention is based, it was found that compounds of the general formula where m is the numbers 0 to 4 and n is the numbers 1 to 5, R1 is a hydrogen atom or a straight-chain or branched alkyl radical with 1 to 5 carbon atoms and R2 and R @ are identical or different and each is an alkoxy radical with 7 to 15 carbon atoms or for one through the group where R4 and R5 are identical or different, hydrogen atoms or alkyl radicals m: t 1 to 6 carbon atoms together with the nitrogen atom a 5- or 6-membered heterocyclic radical, substituted alkoxy radical with 1 to 15 carbon atoms or a phenylalkoxy radical with 1 to 3 Carbon atom: ti allphatic part, where at most one of the radicals R2 and R3 also denotes a hydroxyl group, a 3 optionally substituted amino group or an alkoxy radical with 1 to 6 carbon atoms, as well as the compounds of the general formula I with organic or inorganic bases or acids as well have valuable pharmaceutical properties and can serve as intermediates in the manufacture of pharmaceuticals.

The rest represents, for example, the dimethylamino, diethylamino, morpholino, piperidino, pyrrolidino or thiomorpholino radical. In those cases in which R2 and R3 represent an optionally substituted amino group, this amino group can be the radical defined above represent.

The present invention relates to the new valuable compounds of the general formula I and their salts and a process for their preparation.

The compounds of the general formula I have anabolic properties. They are therefore suitable, among other things, as feed additives for animal husbandry. The favorable influence on weight development, which at the same time acts as hatred for the anabolic effect can be perceived, let z. B. by the following experimental set-up detect: give female Wistar rats with a starting weight of 130 g on five days per week 100 mg of the sulfate of 4-carb (2'-diethylamino) ethoxy-6-phthalimido-3-thiahexanoic acid methyl ester (ie the product obtained according to Example 1) in 0.5 ml of 1% carboxymethyl cellulose solution with the oral tube, a weight gain of 51.0 is observed after 28 days + 4.2 g per animals A comparable control group that during the test period only 1% garboxymethyl cellulose solution by gavage on 5 days a week on the other hand, showed a weight gain of only 35.5+ after 28 days 3.2 g. The difference in weight gain between the two groups is statistical significant. With the sulfate of the 4-carb- (2'-diethylamino) -ethoxy-6-phthalimido-3-thiahexanecarboxylic acid ethyl ester treated rats showed no changes in general behavior, urinary status, the blood count and the blood chemistry values can be observed. Similarly cheap Results can also be achieved with other compounds of general formula 1 will.

Compounds with anabolic effects are already known, however, they are generally derived from steroids. These connections often still have the hormonal effects of their parent bodies. Opposite are the new compounds of formula I are in no way related to hormones.

As weight-increasing feed additives are also already different antibacterial agents, in particular antibiotics, have been used. Of the The effect of these antibacterial agents is not based on the weight gain on an anabolic effect.

The compounds of formula I have no antibacterial effects, d. that is, their beneficial effect on weight gain is due to their anabolic properties is based.

The compounds of general formula I are capable of anabolic To significantly increase the effect of some steroids. So does the 2-a-methyl-dihydrotestosterone propionate in a daily dose of 5 mg / kg rat brought about weight increase Addition of 250 mg of the sulfate of 4-carb- (2'-diethylamino) -ethoxy-6-phthalimido-3-thiahexanoic acid methyl ester increased by almost 20% per kg rat per day. It is therefore possible to increase weight to reduce the required amount of steroid and thus the undesirable ones already mentioned above Reduce or avoid side effects Z'1.

Also those to be observed in the case of terminal hormone-active compounds the compounds of the general formula I significantly reinforced, as by the following experimental set-up can be shown: give female oprague-Dawley rats at the age of 50 days and an average weight of 160 g 3 times 2 mg 7,12-dimethylbenzanthracene intravenously, on their 50th, 53rd and 57th day of the quake, they develop in the area after 30 - 120 days the milk bar tumors, the number of which can be counted and the size of which can be measured. You give a group of 10 animals which induce tumors in this way 3 times a week intramuscularly 1 mg 2a-methyl-dihydrotestosterone propionate Per Rat, the number of tumors increases from 2.4 to 2.8 tumors within 12 weeks per rat, while in a control group in this period the tumor number of 2.4 increases to 6.1. Are treated with 2a-methyl-dihydrotestosterone propionate Rats 250 mg / kg of the sulfate of 4-carb (2'-diethylamino) -ethoxy-6-phthalimido-3-thiahexanoic acid methyl ester orally, the number of tumors drops from 2.4 to 1.1 tumors over 12 weeks per rat (as the mean of 10 animals).

The compounds of general formula I can also be used to reduce the effect of cytotoxic substances (cytostatics) on hormone-independent tumors increase and reduce the occurrence of metastases. In addition, improve the compounds of general formula I the tolerability of the relatively toxic Cytostatics.

Furthermore, the compounds of general formula I are able to to influence the immune reaction in the organism.

The compounds of the general formula I can be prepared by adding a compound of the general formula in which n and R3 have the aforementioned meaning and lial stands for a halogen atom, with a compound of the general formula in which Lot1, R2 and m have the aforementioned meaning, -6- reacts in the presence of hydrogen halide binding agents or with a salt of the compound of the formula III.

To prepare compounds of the general formula I, compounds of the general formulas IV to VI wherein R1, m and n have the aforementioned meaning and R6 represents an optionally substituted amino group or an alkoxy radical having 1 to 6 carbon atoms, the carboxyl group (s) in reactive derivatives, e.g. B. acid chlorides or activated esters, such as thiophenyl, p-nitrophenyl, carboxymethyl mercapto, cyanomethyl ester, and with an alcohol of the general formula H - 0 - R7 VII wherein R7 is an alkyl radical with 7 to 15 carbon atoms, for a through the group in which R4 and R5 have the abovementioned meaning, substituted alkyl radicals having 1 to 15 carbon atoms or a phenylalkyl radical having 1 to 3 carbon atoms in the aliphatic part, to give compounds of the general formula I.

The compounds of the general formula I can also be prepared by adding m to a compound of the general formula in which n and 113 have the aforementioned meaning, or one of their rollers with a compound of the general formulas in which 111, R2 and m have the aforementioned meaning and Hal stands for a halogen atom, or wherein 111, R2, Hal and m have the abovementioned meaning and R8 is a lower alkyl, aryl or aralkyl radical, optionally in the presence of hydrogen halide binding agents, and when using a compound of the formula IXa, which is optionally after saponification of the Group -COOR8 obtained compound of the formula in which 111 to R3, m and n have the aforementioned meaning, decarboxylated.

The compounds of the general formula I can also be prepared by adding a compound of the general formula in which n has the aforementioned meaning and Hal stands for a halogen atom with compounds of the general formula in which 111 to R3, 118 and m have the abovementioned meaning and X is an alkali metal atom and brings about the reaction and the compound of the general formula optionally obtainable after saponification of the -COOR8 group in which R1 to R3, m and n have the aforementioned meaning, decarboxylated.

The compounds of the general formula I can also be prepared by removing the amino group of a compound of the general formula in which R1 to Rf and m and n have the aforementioned meaning, phthalylated with phthalic anhydride or with N-carbalkoxy-phthalimide.

The compounds of the general formula I can also be prepared by adding an olefinic compound of the general formula in which n and R3 have the aforementioned meaning, reacts with a compound of the general formula III or with its salt, optionally in the presence of catalysts such as sulfur or peroxide.

Finally, the compounds of general formula I can be obtained by converting into a compound of general formula wherein m, n and R1 to R3 have the aforementioned meaning, the sulfoxide group is preferably reduced using sulfite.

The compounds of the formula I contain at least one asymmetrical substituted carbon atom and can accordingly occur in isomeric forms. The subject of the invention includes both the rac. Compounds of the formula I or their isomer mixtures as well as the pure isomers such as. B. the optically active Forms of the compounds of formula I and the preparation of these various isomers To shape. The optically active isomers can be prepared by opting from active starting products or by the compounds of the general Formula I, in which 112 and / or R3 are carboxyl groups mean with converts optically active bases and then the stereoisomers by crystallization separates.

The following basic games serve to further explain the invention but without limiting it to that. In performing it was aimed at achieving optimal yields not placed inert.

The melting point data are all uncorrected.

Example 1 In a mixture of 46 ml of thioglycolic acid methyl ester, 145 ml of triethylamine and 100 ml of absolute dimethylformamide are stirred and nitrogen atmosphere at a temperature of 40 ° w 224 g of a-bromo-Y-phthalimido-butyric acid diethylaminoethyl ester hydrochloride added in portions. The mixture is heated to 80 ° C. and allowed to react for 2 hours. After cooling, it is acidified with hydrochloric acid diluted with ice water. The reaction mixture is extracted with ethyl acetate to remove unreacted starting materials and with potassium carbonate solution made alkaline. One extracts with ethyl ethyl ketone and then with moderate ester. The combined extracts of the alkaline reaction solution are dried with sodium sulfate, with activated charcoal treated and then concentrated in vacuo. The oily residue is under strong 23 ml of concentrated ßsulfuric acid are added to the cooling. The resulting crystals are washed with ether and dried in vacuo.

After recrystallization from ethanol / ether, the product which melts at 99 ° C. is obtained Sulphate of 4-carb (2'-diethylamino) ethoxy-6-phthalimido-3-thiahexanoic acid methyl ester. (Cf.

general formula I: m = O, n = 2, R1 = H, R2 = OH3, 113 = OH - OH2- N (O2H5.

The a-bromo-y-phthalimidobutyric acid diethylaminoethyl ester hydrochloride used as the starting product is obtained in the following way: 59.0 g of γ-phthalimidobutyric acid are mixed with 20 ml Thionyl chloride mixed and until the evolution of hydrogen chloride gas ceases heated to 70-80 ° C. It is then cooled to 30 ° C. and a suspension is added of 7.9g of red phosphorus in a little methylene chloride was added. Dripping while stirring vigorously 35 ml of bromine are added so that the reaction temperature remains below 80.degree. One lets react for some time and carry the re action mixture in 250 ml of 50% above aqueous formic acid so that the reaction temperature does not exceed 60 ° C.

The mixture is then heated to 7500 for 1 hour and the solvent is removed by distillation in vacuo. After cooling, the residue becomes with aqueous Sodium bicarbonate solution neutralized. The clear after filtration, if necessary Solution is acidified against Congo red with hydrochloric acid. A-bromo-y-phthalimidobutyric acid is obtained in this way from melting point 155-15700 after recrystallization from benzene.

63.5 g of the above compound are suspended in 100 ml of chlorobenzene and mixed with 5 ml of absolute dimethylformamide. 20 ml of thionyl chloride are left add dropwise and stir for 12 hours at room temperature. The medium solution is im Vacuum removed. The residue is mixed in portions with 24 g of diethylaminoethanol while cooling with ice added, heated to 300C and with a mixture of 50 ml of ethanol and 200 ml of ether digested. The a-bromo-y-phthalimido-butyric acid diethylaminoethyl ester hydrochloride is thus obtained.

Example 2 162 g of 4-carboxy-6-phthalimido-3-thiahexanoic acid are used in 600 ml of benzene dissolved and freed from moisture residues by azeotropic distillation. 150 g of 1-diethylamino-2-chloroethane are added dropwise, followed by 150 ml of triethylamine while stirring at reflux temperature.

The reaction mixture is kept at reflux temperature for 2 hours and then cooled to 1500. The precipitated triethylamine hydrochloride is filtered off and removed the solvent in vacuo. The residue is dissolved in dilute hydrochloric acid dissolved in the cold, extracted with ethyl acetate and made alkaline with potassium carbonate solution. The excreted substance is taken up in ethyl acetate, dried and coated with activated charcoal treated. After removing the solvent, the 4-carb- (2'-diethylamino) -ethoxy-6-phthalimido-3-thiahexanoic acid (2 ? diethylamino) ethyl ester in the form of a slightly yellow colored oil. n20: D 5275; d20 ei1428.

Example 5 63.5 g of or-bromo-y-phthalimidobutyric acid in 100 ml Chlorobenzene suspended and with 5 ml of absolute dimethylformamide offset. 20 ml of uhionyl chloride are added dropwise and the mixture is stirred for 12 hours at room temperature after. The excess thionyl chloride is removed by distillation in vacuo. The mixture is heated to 40 ° C. and 37 g of dodecanol are added. Allow some time to react at 700C and the solution is in a mixture of 13 ml of thioglycolic acid, 66 ml of triethylamine and 50 ml of absolute dimethylformamide. The reaction is allowed to continue for 2 hours at 80.degree. After cooling to room temperature, it is taken up in ethyl acetate and diluted with Washed oleic acid, dried and fermented with activated charcoal. After distilling off the 4-Carbododecyloxy-6-phthalimido-3-thiahexanoic acid is obtained in a vacuum in a yield of 92% of theory.

Example 4 In a mixture of 260 g of thioglycolic acid dodecyl ester, 300 ml of triethylamine and 200 ml of absolute dimethylformamide are stirred and Nitrogen atmosphere at a temperature of 400C 312 g of a-bromo-y-phthalimidobutyric acid added in portions. The mixture is heated to 80 ° C. and allowed to react for 2 hours. After cooling to room temperature, it is taken up in ethyl acetate and diluted with Washed hydrochloric acid, dried and clarified with activated charcoal. After distillation the solvent in vacuo gives the 4-carboxy-6-phthalimido-5-thiahexanoic acid dodecyl ester in a yield of 98 c, 9 of theory.

Example 5 Analogously to Example 3, <-Bromo-y-phthalimidobutyryl chloride is obtained and benzyl alcohol a solution of the α-bromycophthalimido buttersary benzyl ester in Chlorobenzene. A 2 molar solution of this ester is poured into a mixture of 140 ml of thioglycolic acid, 600 ml of triethylamine and 500 ml of absolute dimethylformamide registered. The mixture is heated to 8000 for 2 hours, allowed to cool and acidified with more dilute hydrochloric acid and extracted with a mixture of methyl ethyl ketone and ethyl acetate. The extraction solution is dried, clarified with activated charcoal and concentrated in vacuo. 4-Garbobenzoxy-6-phthalimido-3-thiahexanoic acid is thus obtained in a yield of 88% of theory Example 6 162 g of methyl α-bromo-γ-phthalimidobutyrate are added in portions so in a mixture of 55 g of B-mercaptopropionic acid, 150 ml of triethylamine and 70 ml of absolute dimethylformamide entered that the reaction temperature is not 40 ° C exceeds. The reaction is allowed to continue for 30 minutes and the mixture is heated to 80 ° C. for 2 hours. To The reaction mixture is cooled to room temperature in a Sis-hydrochloric acid mixture pour in and extracted with ethyl acetate. The extraction solution is with Sodium sulfate dried and clarified with activated charcoal. The solvent is in vacuo removed. 5-Carbomethoxy-7-phthalimido-4-thiaheptanoic acid is thus obtained in a yield of 98 C / o of theory.

The methyl α-bromophthalimidobutyrate used as the starting product above is obtained from the acid with methanol and HCl gas.

Example 7 The procedure is as in Example 6 and using 6-carbomethoxy-8-phthalmido-5-thiaoctanoic acid from 60 g of γ-mercapto-butyric acid in a yield of 98 Vo of theory.

Example 8 The procedure is as in Example 6 and using of 67.5 g of methyl y-mercapto-butyric acid 6-carbomethoxy-8-phthalimido-5-thiaoctanoic acid methyl ester in a yield of 80% of theory.

Claims

Claims (14)

Claims 1) Derivatives of mercaptocarboxylic acids as an additive for patent no .... (patent application P 20 25 996.5), characterized by the general formula where m denotes the numbers 0 to 4, n denotes the numbers 1 to 5, 111 denotes a hydrogen atom or a straight-chain or branched alkyl group with 1 to 5 carbon atoms and R2 and 113 are identical or different and each denotes an alkoxy group with 7 to 15 carbon atoms, for one through the group where R4 and R5 are identical or different and are hydrogen atoms or alkyl radicals with 1 to 6 carbon atoms or together with the nitrogen atom a 5- or 6-membered heterocyclic radical, substituted alkoxy radical with 1 to 15 carbon atoms or a phenylalkoxy radical with 1 to 3 carbon atoms aliphatic moiety, where at most one of the radicals R2 and 113 also denotes a hydroxyl group, an optionally substituted amino group or a slkoxy radical with 1 to 6 carbon atoms, as well as salts of these compounds with organic or inorganic bases or acids. 2) derivatives of iviercaptocarboxylic acids of the general formula characterized in that m denotes the numbers 0 to 4, n denotes the numbers 1 to 5, R1 denotes a hydrogen atom or a straight-chain or branched alkyl radical having 1 to 5 carbon atoms. 11 for an alkoxy radical with 7 hi F: \ 5 carbon atoms, for one through the group where R4 and R5 are identical or different and hydrogen atoms or alkyl radicals with 1 to 6 carbon atoms or together with the nitrogen atom a 5- or 6-membered heterocyclic radical, substituted alkoxy radical with 1 to 15 carbon atoms or a phenylalkoxy radical with 1 to 3 carbon atoms in the aliphatic eil stands and R3 'stands for a hydroxyl group, an optionally substituted amino group or an alkoxy radical having 1 to 6 carbon atoms, as well as rolling these compounds with organic or inorganic bases or acids. 3) derivatives of mercaptocarboxylic acids of the general formula characterized in that m denotes the numbers 0 to 4, n denotes the numbers 1 to 5, 111 denotes a hydrogen atom or a straight-chain or branched alkyl group having 1 to 5 carbon atoms, 1121 denotes a hydroxyl group, an optionally substituted amino group or an alkoxy group with 1 to 6 carbon atoms and R3 for an alkoxy radical with 7 to 15 carbon atoms, for one through the group in which R4 and R5 are identical or different and are hydrogen atoms or alkyl radicals with 1 to 6 carbon atoms or together with the nitrogen atom a 5- or 6-membered heterocyclic radical, substituted alkoxy radical with 1 to 15 carbon atoms or a phenylalkoxy radical with 1 to 3 carbon atoms im aliphatic part, and salts of these compounds with organic or inorganic bases or acids. 4) derivatives of mercaptocarboxylic acids of the general formula characterized in that n stands for the numbers 1 to 5, R1 stands for a hydrogen atom or a straight-chain or branched alkyl radical with 1 to 5 carbon atoms, R2 stands for an alkoxy radical with 7 to 15 carbon atoms, for one through the group where 114 and R5 are identical or different and are hydrogen atoms or tilkyl radicals with 1 to 6 carbon atoms or together with the nitrogen atom a 5- or 6-membered heterocyclic radical, substituted alkoxy radical with 1 to 15 carbon atoms or a phenylalkoxy radical with 1 to 3 carbon atoms aliphatic part and R3 stands for a hydroxyl group, an optionally substituted amino group or an alkoxy radical with 1 to 6 carbon atoms, and salts of these compounds with organic or inorganic bases or acids. 5) derivatives of mercaptocarboxylic acids of the general formula characterized in that n stands for the numbers 1 to 5, 111 stands for a carbon atom or for a straight-chain or branched alkyl radical with 1 to 5 carbon atoms, R2 for an hydroxyl group, an optionally substituted amino group csr an alkoxy radical with 1 to 6 carbon atoms and R3 represents an alkoxy radical having 7 to 15 carbon atoms for one through the group where 114 and R5 are identical or different and are hydrogen atoms or alkyl radicals with 1 to 6 carbon atoms or together with the nitrogen atom a 5- or 6-membered heterocyclic radical, substituted alkoxy radical with 1 to 15 carbon atoms or a phenylalkoxy radical with 1 to 3 carbon atoms aliphatic part, and salts of these compounds with organic or inorganic bases or acids. 6) methyl 4-carb (2'-diethylamino) ethoxy-6-phthalimido-3-thiahexanoate and salts of this compound with organic or inorganic acids. 7) 4-Carb- (2'-diethylamino) -ethoxy-6-phthalimido-3-thiahexanoic acid (2 | -diethylamino) ethyl ester and salts of this compound with organic or inorganic acids. 8) 4-carbododecyloxy-6-phthalimido-3-thiahexanoic acid and salts thereof Compound with organic or inorganic bases. 9) 4-Carboxy-6-phthalimido -) - thiahexanoic acid dodecyl ester and salts this compound with organic or inorganic bases. 10) 4-carbobenzoxy-6-phthalimido-5-thiahexanoic acid and salts thereof Compound with organic or inorganic bases. 11) 5-carbomethoxy-7-phthalimido-4-thiaheptanoic acid and salts thereof Compound with organic or inorganic bases. 12) 6-carbomethoxy-8-phthalimido-5-thiaoctanoic acid and salts thereof Compound with organic or inorganic bases. 13) 6-Carbomethoxy-8-phthalimido-5-thiaoctanoic acid methyl ester. 14) Process for the preparation of mercaptocarboxylic acids of the general formula where m is the numbers 0 to 4, n is the numbers 1 to 5, R1 is a hydrogen atom or a straight-chain or branched alkyl radical having 1 to 5 carbon atoms and R2 and R3 are identical or different and each is an alkoxy radical having 7 to 15 carbon atoms mean or for one through the group wherein R4 and R5 are identical or different, hydrogen atoms or alkyl radicals with 1 to 6 carbon atoms or together with the nitrogen atom a 5- or 6-membered heterocyclic radical, substituted alkoxy radical with 1 to 15 carbon atoms or a phenylalkoxy radical with 1 to 3 carbon atoms im aliphatic part, where at most one of the radicals R2 and 113 also denotes a hydroxyl group, an optionally substituted amino group or an alkoxy radical having 1 to 6 carbon atoms, and salts of these compounds with organic or inorganic bases or acids, characterized in that a) a Compound of the general formula in which n and R3 have the aforementioned meaning and Hal stands for a halogen atom, with a compound of the general formula in which R1, R2 and m have the abovementioned meaning in the presence of agents which bind hydrogen halide or react with a salt of the compound of the formula III, or b) in a compound of the general formulas in which 111, m and n have the aforementioned meaning and 116 represents an optionally substituted amino group or an alkoxy radical with 1 to 6 carbon atoms, the carboxyl group (s) is converted into reactive derivatives, acid chlorides or activated esters and converted with an alcohol of the general formula 11 - 0 - R7 VII where R7 is an alkyl radical with 7-15 carbon atoms, for one through the group wherein R4 and R5 have the aforementioned meaning, substituted alkyl radical with 1 to 15 carbon atoms or a phenylalkyl radical with 1 to 3 carbon atoms in the aliphatic part, converts to compounds of the general formula I, or c) a compound of the general formula in which n and R3 have the aforementioned meaning or one of their rollers with a compound of the general formulas where R1, R2 and m have the aforementioned meaning and Hal stands for a ralogen atom or wherein R1, R2, IIal and m have the aforementioned meaning and R8 stands for a lower alkyl, aryl or aralkyl radical, optionally in the presence of hydrogen halide binding agents, and when using a compound of the formula IXa, which is optionally after saponification of the Group R8 obtained compound of the formula in which R1 to R3, m and n have the aforementioned meaning, decarboxylated, or d) a compound of the general formula in which n has the aforementioned meaning and Hal stands for a halogen atom with compounds of the general formula in which 111 to R3, 118 and m have the abovementioned meaning and X is an alkali metal atom and brings about the reaction and the compound of the general formula optionally obtainable after saponification of the -COOR8 group in which R1 to 113 and n have the aforementioned meaning, decarboxylated, or e) the amino group in a compound of the general formula in which m and n and R1 to R3 have the aforementioned meaning, phthalylated with phthalic anhydride or with N-carbalkoxy-ph-thalimide, or f) an olefinic compound of the general formula in which n and R3 have the aforementioned meaning 9 with a compound of the general formula III or its salt, optionally in the presence of catalysts such as sulfur or peroxide, reacts or g) in a compound of the general formula wherein -m, n and R1 to R3 have the aforementioned meaning, the sulfoxide group is preferably reduced using sulfite.