GB2060671A

GB2060671A - Azo Compounds

Info

Publication number: GB2060671A
Application number: GB8024325A
Authority: GB
Original assignee: Hodogaya Chemical Co Ltd; Mochida Pharmaceutical Co Ltd
Current assignee: Hodogaya Chemical Co Ltd; Mochida Pharmaceutical Co Ltd
Priority date: 1979-07-30
Filing date: 1980-07-24
Publication date: 1981-05-07
Also published as: FR2462460A1; JPS5620060A; FR2462460B1; JPS5817769B2; GB2060671B; DE3028928A1; DE3028928C2

Abstract

The azo compounds are represented by the general formula: <IMAGE> wherein X is hydrogen or halogen. The azo compounds are useful as precursors of disperse dyes and basic dyes and effective for therapeutic treatment.

Description

SPECIFICATION Novel Azo Compounds and Process for Preparing Same 1. Field of the Invention The present invention relates to novel azo compounds and a process for preparing the same and, more particularly, to the azo compounds and a process for preparing the azo compounds represented by the formula:

wherein X is hydrogen or halogen.The azo compounds are useful as precursors of disperse dyes and basic dyes and effective for therapeutic treatment.

2. Brief Description of Prior Art Generally, azo compounds are known to be useful as dyes including disperse and basic dyes. It is also known that imidazole can be a component to form various azo compounds. It is not known, however, that the azo compounds of the above formula can be basic and disperse dyes and that in particular they are effective for therapeutic treatment.

It is generally known that, when imidazole is used as a coupling component of azo compounds, it is usually used in an amount of from about 1 to 1.5 moles bases on a diazo component to which imidazole is coupled. In this case, however, the reaction permits the production of by-products in which the diazo component may be coupled to the 4-imidazolyl group or one more diazo component may be coupled to the 4-imidazolyl group. Accordingly, this reaction has a difficulty in providing the azo compounds in a pure form.

Accordingly, the object of the present invention is to provide novel azo compounds having the formula as represented hereinabove.

Another object of the present invention is to provide novel azo compounds which are useful as precursors for the production of disperse and/or basic dyes as well as effective as therapeutic agents.

A further object of the present invention is to provide a process for preparing the azo compounds having the formula as represented hereinabove without any substantial production of by-products.

Other objects, advantages and features of the present invention will become apparent during the course of the description which follows, but any modifications and improvements to be obviously made should be understood not to deviate from the scope of the present invention.

The azo compounds according to the present invention include the azo compounds represented by the formula:

wherein X is hydrogen or halogen, and an acid addition salt. The term "halogen" is intended to mean chlorine, bromine, fluorine and iodine. The azo compounds may be converted in conventional manner into their acid addition salts including an inorganic acid addition salt such as hydrochloride, hydrobromide, sulfate, nitrate and phosphate, and an organic acid addition salt such as acetate, succinate, maleate, oxalate and tartrate.

The azo compounds according to the present invention may be prepared by first reacting a 2methoxyaniline or a reactive derivative thereof with sodium nitrite in the presence of hydrochloric acid and then coupling the resulting diazonium compound to imidazole in the amount of from approximately 5 to 10 moles based on the diazonium compound and, if desired, converting the azo compound into the corresponding acid addition salt.

The diazotization of a 2-methoxy aniline with a nitrite and hydrochloric acid may be carried out in conventional manner. The reaction conditions may be conventional and selected depending upon the type of reactants and other conditions.

The resulting diazonium compounds are then coupled to imidazole by reacting the former with the latter in the amount of from approximately 5 to 10 moles based on the diazonium compound. The resulting diazonium compounds may be used for the coupling reaction with or without being separated from the mixture where the diazonium compounds are formed. This reaction may be carried out in the presence of an alkali such as sodium hydroxide, potassium hydroxide or sodium carbonate or a buffer such as sodium acetate at a temperature of from 0 to 5 F for about 1 hour. It is obvious that the reaction conditions with respect to the reaction time and temperature or the like may be varied depending upon the types of the reactants and solvents and the like.

The azo compounds according to the present invention exhibit a pharmaceutical and therapeutic effects on hypotension, cardiac insufficiency or mucosa hyperemia.

It is shown that in particular, 2-[(2-methoxy-5-chlorophenyl)azo]-1 H-imidazole and 2-[(2methoxy-5-bromophenyl)azo]-1 H-imidazole possess the diuretic activity about 10 times that of furosemide as a control, when applied to rats, and the other compounds are also higher in diuretic activity than furosemide. It is also seen that the azo compounds have an acute toxicity low enough to cause no problem in a usual application.

The following examples serve as an illustration of the present invention, but it should be understood that they are not intended at all in any sense to restrict the present invention thereto. In the examples, the unit "parts" is represented in parts by weight.

Example 1 To a solution of 5.1 parts of 4-chloro-2-amino-anisole and 7.6 parts of 35% hydrochloric acid in 50 parts of water was added 15 parts of water containing 2.2 parts of sodium nitrite at 0--5 OC, and then the diazotization reaction was carried out by stirring the mixture at O-S0C for 1 hour. The resulting diazonium salt solution was then added at 0--5 OC to a solution of 20.4 parts of imidazole, 1.7 parts of sodium hydroxide and 2.5 parts of sodium acetate in 1 50 parts of water, and the mixture was stirred at the same temperature for 1 hour to complete the coupling reaction, thereby forming a crude yellow-orange product. The crude product was filtered, washed with water, and dried at 60 C to provide 7.6 parts of the product.

This crude product (7 parts) was then recrystallized from n-propylalcohol to provide 4.9 parts of 2-[(2-methoxy-5-chlorophenyl)azo]-1 H-imidazole as a yellow-orange columnar crystalline substance. It melted at 205 C (decomposed), when measured in accordance with the designation of the Japanese Pharmacopeia and had a maximum ultraviolet absorption spectrum (AmaX) at 384 mm Elementary Analysis: C H N Cl Calculated (%) 50.75 3.83 23.68 14.98 Found (%) 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 were added to 50 parts of water. To this mixture was added 1 0 parts of water containing 1.38 parts of sodium nitrite at 0--5 OC, and then the mixture was stirred for 1 hour to effect diazotization.The resulting diazonium salt solution was then added at 0-5 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, and the coupling reaction was carried out by stirring the mixture for 1 hour. The yellow-orange azo compound precipitated in the reaction mixture was filtered, washed with water, and then dried at 60 C, thereby giving 4.3 parts of the crude azo compound.

The crude product (4 parts) was then recrystallized from n-butylacohol to provide 2.9 parts of 2 [(2-methoxy-5-fluorophenyl)azo] 1 H-imidazole as yellow-orange acicular crystalline substance. It melted at 204 C (decomposed), when measured in accordance with the designation of the Japanese Pharmacopeia and had a maximum ultraviolet absorption spectrum (w;lmaX) at 388 m Elementary Analysis: C H N F Calculated (%) 54.55 4.09 25.45 8.64 Found (%) 54.60 4.12 25.58 8.69 Example 3 To a solution of 4.04 parts of 4-bromo-2-amino-anisole and 5.2 parts of 35% hydrochloric acid in 60 parts of water was added 10 parts of water containing 1.38 parts of sodium nitrite at 0-5 C, and then the diazotization reaction was carried out by stirring the mixture at 0--5 OC for 1 hour. The resulting diazonium salt solution was then added at 0--5 OC to a solution of 9.53 parts of imidazole, 1.2 parts of sodium hydroxide and 1.64 parts of sodium acetate in 80 parts of water, and the mixture was stirred at the same temperature for 1 hour to complete the coupling reaction, thereby forming a crude yellow-orange product. The crude product was filtered and dried at 60 C to provide 5.1 parts of the product.

This crude product (4 parts) was then recrystallized from ethyl acetate to provide 3.2 parts of 2 [(2-methoxy-5-bromophenyl)azo]-1 H-imidazole as a yellow-orange acicular crystalline substance. It melted at 224.5 C (decomposed), when measured in accordance with the designation of the Japanese Pharmacopeia and had a maximum ultraviolet absorption spectrum (may) at 387 my.

Elementary Analysis: C H N Br Calculated (%) 42.70 3.20 19.93 28.44 Found (%) 42.71 3.27 19.90 28.39 Example 4 The procedure of one of the above examples was followed except for the type of the reactants and solvents thereby providing 2-[(2-methoxyphenyl)azo]-1 H-imidazole as a yellow columnar crystalline substance, m.p. 152--1530C.

Example 5 To a solution of 4.98 parts of4-iodo-2-amino-anisole and 5.2 parts of 35% hydrochloric acid in 70 parts of water was added 10 parts of water containing 1.38 parts of sodium nitrite at O5 C, and then the diazotization reaction was carried out by stirring the mixture at O5 C OC for 1 hour. The resulting diazonium salt solution was then added at O5 C 0 C to a solution of 10.89 parts of imidazole, 1.2 parts of sodium hydroxide and 1.64 parts of sodium acetate in 80 parts of water, and the mixture was stirred at the same temperature for 1 hour to complete the coupling reaction, thereby forming a crude yelioworange product. The crude product was filtered, washed with water, and dried at 60 C to provide 5.9 parts of the product.

This crude product (4.5 parts) was then column-chromatographed on silica gel to provide 3.5 parts of 2-[(2-methoxy-5-iodophenyl)azo] 1 H-imidazole as a yellow-orange columnar crystalline substance. It melted at 217.5 C (decomposed), when measured in accordance with the designation of the Japanese Pharmacopeia and had a maximum ultraviolet absorption spectrum (may) at 385 m Elementary Analysis: C H N Calculated (%) 36.59 2.74 17.07 38.69 Found (%) 36.61 2.70 17.09 38.61

Claims

1. A compound represented by the formula:

wherein X is hydrogen or halogen or an acid addition salt thereof.

2. The compound claimed in Claim 1, wherein the compound is 2-[(2-methoxy-5chlorophenyl)azo]-1 H-imidazole.

3. The compound claimed in Claim 1, wherein the compound is 2-[(2-methoxy-5bromophenyl)azo] 1 H-imidazole.

4. The compound claimed in Claim 1, wherein the compound is 2-2[(2-methoxy-5iodophenyl)azo] 1 H-imidazole.

5. The compound claimed in claim 1, wherein the compound is 2-[(2-methoxy-5 fluorophenyl)azo-1 H-imidazole.

6. The compound claimed in Claim 1, wherein the compound is 2-[(2-methoxyphenyl)azo]1 H midazole.

7. A process for preparing a compound of the formula:

wherein X is hydrogen or halogen, or an acid salt thereof, which comprises reacting a 2-methoxyaniline or a reactive derivative with a nitrite and hydrochloric acid and reacting the resulting diazonium compound with imidazole in the amount of from approximately 5 to 10 moles with respect to the diazonium compound to provide the compound of the above formula and, if desired, converting the compound of the above formula into an acid addition salt therof.

8. A compound as claimed in claim 1 and substantially as described in any one of the specific examples hereinbefore set forth.