TBATB mediated debenzylative cross-coupling of aryl benzyl sulfides with electron rich compounds: Synthesis of diaryl sulfides

Article abstract of DOI:10.1039/c5ra00677e

An efficient TBATB mediated debenzylative cross coupling of aryl benzyl sulfides with electron rich compounds provides diaryl sulfides in moderate to excellent yield. The salient features of the present protocol are simplicity, high efficiency and compati

Full text of DOI:10.1039/c5ra00677e

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
TBATB mediated debenzylative cross-coupling of
aryl benzyl sulfides with electron rich compounds:
synthesis of diaryl sulfides†
Cite this: RSC Adv., 2015, 5, 25765
Received 12th January 2015
Accepted 2nd March 2015
*
Sukanya Hazarika, Prasanta Gogoi and Pranjit Barman
DOI: 10.1039/c5ra00677e
www.rsc.org/advances
An efficient TBATB mediated debenzylative cross coupling of aryl aromatic compounds via addition–elimination (Scheme 1). The
benzyl sulfides with electron rich compounds provides diaryl sulfides main advantage of the present protocol is that it is tolerated by
in moderate to excellent yield. The salient features of the present various electron rich aromatic compounds such as indoles, b-
protocol are simplicity, high efficiency and compatibility of the reac- naphthol, a-naphthol, phenol, pyridine and thiophene etc.
tion with various electron rich compounds.
In our initial work, we investigated a general method for
transition-metal-free C–S cross couplings of 2-nitrophenyl
benzyl sulde (1a) and indole (2a) in DMF. It was chosen as a
model reaction for the optimization of reaction conditions
(Table 1). The initial experiments were carried out to screen
different solvents and bromine sources. When 2-nitrophenyl
benzyl sulde reacted with 1 equiv. of indole in the absence of
any bromine source, the desired product 3c was not obtained.
The results showed that, TBATB (tetrabutylammonium tri-
Aryl sulde moieties are a common functionality present in a
large number of natural products, bioactive molecules, agro-
chemicals, functional materials, and pharmaceuticals.1 Various
synthetic methodologies have been developed to prepare aryl
suldes among which transition-metal-catalyzed reactions such
as Cu,2 Ni,3 Pd,4 Co,5 and Fe6 cross-coupling reactions between
organohalides and thiol reagents are predominant in classical
organic synthesis. Over the past few years, chemists have
discovered a C–S coupling reaction involving C–H sulfenylation
reactions using thiols or disuldes as the sulfur source.7
However; these methods suffer from some inevitable drawbacks
such as the employment of sensitive organometallic reagents or
expensive metal catalysts and are limited to indoles or phenols
only. In addition, transition metal impurities in the products
are also unavoidable using this method.
ꢀ
bromide) in DMF at 40 C, could efficiently initiate the cross-
coupling reaction, and turned out to be optimal with the
Table 1 Optimization of the reaction conditionsa
Recently, Jianyou Mao and co-workers8 developed an effi-
cient methodology for the construction of diaryl suldes from
aryl benzyl suldes as the sulfur source. In this context the
present reaction mode is a normal electrophilic substitution of
Entry
Bromine source
Temperature
120 ꢀ
Solvent
Yieldb (%)
1
2
3
4
5
6
7
—
C
DMF
DMF
DMF
DMF
Toluene
THF
DMF
CH3CN
H2O
No
75
81
58
20
64
45
59
Trace
53
TBATB (1 equiv.)
TBATB (1 equiv.)
TBATB (1 equiv.)
TBATB (1 equiv.)
TBATB (1 equiv.)
TBATB (0.5 equiv.)
NBS (1 equiv.)
TBATB (2 equiv.)
Br2 (1 equiv.)
50 ꢀC
40 ꢀ
rt
C
C
40 ꢀ
60 ꢀC
40 ꢀ
40 ꢀ
40 ꢀ
40 ꢀ
C
C
C
C
Scheme 1 Synthesis of aryl sulfides.
8
9c
10
DMF
Department of Chemistry, National Institute of Technology, Silchar 788010, Assam,
India. E-mail: barmanpranjit@yahoo.co.in; pranjitbarmannits@yahoo.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c5ra00677e
a
Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol) and bromine source
(0.5 to 2 mmol) in 2 mL of solvent 24 h. The purity of 1a is 99.99%.
b
Isolated yield. c 36 h reaction.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 25765–25767 | 25765

View Article Online
RSC Advances
Communication
highest yield (81%, Table 1, entry 3). Other different bromi-
nating sources including NBS and Br2 were then tested with no
fruitful result. Reducing the amount of TBATB also caused a
decreased yield of 3c (45%, Table 1, entry 7). The yield decreased
with a decrease in temperature to room temperature (58%,
Table 1, entry 4).
With the optimized reaction conditions (Table 1, entry 3)
in hand, the scope and generality of the debenzylative
coupling reaction was investigated using several diverse
indoles, b-naphthol, a-naphthol and phenol. As shown in
Table 2, an aryl benzyl sulde containing a strong deacti-
vating group gave the maximum yield of 87% (3a), whereas, a
strong activating group gave a poor yield of 31% (3m). A plot
of time versus yield shows a rapidly progressing reaction for
highly activated substrates (Fig. 1). The reactivity order is as
NO2 > H > NH2 (ESI†). The low yields of amino substrates
could be attributed to the amine itself reacting with the
brominating agent to form an N–Br compound, which would
be hydrolysed on work up. It is noted that the presence of a
strong deactivating group at the ortho position of the aryl ring
favoured bromination at the sulfur end more readily and
formation of reactive sulfenyl bromide which reacted with
the electron rich aromatic ring to give the product in high
yield.
Fig. 1 Progress of the reaction comparing when R ¼ NO2, H, NH2.
The same reaction condition was also applied for the
removal of an acetyl group (Table 3), but found to be not very
useful because the C–S bond in aryl nitrobenzyl sulde is very
weak9 and debenzylation occurs more easily. Further, the reac-
tion conditions were also used to synthesize hetero-aromatic
suldes (6a and 6b) which resulted in intermediate yields
(Table 4).
The proposed mechanism of formation is very simple. The
facility of bromination of the C–S bond in suldes is deter-
mined primarily by the nature of the leaving group, the struc-
ture of the initial sulde, and the bromination conditions.10
Initially, aryl benzyl sulde reacts with in situ generated Br2 to
form an electrophilic species RSBr (A). The reactive sulfenyl
bromide can react with the indole moiety to form intermediate
(B) which on further deprotonation forms the desired product
3c (Fig. 2).
Table 2 Formation of diaryl sulfide: from aryl benzyl sulfidea
In summary, we have developed a simple and efficient
protocol to generate diaryl suldes by a TBATB mediated
coupling reaction of aryl benzyl sulde with electron rich
compounds. The tolerance of various aromatic and hetero
aromatic compounds such as indole, b-naphthol, a-naphthol,
phenol, pyridine and thiophene is an important and useful
aspect of the methodology.
Table 3 Formation of diaryl sulfide: from aryl acetyl sulfides
a
Reaction conditions: 1 (0.5 mmol), 2 (0.5 mmol) and TBATB (0.5
mmol) in 2 mL of DMF for 24 h.
25766 | RSC Adv., 2015, 5, 25765–25767
This journal is © The Royal Society of Chemistry 2015

View Article Online
Communication
RSC Advances
Table 4 Formation of diaryl sulfide: from heteroaromatic compounds
Notes and references
1 (a) B. Bonnet, D. Soullez, S. Girault, L. Maes, V. Landry,
E. Davioud-Charvet and C. Sergheraert, Bioorg. Med. Chem.,
2000, 8, 95; (b) G. Liu, J. T. Link, Z. Pei, E. B. Reilly,
S. Leitza, B. Nguyen, K. C. Marsh, G. F. Okasinski,
T. W. von Geldern, M. Ormes, K. Fowler and M. J. Gallatin,
J. Med. Chem., 2000, 43, 4025; (c) P. S. Herradura,
K. A. Pendola and R. K. Guy, Org. Lett., 2000, 2, 2019; (d)
P. Chauhan, S. Mahajan and D. Enders, Chem. Rev., 2014,
114, 8807.
2 (a) C. Savarin, J. Srogl and L. S. Liebeskind, Org. Lett., 2002, 4,
4309; (b) C. G. Bates, P. Saejueng, Q. Doherty and
D. Venkataraman, Org. Lett., 2004, 6, 5005; (c) Y. J. Chen
and H. H. Chen, Org. Lett., 2006, 8, 5609; (d) H. L. Kao and
C. F. Lee, Org. Lett., 2011, 13, 5204.
3 (a) Y. Zhang, K. C. Ngeow and J. Y. Ying, Org. Lett., 2007, 9,
3495; (b) M. Foa, R. Santi and F. J. Garavalia, J. Organomet.
Chem., 1981, 206, C29; (c) G. T. Venkanna, H. D. Arman
and Z. J. Tonzetich, ACS Catal., 2014, 4, 2941.
´
´
4 (a) M. A. Fernandez-Rodrıguez, Q. Shen and J. F. Hartwig, J.
Am. Chem. Soc., 2006, 128, 2180; (b) T. Itoh and T. Mase, Org.
Lett., 2004, 6, 4587; (c) M. Murata and S. L. Buchwald,
Tetrahedron, 2004, 60, 7397; (d) E. Alvaro and J. F. Hartwig,
J. Am. Chem. Soc., 2009, 131, 7858.
5 (a) Y. C. Wong, T. T. Jayanth and C. H. Cheng, Org. Lett.,
2006, 8, 5613; (b) S. Chowdhury and S. Roy, Tetrahedron
Lett., 1997, 38, 2149.
6 A. Correa, M. Carril and C. Bolm, Angew. Chem., Int. Ed.,
2008, 47, 2880.
7 (a) K. M. Schlosser, A. P. Krasutsky, H. W. Hamilton,
J. E. Reed and K. Sexton, Org. Lett., 2004, 6, 819; (b)
C. D. Prasad, S. Kumar, M. Sattar, A. Adhikary and
S. Kumar, Org. Biomol. Chem., 2013, 11, 8036; (c)
T. Fujisawa and T. Kojima, J. Org. Chem., 1973, 38, 687.
8 J. Mao, T. Jia, G. Frensch and P. J. Walsh, Org. Lett., 2014, 16,
5304.
9 P. Gogoi, S. Hazarika, M. J. Sarma, K. Sarma and P. Barman,
Tetrahedron, 2014, 70, 7484.
10 I. V. Koval, Russ. Chem. Rev., 1995, 64, 731.
Fig. 2 Proposed mechanism.
Acknowledgements
Authors acknowledges All India Council of Technical Education
(AICTE), New Delhi [8023/BOR/RID/RPS (NER)-68/2010-11] for
nancial support.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 25765–25767 | 25767