A Fast and Solvent-Free Conversion of Thioamides into Thioesters

Article abstract of DOI:10.1007/s00706-003-0087-0

Solvent-free irradiation of thiomorpholides with two kinds of methylating agents under microwave or ultrasonic conditions gave the corresponding thioesters in high yield. The method is simple and avoids prolonged heating with solvents.

Full text of DOI:10.1007/s00706-003-0087-0

Monatshefte f€ur Chemie 135, 79–81 (2004)
DOI 10.1007/s00706-003-0087-0
A Fast and Solvent-Free Conversion
of Thioamides into Thioesters
ꢀ
Hossein R. Darabi , Kioumars Aghapoor, and Kourosh Tabar-Heidar
Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186,
Tehran, Iran
Received May 12, 2003; accepted (revised) May 23, 2003
Published online October 20, 2003 # Springer-Verlag 2003
Summary. Solvent-free irradiation of thiomorpholides with two kinds of methylating agents under
microwave or ultrasonic conditions gave the corresponding thioesters in high yield. The method is
simple and avoids prolonged heating with solvents.
Keywords. Thioesters; Thioamides; Solvent-free; Microwave; Ultrasonic.
Introduction
Thioesters are activated carboxylic acid derivatives which are usually prepared by
condensation of a thiol and an acid chloride. They exhibit acylating properties
similar to those of acid anhydrides [1]. They have therefore found widespread
application in synthetic chemistry [2]. A traditional approach to the synthesis of
thioesters 1 is the reaction of thiols or their metal salts with acid halides, anhy-
drides, and esters [3].
Recently, the transformation of a solution of thioamides 2 in THF in presence
of water and an alkylating agent yielded thioesters 1 in high yield [3]. However,
this method may find only limited application because of the high reaction tem-
peratures and very long reaction periods (15–72 h) required.
As thioamides 2 are part of our project [4–7], we became interested in this
reaction to compare the irradiation effects with that of classical heating on the
reaction. Herein we wish to report the solvent-free synthesis of thioesters 1 from
the reaction of selected methylating agents (dimethylsulfate, DMS; methyl iodide)
with the corresponding thiomorpholides 2 under both microwave heating and ultra-
sonic conditions.
ꢀ
Corresponding author. E-mail: darabi@ccerci.ac.ir

80
H. R. Darabi et al.
Scheme 1
Table 1. Solvent-free conversion of thiomorpholides into thioesters
Substrate
Product
Microwave (DMS )
Yield=%
Ultrasonic (CH3I)
Yield=%
2a
2b
2c
2d
2e
1a
1b
1c
1d
1e
73
98
98
99
99
79
91
88
97
98
Results and Discussion
As shown in Table 1, the yields of the products using microwave irradiation for 40 s
are high and comparable to those of the classical reactions which usually require
very long refluxing periods [3]. However, using a domestic microwave oven
resulted in uncontrolled heating of the reaction mixtures, accompanied by a rapid
evaporation of the liquids in open vessels.
Surprisingly, when the same reactions were carried out under ultrasonic con-
ditions at room temperature, similar results were obtained. After 5 h sonication, the
temperature was raised to about 35ꢁC. In accord with these facts, we propose that
there may be non-thermal effects on the reaction.
In general, we have shown that thioamides can be transformed into the corre-
sponding thioesters under microwave and ultrasonic irradiation condition. More-
over, the method is simple, and avoids prolonged heating with solvents.
Experimental
Caution: Experiments should be carried out in an efficient hood to avoid exposure to toxic vapors of
methylating agents.
Syntheses under Microwave Condition
A mixture of 1 mmol of thiomorpholines 2, 2 mmol of DMS, and H2O in an open pyrex glass flask was
exposed to microwave irradiation at 900 W for 40 s. The microwave oven used for this study was a

A Fast and Solvent-Free Conversion of Thioamides to Thioesters
81
domestic National model NN-6755 with 7 power settings (90–900 W). After cooling, the reaction
product 1 was washed with H2O and then purified by flash chromatography on silica gel using ether as
eluent. The products are generally pure as judged by TLC, GC-MS, and NMR analysis.
Syntheses under Ultrasonic Condition
A mixture of 1 mmol of thiomorpholines 2, 2 mmol of methyl iodide, and H2O in a closed pyrex glass
flask was exposed to ultrasonic irradiation for 5 h. The ultrasonic bath used for this study was a
Dandelin model Sonorex RK 156 with a power setting (35 KHz). The reaction product 1 was purified
by flash chromatography on silica gel using ether as eluent.
Methyl 2-Phenyl ethanethionate (1a, C12H15NOS)
Colorless oil; 1H NMR (90 MHz, CDCl3): ꢀ ¼ 7.20 (s, 5H), 3.80 (s, 2H), 2.25 (s, 3H) ppm; MS: m=z
(rel. intensity %) ¼ 166 (Mþ, 20), 119 (45), 91 (100), 47 (15).
Methyl 2-(4-Chlorophenyl)ethanethionate (1b, C12H14ClNOS)
Colorless oil; 1H NMR (90 MHz, CDCl3): ꢀ ¼ 6.80–7.20 (dd, 4H), 3.85 (s, 2H), 2.28 (s, 3H) ppm; MS:
m=z (rel. intensity %) ¼ 200 (Mþ, 10), 153 (10), 125 (100), 75 (40), 47 (70).
Methyl 2-(2-Naphtyl)ethanethionate (1c, C16H17NOS)
Colorless oil; 1H NMR (90 MHz, CDCl3): ꢀ ¼ 7.25–8.05 (m, 7H), 4.80 (s, 2H), 2.29 (s, 3H) ppm; MS:
m=z (rel. intensity %) ¼ 216 (Mþ, 60), 141 (100), 115 (90), 75 (60), 47 (50).
Methyl phenyl methanethionate (1d, C11H13NOS)
Colorless oil; 1H NMR (90 MHz, CDCl3): ꢀ ¼ 7.20 (s, 5H), 2.30 (s, 3H) ppm; MS: m=z (rel. intensity
%) ¼ 152 (Mþ, 70), 105 (90), 74 (100), 46 (80).
Methyl (4-Methoxyphenyl)methanethionate (1e, C12H17NO2S)
1
Colorless oil; H NMR (90 MHz, CDCl3): ꢀ ¼ 6.70–7.20 (dd, 4H), 2.28 (s, 3H) ppm; MS: m=z (rel.
intensity %) ¼ 196 (Mþ, 15), 135 (60), 75 (100), 47 (70).
References
[1] Janssen MJ (1969) In: Patai S (ed) The Chemistry of Carboxylicacids and Esters
[2] Evans DA, Dart MJ, Duffy JL, Yang MG (1996) J Am Chem Soc 118: 4322
[3] Harrowven DC, Lucas MC, Howes PD (1999) Tetrahedron 55: 1187
[4] Nooshabadi M, Aghapoor K, Darabi HR, Mojtahedi MM (1999) Tetrahedron Lett 40: 7549
[5] Aghapoor K, Darabi HR, Nooshabadi M, Tabar-Heydar K (2002) Phosphorus Sulfur Silicon 177:
1183
[6] Darabi HR, Aghapoor K, Tabar-Heydar K (2002) Phosphorus, Sulfur Silicon 177: 1189
[7] Aghapoor K, Darabi HR, Tabar-Heydar K, Nakhshab L (2002) Sulfur Lett 25: 259