SU541428A3 - Method for producing glycol ethers - Google Patents

Description

The invention relates to a process for the production of new glycol glycol that have juvenile hormonal properties (1 H) and can be used in agriculture as insecticides or acaricides.

It is known from the literature that natural (primary hormones Cecropia) or synthetic isecticides with an isopropenoid structure possess juvenile hormonal properties.

Natural (1H) insecticides are characterized by instability, volatility, inaccessibility, and synthetic insecticides obtained from natural modifications of the sesquiterna skeleton, which have an epoxy group or halogen atom on a tertiary carbon atom, have limited use due to the appearance of resistance to them, as well as They are dangerous for transmitting genetic information.

In order to obtain "new active compounds that do not have such Disadvantages and differ from them in their structure, using known reactions, a method has been proposed for preparing simple glycol ethers of the general formula I

E,

R.

Ri-0 - C- (CHa);, - C-0- (CH,) z-X-Ar, (I) 5-5Us

where Ri means normal or, if necessary, branched alkyl with 1-9 carbon atoms; a straight or branched unsaturated radical with one or more C C bonds containing 3 to 9 carbon atoms, an unsubstituted or lower alkyl substituted cycloalkyl with 5 to 7 carbon atoms in the ring;

R2, Rs, R4, Rs independently of one another denote hydrogen, a branched or unbranched alkyl residue of 1 to 4 carbon atoms;

w - integers from 2 to 4;

Z - integers from 2 to 6;

X is sulfur, oxygen, -OSNg- or -SCH2- groups;

AG is a group

.

(CR.Rg)

Uc

As the proposed consent of the compounds of the general formula I should, for example, be called: 65 auviui tt vpv. .. 20 min carefully add 0.34 g (0.0077 mol) of 55% hydride dispersion

3

moreover, it means lower alkyl-, lower a-° -l and-and-n-nyx alkoxy, and the lower nI NII 94: 6 get pure 5 - (6 - isopentyloxyhexyloxy) - peityl - piperonyl ester as a colorless oil. The specific gravity at a temperature of 20 ° C is equal to 1.4897 Mortgage rate ...: ° / p: C..ZQ.fi Ы 9 Q Prnmer 55. 4 - 1,4-Isoproxybutanol is obtained using 1,4-butanediol as the compounds used and isopropyl bromide. Boiling point 90 ° С at 30 mm of mercury. Art. Vychpsleio. %: C 63.6; H 12.2, CyHigOo (Molecular Weight 132.2). Found,%: C 63.7: H 12.2. Example 56. 5 - Butoxpentaiol. 5.05 g (0.126 mol) of powdered sodium hydroxide was added to 19.8 g (0.19 mol) of 1.5 - pentad 1 ol pip at room temperature under a nitrogen atmosphere, while the temperature in the flask increased to 36 ° C. The mixture was warmed to 50 ° C and after the drip, 17.4 g (0.127 mol) of p-butyl bromide was stirred for 18 hours and 65 ° C. The cooled mixture is diluted with water and extracted with ether. To remove the excess pentadiol extract, it is washed three times with water, dried over magnesium sulfate and evaporated. The residue is washed with a mixture of hexane and ethyl acetate In a ratio of 9: 1 to 150 g of silica gel. With fractional distillation, pure 5-p-butoxy-pentaiol is obtained in the form of a bright oil with a boiling point of 137-139 ° C at 30 mm Hg. Art. Bbi4HiC4eHO. %: C, 67.5; H 12.6. C9H2O02 (Molecular Weight 160.3). Found,%: C 67.1; H 12.8. Example 57. 5 - ALLILO.XI - 2 - hexa-nol. 12.0 g (0.25 mol) of 50% sodium hydride dispersion in mineral oil with hexane are freed from mineral oil and zalis F

t with

where RI, R2, Rs, Rj, RS, as well as w, have the above values and M2 is hydrogen, .-. agpium MlC potassium, preferably sodium

S41428

Table 3 Analogously to Example 39, the following compounds of general formula II can also be prepared. Example 40. 1 - Bromo- (4-isopentyloxyGL GGTL., Liter, add 150 ml of absolute 1.2-dimethoxyethane, To the resulting suspension add with stirring this 5-10 ° C for 90 minutes (0.3 mol) of 2,5-hexanediol in 60 ml of absolute 1,2-dimethoxyethane. After 2 hours of stirring at 50 ° C, 24.2 g (0.2 mol) are mixed drop by drop with CMECH cooled to 10 ° C. a) allyl bromide in 40 ml of dry 1,2 - dimetoetaia. The mixture is slowly heated to 60 ° C and stirred at this temperature for 16 h. After that, the reaction mixture is cooled to room temperature. After adding 200 g of ether and water, the mixture is vigorously stirred and the organic phase is separated using a separatory funnel. The ether extract is washed with a saturated solution of sodium chloride, dried over sodium sulfate and evaporated. The residue is purified by chromatography on silica gel with hexane and ethyl acetate in 2: 1 ratio, while 5 - allyloxy-2-1hexanol is obtained as a chromatographically homogeneous, lightless oil. Specific gravity at 20 ° C ipaeeH 1.4423, boiling point 62-63 ° C at 0.75 mm Hg. Art. Calculated,%: C 68.3; H 11.5; About 20.2. C9Hi8O2 (Molecular Weight 158.2). Found,%: C 68.4; H 11.1; About 20.3. Analogously to example 56, compounds of formula IV (examples 58-67), also given in ta-bl, can also be prepared. 3

The starting compounds of the general formula I. And VI used for the preparation of compounds of the general formula VII can be obtained in the same way as the compounds of the general formula II.

Example 68. I - Bromo-b-cyclopentyloxypentane.

68 g (1. 0 mol) of cyclopentanol are gently mixed under nitrogen by stirring for -15 min with 3 g (0.1 mol) of 80% sodium hydride dispersion in oil. At 60 ° C, 17.7 ML (0.13 mol) of 1.5 tons of dibromopentane are added dropwise and the mixture is further stirred for 20 hours at 60 ° C. At room temperature, carefully add water with water and extract the product with ether. The ether extracts are washed with water and with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated. Chromatography of the residue on silica gel with hexane and ethyl acetate in a ratio of 99: 1 yields 1 - bromo-3-cyclo-pentyloxypentane, which is further purified by fractional distillation. Boiling point 54-58 ° C at 0.06. MmHg. Art.

Calculated,%: C 51.1; H 8.1; Br 34.0.

CioHigBrO (Molecular Weight 235.2).

Found,%: C 51.5; H 8.3; Br 33.5.

Analogously to Example 68, the following compounds of general formula VII can also be obtained.

Example 69. 1 - Bromo-5- (2-methylbutyloxy) -pentane is obtained in a manner similar to that described in Example 68, however, 2-methylbutanol and 1.5 - dibROMpentane were used as starting compounds.

Boiling point 112-114 ° C at 12 mm Hg, st.

Calculated,%: C 50.7; H 8.9; Br 33.7.

CioH2iBrO (Molecular Weight 237.2).

Found,%: 51.7; H 9.1; Br 32.7.

Example 70. 1 - Bromo-4-isopropoxybutane is prepared in analogy to Example 68, but the starting compounds are isopropanol and 1,4-dibromobutane using sodium instead of " atri. Boiling point 90-91 ° С at 34, mercury. Art.

Calculated,%: C 43.1; H 7.7; Br 41.0.

CrHisBrO (Molecular Weight 195.1).

Found,%: C 43.2; H 7.6; Br 41.3.

Example 71. b - Bromo-6-isopropoxygvsane is prepared analogously to Example 68, but isopropanol and 1,6 dibromhexane are the starting compounds and sodium is used instead of sodium hydride. The boiling point is 96-98 ° C at 15 mmHg. Art.

Calculated,%: C 48.4; H 8.6; Br 35.8.

CgHjgBrO (Molecular Weight 223.2).

Found,%: 48.7; 8.4; Br 35.9.

The starting compounds of general formula VII can be prepared, for example, by the following methods.

Example 72. 1 - Bromo - 4 - isopentyloxybutane.

To a solution containing 27.5 g (0.174 mol) of 4-isopentyloxybutanol (preparation cf. in example 15) and 1.36 g (0.0172 mol) of pyridine in 150 ml of absolute chloroform are added dropwise at. stirring at 0 ° C for 20 minutes. 6.1 ml (0.0636 mol) of phosphate tribromide. The cooling bath is removed, the mixture is heated to 60 ° C after 1 hour and stirred at this temperature for 18 hours. The reaction mixture is poured into ice-sodium bicarbonate solution, the chloroform phase is separated in a separatory funnel, washed with water and saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The residue is filtered on silica gel with hexane and ethyl acetate (98: 2) by fractionated distillation of one stripped off filtrate to obtain pure 1-bromo-4-iso-nentyloxybutane with a boiling point of 96-97 ° C at 12 mm Hg. Art.

Calculated,%: C 48.4; H 8.6; Br 35.8; About 7.2. CgHjgBrO (Molecular Weight 223.2). Found,%: C H 8.6; Br 35.4; About 7.4.

Example 73. 1 - Bromo-6-isopentyloxyhexane.

This compound 1 is obtained analogously to example 72, but 6 - isopentyloxyhexanol is used as the starting compound (example 54). Boiling point: 123-129 ° С at 11 mmHg. Art. Calculated,%: C 52.6; H 9.2; Br 31.8. CiiH23BrO (Molecular Weight 251.2). Found,%: C 52.2; H 8.7; Вг 31.1. Example 74. 1 - Bromo-6-butyloxyhexane is synthesized analogously to example 72, but b - butyloxyhexanol is used as the starting compound. By fractional distillation, pure I-bromo-6-butyloxyhexane is obtained with a boiling point of 130-132 ° C at 16 mm Hg. Art. Calculated,%: C 50.7; H 8.9; Br 33.7. CioHjiBrO (Molecular Weight 237.2). Found,%: C H 9.0; Br 31.4. Example 75. 1 - Bromo-5-isopentyloxyentane is prepared analogously to Example 74, but 5 - isopentyloxypentanol is used as the starting compound. Boiling point: 133-137 ° С at 30 mmHg. Art.

Calculated,%: C 50.6; H 8.9; Br 33.7. CioHoiBrO (Molecular Weight 237.2). Found,%: C 51.0; H 8.9; Br 34.1. H similar compounds of general formula VII, where LS is a tosyl residue, can be synthesized as follows. EXAMPLE 76 6 - Isopentyloxyhexyl tosylate is obtained by tosylation of b - isopentyloxyhexanol as in Example 42. The normal density at 20 ° C is equal to 1.4901. Calculated,%: C 63.1; H 8.8; S 9.4. C18HZoO4 (Molecular Weight 342.5). Found,%: C 63.3; H 8.8; S 9.4.

Claims (2)

Invention Formula Method for preparing glycol ethers of general formula I K4 RrO-C- (CH,) - C-0- (CH,), - X-Ar (O RS where Ri means a normal or, in the case of .1, a branched alkyl group with 1–9 carbon atoms, a “normal or dispersed non-saturated radical with one or more carbon atoms, containing 3–9 carbon atoms, unbiased or substituted”. Kilom dicloalkyl with 5-7 carbon atoms in the ring; Ra, Rs, R4, RS, independently of one another, denote waterO (genus, branched or unbranched alkyl residue with 1-4 carbon atoms; W are integers from 2 to 4; Z are integers from 2 to 6; -OCH -or X is sulfur, oxygen, bruises -SCH2-; Ag represents grusts - / XV (CRyKg) / J or L. irichem and means lower alkyl-, "izreshshaya alkenyl-, phenyl-, lower alkoxy-, lower alkenyloxy-, formyl-, “islkuyu alkylcarboNIL-, lower alkoxycarbonyl-, mono- or dysamechone,” “isk.imm alkyl carbamoyl-, lower alkoxymethylene-, lower alkylthio-, cyano-, or .nitrocelli or chlorine or bromine; R and Rs independently of one another denote hydrogen or a lower alkyl group and G, denote 1 or 2; Compiled by M. Mirkulova Editor L. Gerasimova Tehred A. Kamyshnikova Order 625/1 Ex. M 1883 Circulation 575 Subscription TSNIIPI State Committee of the Council of Ministers of the USSR for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5 Tinografiya, pr. Sapunova, 2 The corrector E. Hmeleva q denotes 0.1 or 2 and separate substituents and may be different among themselves, characterized in that the compound of formula II Ri-oc- (CH2);, is co- (CH2) zL / 7 3RS where RI, R2, Rs, R4, RS, as well as W and Z are as defined above, and LI is chlorine, bromine or a methyl group or the -O (S) Mi group where MI is hydrogen, sodium or potassium, is reacted with the compound) of the formula of formula 111 where Ar - has the above values; Y is XM or Gr2 L2-CH2-, where X and MI are as defined above; 1,2 is chlorine or bromine, and if the values of LI in compounds of formula II are -0 (S) Mi or C1 (Br), or TOZYL-, the residue, then the value of Y in compounds of formula III, respectively, means L -CH2- or -XMi at temperature O-100 ° C, followed by separation of the target product. 2. Siasob ino n. 1, characterized in that in the case where, in and-similar compounds II or III, the values of MI are hydrogen, the process is carried out in the presence of a halide-binding agent | Hydrogen. Date: 30/07/2001 Number of pages: 4 Previous document: SU 541428 Next Document: SU 541430 about P and with And N And E of the INVENTION TO PATENT (61) Complementary to the patent - (22) Submitted 12.11.74 (21) 1935342/2074752 / (23) Priority 06/29/73 (32) 07/01/72 (31) R 2232457.8 (33) German Federal Republic Published 12/30/76. Bulletin A 48 Date published description 08.08.77 (72) Authors Ansgar Lerkh (71) The applicant (54) METHOD OF OBTAINING PRODUCTION OF B-3-ALKYL-4-SULFAMOILILININ OR THEIR SALTS one The invention relates to a method for producing 3-alkl l-4-sulphamoylaniline derivatives of the general formula I which are not described in the literature. . . ((, H, K02 where RI is a phenyl, furyl or thienyl residue;  - carboxyl group or tetrazolyl- (5) -button; R4 is a linear or branched alkyl residue containing from 2 to 5 carbon atoms, and n is the number 1 or 2, or their salts with biological activity. A known method for the preparation of 4-sulfamoyl-1-toluidine derivatives consists in the interaction of the corresponding 3-methyl 4-sulfamoyl derivative with the amine, which has biological activity. However, there is no mention in the literature of the process for the preparation of compounds of general formula I, which are different from those known to have a heavier alkyl residue. 541429 (eleven) (51) M. Cl.2 C 07C 143/80 C 07C 87/52 / 04 (53) UDC 547.541.521 233.07 (088.8) These compounds exhibit higher physiological activity and can be used in medicine as pharmaceutical preparations. According to the present invention, a process for the preparation of the compounds of the general formula 1 or their salts is described, in that the compound of the general formula I NH, P Y-HNOj E where Ra has the meanings indicated for Ra or is a group, which can be translated into Ra; R4 has the meaning indicated; Y is hydrogen or an acetic residue, is reacted with a compound of general formula III Z- (CH2) nR ,, III where Ri and p have the above meaning, and Z is a reactive ester group at a temperature of 60-180 ° C, followed by Popelak, Egon Roesch and Klaus Hardbeck "Böhringer Mannheim 1T Foreigners (Germany) and Kurt Shtah (Austria) Foreign company D 5 .ibi, fcpT (ji by isolating the desired product as a base or salt, and in the case when Cs is a group that can be converted to carboxyl or tetrazolyl (5) -group, it is converted to residue R2, and when Y is an acyl residue; it is prepared in a known manner. The residue that can be converted to a carboxyl group is preferably an esterified carboxyl group, a carboxamide group or a nitrile group, and in addition, a carboxyl group in the form of its salt with inorganic and organic bases. The group that can be converted to a tetrazolyl (5) -linked residue is predominantly a nitrile group, an imidoester group, or an amidine group. Compounds of general formula III with a reactive ester group Z are halides, quaternary addition salts of these compounds, for example, with pyridine, and easily cleavable sulfonic esters, for example tosylates, brosylates. The starting compounds corresponding to general formula II can be obtained, for example, by sulfoamidation of 4-alkyl-2-nitrobenzoic acid or derivatives of this acid, followed by reduction. The corresponding tetrazolyl compounds are obtained by reacting nitriles with azides. The described method is carried out at temperatures ranging between 60 and, with the most favorable reaction being carried out in the presence of an excess amount of a reaction component with basic properties. The excess amount of the main component of the reaction simultaneously serves to bind the acid released in the free state during the reaction. However, other inorganic or organic bases or compounds that react like bases can also be used for this purpose. Alkali metal carbonates, calcium oxide, triethylamine, dimethylaniline and pyridine can be mentioned as examples. The reaction components can be reacted either in the absence or in the presence of inert solvents or diluents, it being most appropriate to use aromatic hydrocarbons, ethylene glycol, ethylene glycol monomethyl ether, diethylene glycol dimethyl ether, dimethylformamide and dimethyl sulfoxide for this purpose. In the case when Ra is an esterified carboxyl, carboxamide or nitrile group, this group immediately after carrying out the reaction is converted to a carboxyl group by known methods by hydrolysis, preferably in an alkaline medium. When it is desired to obtain a compound corresponding to formula I with R2, which is a tetrazolyl (5) group, the corresponding compounds in which Rs is a nitrile group, an imidoester group or an amidine group can be treated directly after the reaction with nitrous acid, preferably with salts this acid. The reaction is carried out in an inert solvent, preferably in dimethylformamide. The acyl residue Y is cleaved by alkaline saponification, preferably with alkali metal hydroxides. Crude products of formula I can be purified by dissolving alkali metal hydroxides, followed by precipitation with dilute mineral acids. The products obtained in accordance with the described method can be converted into the corresponding salts by treatment with inorganic or organic bases by known methods. Physiologically harmless salts are, in particular, alkali metal salts, alkaline earth metals and ammonium salts, which can be obtained by known methods, for example, by reaction with sodium hydroxide, potassium hydroxide, aqueous ammonia or . The method of the present invention is explained in more detail in the examples below. Example 1. 4-Isopropyl-2-benzylampo-5 sulfamoyl benzoic acid. 1 g of 4-isopropyl-5-sulphamoyl anthranilic acid is heated for 3 hours at a temperature of 120 ° C with 2 ml of bisyl chloride in 10 ml of dimethylformamide. After cooling, the reaction mixture was diluted with 10 ml of water, brought to alkaline with the addition of 2N. soda solution and extracted with ether. The aqueous phase is treated with activated carbon, filtered, and the filtrate is acidified with hydrochloric acid. The crude product is filtered off and recrystallized from a mixture of methyl alcohol and water. Yield 0.70 g (52% of theory). The melting point of the product is 233-234 ° C. The 4-isopropyl-5-sulphamoyl anthranilic acid used as the starting material was prepared as follows. 5 g of 4-isopropyl - 2-bromo-sulphamoylbenzoic acid are reacted in an autoclave with 60 ml of liquid ammonia, and the reaction is carried out for 12 hours at 100 ° C. The reaction mixture is dissolved in water, treated with activated carbon, filtered and the filtrate is made acidic by the addition of 2N. hydrochloric acid solution. The crude product which has precipitated out is dissolved in ethyl acetate. the ester of acetic acid, the organic phase is washed with water, dried and subjected to strong evaporation. As a result of the addition of chloroform, 4-isopropyl-5-sulfamoyl anthranilic acid crystallizes. The melting point of the product obtained is 235-238 ° C (decomp.). In a similar way are obtained: 4-ethyl-2-furfurylamino-5-sulfamoyl benzoic acid; m.p. 228 ° C; 4-ethyl-2-tenylamino-5-sulfamoylbenzoic acid; m.p. 227-228 ° C (from ethyl alcohol); 3-ethyl-4-sulfamoyl-6-tetrazolyl (5) -1Yfurfuryaniline; m.p. 179-180 ° C (from ethyl alcohol); 3 - ethyl-4 - sulfamoyl-6 - tetrazolyl (5) -Benzilaniline; m.p. 237-239 ° C (from a mixture of acetone and ethyl alcohol); 4-isopropyl-2-furfurylamino-5-sulfamoylbenzoic acid; m.p. 180-183 ° C (decomp.) (From methyl alcohol and water); 4-isopropyl-2 - tenylamino - 5-sulphamoylbenzoic acid; m.p. 194-197 ° C (decomp.) (From a mixture of methyl alcohol and water); 4-butyl-2-furfurylamino-5-sulfamoylbenzoic acid; m.p. 239-240 ° C (from a mixture of acetone and ethyl alcohol); 4-butyl-2- (2-furylethylamino) -5 - sulfamoylbenzoic acid; m.p. 227-228 ° C (from a mixture of acetone and ethyl alcohol); B. 4-Alkyl-2-bromobenzoic acid. 50 g of 4-alkyl-2-bromobenzonitrile are heated for 1 hour at a temperature of 130 ° C with the mixture consisting of 130 ml of concentrated sulfuric acid and 40 ml of water. After that, eh; e 100 ml of water was added to the reaction mixture and the temperature was maintained at 160 ° C for 2 hours. The reaction mixture is then allowed to cool, poured into ice-cold water and the precipitate formed is filtered off. Another wet product is dissolved in 300 ml of 2N. sodium hydroxide solution, extraction is carried out with methylene chloride, the aqueous phase is treated with animal charcoal and then acidified with hydrochloric acid. The resulting product is filtered, washed with water and dried. 4-butpl-2-tenylamino-5-sulfamoylbenzoic acid; m.p. 229-230 ° C (from a mixture of acetone and ethyl alcohol); 3-ethyl-4-sulfamoyl - 6-tetrazolyl (5) -M-tenylaniline; m.p. 196-198 ° C (from a mixture of ethyl alcohol and water); 3-isopropyl - 4-sulfamoyl-6-tetrazolyl (5) N-tenilaniline; m.p. 194-195 ° C (decomp.) (From ethyl acetate). The starting compounds are prepared according to the following procedure. A. 4-Alkyl-2-bromobenzonitrpl. 1 mol of 4-alkyl-2-bromoaniline is diazotized in a solution of sulfuric acid at a temperature from About to 5 ° C. A clear ice-cold diazonium salt solution is then added dropwise to a solution of copper cyanide heated to 60 ° C, which is prepared from 1.5 moles of crystalline copper sulfate and 6 moles of sodium cyanide. The mixture is then further stirred for 2 hours at 60 ° C and left to stand overnight. The brown-colored precipitate is sucked off and immediately distilled. with water vapor. The distillate is extracted with methylene chloride. The combined methylene chloride solutions are washed with 1N. sodium hydroxide solution and immediately thereafter with water and dried. The residue resulting from evaporation of the solvent is subjected to fractional distillation in vacuo. B. 4-alkyl-2-bromo-5-sulfamoyl benzoic acid. 50 g of 4-alkyl-2-bromobenzoic acid is heated for 2 hours at 100 ° C together with 150 ml of chlorosulfonic acid. After cooling, the reaction mixture is poured onto ice and the sulfonyl chloride which precipitates is filtered off. The product obtained, while still wet, is introduced at a temperature of 20 ° C in 500 ml of a concentrated ammonia solution and the mixture is kept overnight. The clear solution is then treated with activated charcoal and heated for some time under vacuum to remove most of the ammonia. The solution is then acidified with hydrochloric acid, the crude product which precipitates out is filtered off, and then recrystallized from diluted ethyl alcohol. G. Z-alkl-6-tetrazolyl (5) -bromobenzene. 0.1 mol of 4-alkyl-2-bromobenzonentril is dissolved in 200 ml of dimethylformamide, 20 ml of water, 0.12 mol of sodium azide and 0.12 mol of ammonium chloride are added to the prepared solution and the mixture is heated with stirring for 15 hours at a temperature of 100 ° C. Immediately thereafter, the solvent was distilled off in vacuo and the resulting residue was dissolved in 1N. sodium hydroxide solution. The resulting solution was extracted with methylene chloride, treated with charcoal, and acidified with glacial acetic acid. The precipitated crude product is filtered and dried. Invention Formula The method of obtaining derivatives of 3-alkyl-4 sulfamoylaniline General formula where is RI phenyl, furyl or thienyl residue; R2 is a carboxyl group or tetrazolyl (5) -button; R4 is a linear or branched alkyl residue containing from 2 to 5 carbon atoms, and n is 1 or 2, or their salts, characterized in that the compound of the general formula D. 3-alkyl-4-sulfamoyl-6 is tetrazolyl (5 a) bromobenzene. 3-alkyl-6-tetrazolyl (5) -bromobenzene is sulfochlorinated with two times the weight of chlorosulfoic acid. After complete completion of the reaction, the reaction mixture is poured into ice and the sulfonyl chloride which precipitates is filtered off. The still wet product at a temperature of 20 ° C is introduced into a co-titrated ammonia solution and the mixture is kept overnight. The clear solution is treated with activated carbon, filtered and the filtrate is somewhat evaporated in vacuo. The solution is then acidified with hydrochloric acid, the product which is precipitated is filtered off and recrystallized from a mixture of methyl alcohol and water. jL I, where Cs is as defined above for R2 or is a group that can be converted to R2, R4 is as above, Y is hydrogen or an acyl residue, is reacted with a compound of the general formula Z- (CH2) nR, , III where Ri and p have the above meaning, and Z is a reactive ester group, at a temperature of 60-180 ° C, followed by isolation of the target product as an acid or salt, moreover, when: R3 is a group that can be converted to carboxyl or tetrazolyl- (5) -group It is converted to residue R2, and when Y is an acyl residue, it is cleaved in a known manner.