Synthesis of 2,2′-Bi-2H-3,3′-diaryl-1,4-benzothiazines from α,α-dibromoacetophenones and o-aminothiophenol

Article abstract of DOI:10.1080/00397910701356462

Some 2,2′-bi-2H-3,3′-diaryl-1,4-benzothiazines (5a-f) were synthesized from α,α-dibromoacetophenones and o-aminothiophenol. Copyright Taylor & Francis Group, LLC.

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Synthesis of
2,2′‐Bi‐2H‐3,3′‐diaryl‐1,4‐benzothiazines
from α,α‐Dibromoacetophenones and
o‐Aminothiophenol
Om Prakash a , Nisha Sharma a & Kamaljeet Pannu a
a Department of Chemistry , Kurukshetra University , Kurukshetra, Haryana,
India
Published online: 22 Jun 2007.
To cite this article: Om Prakash , Nisha Sharma & Kamaljeet Pannu (2007) Synthesis of
2,2′‐Bi‐2H‐3,3′‐diaryl‐1,4‐benzothiazines from α,α‐Dibromoacetophenones and o‐Aminothiophenol, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:12,
1995-1999
To link to this article: http://dx.doi.org/10.1080/00397910701356462
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Synthetic Communicationsw, 37: 1995–1999, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701356462
Synthesis of 2,20-Bi-2H-
3,30-diaryl-1,4-benzothiazines from
a,a-Dibromoacetophenones and
o-Aminothiophenol
Om Prakash, Nisha Sharma, and Kamaljeet Pannu
Department of Chemistry, Kurukshetra University, Kurukshetra,
Haryana, India
Abstract: Some 2,20-bi-2H-3,30-diaryl-1,4-benzothiazines (5a–f) were synthesized
from a,a-dibromoacetophenones and o-aminothiophenol.
Keywords: o-aminothiophenol, 2,20-bi-2H-3,30-diaryl-1,4-benzothiazines, a,a-
dibromoacetophenones
Compounds containing the benzothiazine ring system are well known for their
biological activities as tranquilizers,[1] antidepressants,[2] anti-inflammatory
agents,[3] and central nervous system (CNS) depressants.[4] The simplest
route recorded in literature for their synthesis involves the treatment of o-ami-
nothiophenol (1) with a-halocarbonyl compounds[5] (2) [Eq. (1)].
(1)
Received in the UK October 27, 2006
Address correspondence to Om Prakash, Department of Chemistry, Kurukshetra
University, Kurukshetra, Haryana 136119, India. E-mail: dromprakash50@
rediffmail.com
1995

1996
O. Prakash, N. Sharma, and K. Pannu
Despite the fact that a-halocarbonyl compounds are versatile intermedi-
ates in organic synthesis, there has been considerable interest in develop-
ment of alternative approaches that avoid the use of a-halocarbonyl
compounds because of the highly lachrymatory properties associated with
them. In an important development, it has been shown that a,a-dihalocarbo-
nyl compounds behave as synthetic equivalents[6] of their corresponding
a-halocarbonyl compounds. The advantage of a,a-dihalocarbonyl
compounds (for example, a,a-dibromoacetophenones) is that they are not
only devoid of lachrymatory property but also their reactions involve
much milder conditions than those of a-halocarbonyl compounds. In view
of these observations, we investigated the reaction of a,a-dibromocarbonyl
compounds with o-aminothiophenol to compare the behavior of a-bromo-
carbonyl compounds with a,a-dibromocarbonyl compounds. Accordingly,
1 was treated with 1 equivalent of a,a-dibromoacetophenone (4a) at room
temperature in acetonitrile (Scheme 1). The reaction afforded a yellow
1
solid product (5a, mp 236–388C) within 15 min. The H NMR spectrum
of this product showed a 2-proton singlet at d 4.1 and a multiplet of 18
protons in the aromatic region. IR spectrum of the product did not show
any peak in a functional group region (i.e., CO, NH2). These data were
not in accordance with the expected structure 3. Further analysis of the
spectral data (1H NMR, mass, and elemental analysis) of the product
obtained from this reaction established its structure as dimeric 1,4-ben-
zothiazine. The compound 5a is known in literature and its mp matches
the mp of our product. Encouraged by the results of this reaction, we
studied the reaction of various substituted a,a-dibromoacetophenones
(4b–f)with o-aminothiophenol under similar reaction conditions. The
reaction indeed afforded dimeric 1,4-benzothiazines 5b–f in good yields
(Scheme 1, Table 1).
Dimeric products 5 have been reported earlier in the literature using
two methods. The first method involves the oxidation of monomeric
1,4-benzothiazines,[7] which in turn are prepared by the reaction of 1 with
Scheme 1.

Table 1. Physical and spectral data of bis(1,4-benzothiazines) (5a–f)
Molecularb
formula
Compound
R
Mp (8C)
Lit. mp (8C)
Yielda (%)
62
1H NMR (d, CDCl3)
Mass m/z (%)
5a
H
236–38
234–35[5]
C28H20N2S2
4.17 (s, 2H, S-CH), 6.9–7.7 449 (15%) 224 (100%)
(m, 18H, Ar-H)
5b
CH3
238–40
244–45[7]
60
C30H24N2S2
2.4 (s, 3H, -CH3), 4.15
(s, 2H, S-CH), 6.9–7.7
(m, 16H, Ar-H)
—
5c
5d
5e
5f
Cl
218–20
224–26
256–58
267–68
232[8]
230–31[7]
248[8]
74
67
65
60
C28H18N2S2Cl2
C28H18N2S2Br2
C28H18N4O4S2
C28H18N2S2F2
4.08 (s, 2H, S-CH), 6.9–7.8 517 (30%) 258 (100%)
(m, 16H, Ar-H)
Br
NO2
F
4.09 (s, 2H, S-CH), 6.9–7.8 607 (45%) 304 (100%)
(m, 16H, Ar-H)
4.14 (s, 2H, S-CH), 6.9–8.2
(m, 16H, Ar-H)
—
—
4.1 (s, 2H, S-CH), 6.9–7.9
(m, 16H, Ar-H)
—
aThe yields of the isolated pure products 5 with regard to 4.
bElemental analyses (C, H, N) obtained were satisfactory: C + 0.25; H + 0.14; N + 0.21.

1998
O. Prakash, N. Sharma, and K. Pannu
a-halocarbonyl compounds (2) as mentioned in Eq. (1), and the second
method involves the treatment of 1 with isoxazolones[8] 6 [Eq. (2)].
(2)
The procedure developed during this work involving a,a-dibromoace-
tophenones is significant and offers a better alternative to existing literature
procedures for the following reasons: (i) a-halocarbonyl compounds are
associated with high lachrymatory nature, (ii) it is easier to prepare and
handle a,a-dibromoacetophenones than a-bromoacetophenones and
isoxazolones, (iii) the new route developed in this study involves a one-step
convenient procedure, and (iv) the reaction is completed within 15 min.
Although the mechanism of this reaction is not certain, probably it
proceeds through the formation of monomeric benzothiazines, which then
undergo oxidative dimerization under the reaction conditions to give 5.
In conclusion, the present study offers a new application of a,a-dibro-
moacetophenones in a mild and efficient synthesis of dimeric 1,4-
benzothiazines.
EXPERIMENTAL
1
Melting points were taken in open capillaries and are uncorrected. H NMR
spectra were recorded on a Bruker 300-MHz instrument using TMS as an
internal standard. IR spectra were recorded on a Buck Scientific IR M-500
spectrophotometer. Physical and spectral properties of the prepared
compounds are summarized in Table 1. The a,a-dibromoacetophenones
were synthesized according to literature procedure[6a] and were confirmed
by comparison with literature mp.
Synthesis of 2,20-Bi-2H-3,30-diaryl-1,4-benzothiazines (5a–f) from
a,a-Dibromoacetophenones and o-Aminothiophenol
To a solution of the appropriate a,a-dibromoacetophenone (4a–f, 2 mmol) in
acetonitrile, o-aminothiophenol (2 mmol) was added, and the mixture was
stirred for 10–15 min at room temperature. The solid was filtered off, and
the crude product was recrystallized from xylene. The physical and spectral
data of the pure products are listed in Table 1.

2,20-Bi-2H-3,30-diaryl-1,4-benzothiazines
1999
ACKNOWLEDGMENTS
We are thankful to Kurukshetra University, Kurukshetra, for the award of
a university research fellowship to Nisha Sharma and Defense Research
and Development Organization (DRDO) (ERIP/ER/0103294/M/01), New
Delhi, for the award of a senior research fellowship to Kamaljeet Pannu to
carry out this work.
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