Rapid and regiospecific phenylthiolation of some organic acids catalyzed by AlCl3 in the presence of excess anhydrous ZnCl2

Article abstract of DOI:10.1080/00397910903219567

Phenylthiolation of some carboxylic acids catalyzed by AlCl₃ in the presence of excess dehydrating agent (ZnCl₂) has been achieved. Moreover, regiospecificity was tested of some dioic acids and found to be specific at the aliphatic p

Full text of DOI:10.1080/00397910903219567

Synthetic Communications1, 40: 2158–2163, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219567
RAPID AND REGIOSPECIFIC PHENYLTHIOLATION OF
SOME ORGANIC ACIDS CATALYZED BY AlCl3 IN THE
PRESENCE OF EXCESS ANHYDROUS ZnCl2
H. N. Roy, Ashis K. Sarker, and A. H. Al Mamun
Department of Chemistry, University of Rajshahi, Rajshahi, Bangladesh
Phenylthiolation of some carboxylic acids catalyzed by AlCl3 in the presence of excess
dehydrating agent (ZnCl2) has been achieved. Moreover, regiospecificity was tested of
some dioic acids and found to be specific at the aliphatic part of carboxylic functionality.
Keywords: Dioic acids; phenylthiolation; regiospecific esterification
INTRODUCTION
Today, thioesters are made to protect and activate COOH functionality in
organic synthesis.[1] Protection of thiol groups are most important in peptide[2]
and b-lactam synthesis[3] for specific purposes. Thioester synthesis from organic
acids and thiols catalyzed by mineral acids are of limited use because of the reversi-
bility of CꢀS bond-breaking and bond-forming tendencies, the aptitude of the
bridged S compounds, and above all the oxidation tendency of sulfur.[4] Sometimes,
reaction of acylhalides with thiols gave thioester[5] in poor yields because of the CꢀS
bond breaking. The yield and reaction conditions mostly depend on the solvent, the
basic catalyst, and the acidity of the thiols.[5] Sometimes, the reactions require very
long refluxing time.
Now, various methods have been employed including palladium(0)-mediated
alkylation,[6] phase-transfer catalysis,[7] bis(diphenylstannyl) telluride,[8] tin sulfides
with aryl halides,[9] ligand transfer reaction,[10] montmorillonite clay,[11] and CsF–
Celite[12] catalysis. Recently, Yin and Pidgeon[13] reported a facile method for the
preparation of unsymmetrical sulfides using very strong n-BuLi. In all cases, some
restraints were there, either in the yield of the products or in the use of costly reagent
and complicated procedures. In continuation of our interest in developing a new
synthetic route for esterification[14,15] in aromatic acids, we herein report the versatile
use of a mixed AlCl3 and ZnCl2 catalyst for the synthesis of thioesters and some
selective thioesters from some organic dioic acids (Fig. 1).
Received May 9, 2009.
Address correspondence to H. N. Roy, Department of Chemistry, University of Rajshahi, Rajshahi
6205, Bangladesh. E-mail: hnroy01@yahoo.com
2158

PHENYLTHIOLATION OF ORGANIC ACIDS
2159
Figure 1. Specific thioesters.
RESULTS AND DISCUSSION
As a test case leading to phenylthiolation, benzoic acid was chosen as an initial
starting material. It was dissolved into distilled EtOAc, and 5 mol% anhyd. AlCl3
was added to it. One h later, an equivalent amount of distilled thiophenol with excess
anhyd. ZnCl2 was added and allowed to stir at room temperature for about 2 h with
occasional thin-layer chromatography (TLC) monitoring. A tiny growing spot was
observed above the starting acid. To complete the reaction, it was heated to reflux
temperature over 3–4 h. Addition of 0.1 M cold HCl to the reaction mixture helped
to break the salt formed during the reaction. Ether extraction and the usual workup
procedure furnished the thioester 16 in 85% yield. In the same way, some other
organic acids were reacted with PhSH and obtained in fair to good yield (see
Table 1). To test the selectivity, four different dioic acids were reacted with equiva-
lent amounts of PhSH. Dioic acid 12 gave the mono ester 27 with good yield at room
temperature. Selectivity of the two ꢀCOOH functionalities were verified by making
phenylthiolate 19 from phenyl acetic acid 4. Proton magnetic resonance (PMR)
spectra of ester 19 completely matched with the monoester 27, except one proton
appeared at d ¼ 10.87 for the other COOH in 27. So, the monoester 27 contains
the SPh group in the aliphatic part of the two choices. In infrared (IR) spectroscopy,
=
compound 27 indicates two important peaks for C O and CꢀS bonds at 1784 and
1283 cmꢀ1, respectively. Moreover, mass spectrum was taken of 27 to establish its
structure. Three dioic acids (13, 14, and 15) under the same conditions gave three
different monoesters (see Table 1) in excellent yields. AlCl3 increased the electrophi-
licity of both carbon atoms in the COOH group equally, but this may be due to steric
grounds. PhSH likes to attack at the aliphatic carboxylic carbon away from the
phenyl ring. Whatever the mechanism, this is an expedient, regiospecific, inexpen-
sive, and simple method for preparing thioesters, so it would be a valuable addition
with the existing methodologies.
EXPERIMENTAL
General Considerations
The melting points were determined on a capillary melting-point apparatus and
are uncorrected. IR spectra were recorded using KBr pellets for solids and neat for
liquids on Fourier Transform FT–IR-8400 Perkin-Elmer 883 grating spectrometer.
1H NMR spectra was taken on an AC Bruker 400-MHz spectrometer in CDCl3,
containing tetramethylsilane (TMS) as the internal standard. High solution mass
spectra (HRMS) were recorded on an VG Micromass ZaB-2F. All J values are given
in hertz, and chemical shifts are in d units. EtOAc was simply distilled over CaCl2,
and PhSH was collected by the fractionating distillation process. Reactions were

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H. N. ROY, A. K. SARKER, AND A. H. AL MAMUN
Table 1. Phenylthiolation for organic acids
Entry
Acids
Reaction time (h)
Product (esters)
Mp=bp (ꢁC) Yield (%)
1
2
4–5
27
85
90
3–4
52–53
3
4
4
5
50–51
85
90
28
5
6
4–5
4–5
29
32
85
85
7
8
9
5–6
5–6
3–4
73–74
47–48
71–72
83
85
90
(Continued )

PHENYLTHIOLATION OF ORGANIC ACIDS
2161
Table 1. Continued
Entry
Acids
Reaction time (h)
Product (esters)
Mp=bp (ꢁC) Yield (%)
10
3–4
69–70
90
85
11
5–6
64
12
13
3–4
3–4
165
128
84
82
14
15
5–6
4–5
168
172
85
80
Note. Mp=bp were compared with the literature values and the Aldrich chemical catalog.
monitored by TLC, and column chromatography was done on silica gel,
60–120 mesh (E. Merck).
General Method for the Preparation of Phenylthioesters
Anhydrous AlCl3 (0.054 g, 0.41 mmol) was added to a stirred EtOAc (10 mL)
solution of benzoic acid 1 (l g, 8.2 mmol) at 0 ꢁC. Two h later, 1 equivalent of
thiophenol (0.91 mL, 8.2 mmol) and anhyd. ZnCl2 (1 g, 8.1 mmol) were added to
it. To monitor the progress of the reaction, TLC was checked in an n-hexane=EtOAc
(5:1) solvent system, indicating a tiny spot above the starting materials. When the
reaction was deemed to be completed after 4 h at reflux temperature, 0.1 M HCl
(ice cold) was added to it. Subsequent ether (3 ꢂ 12 mL) extraction, washing with
5% NaHCO3 (2 ꢂ 15 mL) followed by water (2 ꢂ 20 mL), drying over Na2SO4, and

2162
H. N. ROY, A. K. SARKER, AND A. H. AL MAMUN
evaporating the bulk ether afforded a white product. Recrystallization from acetone
furnished white crystals in excellent yield (1.49 g, 85%).
Selected Data
Compound 27. Mp 165 ꢁC; IR (KBr): 1737, 1695, 1283 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): d ¼ 10.88 (s, 1H, COOH), 6.98–6.95 (m, 2H, Ar-H), 6.77–6.73
(m, 2H, Ar-H), 6.64–6.59 (m, 5H, Ar-H), 3.65 (s, 2H, CH2). HRMS calcd. for
C15H12O3S, 272.1671; found, 272.1431.
Compound 28. Mp 128 ꢁC; IR (KBr): 1740, 1693, 1287 cmꢀ1 1H NMR
;
(400 MHz, CDCl3) d ¼ 10.85 (s, 1H, COOH), 7.01–6.99 (m, 2H, Ar-H), 6.95–6.92
(m, 2H, Ar-H), 6.66–6.62 (m, 5H, Ar-H), 3.45 (t, J ¼ 6 Hz, 2H, CH2), 2.52 (t,
J ¼ 6 Hz, 2H, CH2). HRMS calcd. for C16H14O3S, 286.3143; found, 286.3103.
Compound 29. Mp 168 ꢁC; IR (KBr): 1735, 1698, 1286 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): d ¼ 10.91 (s, 1H, COOH), 7.43 (d, 1H, J ¼ 2.4 Hz, Ar-H), 7.14
(d, 1H, J ¼ 8 Hz, Ar-H), 6.98 (dd, 1H, J ¼ 2, 8 Hz, Ar-H), 6.65–6.61 (m, 5H,
Ar-H), 4.90 (s, 1H, Ar-OH), 3.40 (s, 2H, CH2). HRMS calcd. for C15H12O4S,
288.5237; found, 288.5215.
Compound 30. Mp 172 ꢁC; IR (KBr): 1735, 1698, 1282 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): d ¼ 10.89 (s, 1H, COOH), 7.50 (d, 1H, J ¼ 2.6 Hz, Ar-H), 7.34
(d, 1H, J ¼ 8 Hz, Ar-H), 6.98 (dd, 1H, J ¼ 2, 8 Hz, Ar-H), 6.77–6.67 (m, 5H,
Ar-H), 3.74 (s, 2H, CH2), 3.45 (s, 3H, CH3). HRMS calcd. for C16H14O4S,
302.2731; found, 302.2233.
ACKNOWLEDGMENT
The authors gratefully acknowledge Mr. M. Shahidul Islam, an instrument
1
engineer at BCSIR Dhaka, Bangladesh, for the necessary H NMR and IR spectra.
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