One-pot, catalyst-free, facile, and efficient sulfenylation of electron-rich substrates with a mild sulfenium carrier azobenzene-2-sulfenyl bromide

Article abstract of DOI:10.1080/00397911.2012.733476

One-pot, catalyst-free, facile, and efficient sulfenylations of resorcinol, 1,3-diaminobenzene, 2-naphthol, 2-aminonaphthalene, indole, pentane-2,4-dione, etc., in aqueous and ethanolic solution by a mild sulfenium carrier azobenzene-2-sulfenyl bromide are described. Efficient sulfenylating reagent, mild reaction conditions, and excellent yields make this method quite simple, convenient, and practical. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.

Full text of DOI:10.1080/00397911.2012.733476

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One-Pot, Catalyst-Free, Facile, and
Efficient Sulfenylation of Electron-Rich
Substrates with a Mild Sulfenium Carrier
Azobenzene-2-sulfenyl Bromide
Nizamuddin Ahmed a , Tirtha Bhattacharjee b , Pranjit Barman b
Saibal Kanti Bhattacharjee a
&
a Department of Chemistry , Gauhati University , Guwahati , Assam ,
India
b Department of Chemistry , National Institute of Technology ,
Silchar , Assam , India
Published online: 26 Jun 2013.
To cite this article: Nizamuddin Ahmed , Tirtha Bhattacharjee , Pranjit Barman & Saibal Kanti
Bhattacharjee (2013) One-Pot, Catalyst-Free, Facile, and Efficient Sulfenylation of Electron-Rich
Substrates with a Mild Sulfenium Carrier Azobenzene-2-sulfenyl Bromide, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 43:19, 2663-2671,
DOI: 10.1080/00397911.2012.733476
To link to this article: http://dx.doi.org/10.1080/00397911.2012.733476
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Synthetic Communications1, 43: 2663–2671, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.733476
ONE-POT, CATALYST-FREE, FACILE, AND EFFICIENT
SULFENYLATION OF ELECTRON-RICH SUBSTRATES
WITH A MILD SULFENIUM CARRIER
AZOBENZENE-2-SULFENYL BROMIDE
Nizamuddin Ahmed,1 Tirtha Bhattacharjee,2 Pranjit Barman,2
and Saibal Kanti Bhattacharjee1
1Department of Chemistry, Gauhati University, Guwahati, Assam, India
2Department of Chemistry, National Institute of Technology, Silchar,
Assam, India
GRAPHICAL ABSTRACT
Abstract One-pot, catalyst-free, facile, and efficient sulfenylations of resorcinol, 1,3-diami-
nobenzene, 2-naphthol, 2-aminonaphthalene, indole, pentane-2,4-dione, etc., in aqueous and
ethanolic solution by a mild sulfenium carrier azobenzene-2-sulfenyl bromide are described.
Efficient sulfenylating reagent, mild reaction conditions, and excellent yields make this
method quite simple, convenient, and practical.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Aqueous medium synthesis; azobenzene-2-sulfenyl bromide; azo-sulfur
interaction; hypervalent episulfonium ion; sulfenylation
Received May 11, 2012.
Address correspondence to Tirtha Bhattacharjee, Department of Chemistry, National Institute of
Technology, Silchar 788010, Assam, India. E-mail: tirtha.bhattacharjee@gmail.com
2663

2664
N. AHMED ET AL.
INTRODUCTION
Sulfenylation of electron-rich compounds such as 1-naphthol, resorcinol, 2-
naphthylamine, and indole have versatile synthetic and pharmaceutical utility. 3-Sulfe-
nylindoles are of particular interest as the precursor of anti-HIV active compounds,[1,2]
antinociceptive active compounds,[3] 5-lipoxygenase inhibitors,[4] and organic nonlinear
optical materials.[5] Again sulfenylated 2-naphthols could be used as agricultural chemi-
cals for powdery mildew.[6] Divalent organosulfur compounds, especially alkane and
arene sulfenyl chlorides, and their sulfenylation reactions have been extensively studied
over the past three decades.[7–15] Although many useful methods for the sulfur–carbon
bond formation have been reported using a variety of reagents such as disulfide,[16]
thiols in the presence of iodine,[17,18] N-chlorosuccinimide,[19] phenyliodine (III) bis-
(trifluoroacetate),[20] and vanadium catalyzed thiol under molecular oxygen[21] most of
them require hazardous solvents, severe reaction conditions, and long reaction times.
Quantum mechanical calculations[22] have shown that the ground-state electronic
configuration of sulfenium cation is a high-energy triplet state for which sulfenylation
reactions involving such intermediates should be highly endothermic. The reactive
species, sulfenium cation, exists as a sulfenium cation carrier species, where it is
stabilized by an external (nucleophilic solvent) or an internal nucleophilic group.
Conductometric and spectroscopic studies of 2,4-dinitrobenzene sulfenyl chloride have
revealed the existence of strong intramolecular interaction between sulfenyl sulfur and
the ortho nitro group.[23] Again aromatic sulfenyl chlorides undergo solvolytic cleavage
in hydroxylic solvents even at room temperature,[24] so these electrophilic sulfenyl
reagents cannot be employed in aqueous medium sulfenylation reactions.
In this article, catalyst-free, one-pot sulfenylation of electron-rich substrates
with a mild sulfenium carrier azobenzene-2-sulfenyl bromide (ABS-Br) is presented.
ABS-Br belongs to the class of ortho mercapto-azo compounds[25–28] which have
been mentioned in the synthesis of sulfonamides,[29] sulfenylation of resorcinol[30]
and ketones,[31] and oxidation of amino acids.[32] Some exceptional features such
as thermal stability, crystalline nature, and nonreactive solubility in water and
ethanol encourage us to take ABS-Br as sulfenylating agent. The unusual stability
can be attributed to the existence of a strong ortho azo-sulfur interaction[33] 1b
(Fig. 1) in the molecule of the compound. This ortho azo-sulfur interaction arises
as a result of the flow of electron density from proximate ortho-azo group to the
low-energy lowest unoccupied molecular orbital (LUMO) of sulfenyl sulfur atom.
However, in spite of the strong ortho azo-sulfur interaction, its sulfenylating
ability has not been totally sacrificed, as evident from its application as selective
reagent for polypeptides and proteins[34] and for sulfenylation of alkyl methyl
ketones and phenolics.[35]
Figure 1. Thiadiazolium salt structure azobenzene-2-sulfenyl bromide.

AZOBENZENE-2-SULFENYL BROMIDE
2665
RESULTS AND DISCUSSION
The intramolecular cyclization of the azobenzene-2-sulfenyl bromide 1b was
due to the interaction between low-energy LUMO of sulfenyl sulfur atom and the
ortho-azo group. It was expected that external nucleophiles stronger than the pheny-
lazo group should be able to attack the sulfur atom of the 1b and could cause a ring
opening of the compound. This was possible because the sulfur atom of 1b remains
attached to a quaternary nitrogen atom and is also capable of expanding its octet to
receive a pair of electrons, so 1b should behave as a sulfenium carrier to take part in
electrophilic sulfenylation reactions with electron-rich substrates. Because of the
solubility of 1b in water, all the reactions were performed in water, ethanol, or neat.
The results are summarized in Table 1.
In the catalyst-free aqueous medium reactions between equimolar quantities
of ABS-Br and water-soluble, electron-rich substrates such as resorcinol 2a and
m-phenylenediamine 2b, sulfenylation took place at the para-position to give water-
insoluble sulfenylated products via episulfonium ion intermediate 3 (Scheme 1).
In the case of 2-naphthol, the sulfenylation reaction proceeded very slowly in
ethanol and took more than 24 h for completion, but when 2-naphthol was pasted
with 1b in the solid state, we got the desired a -sulfenylated product in 10 min.
Sulfenyl halides had special reactivity toward indole nucleus in tryptophan,[36] so
we employed 1b for sulfenylation of indole 5 and 3-methylindole in water. Here,
1b rapidly reacted with 5 to give b-thioarylated product 7 via indolenine form 6
(Scheme 2), whereas in the case of 3-methylindole, a -thioarylation took place.
In the case of active methylene compounds such as acetyl acetone 8 and
5,5-dimethyl-1,3-cyclohexanedione (dimedone), sulfenylation by 1b in solid state
(neat) took place via the enolic form of the substrates as shown in Scheme 3.
So, ABS-Br was found to be a suitable reagent for catalyst-free, one-pot
sulfenylation (carbon–sulfur bond formation) of electron-rich substrates in ethanol,
water, or solid (neat) at room temperature. In addition, simple workup, mild
reaction conditions, comparative yields, and short reaction times make this method
quite simple, convenient, and practical over the existing methods in the literature.
EXPERIMENTAL
Melting points were recorded on a Veego melting-point apparatus and were
uncorrected. CHN analyses were recorded on a Perkin-Elmer Series II CHNS=O
analyzer. Infrared (IR) spectra were recorded on an IR-affinity-I FTIR spectrometer
1
(Shimadzu) as KBr Pellet. H and 13C NMR spectra were recorded on Ultrasonic
Bruker 300-MHz FT NMR spectrometer, using tetramethylsilane (TMS) as
internal standard and CDCl3 as solvent. All the chemicals used were from
Merck. Azobenzene-2-sulfenyl bromide was synthesized as described by Burawoy
and Vellins.[28]
General Procedure for Sulfenylation of Electron-Rich Substrates
A solution of the substrates (1 mmol) in 5 mL water or ethanol [for neat, solid
substrate taken in agate mortar] was added dropwise to a clear solution of

2666
N. AHMED ET AL.
Table 1. Reactions of ABS-Br (1b) with electron-rich substrates
Entry
Substrate
Reaction medium
Product
Time (min)
Yield (%)
1
H2O
5
77
2
H2O
5
82
3
H2O
15
77
4
Neat
3
89
5
Neat
3
88
6
H2O
15
63
(Continued )

AZOBENZENE-2-SULFENYL BROMIDE
2667
Table 1. Continued
Entry
Substrate
Reaction medium
Product
Time (min)
Yield (%)
7
Neat
10
90
8
EtOH
120
72
azobenzene-2-sulfenyl bromide (1 mmol, 0.292 g) in 25 mL water or ethanol [for neat
reaction condition, solid azobenzenes-2-sulfenyl bromide was used]. The mixture
was then further stirred (ground for neat reaction) at room temperature until the
completion. The precipitate formed was filtered, washed with water, dried, and
recrystallized from ethanol. [For reaction in ethanol, solvent was evaporated in
vacuum and the pasty residue was chromatographed on a column of silica gel using
dichloromethane–petroleum ether (1:4) as the eluent.]
Scheme 1. Proposed pathway to the formation of sulfenylated resorcinol and m-phenylenediamine.

2668
N. AHMED ET AL.
Scheme 2. Aqueous medium sulfenylation of indole by azobenzene-2-sulfenyl bromide.
Azobenzene-2-sulfenyl Bromide[28] (1b of Fig. 1)
1
Yellow crystal. Mp 220–222 ꢀC; H NMR (CDCl3, 300 MHz) d: 9.6 (2H, d,
J ¼ 8.1 Hz), 8.5 (1H, d, J ¼ 8.1 Hz), 8.1 (2H, d, J ¼ 6.6 Hz), 7.9–8.0 (2H, m), 7.6
(3H, d, J ¼ 6.9 Hz); 13C NMR (CDCl3, 300 MHz): 122.5, 125.7, 128.8, 130.6,
130.8, 133.1, 134.1, 140.2, 145.2, 151.1; IR (KBr) (nmax=cmꢁ1): 2997.3 (C-H str),
Scheme 3. Proposed pathway to the formation of mono-sulfenylated acetyl acetone.

AZOBENZENE-2-SULFENYL BROMIDE
2669
=
1598.3 (N N str.), 1365.6 (Ar. C-N str.), 763.8 (C-S str). Anal. calcd. for
C12H9BrN2S: C, 49.16; H, 3.09; N, 9.55. Found: C, 49.0; H, 3.1; N, 9.4.
2,4-Dihydroxyphenyl-o-phenylazophenyl Sulfide[35] (Table 1, entry 1)
1
Orange powder. Mp 173–174 ꢀC; H NMR (CDCl3, 300 MHz) d: 6.52–6.59
(1H, m), 6.9 (2H, s), 7.2 (1H, s), 7.4–7.5 (4H, m), 7.7 (1H, m), 8.0 (2H, m); 13C
NMR (CDCl3, 300 MHz): 102.7, 107.1, 109.3, 117.2, 123.2, 126.4, 127.5, 129.2,
131.5, 131.7, 138.3, 149.0, 152.6, 159.1, 159.4; IR (KBr) (nmax=cmꢁ1): 3367.71 (s,
=
OH str.), 2931.80 (w, ArH), 1598.99 (N N str.). Anal. calcd. for C18H14N2O2S:
C, 67.08; H, 4.34; N, 8.69. Found: C, 66.90; H, 4.30; N, 8.62.
2-Hydroxynaphthyl-1-(o-phenylazophenyl) Sulfide[35]
(Table 1, entry 7)
1
Red powder. Mp 152–153 ꢀC; H NMR (CDCl3, 300 MHz) d: 3.7 (1H, s), 6.6
(1H, d, J ¼ 8.1), 7.086–7.136 (1H, m), 7.2 (1H, t, J ¼ 7.5), 7.326–7.438 (3H, m),
7.5–7.6 (4H, m), 7.7 (1H, d, J ¼ 7.8), 7.8 (1H, d, J ¼ 8.1), 8.6 (2H, m), 8.3 (1H,
m); 13C NMR (CDCl3, 300 MHz): 107.8, 117.1, 117.2, 123.3, 123.9, 124.7, 126.3,
127.1, 128.0, 128.6, 129.3, 129.5, 131.5, 131.7, 132.8, 135.7, 137.3, 149.3, 152.7,
157.4; IR (KBr) (nmax=cmꢁ1): 3392.79 (s, OH str.), 2935.66 (w, ArH), 1597.06
=
(N N str.). Anal. calcd for C22H16N2OS: C, 74.20; H, 4.52; N, 7.86. Found: C,
74.09; H, 4.7; N, 7.72.
2-Aminonaphthyl-1-(o-phenylazophenyl) Sulfide (Table 1, Entry 8)
1
Red powder. Mp 118–119 ꢀC; H NMR (CDCl3, 300 MHz) d: 3.0 (2H, s), 6.6
(1H, d, J ¼ 6.9 Hz), 7.0–7.1 (3H, m), 7.2–7.3 (1H, m), 7.4–7.5 (4H, m), 7.7–7.8 (3H,
m), 8.0 (2H, d, J ¼ 8.1 Hz), 8.3 (1H, d, J ¼ 9.6 Hz); 13C NMR (CDCl3, 300 MHz):
103.8, 117.0, 117.7, 122.6, 123.3, 124.2, 125.1, 125.7, 127.8, 128.4, 128.4, 129.2,
131.2, 131.5, 131.9, 136.8, 139.0, 148.8, 148.9, 152.8; IR (KBr) (nmax=cmꢁ1):
=
3464.15, 3367.71 (s, NH str. for NH2), 2926.01 (w, ArH), 1606.70 (N N str.). Anal.
calcd. for C22H17N3S: C, 74.34; H, 4.82; N, 11.82. Found: C, 74.4; H, 4.8; N, 11.8.
CONCLUSIONS
In conclusion, we have successfully employed azobenzene-2-sulfenyl bromide
as a mild electrophilic sulfenylating agent for the one-pot, catalyst-free sulfenylation
of electron-rich substrates neat or in water or ethanol medium at room temperature.
Simple workup, mild reaction conditions, comparative yields, and short reaction
time make this method more simple, convenient, and practical than the existing
methods in the literature.
SUPPORTING INFORMATION
1
Full experimental details and H and 13C NMR spectra can be found via the
‘‘Supplementary Content’’ section of this article’s Web page.

2670
N. AHMED ET AL.
ACKNOWLEDGMENTS
The authors thank the director of NIT, Silchar, and Department of Chemistry,
Gauhati University, for laboratory facilities. The authors also thank the Council of
Scientific and Industrial Research (CSIR), New Delhi, for the award of a senior
research fellowship (T. B.) and the University Grants Commission for BSR fellow-
ship (N. A).
REFERENCES
1. Williams, T. M.; Ciccarone, T. M.; MacTough, S. C.; Rooney, C. S.; Balani, S. K.;
Condra, J. H.; Emini, E. A.; Goldman, M. E.; Greenlee, W. J. J. Med. Chem. 1993, 36,
1291–1294.
2. Silvestri, R.; De Martino, G.; La Regina, G.; Artico, M.; Massa, S.; Vargiu, L.; Mura, M.;
Loi, A. G.; Marceddu, T.; La Colla, P. J. Med. Chem. 2003, 46, 2482–2493.
3. Potin, D.; Parnet, V.; Teulon, J. M.; Camborde, F.; Caussade, F.; Meignen, J.; Provost,
D.; Cloarec, A. Bioorg. Med. Chem. Lett. 2000, 10, 805–809.
4. Hutchinson, J. H.; Riendeau, D.; Brideau, C.; Chan, C.; Delorme, D.; Denis, D.;
Falgueyret, J. P.; Fortin, R.; Guay, J. J. Med. Chem. 1993, 36, 2771–2787.
5. Kawamonzen, Y.; Mori, Y. Japanese Patent 05,196,975; Chem. Abstr. 1993, 119, 237604.
6. Magee, P. S. U. S. Patent 3,409,724; Chem. Abstr. 1969, 70, 95745.
7. Kwart, H.; Miller, R. K.; Nyce, J. L. J. Am. Chem. Soc. 1958, 80, 887–893.
8. Boccu, E.; Veronese, F. M.; Fontana, A.; Benassi, C. A. Eur. J. Biochem. 1970, 13, 188–192.
9. Harris, J. F. J. Am. Chem. Soc. 1960, 82, 155–158.
10. Welch, W. M. J. Org. Chem. 1976, 41, 2220–2222.
11. Schmid, G. H.; Nowlan, V. J. Can. J. Chem. 1976, 54, 695–702.
12. Carpino, L. A.; Williams, J. R. J. Org. Chem. 1979, 44, 1177–1178.
´
´
´
13. Gerland, B.; Desire, J.; Lepoivre, M.; Decout, J. L. Org. Lett. 2007, 9, 3021–3023.
14. Scoffone, E.; Fontana, A.; Rocchi, R. Biochemistry 1968, 7, 971–979.
15. Fontana, A.; Scoffone, E.; Benassi, C. A. Biochemistry 1968, 7, 980–986.
16. Davis, F. A. J. Org. Chem. 2006, 71, 8993–9003.
17. Beveridge, S.; Harris, R. L. N. Aust. J. Chem. 1971, 24, 1229–1236.
18. Levkovskaya, G. G.; Rudyakova, E. V.; Mirskova, A. N. Russ. J. Org. Chem. 2002, 38,
1641–1646.
19. Schlosser, K. M.; Krasutsky, A. P.; Hamilton, H. W.; Reed, J. E.; Sexton, K. Org. Lett.
2004, 6, 819–821.
20. Campbell, J. A.; Broka, C. A.; Gong, L.; Walker, K. A. M.; Wang, J.-H. Tetrahedron
Lett. 2004, 45, 4073–4075.
21. Maeda, Y.; Koyabu, M.; Nishimura, T.; Uemura, S. J. Org. Chem. 2004, 69, 7688–7693.
22. Bortolini, O.; Guerrini, A.; Lucchini, V.; Modena, G.; Pasquato, L. Tetrahedron Lett.
1999, 40, 6073–6076.
23. Kharasch, N.; Buess, C. M.; King, W. J. Am. Chem. Soc. 1953, 75, 6035–6038.
24. Kharasch, N.; Potempa, S. J.; Wehrmeister, H. L. Chem. Rev. 1946, 39, 269–332.
25. Barman, P.; Bhattacharjee, T.; Sarma, R. Acta Cryst. 2010, E66, o1943.
26. Karmakar, S.; Patowary, K.; Bhattacharjee, S. K.; Deka, B.; Chakraborty, A. Indian J.
Pure Ap. Phy. 2009, 47, 863–866.
27. Sanjib, K.; Kabita, P.; Barman, P.; Hazarika, D.; Bhattacharjee, S. K. Acta Cryst. 2004,
E60, o179–o180.
28. Burawoy, A.; Vellins, C. E. J. Chem. Soc. 1954, 90–95.
29. Bhattacharjee, S. K.; Dasgupta, S. K. Curr. Sci. India 1981, 50, 813–814.

AZOBENZENE-2-SULFENYL BROMIDE
2671
30. Chaudhuri, A.; Bhattacharjee, S. K.; Dasgupta, S. K. Curr. Sci. India 1980, 49, 859–860.
31. Chaudhuri, A.; Thakuria, T.; Bhattacharjee, S. K. Curr. Sci. India 1979, 48, 533–534.
32. Barman, P.; Bhattacharjee, S. K.; Bhattacharjee, T. Synth. Commun. 2011, 41, 2870–2875.
33. Karmakar, S.; Talukdar, A. N.; Barman, P.; Bhattacharjee, S. K. Indian J. Pure Ap. Phy.
2001, 39, 357–360.
34. Fontana, A.; Veronese, F. M.; Scoffone, E. Biochemistry 1968, 7, 3901–3905.
35. Chaudhuri, A.; Sarma, P. K. Indian J. Chem. 1973, 11, 315–317.
36. Scoffone, E.; Fontana, A.; Rocchi, R. Biochemistry 1968, 7, 971–979.