IL42843A - 1h-tetrazole-1-acetic acid and esters and processes for their preparation - Google Patents

Abstract

1435809 1 - H - Tetrazole - -1 - acetate esters and acids ELI LILLY & CO 13 Aug 1973 [14 Aug 1972] 38132/73 Heading C2C Novel tetrazolylacetate esters and acids having the general formula wherein R is a (C 1 -C 12 ) hydrocarbon radical free from aliphatic unsaturation, a (C 1 -C 12 ) hydrocarbon -O- radical free from aliphatic unsaturation or an -O- alkali metal radical; and R<SP>1</SP> is hydrogen, an alkali metal cation or a (C 1 -C 12 ) alkyl, (C 4 -C 8 ) cycloalkyl, phenyl, behzyl, p-nitrophenyl, p-nitrobenzyl, 2,2,2-trichloroethyl or phenacyl radical, as well those compounds of the above formula wherein R<SP>1</SP> may also be tolyl, xylyl or phenylethyl, are prepared by reacting an acyl cyanide of the formula (II) with an azidoacetic acid or ester thereof having the formula (III) at a temperature of from 80‹ to 135‹ C. The resultant tetrazolylacetate ester may be further reacted with either (a) an alcoholic alkali metal hydroxide to form the corresponding alkali metal salt, (b) a base to remove the 5-acyl substituent and form the alkali metal salt of 1-tetrazoleacetic acid, provided that R is a (C 1 -C 12 ) hydrocarbon radical, or (c) with an acid to remove the 5-acyl substituent and form the 1-tetrazoleacetic acid, provided that R is a (C 1 -C 12 ) hydrocarbon -O- radical. [GB1435809A]

Claims (20)

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1. A process for preparing tetrazolylacetate esters or acids or alkaline metal salts of the formula wherein is a C.- to C, alkyl, C.- C, alkoxy, C. - C, . , 1 6 ' ' 1 6 " 4 6 -cycloalkyl, C4- C6~ cycloalkoxy, phenyl, tolyl, xylyl, benzyl, phenoxy, tolyloxy, xjrlyloxy, or benzyloxy; and R1 is hydrogen, Cj- to C^-alkyl, C^- to Cg-cycloalkyl, phenyl, phenylethyl, 2,2,2-trichloroethyl, or phenacyl, which comprises heating a mixture containing a compound of the formula 0 II R-C-CN wherein R is as defined above, and a compound of the formula N3-CH2-C00R' wherein R1 is as defined above, at a temperature of from about 80 to about 135eC. for a time sufficient to form the tetra-zoleacetate ester or acid.

2. The process of Claim 1 wherein a compound of the formula 0 II R-C-CN and a compound of the formula 0 II N3-CH^-C-0R' 42843/2 are heated in an inert solvent.

3. The process of claims 1 or 2 wherein the tetrazolylacetate ester so obtained is reacted further with alcoholic alkali metal hydroxide to form the corresponding alkali metal salt.

4. The process of claims 1 or 2 wherein R is a S^- to C^- alkyiaxy, and R' is - to Cg-alkyl

5. The process of claim 4 wherein ethyl cyanoformate is reacted with ethyl azidpacetate to form ethyl 5-(ethoxycarbonyl) *·1Η- tetrazole -1 -acetate♦

6. The process of claims 1 or 2 wherein is a C^- to Cfi- alkyloxy, and R* is hydrogen.

7. The process of claim 6 wherein ethyl cyanoformate is reacted with azidoacetic acid to form 5-(ethoxycarbonyl) -lH-tetrazole-l-acetic acid.

8. The process of claims 1 or 2 wherein R is phenyl, and R' is a Cj to Cg- alkyl..

9. The process of claim 8 wherein benzoyl cyanid is reacted with ethyl azidoacetate to form ethyl 5 -benzoyl -lH-tetrazole-1 -acetate.

10. Compounds of the formula CH2C-0R' N wherein R is cyclo - alkoxy, phenyl, tolyl, xylyl, benzyl, phenoxy, tolyloxy, xylyloxy, benzyloxy, or -0-alkali metal; and R* is hydrogen, an alkali metal cation, C^- to C6-alkyl, phenyl, benzyl, p-nitrophenyl, p-nitrobenzyl, 2,2,2-trtchloroethyl, phenacyl, C4~C6 cycloalkyl, tolyl, xylyl, or phenylethyl. 42843/2

11. The compound of claim 10 wherein R is C^- to C^-alkyloxy and R' is C]- to Cg-alkyl.

12. The compound of claim 11 wherein the compound is ethyl 5 -(ethpxycarbonyl) -lH-tetrazole-l -acetate.

13. The compound of claim 10 wherein R is Cj- to C& alkyloxy and R' is hydrogen.

14. The compound of claim 13 wherein the compound is 5-(ethoxycarbonyl) -lH-tetrazole-l -acetic acid,

15. The compohd of claim 10 Wherein R is phenyl and R1 is Cj- to Cg-alkyl.

16. The compound of claim 15 wherein the compound is ethyl 5-benzoyl^-lH-tetrazole-l-acetate*

17. The compound of claim 10 wherein R is -O-alkali metal and R' is an alkali metal cation;

18. The compound of claim 17 Wherein the compound is the di -potassium salt of 5-carboxy-lH-tetrazole-1 -acetic acid.

19. A process for preparing tetrazolylacetate acids and esters of the formula R t o=c r 0 M-CH„-C-OR' '2 Wherein R and R' are as defined in claim 1, substantially as herein before described with particular reference to Examples 1 to 6.

20. Tetrazolylacetate acids, esters and salts of the formul R I 0=C ' r 0 N ^3™- 42843/2 wherein R and R* are as defined in claim 10, substantially as hereinbefore described with particular reference to Examples 1 to 7. S.HOROWITZ § Co} AGENTS FOR APPLICANTS