Process for preparation of aromatic thiol esters

A process for producing an aromatic thiolester by mixing an alkyl or aryl thiol with an alkali metal hydroxide aqueous solution and, in the presence of a phase transfer catalyst, reacting it with an aromatic acid halide. Diacid halides may be used to produce bisthiol esters.

FIELD OF THE INVENTION 
The present invention provides a process for the preparation of aromatic 
thiol esters, including bisthiol esters. 
BACKGROUND OF THE INVENTION 
It is well known that the esterification of acid chlorides and alcohols can 
be carried out in the presence of a base, such as sodium or potassium 
hydroxide, in aqueous solution. Even when a two-phase system is necessary 
due to solubility limitations, the reaction will proceed readily. However, 
when a thiol ester is desired and thus a mercaptan is used instead of an 
alcohol, the reaction does not proceed under the same conditions. 
Different and less effective anhydrous reaction conditions have been used. 
For example, U.S. Pat. No. 4,692,184 (Lee, Sept. 8, 1987) discloses a 
method of making pyridine carbothioates in Examples 141and 146-149, but 
the only yield reported is 17.21%. The pyridine carboxyl chloride was 
mixed with the desired alkyl thiol and tetrahydrofuran in the presence of 
potassium tert-butoxide, and the resulting pyridine carbothioate was 
isolated. Therefore, there remains a need in the art for an improved 
process having improved yields, and preferably requiring less expensive 
solvents and/or less expensive bases. 
SUMMARY OF THE INVENTION 
The present invention provides a process for the preparation of an aromatic 
thiol ester comprising the steps of mixing an alkyl or aryl thiol with an 
aqueous solution of an alkali metal hydroxide; and reacting the ion thus 
formed, in the presence of a phase transfer catalyst (PTC), with an 
aromatic acid halide in an organic solvent. This is illustrated by the 
following: 
##STR1## 
An advantage of the process of the present invention is that essentially 
all of the desired thiol ester will be present in the organic phase of the 
reaction mixture. The aqueous layer, containing the phase transfer 
catalyst and any excess alkyl thiol or alkali metal hydroxide, may be 
easily separated and then refortified for subsequent reactions. Thus the 
amount of waste from the reaction may be minimized. 
DETAILED DESCRIPTION OF THE INVENTION 
Most phase transfer catalysts will be operable in the present invention 
process. It is preferred that the catalyst be a quaternary ammonium salt, 
for example, benzyl triethyl ammonium hydroxide, tetra-n-propyl ammonium 
chloride, tetra-n-butyl ammonium chloride, tetrapentyl ammonium chloride, 
tris(dioxa-3,6-heptyl)amine, methyl tributyl ammonium hydroxide, or 
tricaprylyl methyl ammonium chloride. The catalysts may be used in liquid 
or solid form. 
The organic solvent may be any solvent which is capable of dissolving the 
aromatic acid halide and which does not substantially interfere with the 
reaction. It is preferred that the solvent be immiscible with water. 
Examples include, but are not limited to, methylene chloride, cyclohexane, 
methylcyclohexane, and toluene. Mixtures of solvents, for example Aromatic 
150 may also be used. The optimum solvent may be selected by routine 
experimentation based on the desired product and the catalyst chosen. 
The temperature under which the reaction may be carried out may range from 
about 5.degree. C. to the boiling point of the solvent chosen, preferably 
between about 10.degree. and about 50.degree. C., and more preferably at 
about 25.degree. C. Ambient pressure is preferred, but not required. The 
reaction will proceed to substantial completion within about one to about 
twelve hours, depending on the temperature chosen. At the preferred 
temperature, a minimum reaction time of about 21/2 hours may be needed to 
achieve greater than 90 percent completion. 
The alkali metal hydroxide is preferably sodium or potassium hydroxide. It 
is used as an aqueous solution. Any concentration may be used, but it is 
preferred to use from about 10 to about 20 percent by weight in water. 
Examples of alkyl thiols which may be used in the process of the present 
invention include methane thiol, ethane thiol, propane thiol, or butane 
thiol. Aryl thiols may also be used, such as benzyl mercaptan. Some 
substituted alkyl or aryl thiols may be used if the substituted group or 
groups do not appreciably interfere with the reaction steps. 
The aromatic acid halide is selected according to the desired product. It 
may be a benzene derivative, for example, benzoyl chloride, or it may be a 
hetero aromatic derivative, such as pyridine carbonyl halide. It may 
contain more than one acid halide group, as in a diacid halide. A 
preferred pyridine carbonyl halide is 
2-difluoromethyl-4-(2-methylpropyl)-6-trifluoromethyl-3,5-pyridine 
dicarbonyl chloride. Thiol esters of this pyridine are disclosed as useful 
as herbicides in U.S. Pat. No. 4,692,184, incorporated herein by 
reference. One such bisthiol ester is dimethyl 
2-difluoromethyl-4-(2-methylpropyl)-6-trifluoromethyl-3,5-pyridine 
dicarbothioate, hereinafter referred to by the herbicide common name, 
dithiopyr. 
The molar ratio of reactants is not critical; however, it is preferred that 
the alkyl or aryl thiol be present in molar excess over the aromatic acid 
halide it is to be reacted with. More preferably it is present at about a 
30 percent molar excess. The base must be present in at least a 
stoichiometric amount for each esterification, that is, when one mole of a 
monoacid halide is reacted with one mole of an alkyl thiol, at least one 
mole of alkali metal hydroxide must be present. It is preferred that an 
excess from about 5 to about 30 percent be used, and more preferably, a 10 
percent excess. 
The phase transfer catalyst may be first dissolved in the aqueous mixture 
of the alkyl or aryl thiol and the alkali metal hydroxide, or it may be 
added to the reaction mixture with the aromatic acid halide or organic 
solvent. The organic solvent and aromatic acid halide be added to the 
aqueous mixture, or the aqueous mixture may be added to the organic phase. 
The rate of addition would be adjusted depending of the order chosen. 
The desired aromatic thiol ester may be isolated from the reaction mixture 
by conventional methods. For example the aqueous and organic phases may be 
separated and the organic solvent removed under reduced pressure to 
provide the product.

The following examples are illustrative of the present invention, but in no 
way are meant to limit its application to the specific reactants or 
conditions described. As used therein, A336 refers to tricaprylyl methyl 
ammonium chloride; Tris refers to tris(dioxa-3,6-heptyl)amine; BTE refers 
to benzyl triethyl ammonium hydroxide; TP refers to tetrapropyl ammonium 
chloride; TB refers to tetra-n-butyl ammonium chloride; MTBA refers to 
methyl tributyl ammonium hydroxide; and TPENT refers to tetrapentyl 
ammonium chloride. Mecyclohexane means methylcyclohexane. 
EXAMPLE 1 
Preparation of Dithiopyr 
Methane thiol, 0.5 g, was added to 4.3 g 10 percent sodium hydroxide 
aqueous solution with stirring at 25.degree. C. To this was added 0.1 g 
A336. 2-difluoromethyl-4-(2-methylpropyl)-6-trifluoromethyl-3, 5-pyridine 
dicarbonyl chloride, 2 g, prepared as in Example 141of U S. Pat. No. 
4,692,184, dissolved in 2 g methylene chloride, was added. The resulting 
mixture, having a 20 percent excess of alkyl thiol and a 20 percent excess 
of base, was vigorously stirred for 12 hours at 25.degree. C. The organic 
layer was separated, washed with water, and dried over magnesium sulfate. 
The solvent was removed under reduced pressure leaving an oil that 
solidified on standing. The solid was assayed by nmr and found to be the 
desired product, dithiopyr. The yield was 100%. 
The following examples were done following the general procedure of Example 
1, varying the ratios, conditions, or catalyst as shown in Table 1. In 
Examples 13, 14, and 15, a 20 percent potassium hydroxide aqueous solution 
was used instead of a 10 percent sodium hydroxide solution. 
TABLE 1 
__________________________________________________________________________ 
Ex. Catalyst 
Excess 
Excess 
Temp. 
Time 
Percent 
No. 
Solvent Catalyst 
Charge 
Thiol 
Base 
.degree.C. 
(hrs) 
Yield 
__________________________________________________________________________ 
2 cyclohexane 
Tris 1% 10% 10% 25 7 54 
3 cyclohexane 
BTE 1% 10% 10% 25 6.5 
50 
4 cyclohexane 
TP 1% 10% 10% 25 7 47 
5 cyclohexane 
BTE 2% 10% 10% 25 5 57 
6 cyclohexane 
TP 2% 10% 10% 25 5 63 
7 cyclohexane 
TP 4% 10% 10% 25 4 58 
8 cyclohexane 
TP 5% 30% 30% 25 1.5 
84 
9 Mecyclohexane 
TP 5% 30% 30% 25 2.5 
99 
10 Mecyclohexane 
TP 5% 30% 30% 25 2.5 
99 
11 toluene TB 5% 30% 30% 65 1.5 
99 
12 cyclohexane 
TB 5% 30% 30% 65 1.0 
83 
13 aromatic 150 
TB 5% 30% 30% 25 1.5 
97 
14 toluene MTBA 4% 12% 12% 25 2.5 
89 
15 toluene TPENT 
1% 12% 12% 25 2.5 
87 
__________________________________________________________________________ 
EXAMPLE 16 
Comparative Preparation of Dithiopyr 
The process of Example 1 was followed except that no phase transfer 
catalyst was used, but a 100 percent excess of methane thiol and a 100 
percent excess of sodium hydroxide were used. No dithiopyr was detected in 
the organic layer after the twelve hour reaction.