DE1954839A1 - Tetrazole derivatives - Google Patents

Description

Dr. Ing. E. BERKENFELD · Dipl.-Ing. H. BERKENFELD, patent attorneys, Cologne Attachment file number

for entering JQ. October 1909 Sch / Name d. Note TJ Smith & NepheW Ltd.

Tetrazole derivatives.

The invention relates to tetrazole derivatives and a method for their manufacture.

The invention relates to tetrazole derivatives of the general formula

in which R _{1 is} hydrogen, alkyl having up to 6 carbon atoms, alkoxy, halogen or trifluoromethyl having up to 6 carbon atoms »

Derivatives of the general formula I are according to the invention in made in such a way that one can connect the general formula

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i NN

II H

dehydrated, in which R _{1 has} the meaning given above.

Dehydration can be carried out using thionyl chloride, for example will.

The compounds of the general formula II are new and are the subject matter the invention.

The invention also relates to a method for producing the Compounds of the general formula II, according to which a compound of the general formula

HI.

hydrolyzed, in which R ^ has the meaning given above, and R ₁ J and R, which have the meaning as R _t .

The hydrolysis can be carried out, for example, by means of a 20 # strength aqueous sodium hydroxide solution be performed.

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-3 * '195A839

The compounds of general formula I can be used as intermediates for the production of the pending application S 34/25 + substituted tetrazoles disclosed which are anaigetics and anti-inflammatory agents can be used.

+ P 18 06 5 ^ 6.8

The invention is described in more detail in the following examples.

Example I. Tetrazole (5.1-c) 2,3 «4,5-tetrahydro-1,4-benzoxazepin-5-one

• 44 g (0.20 mol) of 5- (2-carboxyphenoxymethyl) tetrazole were treated in the cold with 82 g (0.69 mol) of thionyl chloride containing 2 drops of N, N-dimethylformamide. After one hour, the reaction mixture was slowly heated to the return flow temperature and held for two hours at this temperature, excess thionyl chloride was obtained away and 31.2 g (785ε) of a brown solid substance having a melting point with decomposition at 128 - was 133 ^O C. Crystallization from benzene yielded the desired product having a melting point .of 135-136 ⁰ C with decomposition.

C ₉ H ₆ N ₄ O ₂

C. 16; 2 H N found: 53 46 2 , 94 27, requires 53 , 99 27,

The following compounds have been appropriately substituted from Intermediate products prepared by a method corresponding to Example I.

Example II 7-chloro-tetrazole (5j1-c) * - 2,3,4,5-tetrahydro-1,4-benzoxazepln -

White needles made of acetone, F = 19I - 192 ° C

H N

found: 45.91 2.35 23.1

Requires: 45.68 2.13 23.68 #

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Example III

7-methyl-tetrazole- (5j1-c) -2,3,4,5-tetrahydro-1,4-benzoxazepine-

5-on

Colorless sticks made from acetone; P = 174-175 ° C.

C H N

₂ found ϊ 55.82 3.85 25.74 # requires: 55.55 3.73 25.92 #

Example IV

8-methoxy-tetrazole- (5 _J 1-c) -2,3,4 _f 5-tetrahydro-1,4-benzoxazepine-

Pale yellow needles made from benzene; F = 186-187

C H N

found : 51 , 77 3, 53 24, requires: 51 , 72 3, 47 24,

The manufacture of intermediates, which is not yet in the literature is given below.

Preparation 1 5- (2-carboxyphenoxymethyl) tetrazole

8.55 g (0.029 mol) of 5- (2-phenylcarbamoyl) phenoxymethyl) tetrazole were dissolved in 75 ml of a 20% sodium hydroxide solution and refluxed for five hours. The cooled solution was extracted with 2 × 50 ml of ethyl acetate and then carefully acidified to pH 2 with concentrated hydrochloric acid to precipitate a white solid. The solid was filtered off, washed with water and dried, and 5.76 g (90 $) of a product having a melting point of 201 - 202 obtained ^0C. Crystallization from acetone: water mixture (1: 1 v / v) gave a

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white crystalline solid with a melting point of 204 - 205 ° C.

CHN

found: 48.94 3.39 25.225g

requires: 49.09 3.66 25,

Preparation 2

5- (2-carboxy-4-chlorophenoxymethyl) tetrazole

Made from 5- ^ ~ 2- (phenylcarbamoyl) -4-chlorophenoxymethyl_7

tetrazole White needles with acetone; P = 210-211 ⁰ C.

CHN

C ₉ H ₇ ClN ₄ O ₃ found: 42.18 $ 2.95 22.31

Requires: 42.45 $ 2.77 $ 22.01

Preparation 3

5- (2-carboxy-4-methylphenoxymethyl) tetrazole

Made from 5- ^ ~ 2- (phenylcarbamoyl) -4-methylphenoxymethyl7

tetrazole

White microneedles made from N, N-dimethylformamide: water (1: 2 v / v); P = 188-189 ⁰ C.

CHN

found: 51.37 4.15 24, requires: 51.28 4.30 $ 23.92

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-> - '1954Ö39

Preparation 4

5- (2-carboxy-5-methoxyphenoxymethyl) tetrazole

Made from 5- / ~ 2- (3,4-dichlorophenylcarbanioyl) -5-methoxyphenoxymethyl_7g tetrazole.

White crystalline substance made from N, N-Din & hylformamide: water (1: 2 v / v); P = 220-221 ° C.

CHN

found: 48.06 4.0b 22.15 #

requires: 4ö, 00 4.02

Claims

009819/1882

Claims (1)

Dr. Ing. E. BERKENFELD · Dipl.-Ing. H. BERKENFELD, patent attorneys, Cologne Annex «file number to the input "from October 30, 1909 Seh / Na", d. Note τ. J. Smith & Nephew Ltd. Claims tetrazole derivative of the general formula: in which R _{1 is} hydrogen, alkyl containing up to 6 carbon atoms, alkoxy containing up to 6 carbon atoms, halogen or trifluoromethyl. 2. Process for the preparation of compounds of the general formula I according to claim 1, characterized in that that one has a compound of the general formula: NN
1 COOH in which R _{1 has} the meaning given in claim 1, dehydrated. 3 24/30 -7 009819/1882 - »- 1354839 j5. Method according to claim 2, characterized in that the dehydration is carried out using thionyl chloride. a compound of the general formula: 0-CH ₂ -C COOH N-N Il Il in which R _{1 has} the meaning given in claim 1. 5. Process for the preparation of compounds of the general formula II according to claim 2, characterized in that one compound of the general formula: III. in which R _{1 has} the meaning given in claim 1 and R ₂ and Rz are hydrogen, alkyl having up to 6 carbon atoms, alkoxy having up to 6 carbon atoms, halogen or tri-fluoromethyl, hydrolyzed. 0 09819/18 82 6. The method according to claim 5 *, characterized in that the hydrolysis is carried out using a 20 # aqueous sodium hydroxide solution carries out. 7. 7-chloro-tetrazot (5 »1-c) -2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one. 8. 7-Methyl-tetrazol- (5,1-c) -2,; 3,4,5-tetrahydro-1,4-benzoxazepin-5-one. 9. 8-Methoxy-tetrazol- (5,1-c) -2,3,4,5-tet? Rahydro-1,4-benzoxazepin-5-one. 10. 5- (2-Carboxyphenoxymethyl) tetrazole. 11. 5- (2-Carboxy-4-chlorophenoxymethyl) tetrazole. 12. 5- ^ -Carboxy ^ -methylphenoxymethyl) tetrazole. 13 • 5- (2-Carboxy-5-Itiethoxyphenoxymethyl) -tetrazole. 009819/1882