CA1139316A - Process for preparing 1,2-bis (2-aminophenylthio) ethane - Google Patents
Process for preparing 1,2-bis (2-aminophenylthio) ethaneInfo
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- CA1139316A CA1139316A CA000354682A CA354682A CA1139316A CA 1139316 A CA1139316 A CA 1139316A CA 000354682 A CA000354682 A CA 000354682A CA 354682 A CA354682 A CA 354682A CA 1139316 A CA1139316 A CA 1139316A
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
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Abstract
27,745 TITLE OF THE INVENTION
PROCESS FOR PREPARING 1,2-BIS(2-AMINOPHENYLTHIO)ETHANE
ABSTRACT OF THE DISCLOSURE
A process for preparing 1,2-bis(2-aminophenylthio)-ethane is disclosed wherein the reaction is conducted in the presence of a reducing agent, a water-immiscible organic solvent and from about 0.40 to about 0.49 mole of 1,2-di-chloooethane per mole of 2-aminobenzenethiol is employed.
PROCESS FOR PREPARING 1,2-BIS(2-AMINOPHENYLTHIO)ETHANE
ABSTRACT OF THE DISCLOSURE
A process for preparing 1,2-bis(2-aminophenylthio)-ethane is disclosed wherein the reaction is conducted in the presence of a reducing agent, a water-immiscible organic solvent and from about 0.40 to about 0.49 mole of 1,2-di-chloooethane per mole of 2-aminobenzenethiol is employed.
Description
li39316 TITLE O THE INVENTION
PROCESS FOR PREPARING 1,2-BIS(2-AMINOPHE~YLT~IO)ETHANE
BACKGROUND OF THE INVENTION
The preparation of 1,2-bis(2-aminophenylthio)ethane ~ 2 2 ~
by the reaction of 1,2-dichloroethane with the sodium salt of 2-aminobenzenethiol is disclosed by Hirosawa and Lee in U.S. Patent 3,920,617. However, the crude reaction product obtained thereby has been found to melt at 72-74C, versus 76.5-77C for the pure compound. The product obtained in Example 1 of U.S. Patent 3,920,617 has to be recrystallized three times to obtain a product having a melting point of 75.5-76.5C. The extra procedural steps entail a necessary loss in yield due to the retention of some of the product in the mother liquor. Multiple recrystallization is also laborious and hazardous due to the handling of the necessary solvents~
Furthermore, some of the impurities which are present in the curing agent 1,2-bis(2-aminophenylthio)ethane when it is prepared by methods of the prior art are yellow in color and cause a strong coloration in urethane polymers cured therewith. While the colors may not be considered deleterious in polymers used for mechanical goods, wheels, printing rollers and the like, there are many uses for ure-thane polymers where clear light colors are very desirable, if not required, and thus a lighter-colored, purer grade of 113'3~`16 the cur~tive, 1,2-bis(2-a~inophenylthio)ethane, is nee~P~ in the industry.
Additionally, the impure products made by methods of the prior art oontain some i~purity or impurities which are very undesirable because they cause the product to show a positive test fox mutagenicity, when tested via the well kncwn Ames Test with salmDnella ~acteria strains (s,ee Ames et al., Mutation Re~ nch 31: 347-364 (1975)). This mutagenic pr~perty of chemical products is an important factor in determining their acoeptability for use in industry.
The potential health hazard to persons employed to handle mutagenic chemicals requires elaborate precautions to prevent any exposure to the products, for mutagenicity is presumed to indicate the presence of a carcinogen.
SUMM~RY OF T9E INUENTION
In aco~rdan oe with the pres~ent invention, there is provided an improved prooess for pre~aring 1,2-bis(2-amlno-phenylthio)ethane w~n~in 1,2-dichlornethane is reacted with a solution of an alkali metal salt of 2-amino-benzenethiol in water at an elevated temperature, in the presenoe of a water-immiscible organic solvent, a suitable phase-transfer catalyst and a reduGLng agent. The resultant aqueous phase is separated from the resulting twc-phase mixture, and the product is recovered from the organic phase. m e reducing agent is soluble in water, stable in water and capable of reducing at a pH of about 9 or above. F m m about 0.40 to about 0.49 mDle of 1,2-dichloroethane, per m~le of 2-aminobenzenethiol aLkali metal salt is employed.
Preferably, thle process is carried out in the presen oe of about 0.02 to 0.05 mDle of scdium hydrosulfite per mDle of 1,2-dichloroethane as the reducing agent, utilizing about 0.44 to 0.47 mDle of 1,2-dichloroethane per mDle of 2-a~inobenzenethiol alkali metal salt.
The proaess is mDre preferably carried out with the additional steps of w~shing the reoovered organic phase w~ith a dilute a~ueous alkaline solution B f a reducing agent to rlemDve any residual oolored impurities and separating 3 ~
the res~ltant aIkaline aqueous phase before reoovering the 1,2-bis(2-a~ino-phenylthio)ethane from the organic phase.
- 2a -,~ ~
li3.'~16 Optionally, the process may be carried out without the presence of a reducing agent in the initial reaction mixture but with the additional steps of washing the recov-ered organic phase with an aqueous alkaline solution of a reducing agent and separating the alkaline aqueous phase before recovering the 1,2-bis(2-aminophenylthio)ethane from the organic phase.
In the improved processes of this invention, 1,2-bis(2-aminophenylthio)ethane of high purity is produced in essentially quantitative yield using simple steps and mild conditons~ No solvent recrystallization with its attendant yield loss is needed to obtain a product which is very light in color, has a melting range equal to that previously ob-tained only after recrystallization, and, furthermore, does not show a positive test for mutagenicity in the "Ames" test.
DESCRIPTION OF THE INVENTION
INCLUDING PREFERRED EMBODIMENTS
. . .
In carrying out the process of this invention, 1,2-dichloroethane is reacted with an aqueous solution of an alkali metal salt of 2-aminobenzenethiol in the presence of an inert water-immiscible organic solvent, a reducing agent, and a phase-transfer catalyst while stirring the two-phase mixture below the boiling point of the 1,2-dichloroethane.
It is critical that the 1,2-dichloroethane be em-ployed at a range from about 0.40 to about 0.49, preferably from about 0.44 to about 0~47, mole per mole of 2-a~inoben-zenethiol alkali metal salt in order that a product of high quality be obtained.
Suitable inert water-immiscible organic solvents include aliphatic hydrocarbons such as heptane and cyclo-hexane; benzene and its homologues and their halogenated derivatives, and the like. Hydrocarbons and halogenated hydrocarbons of the benzene series, especially toluene and monochlorobenzene, have been found to be particularly suit-able solvents In order to obtain the superior results ofthis improved process, it is desirable to have some or all of the water-immiscible solvent present during the reaction 113~316 period, and to vigorously agitate the two-phase reaction mixture. Some of the solvent may be added after the reaction is completed in order to facilitate separation of the product from the aqueous solution of salts.
It has been found that the inclusion of about 0.01 to about 0.1, preferably about 0.02 to about 0.05 mole, of a reducing agent in the initial reaction mixture reduces the formation of colored by-products in the product. Suitable reducing agents are those which are soluble in water, stable in water and capable of reducing at a pH of 9 or higher and include sodium hydrosulfite, sodium sulfite, sodium bisulfite, and the like.
The inclusion of a phase-transfer catalyst, about 0.0001 to about 0.005 mole, preferably about 0.001 to about 0.003 mole, per mole of 1,2-dichloroethane, promotes a rapid and complete reaction between the reactants. Suitable phase-transfer catalysts include symmetrical quaternary ammonium and phosphonium salts such as:
tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, tetra-n-butylammonium iodide, tetra-n-butylphosphonium bromide, tetra-n-butylphosphonium chloride, tetra-n-butylphosphonium iodide, tetra-n-hexylammonium iodide, and tetra-n-hexylammonium chloride.
Tetra-n-butylphosphonium bromide, chloride, and iodide are particularly effective phase-transfer catalysts in the process of this invention.
We have found that reaction temperatures below the reflux temperature of the reaction mixture are particularly beneficial. During the early stages of the reaction, it is desirable to maintain the reaction temperature below about B7C, the boiling point of 1,2-dichloroethane. After several hours in the range of about 75-85C, the temperature is increased to about 95-100C (the reaction mixture at this time refluxes at 101-103C). and held thereat for about one hour. The use of temperatures below reflux allows utiliza-tion of simpler equipment and a saving in energy.
The water-immiscible phase containing the reaction product is separated from the aqueous phase and the product is recovered by evaporating the solvent.
Preferably, the water-immiscible phase is washed with an alkaline aqueous solution of a reducing agent to remove any colored impurities before recovering the product from the organic phase. More preferably, the wash solution has a pH of about 11-12 and a temperature of about 80-90C, and the reducing agent is sodium hydrosulfite.
The product (m.p. 74-76C), which is obtained in a yield about 97% of theoretical, is very light in color and can be used as a polyurethane curing agent without further puri-fication. Most importantly, the product obtained is non-mutagenic.
The following examples are set forth for purposes of illustration only and are not to be construed as limitations on the present invention except as set forth in the appended claims. All parts and percentages are by weight unless other-wise indicated. All melting points were measured in a Hersh-berg apparatus with a heating rate of 1C per minute.
Example 1 In the following example, 0.47 mole of 1,2-dichloro-ethane is used per mole of 2-aminobenzenethiol sodium salt.
A solution (657 mls) of the sodium salt of 2-amino-benzenethiol (1.40 moles) in water is charged to a suitable reaction vessel equipped with a mechanical stirrer, thermo-meter, reflux condenser, addition funnel, and heating and cooling means, along with monochlorobenzene (100 mls), sodium hydrosulfite (4.5 grams; 0.0214 mole) and tetra-n-butyl-phosphonium bromide (0.30 grams; 0.00088 mole), and the re-sulting mixture is stirred vigorously and heated to 85C.
While maintaining the temperature at 85C, 1,2-dichloroethane (~5.0 grams; 0.65~ mole) is added over a period of 29 minutes.
The reaction mixture is stirred vigorously at 85C for an additional 2 1/2 hours, heated to 100C and held thereat for ~l~3~
one hour and then cooled to 85C. The resultant reaction mixture is allowed to settle and the aqueous phase is separ-ated therefrom~ The organic phase is then washed with water (300 mls) at 80C containing sodi-Im hydrosulfite (0.5 gram) and sodium hydroxide (0.2 gram). The water wash layer is then separated and the organic phase is concentrated at about gO-100C under a pressure of about 1-20 mm of mercury, fin-ishing under a pressure of about 1-5 mm. The molten product is then spread in a thin layer on a flat glass dish to solidify and give off white-colored flakes of 1,2-bis(2-aminophenylthio)ethane (174.0 grans; 96% of theoretical;
m.p. 74.3-75.6C).
Example 2 In the following example, 0.41 mole of 1,2-dichloro-ethane is used Per mole of 2-aminobenzenethiol sodium salt.
-A solution (3600 mls) of the sodium salt of 2-amino-benzenethiol (6.67 moles) is prepared by hydrolyzing benzo-thiazole in water at 150-175C, using 2.2 moles of sodium hydroxide per mole of benzotriazole. The solution is cooled to 40-50C and charged to a suitable reaction vessel, equipped as described in Example 1, along with monochlorobenzene (450 mls), sodium hydrosulfite (15 grams, 0.0714 mole) and tetra-n-butylphosphonium bromide (1.25 grams; 0.0037 mole).
The resulting mixture is stirred vigorously and 1,2-dichloro-ethane (273 grams; 2.76 moles) is added over a period of 30minutes while maintaining the temperature at about 76-78C.
The temperature is then raised to 80-81C and stirring is continued for an additional 2 1/2 hours, after which it is raised to 96-97C and held thereat for one hour. The re-action mixture is allowed to settle, the aqueous phase isseparated therefrom and the organic phase is washed with water (1200 mls) at 80-85C containing sodium hydrosulfite (8 grams) and sodium hydroxide (16 grams). The water wash layer is then separated and the organic phase is concentrated and processed as described in Example 1. 1,2-Bis(2-amino-phenylthio)ethane is obtained as very light, off-white flakes (732.7 grams; 96~ of theoretical; m.p. 74-75.8C), after flak-113,'~;~16 ing on a stainless steel dip-fed drum flaker.
Example 3 (Comparative) In the following example, 0.525 mole of 1,2-di-chloroethane is used per mole of 2-aminobenzenethiol sodium salt~
The procedure of Example 1 is followed using a solu-tion (613 mls) of the sodium salt of 2-aminobenzenethiol (1.20 moles) in water, monochlorobenzene (100 mls), sodium hydrosulfite (3 grams; 0.0143 mole) and tetra-n-butylphos-phonium bromide (0.20 gram). The 1,2-dichloroethane (62.5 grams; 0.63 mole) is added at 85C over 30 minutes and the mixture is ~ept at 85C for an additional 30 minutes, then heated to 95C, stirred thereat for one hour, heated to 100C, and stirred thereat for an additional hour. The organic layer is separated by decantation and washed with water (200 mls) at 80C containing sodium sulfhydrate (1 gram) and sodium hydroxide (1 gram) for 15 minutes. After separating the wash liquor, the organic phase is concen-trated and processed as described in Example 1 to obtain 1,2-bis(2-aminophenylthio)ethane in the form of a tan solid (163.7 grams; b8.7% of theoretical; m.p. 72.3-74.3C). The product turned brown after storage at ambient conditions for 8 months.
Example 4 (Comparative) In the following example, 0.523 mole of 1,2-dithloro-ethane is employed per mole of 2-aminobenzenethiol A preparation is carried out in the manner of Exam-ple 2 utilizing a solution (10.2 liters) in water of the sodium salt of 2-aminobenzenethiol obtained by the hydrolysis of benzothiazole (2433~4 grams; 18.0 moles) in water with 2.2 moles of sodium hydroxide per mole of benzothiazole. The resulting solution is cooled to 40-50C and charged to a suitable reaction vessel equipped as previously described, along with monochlorobenzene (1.38 liters), sodium hydrosul-fite (62 grams; 0.295 mole), and tetra-n-butylphosphonium bromide (3.4 grams; 0.01 mole). The two-phase mixture is stirred vigorously at 85C and 1,2-dichloroethane (930 grams;
113~
9.42 moles) is added over a period of 90 minutes while main-taining the temperature at 85C.
After the completion of the addition of 1,2-dichloro-ethane, the reaction mixture is heated at 100C for 2 hours, and another liter of monochlorobenzene is added to the re-action mixture before cooling it to 85C and separating the aqueous layer. The residual organic layer is washed with water (3.1 liters) at 85C and separated by decantation.
After separation from the wash liquor, the organic solution is evaporated under vacuum, as previously described, to re-move the solventO The molten product solidifies to form a tan product (2367.5 grams; 95.1% of theoretical; m.p. 73.4-74.4C).
A comparison was made of the results of tests for mutagenicity on the products made in Examples 1-4 along with the molar ratio of the reactants, 1,2-dichloroethane ("A") and 2-aminobenzenethiol ("B"). The results obtained, when tested with the bacterial strains and methods of Ames et al., are s~own below:
20 Product Percent Melting of Molar of Range Muta-Example Ratio A/B*Stoichiometricof Product genicity 1 0.47 94 74.3-75.6C negative
PROCESS FOR PREPARING 1,2-BIS(2-AMINOPHE~YLT~IO)ETHANE
BACKGROUND OF THE INVENTION
The preparation of 1,2-bis(2-aminophenylthio)ethane ~ 2 2 ~
by the reaction of 1,2-dichloroethane with the sodium salt of 2-aminobenzenethiol is disclosed by Hirosawa and Lee in U.S. Patent 3,920,617. However, the crude reaction product obtained thereby has been found to melt at 72-74C, versus 76.5-77C for the pure compound. The product obtained in Example 1 of U.S. Patent 3,920,617 has to be recrystallized three times to obtain a product having a melting point of 75.5-76.5C. The extra procedural steps entail a necessary loss in yield due to the retention of some of the product in the mother liquor. Multiple recrystallization is also laborious and hazardous due to the handling of the necessary solvents~
Furthermore, some of the impurities which are present in the curing agent 1,2-bis(2-aminophenylthio)ethane when it is prepared by methods of the prior art are yellow in color and cause a strong coloration in urethane polymers cured therewith. While the colors may not be considered deleterious in polymers used for mechanical goods, wheels, printing rollers and the like, there are many uses for ure-thane polymers where clear light colors are very desirable, if not required, and thus a lighter-colored, purer grade of 113'3~`16 the cur~tive, 1,2-bis(2-a~inophenylthio)ethane, is nee~P~ in the industry.
Additionally, the impure products made by methods of the prior art oontain some i~purity or impurities which are very undesirable because they cause the product to show a positive test fox mutagenicity, when tested via the well kncwn Ames Test with salmDnella ~acteria strains (s,ee Ames et al., Mutation Re~ nch 31: 347-364 (1975)). This mutagenic pr~perty of chemical products is an important factor in determining their acoeptability for use in industry.
The potential health hazard to persons employed to handle mutagenic chemicals requires elaborate precautions to prevent any exposure to the products, for mutagenicity is presumed to indicate the presence of a carcinogen.
SUMM~RY OF T9E INUENTION
In aco~rdan oe with the pres~ent invention, there is provided an improved prooess for pre~aring 1,2-bis(2-amlno-phenylthio)ethane w~n~in 1,2-dichlornethane is reacted with a solution of an alkali metal salt of 2-amino-benzenethiol in water at an elevated temperature, in the presenoe of a water-immiscible organic solvent, a suitable phase-transfer catalyst and a reduGLng agent. The resultant aqueous phase is separated from the resulting twc-phase mixture, and the product is recovered from the organic phase. m e reducing agent is soluble in water, stable in water and capable of reducing at a pH of about 9 or above. F m m about 0.40 to about 0.49 mDle of 1,2-dichloroethane, per m~le of 2-aminobenzenethiol aLkali metal salt is employed.
Preferably, thle process is carried out in the presen oe of about 0.02 to 0.05 mDle of scdium hydrosulfite per mDle of 1,2-dichloroethane as the reducing agent, utilizing about 0.44 to 0.47 mDle of 1,2-dichloroethane per mDle of 2-a~inobenzenethiol alkali metal salt.
The proaess is mDre preferably carried out with the additional steps of w~shing the reoovered organic phase w~ith a dilute a~ueous alkaline solution B f a reducing agent to rlemDve any residual oolored impurities and separating 3 ~
the res~ltant aIkaline aqueous phase before reoovering the 1,2-bis(2-a~ino-phenylthio)ethane from the organic phase.
- 2a -,~ ~
li3.'~16 Optionally, the process may be carried out without the presence of a reducing agent in the initial reaction mixture but with the additional steps of washing the recov-ered organic phase with an aqueous alkaline solution of a reducing agent and separating the alkaline aqueous phase before recovering the 1,2-bis(2-aminophenylthio)ethane from the organic phase.
In the improved processes of this invention, 1,2-bis(2-aminophenylthio)ethane of high purity is produced in essentially quantitative yield using simple steps and mild conditons~ No solvent recrystallization with its attendant yield loss is needed to obtain a product which is very light in color, has a melting range equal to that previously ob-tained only after recrystallization, and, furthermore, does not show a positive test for mutagenicity in the "Ames" test.
DESCRIPTION OF THE INVENTION
INCLUDING PREFERRED EMBODIMENTS
. . .
In carrying out the process of this invention, 1,2-dichloroethane is reacted with an aqueous solution of an alkali metal salt of 2-aminobenzenethiol in the presence of an inert water-immiscible organic solvent, a reducing agent, and a phase-transfer catalyst while stirring the two-phase mixture below the boiling point of the 1,2-dichloroethane.
It is critical that the 1,2-dichloroethane be em-ployed at a range from about 0.40 to about 0.49, preferably from about 0.44 to about 0~47, mole per mole of 2-a~inoben-zenethiol alkali metal salt in order that a product of high quality be obtained.
Suitable inert water-immiscible organic solvents include aliphatic hydrocarbons such as heptane and cyclo-hexane; benzene and its homologues and their halogenated derivatives, and the like. Hydrocarbons and halogenated hydrocarbons of the benzene series, especially toluene and monochlorobenzene, have been found to be particularly suit-able solvents In order to obtain the superior results ofthis improved process, it is desirable to have some or all of the water-immiscible solvent present during the reaction 113~316 period, and to vigorously agitate the two-phase reaction mixture. Some of the solvent may be added after the reaction is completed in order to facilitate separation of the product from the aqueous solution of salts.
It has been found that the inclusion of about 0.01 to about 0.1, preferably about 0.02 to about 0.05 mole, of a reducing agent in the initial reaction mixture reduces the formation of colored by-products in the product. Suitable reducing agents are those which are soluble in water, stable in water and capable of reducing at a pH of 9 or higher and include sodium hydrosulfite, sodium sulfite, sodium bisulfite, and the like.
The inclusion of a phase-transfer catalyst, about 0.0001 to about 0.005 mole, preferably about 0.001 to about 0.003 mole, per mole of 1,2-dichloroethane, promotes a rapid and complete reaction between the reactants. Suitable phase-transfer catalysts include symmetrical quaternary ammonium and phosphonium salts such as:
tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, tetra-n-butylammonium iodide, tetra-n-butylphosphonium bromide, tetra-n-butylphosphonium chloride, tetra-n-butylphosphonium iodide, tetra-n-hexylammonium iodide, and tetra-n-hexylammonium chloride.
Tetra-n-butylphosphonium bromide, chloride, and iodide are particularly effective phase-transfer catalysts in the process of this invention.
We have found that reaction temperatures below the reflux temperature of the reaction mixture are particularly beneficial. During the early stages of the reaction, it is desirable to maintain the reaction temperature below about B7C, the boiling point of 1,2-dichloroethane. After several hours in the range of about 75-85C, the temperature is increased to about 95-100C (the reaction mixture at this time refluxes at 101-103C). and held thereat for about one hour. The use of temperatures below reflux allows utiliza-tion of simpler equipment and a saving in energy.
The water-immiscible phase containing the reaction product is separated from the aqueous phase and the product is recovered by evaporating the solvent.
Preferably, the water-immiscible phase is washed with an alkaline aqueous solution of a reducing agent to remove any colored impurities before recovering the product from the organic phase. More preferably, the wash solution has a pH of about 11-12 and a temperature of about 80-90C, and the reducing agent is sodium hydrosulfite.
The product (m.p. 74-76C), which is obtained in a yield about 97% of theoretical, is very light in color and can be used as a polyurethane curing agent without further puri-fication. Most importantly, the product obtained is non-mutagenic.
The following examples are set forth for purposes of illustration only and are not to be construed as limitations on the present invention except as set forth in the appended claims. All parts and percentages are by weight unless other-wise indicated. All melting points were measured in a Hersh-berg apparatus with a heating rate of 1C per minute.
Example 1 In the following example, 0.47 mole of 1,2-dichloro-ethane is used per mole of 2-aminobenzenethiol sodium salt.
A solution (657 mls) of the sodium salt of 2-amino-benzenethiol (1.40 moles) in water is charged to a suitable reaction vessel equipped with a mechanical stirrer, thermo-meter, reflux condenser, addition funnel, and heating and cooling means, along with monochlorobenzene (100 mls), sodium hydrosulfite (4.5 grams; 0.0214 mole) and tetra-n-butyl-phosphonium bromide (0.30 grams; 0.00088 mole), and the re-sulting mixture is stirred vigorously and heated to 85C.
While maintaining the temperature at 85C, 1,2-dichloroethane (~5.0 grams; 0.65~ mole) is added over a period of 29 minutes.
The reaction mixture is stirred vigorously at 85C for an additional 2 1/2 hours, heated to 100C and held thereat for ~l~3~
one hour and then cooled to 85C. The resultant reaction mixture is allowed to settle and the aqueous phase is separ-ated therefrom~ The organic phase is then washed with water (300 mls) at 80C containing sodi-Im hydrosulfite (0.5 gram) and sodium hydroxide (0.2 gram). The water wash layer is then separated and the organic phase is concentrated at about gO-100C under a pressure of about 1-20 mm of mercury, fin-ishing under a pressure of about 1-5 mm. The molten product is then spread in a thin layer on a flat glass dish to solidify and give off white-colored flakes of 1,2-bis(2-aminophenylthio)ethane (174.0 grans; 96% of theoretical;
m.p. 74.3-75.6C).
Example 2 In the following example, 0.41 mole of 1,2-dichloro-ethane is used Per mole of 2-aminobenzenethiol sodium salt.
-A solution (3600 mls) of the sodium salt of 2-amino-benzenethiol (6.67 moles) is prepared by hydrolyzing benzo-thiazole in water at 150-175C, using 2.2 moles of sodium hydroxide per mole of benzotriazole. The solution is cooled to 40-50C and charged to a suitable reaction vessel, equipped as described in Example 1, along with monochlorobenzene (450 mls), sodium hydrosulfite (15 grams, 0.0714 mole) and tetra-n-butylphosphonium bromide (1.25 grams; 0.0037 mole).
The resulting mixture is stirred vigorously and 1,2-dichloro-ethane (273 grams; 2.76 moles) is added over a period of 30minutes while maintaining the temperature at about 76-78C.
The temperature is then raised to 80-81C and stirring is continued for an additional 2 1/2 hours, after which it is raised to 96-97C and held thereat for one hour. The re-action mixture is allowed to settle, the aqueous phase isseparated therefrom and the organic phase is washed with water (1200 mls) at 80-85C containing sodium hydrosulfite (8 grams) and sodium hydroxide (16 grams). The water wash layer is then separated and the organic phase is concentrated and processed as described in Example 1. 1,2-Bis(2-amino-phenylthio)ethane is obtained as very light, off-white flakes (732.7 grams; 96~ of theoretical; m.p. 74-75.8C), after flak-113,'~;~16 ing on a stainless steel dip-fed drum flaker.
Example 3 (Comparative) In the following example, 0.525 mole of 1,2-di-chloroethane is used per mole of 2-aminobenzenethiol sodium salt~
The procedure of Example 1 is followed using a solu-tion (613 mls) of the sodium salt of 2-aminobenzenethiol (1.20 moles) in water, monochlorobenzene (100 mls), sodium hydrosulfite (3 grams; 0.0143 mole) and tetra-n-butylphos-phonium bromide (0.20 gram). The 1,2-dichloroethane (62.5 grams; 0.63 mole) is added at 85C over 30 minutes and the mixture is ~ept at 85C for an additional 30 minutes, then heated to 95C, stirred thereat for one hour, heated to 100C, and stirred thereat for an additional hour. The organic layer is separated by decantation and washed with water (200 mls) at 80C containing sodium sulfhydrate (1 gram) and sodium hydroxide (1 gram) for 15 minutes. After separating the wash liquor, the organic phase is concen-trated and processed as described in Example 1 to obtain 1,2-bis(2-aminophenylthio)ethane in the form of a tan solid (163.7 grams; b8.7% of theoretical; m.p. 72.3-74.3C). The product turned brown after storage at ambient conditions for 8 months.
Example 4 (Comparative) In the following example, 0.523 mole of 1,2-dithloro-ethane is employed per mole of 2-aminobenzenethiol A preparation is carried out in the manner of Exam-ple 2 utilizing a solution (10.2 liters) in water of the sodium salt of 2-aminobenzenethiol obtained by the hydrolysis of benzothiazole (2433~4 grams; 18.0 moles) in water with 2.2 moles of sodium hydroxide per mole of benzothiazole. The resulting solution is cooled to 40-50C and charged to a suitable reaction vessel equipped as previously described, along with monochlorobenzene (1.38 liters), sodium hydrosul-fite (62 grams; 0.295 mole), and tetra-n-butylphosphonium bromide (3.4 grams; 0.01 mole). The two-phase mixture is stirred vigorously at 85C and 1,2-dichloroethane (930 grams;
113~
9.42 moles) is added over a period of 90 minutes while main-taining the temperature at 85C.
After the completion of the addition of 1,2-dichloro-ethane, the reaction mixture is heated at 100C for 2 hours, and another liter of monochlorobenzene is added to the re-action mixture before cooling it to 85C and separating the aqueous layer. The residual organic layer is washed with water (3.1 liters) at 85C and separated by decantation.
After separation from the wash liquor, the organic solution is evaporated under vacuum, as previously described, to re-move the solventO The molten product solidifies to form a tan product (2367.5 grams; 95.1% of theoretical; m.p. 73.4-74.4C).
A comparison was made of the results of tests for mutagenicity on the products made in Examples 1-4 along with the molar ratio of the reactants, 1,2-dichloroethane ("A") and 2-aminobenzenethiol ("B"). The results obtained, when tested with the bacterial strains and methods of Ames et al., are s~own below:
20 Product Percent Melting of Molar of Range Muta-Example Ratio A/B*Stoichiometricof Product genicity 1 0.47 94 74.3-75.6C negative
2 0.41 82 74O0-75O8 C negative
3 0.525 105 7203-74.3 C positive
4 0.523 105 73.4-74.7C positive *The stoichiometric ratio (A/B) of the reactants is 0.50.
~xample 5 The procedure of Example 1 is followed except that the sodium hydrosulfite is not added to the initial reaction mixture. After the aqueous layer is separated from the two-phase mixture, the organic layer is washed at 80-85C with an alkaline solution of sodium hydrosulfite prepared by mix-ing 0.75 and 1.0 part by weight, respectively, of sodium hydrosulfite and 50~ caustic soda, per 30 parts by weight of water. After stirring for 30 minutes at 80-85C, the mix-ture is allowed to settle and the water layer is separated.
11~3~
_g The organic layer is recovered and evaporated under reduced pressure to obtain 1,2-bis(2-aminophenylthio)ethane (m.p.
73-75C).
~0
~xample 5 The procedure of Example 1 is followed except that the sodium hydrosulfite is not added to the initial reaction mixture. After the aqueous layer is separated from the two-phase mixture, the organic layer is washed at 80-85C with an alkaline solution of sodium hydrosulfite prepared by mix-ing 0.75 and 1.0 part by weight, respectively, of sodium hydrosulfite and 50~ caustic soda, per 30 parts by weight of water. After stirring for 30 minutes at 80-85C, the mix-ture is allowed to settle and the water layer is separated.
11~3~
_g The organic layer is recovered and evaporated under reduced pressure to obtain 1,2-bis(2-aminophenylthio)ethane (m.p.
73-75C).
~0
Claims (7)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. In a process for preparing 1,2-bis(2-amino-phenylthio)ethane by reacting 1,2-dichloroethane with a solution of an alkali metal salt of 2-aminobenzenethiol in water at an elevated temperature, in the presence of a water-immiscible organic solvent and a suitable phase-transfer catalyst, separating the aqueous phase of the resulting two-phase mixture, and recovering the product from the organic phase, the improvement which comprises carrying out the reaction in the presence of a reducing agent which is soluble in water, stable in water and capable of reducing at a pH of about 9 or above, and utilizing from about 0.40 to about 0.49 mole of 1,2-dichloroethane per mole of 2-aminobenzenethiol alkali metal salt.
2. The process of claim 1 wherein the reaction is carried out in the presence of about 0.02 to about 0.05 mole of sodium hydrosulfite per mole of 1,2-dichloroethane and from about 0.44 to about 0.47 mole of 1,2-dichloroethane per mole of 2-aminobenzenethiol alkali metal salt is used.
3. The process of claim 1 wherein the recovered organic phase is washed with a dilute alkaline solution of a reducing agent in water, the resulting alkaline aqueous phase is separated and the product is recovered from the organic phase.
4. The process of claim 3 wherein the reducing agent is sodium hydro-sulfite, and the solution has a pH of about 11-12 and a temperature of about 80-90°C.
5. In a process for preparing 1,2-bis(2-amino-phenylthio)ethane by reacting 1,2-dichloroethane with a solution of an alkali metal salt of 2-aminobenzenethiol in water at an elevated temperature, in the presence of a water-immiscible organic solvent and a suitable phase transfer catalyst, separating the aqueous phase of the resulting two-phase mixture, and recovering the product from the organic phase, the improvement which comprises utilizing from about 0.40 to about 0.49 mole of 1,2-dichloroethane per mole of 2-amino-benzenethiol alkali metal salt in the reaction, washing the organic phase with a dilute aqueous alkaline solution of a reducing agent which is soluble in water, stable in water and capable of reducing at a pH of about 9 or above and separating the aqueous phase of the resulting two-phase mixture, before recovering the product from the organic phase.
6. The improved process of Claim 5 wherein from about 0.44 to about 0.47 mole of 1,2-dichloroethane is used per mole of 2-aminobenzenethiol alkali metal salt and the reducing agent is a solution of sodium hydrosulfite having a pH of about 11-12 and a temperature of about 80°-90°C.
7. The process of Claim 1 wherein the reducing agent is sodium hydrosulfite.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6361779A | 1979-08-03 | 1979-08-03 | |
| US63,617 | 1979-08-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1139316A true CA1139316A (en) | 1983-01-11 |
Family
ID=22050386
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000354682A Expired CA1139316A (en) | 1979-08-03 | 1980-06-24 | Process for preparing 1,2-bis (2-aminophenylthio) ethane |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS5626869A (en) |
| CA (1) | CA1139316A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06147022A (en) * | 1992-11-04 | 1994-05-27 | Mitsubishi Motors Corp | Cylinder injection type internal combustion engine |
-
1980
- 1980-06-24 CA CA000354682A patent/CA1139316A/en not_active Expired
- 1980-07-31 JP JP10444680A patent/JPS5626869A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5626869A (en) | 1981-03-16 |
| JPS6351147B2 (en) | 1988-10-13 |
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