The present invention relates to an improved process for preparation of 2-aminothiophenol starting from 2-chloronitrobenzene.
This invention particularly relates to a process developed for the preparation of a stable adduct of 2-aminothiophenol from 2-chloronitrobenzene and sodium hydrogen sulfide uiilizing a base, without addition of any other stabilizers. This adduct has a longer shelf life and the air-sensitive thiol can be obtained by just warming the solid to 35-50 °C. In this process, the first reaction step is the exchange of chlorine against the hydrogen sulfide group, which is iollowed by reduction of the nitro group. The free aminothiophenol, however, cannot be isolated by simple neutralization of the alkaline solution. Hence it is isolated from the alkaline solutions by neutralization with a mineral acid in the presence of a water-soluble sulfite or disuifite controlling the temperature and pH of the solution. Even when excluding the oxygen of the air, quantitative oxidation occurs to yield 2,2'-diaminodiphenyl sulfide. To avoid this we have addcd base to form solid adduct which is stable for few hours even when it is exposed to air.
2-aminothiophenol is a versatile intermediate used extensively in industry as raw material for the production of medicines, agrochemicals, dyes and a variety of heterocyclic derivatives of synthetic importance. It is largely used as precursor for several biologically active molecules such as piperazine derivatives, which find therapeutic applications in many cardiovascular diseases, namely eschemic heart, thrombus, hypertension, etc. Similarly, benzothiazole derivatives (herbicide) and azophenothiazine, a valuable precursor for various pharmaceutically active substances, are prepared from 2-
aminothiophenol. It is an important reagent for a key step in the synthesis of Ranitidine. which is an H-2 receptor antagonist used in the treatment of ulcers and heartburn. Thiazepines, also derived from 2-aminothiophenol, are important ingredients for agricuitural and horticultural fungicides apart from being antihypertensive and antiviral agents. Phthalonitrile compound containing 2-aminothiophenol is employed in the production of phthalocyanine derivative, which is characterized as a near infrared ray absorbing colorant having a high light resistance and are suitable for making optical cards. organic photo-conductors, filters. heat ray shielding films, protecting spectacles, etc. 2-aminothiophenol is also used for the synthesis of anthraquinone and naphthaquinone-based pigments and dyes, which are particularly useful for electronic applications such as absorbent materials for laser beams, colorant for liquid crystals, etc. 2-arylbenzoxazoles and 2-arylbenzothiazoles prepared from 2-aminothiophenol are constituents of optical brighteners and fmd use in dyes, cosmetics and heat resistant fibers.
Reference may be made to the Japanese patent JP 07, 278, 100, 1995, wherein 2-aminothiophenols are prepared by alkali hydrolysis of 2-aminobenzothiazoles in presence of ethylene glycol. The inherent disadvantage is the usage of expensive 2-aminobenzothiazole as a starting material.
References may be made to the publications, Synth. Commun., 1997, 27, 1347, Synth. Commun., 1989, 19, 3143 and patent WO 96, 16,034, 1996 wherein reduction of
disulfides to thiols usmg reducing agent is carried out. The inherent disadvantage is the
usage of the expensive materials.
Keference may be made to Czech patent CS 265, 614, 1989, wherein hydrogenation of disulfide in the presence of metal sulfides and aqueous Na2CC>3 at 6 MPa was done to obtain 2-aminothiophenol. The inherent disadvantages are the use of metal salts and high pressure.
Reference may be made to the European patent, EP 409, 009, 1991, wherein halides were reacted with sulfides in aqueous medium and isolating the product with organic solvent at pH 4-8. The inherent disadvantages are the cumbersome workup procedure and use of high pressure.
Reference may be made to Japanese patent, JP 07, 188, 156, 1995, wherein
aminothiophenol is prepared by treating 2-mercaptobenzothiazole with caustic alkali at 200 °C in iron free reactors followed by acidic treatment of reaction products and distillation. The drawback is mat high temperature is needed for the reaction.
Reference may be made to a publication Synth. Commun., 1980, 10, 167, wherein aminobenzothiazole were diazotised and hydrolysed to give benzothiazoles, which on reduction with hydrazine resulted in the formation of thiol. The drawback is the multistep procedure.
Objects of the invention
Flie main object of the present invention is an improved process for the preparation and isolation of 2-aminothiophenoi by forming a stable adduct of 2-aminothiophenol from 2-chloronitroben/ene and sodium hydrogen sulfide utilizing a base, without addition of any other stabilizers. This solid adduct has a longer shelf life and the air-sensitive thiol can be obtained by just warming the solid to 35-50 °C. The reaction is advantageously carried out by introducing the ortho compound together with water into the stirring apparatus while working under a protective inert gas, preferably under nitrogen atmosphere, and the water soluble sulfide or hydrogen sulfide are added to the mixture in usual manner at temperatures in the range from 80 to 95 °C within a period of 4-6 hours. After cooling, water soluble alkali sulfite and organic solvent selected from petroleum ether, benzene, toluene, xylene, etc, was added and the neutralization was carried out with mineral acid selected from sulfuric acid, phosphoric acid, hydrohalous acid, etc. adjusting the pH between 5 to 7. After neutralization the organic phase is separated and concentrated to around 50-100 ml and a base such as pyridine, triethyl amine, tributyl amine is added to give solid adduct which on further warming to temperature between 30 to 50°C gives the desired product.
Accordingly, the present invention provides an improved process for the preparation of 2-
aminothiophenol from 2-chloronitobenzene which comprises introducing 2-
chloronitrobenzene together with water into a stirring apparatus under a protective inert gas, preferably under nitrogen atmosphere, adding water soluble sulfide or hydrogen sulfide to the said mixture at temperature in the range of 80 to 95°C within a period of 4-6 hours, after cooling the said reaction mixture adding a water soluble alkali sulfite and an organic solvent selected from the group constitution of petroleum ether, benzene, toluene, xylene, followed by neutralization of the solution with a mineral acid selected from sulfuric acid, phosphoric acid or hydrochloric acid, at pH between 5 to 7, separating organic phase, and concentrating the organic phase, adding a base selected from pyridine, triethyl amine, tributyl amine to obtain the solid adduct, warming the said solid adduct to temperature between 30 to 50°C to obtain 2-aminothiophenol.
In an embodiment of the present invention, the said process for the preparation of the solid adduct avoids the usage of stabilizer, since the said adduct as obtained above can be stored from few days as such.

In another embodiment of the present invention, workup time is reduced and the formation of disulfides is avoided.
In yet another embodiment of the present invention, the solvents selected for the workup process is petroleum ether, benzene, toluene or xylene.
In still another embodiment of the present invention, the base used for the formation of adduct is selected from the known group consisting of triethyl amine, tributyl amine, pyridine, etc.
In further embodiment of the present invention, the reactions are preferably, effected at a known temperature in the range of O to 100 °C for a period 2 to 24 h.
In yet another embodiment of the present invention, the product is prepared in one-stage process starting from o-chloronitrobenzene.
Detailed Description of the Invention:
An improved process is developed for the isolation and purification of 2-aminothiophenol
as a stable adduct from 2-chloronitrobenzene and sodium hydrogen sulfide utilizing a
base, without addition of any other stabilizers. This adduct has a longer shelf life and the
air-sensitive thiol can be obtained by just warming the solid to 35-50 °C. The reaction is
advantageously carried out by introducing the compound together with water into
the stirring apparatus while working under a proiective inert gas, preferably under nitrogen atmosphere, and the water soluble sulfide or hydrogen sulfide are added to the mixture in usual manner at temperatures in the range from 80 to 95 °C within a period of 4-6 hours. After cooling, water soluble alkali sulfite such as sodmm sulfite and organic solvent selected from petroleum ether, benzene. toluene, xylene. etc, was added and the neutralization was carried out with mineral acid selected from sulfuric acid, phosphoric acid. hydrohalous acid, etc. adjusting the pH between 5 to 7. After neutralization the organic phase is separated and concentrated to around 50-100 ml and bases such as r yndine, triethyl amine, tributyl amine is added to give solid adduct which on rurther warmmg to temperature between 30 to 50 °C gives the desired product.
The usage of stabilizer is avoided since adduct as synthesized above can be stored for few days as such. The workup time is also reduced and the formation of disulfides is avoided. The solvent for the workup is selected from petroleum ether, benzene, toluene, xylene, etc, and the neutralization was carried out with mineral acid selected from sulfuric acid, phosphoric acid, hydrohalous acid, etc. adjusting the pH between 5 to 7. The base for the formation of solid adduct is selected from the known group of pyridine, triethyl amine, and tributyl amine.
Scientific Explanation:
In the present invention, an improved process is developed for the isolation and puriftcation of 2-aminothiophenol as a stable adduct from 2-chloronitroben/ene and
sodium hydrogen sulfide utilizing a base. without addition of any other stabilizers. This adduct has a longer shelf life and the air-sensitive thiol can be obtained by just warming the solid to 35-50 °C.
In this process, the first reaction step is the exchange of chlorine against the hydrogen sulfide group, which is followed by reduction of the nitro group. The o-aminothiophenol in alkaline solution can be rurther reacted in this medium by various methods. The free aminothiophenol, however, cannot be isolated by simple neutralization of the alkaline solution. Instead it can be isolated from the alkaline solutions by neutralization with a mineral acid in the presence of a water-soluble sulfite or disulfite controlling the temperature and pH of the solution.
Even when excluding the oxygen of the air, quantitative oxidation occurs to yield 2,2'-diaminodiphenyl sulfide. To avoid this an amine is added to form adduct which is stable for few days even on exposure to air. The air-sensitive thiol can be obtained by just warming the solid to 35-50 °C. Ortho aminothiophenol compounds are important intermediates for the preparation of dyestuffs, pharmaceutics and herbicides. Thus this invention offers the best techno-economic route for the synthesis of o-aminothiophenol adducts which has a longer shelf life.
An improved process is developed for the isolation and purification of 2-aminothiophenol as a solid stable adduct from 2-chloronitrobenzene and sodium hydrogen sulfide utilizing
a base. The following example is given by way of illustration of the present invention and therefore should not be construed to Urnit the scope of the invention.
Preparation of 0-aminothiophenol:
(Figure Removed)
o-chloronitrobenzene (197g, 1.25mol) and water (125 ml) were introduced into a 4-necked 5 litre round-bottomed flask. The mixture was heated to 85 °C while stirring and at that temperature 27% aqueous sodiuin hydiogeii sulfide (967 ml, 4.65 mol) was added within 4 h under nitrogen atmosphere, and subsequently within 2 h, again 27% aqueous sodium hydrogen sulfide (967 ml, 4.65 mol) was added drop wise to the reaction mixture. To complete the reaction, stirring was continued for 8 h at a temperature of 85 °C. The nitrogen atmosphere was maintained to proiect the following reaction steps. After cooling to room temperature aqueous sodium sulfite solution (250 g in 500 ml of water) and toluene (500 ml) was added successively and the pH was adjusted at 6 with 1.1 litre of 30% con. HC1, maintaining the temperature between 5 to 10 °C within 3 hours, while stirring continuously. After precipitation and separation of organic phase, the aqueous mother liquor was stirred with 750 ml of petroleum ether and collected. The combined organic phases was concentrated on rotavapor to 250 ml and triethyl amine (300 ml) was
added to form solid adduct which is separated by filtration. This solid (216 g) on warming to 40 °C gives o-aminothiophenol (l 16 g).
Yield : 74 % , calculated with respect to o-chloronitrobenzene. The main advantages of the present invention are:
1. An improved process is developed for the isolation and purification of 2-
aminothiophenol as a solid stable adduct from 2-chloronitrobenzene and sodium
hydrogen sulfide utilizing a base, without addition of any other stabilizers.
2. The solid adduct is stable and has a longer shelf life. The air-sensitive thiol can
be obtained by just warming the solid to 35-50 °C.
3. In the normal workup even when excluding the oxygen of the air, quantitative
oxidation occurs to yield 2,2'-diaminodiphenyl sulfide. The solid adduct so formed is
stable for few days even on exposure to air.
4. The yields are good.
5. The work-up procedure is simple and oxidation to disulfide is avoided.
6. The solid adduct can be conveniently stored for longer periods of time.
7. The process is economical.

We Claim:
1. An improved process for the preparation of 2-aminothiophenol from 2-chloronitobenzene which comprises introducing 2-chloronitrobenzene together with water into a stirring apparatus under a protective inert gas, preferably under nitrogen atmosphere, adding water soluble sulfide or hydrogen sulfide to the said mixture at temperature in the range of 80 to 95°C within a period of 4-6 hours, after cooling the said reaction mixture adding a water soluble alkali sulfite and an organic solvent selected from the group constitution of petroleum ether, benzene, toluene, xylene, followed by neutralization of the solution with a mineral acid selected from sulfuric acid, phosphoric acid or hydrochloric acid, at pH between 5 to 7, separating organic phase, and concentrating the organic phase, adding a base selected from pyridine, triethyl amine, tributyl amine to obtain the solid adduct, warming the said solid adduct to temperature between 30 to 50°C to obtain 2-aminothiophenol.
2. A process as claimed in claim 1, wherein the product is prepared in one-stage process starting from o-chloronitrobenzene.
3. An improved process for the preparation of 2-aminothiophenol from 2-chloronitrobenzene, substantially as herein described with reference to the examples.