GB2323595A

GB2323595A - Preparation of 2-Mercaptothiazole

Info

Publication number: GB2323595A
Application number: GB9816533A
Authority: GB
Inventors: Martin Charles Bowden
Original assignee: Zeneca Ltd
Current assignee: Syngenta Ltd
Priority date: 1998-07-29
Filing date: 1998-07-29
Publication date: 1998-09-30
Also published as: GB9816533D0

Abstract

A process for preparing 2-mercaptothiazole in which (a) 2-aminothazole is converted to the corresponding 2-diazonium salt, (b) the 2-diazonium salt is treated with a source of halide ions to produce a 2-halothiazole, and (c) the 2-halothiazole is reacted with a source of hydrosulfide ions to yield 2-mercaptothiazole.

Description

PREPARATION OF HETEROCYCLIC THIOLS This invention provides a simple process for preparing a heterocyclic thiol. More particularly it provides a process for preparing 2-mercaptothiazole.

2-Mercaptothiazole is a known compound which has a variety of uses as a chemical intermediate in the preparation of pharmaceuticals and agrochernicals and in the preparation of products used in the processing of rubber products. Previously described processes for its preparation involve the reaction of chloroacetaldehyde with ammonium dithiocarbamate but the yields obtained are unsatisfactory. In addition the manufacture of ammonium dithiocarbamate from carbon disulfide and liquid ammonia requires specialised gas handling and storage facilities.

The present invention provides an alternative and simple process avoiding the disadvantages of the known process in which 2-mercaptothiazole is prepared from the readily available 2-aminothiazole by conversion to the corresponding diazonium salt and reaction thereof with a source of halide ions to produce a 2-halothiazole which is subsequently reacted with a source of hydrosulfide ions to yield the required product.

Suitable sources of halide ions are alkali metal halides such as sodium and potassium halides, and preferred halides are chlorides and bromides. Suitable sources of hydrosulfide ions are alkali metal hydrosulfides such as sodium and potassium hydrosulfides.

In a preferred form the process of the invention 2-aminothiazole is converted to its diazonium salt which is treated with an alkali metal chloride to produce 2-chlorothiazole which is treated with an alkali metal hydrosulfide to yield 2-mercaptothiazole. This sequence is shown in the f & llowing scheme.

The process of the invention is illustrated by the following Example.

EXAMPLE This Example illustrates the preparation of 2-mercaptothiazole by the process of the invention.

(a) Conversion of 2-aminothiazole to its diazonium salt

Material Act. Wt. (g) Str. (%) 100% Wt MWt Moles Mole/ Mole 2-aminothiazole 10.0 97 9.7 100 0.097 1.0 H3P04 84.3 85 71.6 98 0.731 7.5 HNO3 28.4 70 19.9 63 0.316 3.3 NaNO2 8.0 97 7.8 69 0.112 1.2 NaCI 16.7 100 16.7 58.4 0.280 2.9 CuS04 16.7 98 16.4 160 0.100 1.0 NaOH 130ml 24 - - - - A 250ml 3-necked round bottomed flask was fitted with a thermometer, condenser and mechanical agitator. Orthophosphoric acid (84.3g) and 2-aminothiazole (10g) were added ( an exotherm producing a temperature rise of 35"C was observed) after which a further 10ml orthophosphoric acid added and the mixture was then warmed to 400C to dissolve all the substrate. The mixture was then cooled to 0 C and nitric acid (28.4g) was added. The reaction mass was then cooled further to -5 C, and sodiun nitrite (8g) was added in 5 portions over 20 minutes, then the reaction was stirred at -50C for 50 minutes.

(b) Preparation of 2-chlorothiazole A 500ml 3-necked round bottomed flask was fitted with a thermometer and mechanical agitator. Sodium chloride (16.7g), water (67ml) and copper sulfate (16.7g) were added and the mixture cooled to 10"C. The diazonium salt solution prepared in (a) above was added to the reactor by pipette, maintaining the temperature at 1 00C, then the mixture was allowed to warm to ambient over 1.5hr. The reaction mass pH was adjusted to 7 with sodium hydroxide solution, then the mixture was steam distilled. The distillate was extracted with diethyl ether (2x50ml), dried over anhydrous sodium sulfate and then concentrated by rotary evaporation to give the product (8.1 g, 62% yield).

'H nmr (CDC13): 7.25 (d, 1H, ArO, 7.60 (d, H, ArO.

MS: l19(M+), 79, 58, 45.

(c) Preparation of 2-Mercaptothiazole

Material Act. Wt. (g) Str. (%) 100% Wt MWt mMole Molel s Mole 2-Chlorothiazole 3.1 89 2.7 120 23 1.0 NaSH 5.5 72 1 4.2 56 75 3.3 KI 0.1 99 0.1 166 0.6 0.03 aqueous MeOH 25ml 80 - - - - conc. HCI 36 A 50ml round botoomed flask was fitted with a condenser, bubbler, thermometer and magnetic agitator. 2-Chlorothiazole (3.1g), sodium hydrosulphide (5.5g), potassium iodide (0.1 g) and aqueous methanol (25ml) were charged and the mixture was then heated to 700C and held for 24hr. The reaction was cooled to ambient, acidified with conc hydrochloric acid, then filtered to remove a brown solid. The filtrate was concentrated by rotary evaporation and the residue was then dissolved in dichloromethane (50ml). The DCM solution was dried (MgS04) and concentrated by rotary evaporation to give tge product (13) (2.3g, 74% yield).

'H nmr (CDC13): 6.75 (d, 1H, ArO, 7.10 (d, H, ArO, 12.5 (br s, 1H, ArSO.

13C nmr (CDC13): 115 (s), 128 (s), 190 (s).

MS: 117 (M+), 90, 72, 58, 44.

Claims

1. A process for preparing 2-mercaptothiazole in which (a) 2-aminothazole is converted to the corresponding 2-diazonium salt, (b) the 2-diazonium salt is treated with a source of halide ions to produce a 2-halothiazole, and (c) the 2-halothiazole is reacted with a source of hydrosulfide ions to yield 2-mercaptothiazole.

2. A process according to claim 1 in which the source of halide ions is an alkali metal halide.

3. A process according to claim 1 wherein the halide ions are chloride ions and the 2 halothiazole is 2-chlorothiazole.

4. A process according to claiml in which the source of hydrosulfide ions is an alkali metal hydrosulfide.