Solvent-free acetylation of thiols under catalysis of MgBr 2·OEt2

Article abstract of DOI:10.1080/10426501003645878

Solvent-free protection of aromatic and aliphatic thiols with acetic anhydride was performed at room temperature under trace quantities of magnesium bromide ethyl etherate, affording rapid formation of various thiol esters in excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426501003645878

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Phosphorus, Sulfur, and Silicon and the
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Solvent-Free Acetylation of Thiols Under
Catalysis of MgBr2·OEt2
Mohammad M. Mojtahedi a , M. Saeed Abaee a & Mashal Javadpour a
a Chemistry and Chemical Engineering Research Center of Iran,
Tehran, Iran
Published online: 05 Nov 2010.
To cite this article: Mohammad M. Mojtahedi , M. Saeed Abaee & Mashal Javadpour (2010): Solvent-
Free Acetylation of Thiols Under Catalysis of MgBr2·OEt2 , Phosphorus, Sulfur, and Silicon and the
Related Elements, 185:11, 2362-2365
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Phosphorus, Sulfur, and Silicon, 185:2362–2365, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003645878
SOLVENT-FREE ACETYLATION OF THIOLS UNDER
CATALYSIS OF MgBr2·OEt2
Mohammad M. Mojtahedi, M. Saeed Abaee,
and Mashal Javadpour
Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran
Solvent-free protection of aromatic and aliphatic thiols with acetic anhydride was performed
at room temperature under trace quantities of magnesium bromide ethyl etherate, affording
rapid formation of various thiol esters in excellent yields.
Keywords Acylation; catalysis; magnesium bromide ethyl etherate; solvent-free reaction; thiol
esters
Thiol esters constitute an important class of organic compounds due to their bioorganic
applications.1 In addition they are key synthetic precursors in the preparation of hete-
rocyclic compounds,2 acyl radicals,3 asymmetric aldol products,4 and various ketones.5
Among available methods for the preparation of thiol esters,6 direct acylation of thiols
with acetic anhydride or acetyl chloride is very common. This preparation is traditionally
carried out in the presence of amine bases or protic acids. Recent developments include
the use of various Lewis acids such as niobium(V) chloride,7 pyridine/alumina in combina-
tion with microwave irradiation,8 acetonyltriphenylphosphonium bromide,9 ruthenium(III)
chloride,10 copper-based reagents,11 and aluminum dodecatungstophosphate.12 However,
many of these procedures usually require the use of environmentally unsafe conditions,
demand application of expensive or commercially unavailable reagents, or involve the use
an additional stimulant.
Recently, we released a self-promoted chemoselective acylation of amines and thiols
in the presence of no extra catalyst or additive.13 However, protection of thiols was limited
to aromatic substrates and took relatively longer reaction time periods. Based on our
previous experience on the use of magnesium bromide ethyl etherate (MgBr2·OEt2) as an
efficient Lewis acid to catalyze various organic transformations under mild conditions,14
we envisioned that the acetylation of thiols could be boosted by using trace quantities of the
catalyst. As a result, we report in this article a facile and room-temperature transformation
of thiols to their corresponding acylated derivatives under very mild conditions (Scheme 1).
Received in final form on 15 January 2010.
Partial financial support by the Ministry of Science, Research, and Technology of Iran is greatly acknowl-
edged.
Address correspondence to Mohammad M. Mojtahedi and M. Saeed Abaee, Chemistry and Chemi-
cal Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran. E-mail: mojtahedi@ccerci.ac.ir;
abaee@ccerci.ac.ir
2362

SOLVENT-FREE ACETYLATION OF THIOLS
2363
O
O
O
MgBr2.OEt2
+
RSH
O
SR
2a-h
1a-h
R = aliphatic or aromatic
Scheme 1
Table I MgBr2.OEt2-catalyzed acetylation of various thiols with Ac2O
Entry
1
Thiol
Thiol ester
MP (◦C) found/reported
oil/oil6c
Yield %a
98
HS
AcS
1a
2a
2
33–34/38–396c
90
Cl
Cl
HS
AcS
AcS
1b
2b
3
4
oil/oil6c
82
96
HS
1c
2c
48–49/50–511b
HS
AcS
1d
2d
5
6
oil/oil6f
oil/oil6f
86
86
HS
AcS
1e
2e
HS
AcS
1f
2f
7
8
65–67/68–6911b
oil/oil6f
88b
86
SH
SAc
HS
AcS
1g
2g
2h
HS
AcS
1h
aIsolated yields.
bTwo equivalents of Ac2O.

2364
M. M. MOJTAHEDI ET AL.
Results for the acetylation of various aliphatic and aromatic thiols are summarized in
Table I. The synthesis of S-phenyl ethanethioate (entry 1) represents the typical procedure
for solvent-free magnesium bromide ethyl etherate–catalyzed conversion of different thiols
to their respective acetyl protected derivatives. An equimolar mixture of acetic anhydride
and thiophenol in the presence of 4 mol% of the catalyst yields complete formation of the
product 2a in less than 1 h at room temperature under solventless conditions. The generality
of the methodology is demonstrated by reacting other thiols with acetic anhydride under
similar conditions. The course of the reactions were monitored by TLC and GC, products
were easily separated in good yields from the reaction mixtures by simple aqueous workup,
and the identity of the products was confirmed by comparing their spectroscopic data with
those of known samples.
TYPICAL PROCEDURE
A mixture of acetic anhydride (5.1 mmol), a thiol (5.0 mmol), and magnesium
bromide ethyl etherate (0.2 mmol, 4 mol%) was stirred in a flask at room temperature. The
course of the reaction was monitored by TLC, and complete disappearance of the starting
thiol was observed within 1 h. The mixture was dissolved in ether (20 mL) and washed
twice by water (25 mL portions). The organic phase was dried over sodium sulfate, the
volatile portion was removed at reduced pressure, and the product was isolated in good
purity. All products are known, and their spectral and physical data are compared with
those existing in the literature.
Selected Spectral Data
1
S-4-Chlorophenyl ethanethioate (2b). H NMR (CDCl3): δ 2.34 (s, 3H), 7.29
(s, 4H); MS: m/z (%) 186 (60) [M+], 144 (100), 108 (36); IR (KBr): cm−1 2929, 1713,
1092.
1
S-Naphthalen-2-yl ethanethioate (2d). H NMR (CDCl3): δ 2.45 (s, 3H),
7.62–8.00 (m, 7H); MS: m/z (%) 202 (30) [M+], 160 (100), 115 (24); IR (KBr): cm−1 3050,
1699, 1117.
1
S-Benzyl ethanethioate (2e). H NMR (CDCl3): δ 2.29 (s, 3H), 4.08 (s, 2H),
7.24 (s, 5H); MS: m/z (%) 166 (33) [M+], 123 (26), 91 (100); IR (KBr): cm−1 3030, 1694,
1133.
1
S,S’-Ethane-1,2-diyl diethanethioate (2g). H NMR (CDCl3): δ 2.45 (s, 6H),
2.96 (s, 4H); MS: m/z (%) 178 (13) [M+], 119 (100), 103 (48); IR (KBr): cm−1 1693, 1142.
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