A facile synthesis of thioacids by hydrolysis of 1-(acylthio)ethaniminium chlorides

Article abstract of DOI:10.1080/10426500307837

A facile method for the preparation of thioacids in moderate to good yields has been developed by hydrolysis of 1-(acylthio)ethaniminium chlorides under a liquid-liquid two phase system consisting of benzene and a sodium hydroxide aqueous solution at room temperature. We have achieved facile preparation of these compounds without use of toxic compounds such as hydrogen sulfide.

Full text of DOI:10.1080/10426500307837

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Phosphorus, Sulfur, and Silicon and the Related
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A Facile Synthesis of Thioacids by Hydrolysis of 1-
(Acylthio)ethaniminium Chlorides
Masaharu Toriyama a , Haruo Kamijo a , Shigeyasu Motohashi a , Toshio Takido a & Kunio
Itabashi a
a Nihon University, Narashinodai, Funabashi-shi, Chiba, Japan
Version of record first published: 27 Oct 2010
To cite this article: Masaharu Toriyama, Haruo Kamijo, Shigeyasu Motohashi, Toshio Takido & Kunio Itabashi (2003): A Facile
Synthesis of Thioacids by Hydrolysis of 1-(Acylthio)ethaniminium Chlorides, Phosphorus, Sulfur, and Silicon and the Related
Elements, 178:8, 1661-1665
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Phosphorus, Sulfur, and Silicon, 178:1661–1665, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390218036
A FACILE SYNTHESIS OF THIOACIDS BY
HYDROLYSIS OF 1-(ACYLTHIO)ETHANIMINIUM
CHLORIDES
Masaharu Toriyama, Haruo Kamijo, Shigeyasu Motohashi,
Toshio Takido, and Kunio Itabashi
Nihon University, Narashinodai, Funabashi-shi, Chiba, Japan
A facile method for the preparation of thioacids in moderate to good
yields has been developed by hydrolysis of 1-(acylthio)ethaniminium
chlorides under a liquid-liquid two phase system consisting of benzene
and a sodium hydroxide aqueous solution at room temperature. We
have achieved facile preparation of these compounds without use of
toxic compounds such as hydrogen sulfide.
Keywords: Acyl halides; acylthioethaniminium salt; thioacetamide;
thioacids; thiocarboxylate ions
Many different methods1−8 for preparing thioacids have been reported
and they recently have begun to attract notice because functionalized
organic thioacids are useful and efficient acylating agents for amines,
amino acids, and peptides in biochemical reactions.9,10 However, most
of these preparations have involved the use of toxic and unpleasantly
smelling compounds such as hydrogen sulfide, and have sometime suf-
fered from cumbersome manipulations due to the formation of car-
boxylic acids or thioacid anhydrides (diacyl sulfides) as by-products. We
have achieved the preparation of thioacids without the use of hydrogen
sulfide. Herein, we report a novel and facile method for the preparation
of thioacids by hydrolysis of 1-(acylthio)ethaniminium halide.
We have previously reported11 the preparation of thiobenzoic
acid by hydrolysis and methanolysis of N,N-dimethyl-1-(benzoylthio)-
methaniminium chloride prepared from N,N-dimethylthioformamide12
This work was partly supported by the High-Tech Research Center at Nihon Univer-
sity, and a Grant from the Ministry of Education, Culture, Sports, Science, and Technology
to promote multi-disciplinary research projects.
Address correspondence to Toshio Takido, Department of Materials and Applied
Chemistry, College of Science and Technology, Nihon University, Kanda Surugadai,
Chiyoda-Ku, Tokyo 101-8308, Japan. E-mail: takido@chem.cst.nihon-u.ac.jp
1661

1662
M. Toriyama et al.
(DMTF) with benzoyl chloride. We also have attempted to apply an
aliphatic acyl chloride in this method, but this reaction afforded a car-
boxylic acid and a methyl carboxylate as the major products together
with a small amount of an aliphatic thioacid. This result suggested
that the stability of aliphatic acyl chloride/DMTF adducts are rela-
tively low, and the rates of hydrolysis13 and esterification14 of aliphatic
acyl chlorides are faster than those benzoyl chloride. We also earlier
have reported15 an efficient method for synthesizing thiol esters using
1-(acylthio)ethaniminium halides as s source of thiocarboxylate ions.
It was found that when this reaction carried out in the absence of
the phasetransfer catalyst and an alkyl halide, the hydrolysis of 1-
(acylthio)ethaniminium halide proceeded to produce a thioacid. In an
extension of these investigations, this article describes a novel and facile
synthesis of thioacids by hydrolysis of 1-(acylthio)ethaniminium chlo-
rides prepared from acylation of thioacetamide under a liquid-liquid two
phase system consisting of benzene and a sodium hydroxide aqueous so-
lution. Our facile method for the preparation of thioacids by hydrolysis
of 1-(acylthio)ethaniminium chlorides hitherto has not been reported,
and a wide range of functionalized thioacids could be prepared.
RESULTS AND DISCUSSION
In our present method, 1-(acylthio)ethaniminium chlorides, 3, were
prepared from thioacetamide, 1, and acyl chlorides, 2, in benzene
at 30◦C for 3 h. The attempts to isolate of 3 were unsuccessful
due to their instability in air (this was in contrast to the stable 1-
(alkylthio)ethaniminium halides which were prepared from thioac-
etamide and alkyl halides). It therefore is reasonable to assume that the
preparation of thioacids by means of a one-pot reaction would be effec-
tive as a synthetic strategy. They were hydrolyzed to give thioacids, 4,
in a liquid-liquid two phase system consisting of benzene and a sodium
hydroxide aqueous solution at room temperature for 30 min.
The reactions were carried out under mild conditions, and thioacids,
4, were obtained in 42–86% yields and the results are summarized in
Table I. These reactions also have afforded a small amount of corre-
sponding carboxylic acids as a by-product, formed by direct hydrolysis
of remaining acyl chloride as an unreactant, because the formation
of 3 would be reversible reaction.16 The separation of desired 4 and
carboxylic acids was easily achieved by using column chromatographic
purification. The attempts to increase yields of 4 by using excess thioac-
etamide, 1, or an acyl chloride, 2, to drive the equilibrium were ex-
amined. When the reaction of 1 (1.5 eq. and 2.0 eq.) with n-octanoyl

A Facile Synthesis of Thioacids by Hydrolysis
1663
4
R
4
R
a
b
c
d
e
f
n-C4H9
n-C5H11
n-C6H13
n-C7H15
n-C8H17
n-C9H19
g
h
i
CH3(CH2)3CH(C2H5)
tert-C4H9
cyclo-C6H11
C6H5
p-CH3OC6H4
p-NO2C6H4
j
k
l
SCHEME 1
chloride, 2d (1.0 eq.) produced thiooctanoic acid (4d) in 81% and 83%
yield respectively. The use of 1 (1.0 eq.) with 2d (1.5 eq.) in this re-
action produced 4d in 88% yield by GLC calculation, but the reaction
also afforded a large amount of n-octanoic acid as a by-product. Accord-
ingly, the isolation of 4d was unsuccessful due to the formation of the
by-product in good yield; so it was found that the equimolar reaction of
1 and 2 would be reasonable in this reaction.
The application of various acyl chlorides to this reaction was exam-
ined. It was found that the corresponding thioacids could be prepared
in good yield from the linear aliphatic acyl chlorides, trimethylacetyl
chloride, and cyclohexanecarbonyl chloride having branches on the α-
position of acyl chlorides, but the yield of 4 was decreased by using
the acyl chloride with ethyl group on its α-position. In the case of the
reaction using p-substituted benzoyl chlorides, the yields of 4 were in-
creased by an electron-releasing group on the benzene ring, whereas
electron withdrawing groups decreased the yield of 4. The yields of 4
depended on the structure of thioamides; they decreased in the order:
thioacetamide > DMTF > N,N-dimethylthioacetamide (DMTA). For ex-
ample, the yields of thiobenzoic acid, obtained from the hydrolyses of
corresponding benzoylthioiminium salt were 84% (thioacetamide; 1),
55% (DMTF), 37% (DMTA) respectively. In hydrolysis using a higher
than 10% (w/w) concentration of a sodium hydroxide aqueous solu-
tion, the yields of 4 were decreased due to the formation of carboxylic
acids as by-products by the decomposition of 3 and 4. It was found
that a 10% (w/w) concentration of sodium hydroxide aqueous solution
was reasonable for the hydrolysis of 3, and this result was in com-
plete contrast to the synthesis of unsymmetrical sulfides. As reported
before,17 1-alkylthioiminium salt reacted with alkyl halides to form

1664
M. Toriyama et al.
TABLE I Thioacids 4 Prepared
13C-NMR
(CDCI3/TMS): δ
[1H-NMR
IR (neat
or KBr)
HR-MS
(FAB-) or
Lit. data
Producta Yieldb b.p. (◦C/torr)
4
(%)
m.p. (◦C) or
νS
νC
(CDCI3/ TMS): δ]
H
O
a
b
c
72 (75)
63–64/13
113–140/76018
98–101/6518
81/1118
2550 1708 13.6, 21.9, 27,4, 45.6,
197.7
2547 1709 13.8, 22.3, 25.0, 30.9,
45.7, 196.6
2551 1709 13.9, 22.4, 25.3, 28.4,
31.4, 45.7, 197.7
2548 1710 14.0, 22.5, 25.3, 28.7,
28.9, 31.5, 45.7,
71 (77)
75 (77)
80 (82)
77–78/13
72–73/9
95–96/3
d
72/319
197.7
e
f
76 (80) 114–115/13
105/1018
2550 1709 14.0, 22.6, 25.3, 28.7,
29.0, 29.2, 31.7,
45.7, 196.6
75 (80)
115–116/5 187.1152 (M − H+) 2546 1710 14.0, 22.6, 25.4,
Calcd. 187.1157
28.8 × 2, 29.2 × 2,
31.8, 45.8, 195.7
[0.88 (3H, t, J = 7
Hz, CH3),
1.20–1.38 (12H,
m, CH3 (CH2)6),
1.59–1.72 (2H, m,
CH2CH2CO), 2.60
(2H, t, J = 7 Hz,
CH2CO)]
g
42 (49)
72–73/5
159.0845 (M − H+) 2547 1709 11.5, 13.8, 22.6, 25.8,
Calcd. 159.0844
29.3, 32.1, 57.4,
202.0 [0.86–1.01
(6H, m, CH3 × 2),
1.24–1.37 (4H, m,
CH2CHCH2),
1.42–1.80 (4H, m,
CH3CH2CH2),
2.43–2.52 (1H, m,
CH)]
h
71 (75)
71 (75)
53–54/11
117.0374 (M − H+) 2555 1699 27.2, 47.2, 204.8
Calcd. 117.0374
78–79/7.58
82–85/78
82–8320
[1.30 (9H,s,
(CH3)3C)]
i
78–79/8
85–87/10
82–83
2550 1702 25.4, 25.6, 29.5, 51.9,
201.3
2557 1665 127.7, 128.5, 133.7,
136.4, 190.2
j
72 (76)
84 (86)c
86 (89)
k
l
2512 1638 55.3, 113.5, 129.2,
130.0, 163.5, 190.3
2550 1669 123.7, 128.0, 141.7,
150.3, 190.3
54 (59)
97–98
9419
aAll products were characterized by 1H-NMR, mass spectra.
bYields were pure isolated 4 based on 2 and in parentheses were calculated by GLC.
cC6H6COBr was used instead of C6H6COCI.

A Facile Synthesis of Thioacids by Hydrolysis
1665
the corresponding unsymmetrical sulfides under liquid-liquid phase
transfer conditions; however, this reaction required a 30% (w/w) con-
centration of sodium hydroxide aqueous solution for the generation
of alkanethiolate ions from the salt. These results suggest that the
iminium carbon-sulfur linkage of 3 would be weaker than that of 1-
alkylthioiminium salt in alkaline solution.
As far as we know, this is the first example of the preparation of
thioacids by hydrolysis of acylthioiminium salt. Our method does not
use harmful or malodorous compounds such as hydrogen sulfide, and
can be applied widely to the synthesis of functionalized thioacids. We
expect it to become one of the most convenient syntheses for thioacids
without use of hydrogen sulfide.
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