FR2462460A1 - NOVEL AZOIC COMPOUNDS AND PROCESS FOR PREPARING THEM - Google Patents

Abstract

THE NEW AZOIC COMPOUNDS OF THE INVENTION MEET THE GENERAL FORMULA: (CF DRAWING IN BOPI) IN WHICH X IS HYDROGEN OR A HALOGEN. THESE AZOIC COMPOUNDS ARE USEFUL AS PRECURSORS OF DISPERSED COLORS AND BASIC COLORS AND THEY ARE EFFECTIVE FOR THERAPEUTIC TREATMENTS.

Description

The subject of the present invention is new azo compounds and a

  process for their preparation; it relates more particularly to the azo compounds represented by the following formula, in which X is hydrogen or a halogen, and a process for preparing them X

/ =

OCH3 H

  These azo compounds are useful as precursors for disperse dyes and basic dyes and are

  effective for therapeutic treatment.

  In general, it is known that azo compounds are useful as dyestuffs comprising disperse dyes and basic dyes. It is also known that imidazole can be used to prepare various azo compounds. However, it is not known that the azo compounds of the above formula can be basic dyes and disperse dyes and that, in particular, they are effective for

therapeutic treatments.

  It is generally known that the imi-

  dazole is used as the coupling component to prepare azo compounds in an amount of about 1 to 1.5 moles per mole of diazo component with which said imidazole is copulated. However, in this case the reaction gives by-products in which the

  diazo component can be copulated to 4-imidazolyl group.

  As a result, it is difficult to obtain the compounds

  azoics in pure form using this reaction.

  The present invention proposes: - to provide new azo compounds corresponding to the previously given formula;

  - to be able to dispose of new azol compounds

  useful as precursors for the production of disperse and / or basic dyes;

  - to provide new azo compounds

  providing effective therapeutic agents; and to be able to dispose of a process for the preparation of azo compounds corresponding to the abovementioned formula without

  significant production of by-products.

  Other goals, benefits and features of

  the present invention will appear in the description below.

  after. The azo compounds of the present invention include the compounds of the following formula

/ \ NI

OCH3 H

  wherein X is hydrogen or halogen and their acid addition salts. The term "halogen" is used

  to designate chlorine, bromine, fluorine and iodine.

  The azo compounds can be converted, in the usual way, into their addition salts with acids comprising the addition salts with mineral acids such as hydrochloride, hydrobromide, sulphate, nitrate and phosphate, and the salts thereof. addition with organic acids such as acetate,

  succinate, maleate, oxalate and tartrate.

  The azo compounds according to the present invention can be prepared by first reacting a 2-methoxyaniline or a reactive derivative thereof with sodium nitrite in the presence of hydrochloric acid and then coupling the resulting diazonium compound with imidazole in an amount of about 5 to 10 moles per mole of diazonium compound, the azo compound and

  obtained being converted, if desired, into the additive salt

corresponding acidity.

  The diazotation of a 2-methoxyaniline with a nitrite and hydrochloric acid can be carried out in the usual manner. The reaction conditions may be the usual conditions of the diazotization reactions and are selected depending on the particular nature of the reaction substances and other parameters.

  The resulting diazonium compounds are then

  impregnated with imidazole by reacting about 5 to 10 moles of imidazole per mole of diazonium compound. The diazonium compounds can be used for the coupling reaction, after being isolated from the mixture in which they have been formed. This reaction

  can be carried out in the presence of an alkali such as hydro-

  sodium hydroxide, potassium hydroxide or carbonate

  sodium or a buffer such as sodium acetate,

  a temperature of 0 to 50C, for about 1 hour. It is obvious that the reaction conditions relating to reaction time and temperature or the like can

  in particular depend on the nature of the reaction

and solvents.

  The azo compounds according to the present invention

  produce pharmaceutical and therapeutic effects

  on hypotension, heart failure or mucous membrane hyperemia. In particular, it is shown that 2 - [(2-methoxy-5-chlorophenyl) azo] -1H-imidazole and 2- [(2-methoxy-5-bromophenyl) azo] -1-imidazole have diuretic activity. which is about 10 times that of Furosemide used as a control, when these substances are administered to rats, and that the other compounds also have a higher diuretic activity than Furosemide. In addition, the above-mentioned azo compounds have

  an acute toxicity sufficiently weak not to

  void problems during the usual administration.

  The following examples are given, as a non

  limiting, to illustrate the present invention.

  In these examples, the parts are by weight.

EXAMPLE 1

  To a solution of 5.1 parts of 4-chloro-2-

  aminoanisole and 7.6 parts of 35% hydrochloric acid in 50 parts of water, 15 parts of water containing 2.2 parts of sodium nitrite at 0-5 ° C are added and then diazotization reaction by stirring the mixture at 0-5 C for 1 hour. The resulting diazonium salt solution is then added at 0-5 ° C to a solution of 20.4 parts of imidazole, 1.7 parts of sodium hydroxide and 2.5 parts of sodium acetate in 150 parts. of water, whereupon the mixture is stirred at this same temperature for one hour to make the copulation reaction complete, resulting in a crude orange-yellow product. The crude product is filtered, washed with water and dried at 60 ° C., which gives 7.6 parts

said product.

  This raw product (7 parts) is then recrystallized

  in n-propyl alcohol to give 4.9 parts of 2- [2- (2-methoxy-5-chlorophenyl) azo] -1H-imidazole in the form of an orange-yellow crystalline substance in the form of columns. 205 C (decomposition)

  in accordance with the provisions of the Pharma-

  Japanese copa and its ultraviolet absorption spectrum

  has a maximum (A max) of 384 mym.

  Elemental analysis: C H N Cl Valeumscalculated (%) 50.75 3.83 23.68 14.98

Experimental values -

(%) 50.55 4.01 24.10 15.05

EXAMPLE 2

  2.82 parts of 4-fluoro-2-aminoanisole and 5.2 parts of 35% hydrochloric acid are added to 50 parts of water. To the mixture thus obtained, 10 parts of water containing 1.38 parts are added. sodium nitrite, at 0-5 C,

  and this mixture is then stirred for 1 hour to effect

  kill the diazotation. The resulting diazonium salt solution

  The mixture is then added, at 0 ° -50 ° C., to a solution of 13.6 parts of imidazole, 1.2 parts of sodium hydroxide and 1.64 parts of sodium acetate in 100 parts of water, following of which the coupling reaction is carried out by stirring the mixture for 1 hour. The orange-yellow azo compound which precipitated in the reaction mixture was filtered, washed with water and then dried at 60 ° C., giving 4.3 parts of crude product. The crude product (4 parts) is then recrystallized from n-butyl alcohol

  to give 2.9 parts of 2 - / (2-methoxy-5-fluorophenyl) azo7-

  1H-imidazole in the form of a crystalline substance acicular, orange-yellow in color. This substance melts

  at 204 C (decomposition), by measure in accordance with the

  of the Japanese Pharmacopoeia, and its ultraviolet absorption spectrum has a maximum (max)

388 mY.

Elemental analysis:

C H N F

  Values (%) 54.55 4.09 25.45 8.64 Experimental values (%) 54, 60 4.12 25.58 5.69

EXAMPLE 3

  To a solution of 4.04 parts of 4-bromo-2-

  amino-anisole and 5.2 parts of% hydrochloric acid in 60 parts of water, 10 parts of water containing 1.38 parts of sodium nitrite at 5 ° C. are added, and then the diazotization reaction is carried out. stirring the mixture at 0-5 C for 1 hour. The resulting diazonium salt solution is then added, at 0-5 ° C., to a solution of 9.53 parts of imidazole, 1.2 parts of sodium hydroxide and 1.64 parts of sodium acetate in 80% strength. parts of water, whereupon the mixture is stirred at this same temperature for 1 hour to make the complete coupling reaction, resulting in a crude product yellow-orange. This raw product is

  filtered and dried at 70 ° C. to give 5.1 parts of product.

  This raw product (4 parts) is then recreated

  in ethyl acetate to give 3.2 parts of 2-L (2-methoxy-5-bromophenyl) azo-1H-imidazole as a yellow-orange, acicular crystalline substance. This substance melts at 224.5 C (dec), by measurement in accordance with the requirements of the Japanese Pharmacopoeia and its ultraviolet absorption spectrum present

a maximum (A max) at 387 m.

  Elemental analysis: C H N Br Calculated values (%) 42.70 3.20 19.93 28, 44 Experimental values (%) 42.71 3.27 19.90 28.39

EXAMPLE 4

  We follow the process of one of the above examples

  except as regards the nature of the reaction

  and 2-methoxyphenyl azo-1H-imidazole as a yellow crystalline substance, which is

152-153 C.

EXAMPLE 5

  To a solution of 4.98 parts of 4-iodo-2-amino

  anisole and 5.2 parts of 35% hydrochloric acid in parts of water, 10 parts of water containing 1.38 parts of sodium nitrite are added at 0 ° -50 ° C., and the diazotization reaction is then carried out. stirring the mixture at 0-50C for 1 hour. The resulting diazonium salt solution is then added, at 0 ° C., to a solution of 89 parts of imidazole, 1.2 parts of sodium hydroxide and 1.64 parts of sodium acetate in 80 parts. of water,

  following which the mixture is agitated at the same temperature.

  ture for 1 hour to make the copulation reaction complete, resulting in a crude orange-yellow product. This crude product is filtered, washed with water and dried at 60 ° C. This

which gives 5.9 parts of product.

  This raw product (4.5 parts) is then

  silica gel column chromatographed to give 3.5 parts of 2 - [(2-methoxy-5-iodophenyl) azo] -1H-imidazole as an orange-yellow crystalline material (columnar crystals). This substance melts at 217.5WC (decomposition), by measurement in accordance with the requirements of the Japanese Pharmacopoeia, and its absorption spectrum

  ultraviolet light has a maximum (δ max) at 385 mYm.

Elemental analysis:

C H

  Calculated Values (%) 36.59 2.74 Experimental Values (%) 36.61 2.70

N I

17.07 38.69

17.09 38.61

Claims (7)

  1. Azoic compound of formula: X OC N, -3_ N = N4 NOT H3 H   wherein X is hydrogen or halogen, and its addition salts with acids. 2. Compound according to claim 1, characterized   in that it consists of 2 - ((2-methoxy-5-chlorophen)   nyl) azo7-H-imidazole. 3. Compound according to claim 1, characterized   in that it consists of 2-L (2-methoxy-5-bromophene)   nyl) azo7-1H-imidazole. 4. A compound according to the fact that it is phenyl) azo7-1H-imidazole. 5. Compound in that it is phenyl) azo / 1H-imidazole. 6. Compound according to what is constituted IH-imidazole. claim 1, characterized by 2 - / (2-7methoxy-5-iodo) claim 1, characterized by 2 - / (2-methoxy-5-fluoro) claim 1, characterized by 2 - / (2-methoxyphenyl) azo / -   7. Process for preparing a compound of formula: XH OCH3 in which X is hydrogen or a halogen, or one of its addition salts with an acid, characterized in that it consists in reacting a 2-methoxyaniline or a reactive derivative thereof, with a nitrite and hydrochloric acid and reacting the resulting diazonium compound with imidazole, at about 10 moles of imidazole per mole of diazonium compound, for obtain the compound of the aforementioned formula and, if desired, to convert this compound into one of its salts addition with an acid.