An efficient synthetic route to biologically relevant 2- phenylbenzothiazoles substituted on the benzothiazole ring

Article abstract of DOI:10.1016/j.tet.2011.08.004

Certain 2-phenylbenzothiazoles containing substituents on the benzothiazole ring possess important biological properties, yet the majority of synthetic methods to 2-phenylbenzothiazoles described to date focus on their unsubstituted ring counterparts. Her

Full text of DOI:10.1016/j.tet.2011.08.004

Tetrahedron 67 (2011) 7743e7747
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An efficient synthetic route to biologically relevant 2-phenylbenzothiazoles
substituted on the benzothiazole ring
,
Ashley A. Weekes a, Mark C. Bagley b, Andrew D. Westwell a
*
a Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK
b School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff CF10 3AT, Wales, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 April 2011
Received in revised form 18 July 2011
Accepted 2 August 2011
Available online 7 August 2011
Certain 2-phenylbenzothiazoles containing substituents on the benzothiazole ring possess important
biological properties, yet the majority of synthetic methods to 2-phenylbenzothiazoles described to date
focus on their unsubstituted ring counterparts. Here we describe a new concise and efficient synthetic
route to biologically relevant 2-phenylbenzothiazoles in high yield from the reaction of substituted 2-
aminothiophenol disulfides and benzaldehydes, promoted by the inexpensive and non-toxic inorganic
oxidant sodium metabisulfite in DMSO at 120 ꢀC. Our new method is tolerant of a range of substituents
on both the benzothiazole and phenyl ring, and affords efficient access to substituted 2-
phenylbenzothiazoles without the need for column chromatography.
Keywords:
2-Phenylbenzothiazoles
Sodium metabisulfite
Benzaldehydes
Ó 2011 Elsevier Ltd. All rights reserved.
Aromatic heterocycle synthesis
1. Introduction
Me
F
H
N
S
N
Certain substituted 2-phenylbenzothiazoles have emerged as
agents of considerable biological importance in recent years in
a variety of diagnostic and therapeutic settings.1 Particularly
noteworthy applications have come in the fields of the potential
diagnosis of Alzheimer’s disease2 and cancer therapy.3
An important milestone in the development of substituted 2-
phenylbenzothiazoles as non-invasive diagnostic imaging agents
came with the development of the 11C-labelled 2-(4-methylami
nophenyl)-6-hydroxybenzothiazole (known as Pittsburgh com-
pound B; PiB; 1; Fig. 1).2aed PiB is currently in clinical trials for di-
agnostic imaging of Alzheimer’s disease by Positron Emission
N
NH2
O
S
11CH3
HO
1 (PiB)
2 (5F 203)
OMe
N
F
N
F
OMe
S
HO
4 (fluorinated "quinol")
S
3 (PMX 610)
Fig. 1. Biologically relevant 2-phenylbenzothiazole derivatives substituted on the
benzothiazole ring.
Tomography (PET), through selective binding to Ab (amyloid) pla-
be crucial in subverting metabolic deactivation, when compared to
its non-fluorinated counterpart.3e The water-soluble lysyl amide
prodrug of 5F 2033f (known as Phortress) is currently in Phase 1
clinical trials for cancer in the U.K. Further potent and selective
fluorinated benzothiazole-based antitumour agents that have been
identified including 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiaz
ole (PMX 610; 3; Fig. 1)3g and fluorinated benzothiazole-
substituted hydroxycyclohexa-2,5-dienones (‘quinols’ 4; Fig. 1).3h
A range of synthetic approaches to 2-phenylbenzothiazoles
unsubstituted on the benzothiazole ring are available, and have
recently been reviewed.1 Most commonly these routes involve the
condensation between commercially available 2-aminothiophenol
and either benzoic acids/benzoic acid derivatives (esters/acyl
chlorides etc.);4aec or benzaldehydes (Scheme 1).5a,b In the case of
benzaldehydes as condensation partners, the initial formation of
ques, a hallmark pathological feature of Alzheimer’s.2e The poten-
tial application of fluorinated 2-(4-aminophenyl)benzothiazoles as
potential PET imaging agents in this context has also been
described.2f
2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203;
2; Fig. 1) is
a potent and selective member of the 2-(4-
aminophenyl)benzothiazole class of antitumour agents3a,b with
a novel cellular mechanism of action involving induction of the
cytochrome P450 isoform CYP1A1 in selected cancer cells.3c,d The
presence of a fluorine atom on the benzothiazole ring was found to
* Corresponding author. Tel.: þ44 2920 875800; fax: þ44 2920 874149; e-mail
address: WestwellA@cf.ac.uk (A.D. Westwell).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.004

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A.A. Weekes et al. / Tetrahedron 67 (2011) 7743e7747
a putative dihydrobenzothiazole product has necessitated the fur-
ther addition of an external oxidant in a number of cases (Scheme
1), under both thermal5a and microwave-promoted conditions.5b
Although 2-aminothiophenol is readily available, the synthesis of
ring-substituted 2-aminothiophenols presents particular difficul-
ties due to their instability and propensity towards oxidation/
degradation.
We have previously described the regiospecific synthesis of 2-
phenylbenzothiazoles in moderate yields from the reaction of sta-
ble ortho-aminothiophenol disulfides with benzaldehydes, using
triphenylphosphine to reduce the disulfide bond in situ prior to
reaction with the benzaldehyde (Scheme 2).3g This method has re-
quired the use of column chromatography for final purification to
remove the triphenylphosphine by-product. We now report an op-
Scheme 1. General synthetic routes to 2-phenylbenzothiazole from o-aminothiophenol.
Alternative synthetic routes to 2-phenylbenzothiazoles have
been developed. For example thioanilide (Jacobsen) cyclisation has
been commonly used (Scheme 2), particularly where substituents
on the benzothiazole ring are required, such as in the antitumour 2-
(4-aminophenyl)benzothiazole series.3c,e However, this thioamide
cyclisation reaction onto the ortho-position gives rise to regioiso-
meric product mixtures in certain cases (such as the 5-fluoro-2-
phenylbenzothiazole antitumour agents), necessitating in-
stallation of an ortho-halide group to direct thioanilide cyclisation.6
The necessity to synthesise thioamides using agents such as the
toxic and malodorous Lawesson’s reagent is a further limitation of
this method, which is generally not applicable to substrates con-
taining other carbonyl functionalities.
erationally simple and concise route to substituted 2-
phenylbenzothiazoles from ortho-aminothiophenol disulfides and
benzaldehydes, using sodium metabisulfite as an oxidant9 to give
a rangeof benzothiazole products in highyield and without the need
for column chromatography. Remarkably these new reaction con-
ditions allow clean synthesis of benzothiazole product in just a few
hours without the need for a reducing agent to initiate reaction.
2. Results and discussion
2.1. Synthesis of 2-phenylbenzothiazoles containing
benzothiazole-ring substituents
The starting point for our new benzothiazole synthesis was the
substituted 2-aminothiophenol disulfides 5aeh. The required 5-
substituted 2-aminothiophenol disulfides (5a, 5ceg) can be syn-
thesised as stable solid products from the corresponding commer-
cially available 2-amino-6-substituted benzothiazoles via potassium
hydroxide-mediated hydrolytic cleavage followed by air oxidation,
according to previously published methods.3e,10,11 2-Amino-5-
fluorobenzothiazole was synthesised from 3-fluoroaniline as pre-
viously described, and was converted to 2-amino-4-fluorothiophenol
disulfide (5b) by the basic hydrolysis/oxidation method.3e Unsub-
stituted 2-aminothiophenol disulfide (5h) is commercially available
(SigmaeAldrich, U.K; 97% purity). It is noteworthy that the 2-
aminothiophenol disulfide substrates prepared by this method exist
as stable powders that are easily handled. In comparison unsub-
stituted2-aminothiophenol(substituted2-aminothiophenolsarenot
generally commercially available) is a harmful and corrosive liquid
with toxic effects in the aquatic environment. In this respect 2-
aminothiophenol disulfide represents an environmentally attractive
alternative for benzothiazole synthesis.
The key step in the synthesis involves reaction of substituted 2-
aminothiophenol disulfides (5aeh) with benzaldehydes 6ael
containing both electron-donating (e.g., OMe) and electron-
withdrawing (e.g., CN, NO2) groups, promoted by the non-toxic
and inexpensive oxidant sodium metabisulfite (Na2S2O5) in DMSO
at 120 ꢀC. Reaction progress was monitored by TLC, with complete
formation of benzothiazole product in 40e90 min. Product iso-
lation and purification was straightforward, involving addition of
water to precipitate the product with further aqueous washing to
remove traces of inorganic by-products derived from sodium
metabisulfite. This simple workup procedure gave pure benzo-
thiazole products (7aae7hc) without the need for purification by
column chromatography; although recrystallisation of product was
necessary in some cases (Scheme 3). Isolated product yields in the
Scheme 2. Alternative synthetic routes to 2-phenylbenzothiazoles, including products
containing benzothiazole-ring substituents.
Ma and co-workers have recently described an attractive alter-
native route to 2-substituted benzothiazoles from 2-haloanilides
using sodium sulfide (Na2S$9H2O) as coupling partner under cop-
per (I)-catalysed conditions (Scheme 2).7 Reports of transition
metal-catalysed carbonecarbon bond forming reactions between
2-halobenzothiazoles and leaving group-containing aryl rings (e.g.,
aryl Grignards in the KumadaeTamaoeCoriu reaction)8 have also
been increasing in recent years (Scheme 2).

A.A. Weekes et al. / Tetrahedron 67 (2011) 7743e7747
7745
majority of cases were >80% (Table 1). A further notable feature of
this method is the ability to synthesise phenolic benzothiazoles
without the need for phenol protecting groups (products 7ae, 7af,
7cf, 7de, 7df, 7fe and 7ff).
benzaldehydes under oxidising reaction conditions; our working hy-
pothesis for the possible reaction mechanism(s) is overviewed in
Scheme 4. We assume that the amino group of substituted 2-
aminothiophenol disulfide (A) initially reacts with the benzaldehyde
Scheme 3. Synthesis of substituted 2-phenylbenzothiazoles using sodium metabisulfite as oxidant.
Table 1
to form the imine disulfide compound denoted (B). Cyclisation of the
disulfide onto the imine would then lead to intermediate (C), followed
by spontaneous disulfide bond cleavage to give (D), the tautomer of
the 2-phenylbenzothiazole product, and iminothiophenol (E). The
iminothiophenol (E) could then either cyclise onto the imine to gen-
erate dihydrobenzothiazole (G), or be re-oxidised to intermediate (B),
which would then cyclise to further benzothiazole product via (C) and
(D). An alternative mechanistic explanation involves the exchange of
disulfide and thiol forms in equilibrium in DMSO, although it should
be noted that the unsubstitutedthiophenol disulfide(5h)wasfoundto
be entirely stable in DMSO-d6 by NMR, even upon heating. It is known
that the interchange between alkyl disulfides and thiolates is de-
pendent on choice of solvent, and that solvents with high dielectric
constants, such as DMSO and DMFincreasetherateof interchange.13 It
is alsopossiblethata small amountofwater presentinthe ‘anhydrous’
DMSO used would react with sodium metabisulfite to produce SO2,
which would act as a reductant to facilitate formation of thiophenol,
either before or after initial reaction with substituted benzaldehyde.
Such disulfideethiol interchange would lead to the formation of in-
termediates such as (E) and (F), which could then cyclise to the dihy-
drobenzothiazole(G)andsubsequentlytoproductundertheoxidising
conditions of the reaction.
Substituted 2-phenylbenzothiazole product designations and yields
Cpd.
R
R0
Yield (%) Cpd.
R
R0
Yield (%)
7aa 6-F
7ab 6-F
7ac 6-F
7ad 6-F
7ae 6-F
7af 6-F
7ag 6-F
7ah 6-F
7ai 6-F
7aj 6-F
7ak 6-F
7bc 5-F
7bk 5-F
7ca 6-Cl
7cb 6-Cl
7cc 6-Cl
7cd 6-Cl
7cf 6-Cl
4-OMe
3-OMe
3,4-DiOMe
3,4,5-TriOMe 97
4-OH
3-OH
3-F
3-Cl
88
84
83
7db 6-OEt 3-OMe
7dc 6-OEt 3,4-DiOMe
7dd 6-OEt 3,4,5-TriOMe 82
92
91
7de 6-OEt 4-OH
7df 6-OEt 3-OH
7dg 6-OEt 3-F
7dh 6-OEt 3-Cl
7di 6-OEt 4-Br
7dj 6-OEt 4-CN
7dk 6-OEt 4-NO2
7dl 6-OEt 3-NO2
7ec 6-OMe 3,4-DiOMe
7fa 6-Me
7fc 6-Me
7fd 6-Me
7fe 6-Me
91
93
84
67
93
82
86
80
93
94
81
91
93
91
91
89
86
96
87
90
83
89
88
4-Br
4-CN
4-NO2
3,4-DiOMe
4-NO2
4-OMe
3-OMe
3,4-DiOMe
3,4,5-TriOMe 84
3-OH
4-Br
4-OMe
3,4-DiOMe
3,4,5-TriOMe 84
4-OH
3-OH
3-Cl
90
86
90
83
91
7ff
7fh 6-Me
7fi 6-Me
7gc 6-NO2 3,4-DiOMe
7gd 6-NO2 3,4,5-TriOMe 88
7hc 3,4-DiOMe 72
6-Me
90
85
95
90
91
88
7ci
7cj
7ck 6-Cl
7cl 6-Cl
6-Cl
6-Cl
4-Br
4-CN
4-NO2
3-NO2
H
7da 6-OEt 4-OMe
3. Conclusion
2.2. Mechanistic considerations
Substituted 2-phenylbenzothiazoles containing benzothiazole-
ring substituents are an important class of molecules from both
a disease diagnostic and therapeutic standpoint. There are relatively
few reported methods for the synthesis of 2-phenylbenzothiazoles
containing benzothiazole-ring substituents compared to their
non-substituted counterparts. Here we present an operationally
simple route to substituted 2-phenylbenzothiazoles containing
a diversity of ring substituents, through heating thiophenol disul-
fides with commercially available benzaldehydes in the presence of
sodium metabisulfite in DMSO. Our method features short reaction
times (<2 h) and simple workup leading to the isolation of pure
benzothiazole products without the need for column chromato-
graphic purification, and is applicable to the synthesis of a wide
range of substituted 2-phenylbenzothiazoles.
Our previously reported protocol for substituted 2-
phenylbenzothiazole synthesis made use of triphenylphosphine, a re-
agent previously reported for the reduction of disulfides to the corre-
sponding thiols.3g,12 Reduction of the substituted thiophenol disulfide
to the corresponding thiophenol using triphenylphosphine was as-
sumed to be a necessary pre-requisite to the condensation/cyclisation
reaction with benzaldehydes to form 2-phenylbenzothiazoles. In-
triguingly, in our new protocol we were able to efficiently react
substituted thiophenol disulfides with benzaldehydes to form 2-
phenylbenzothiazoles within an apparent oxidising environment
(Na2S2O5 in DMSO). The ‘oxidised’ nature of our disulfide starting
materials was confirmed by analytical methods (NMR and mass
spectrometry, by comparison to previously reported compounds3g),
and by their physical appearance as pale yellow solids (disulfide)
rather than oils (thiol). Furthermore the commercially available
unsubstituted thiophenol disulfide (5h), supplied in 97% purity (Sig-
maeAldrich, U.K.), reacted smoothly with 3,4-dimethoxybenzald
ehyde (6c) to give 2-(3,4-dimethoxyphenyl)benzothiazole (7hc) in
72% yield within 2 h.
4. Experimental
4.1. General methods
Our new method describes the synthesis of substituted 2-
Melting points were measured on a Griffin melting point ap-
paratus and are uncorrected. 1H (500 MHz), 13C NMR (125 MHz)
phenylbenzothiazoles
from
thiophenol
disulfides
and

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A.A. Weekes et al. / Tetrahedron 67 (2011) 7743e7747
Scheme 4. Postulated mechanism for formation of substituted 2-phenylbenzothiazoles under ‘oxidising’ conditions.
and 19F NMR (471 MHz) spectra were recorded on a Bruker AVANCE
500 MHz instrument; chemical shift values are in parts per million
and coupling constants (J values) are in hertz. Mass spectra were
recorded on a Bruker MicroTOF LC instrument or at the EPSRC
National Mass Spectrometry Centre (Swansea, U.K.). All commer-
cially available starting materials were used without further puri-
fication, and synthesis of the required 2-aminothiophenol disulfide
starting materials (5aeg) was carried out according to well estab-
lished literature methods as described in the chemistry results
section. Compound 5h is commercially available (SigmaeAldrich).
5.0 Hz, H-4), 7.66e7.58 (3H, m, H-7, H-20, H-60), 7.42 (1H, t, J 8.2 Hz,
H-50), 7.25 (1H, dt, J 9.0, 2.5 Hz, H-5), 7.08e7.06 (1H, m, H-40), 3.94
(3H, s, OCH3); dC (125 MHz, CDCl3) 167.7, 161.5, 159.7 (d, J 270 Hz),
150.7, 136.1 (d, J 10.0 Hz), 134.6, 130.1, 124.2 (d, J 10.0 Hz), 120.1,
117.4, 115.0 (d, J 25.0 Hz), 112.0, 107.8 (d, J 26.3 Hz), 55.5; dF
(471 MHz, CDCl3) 115.76; m/z (EI) 259 (100, Mþ).
4.3.2. 6-Fluoro-2-(3-fluorophenyl)benzothiazole (7ag). Bis(2-amino-
5-fluorophenyl)disulfide and 3-fluorobenzaldehyde were reacted to
give the title compound 7ag (196 mg, 91%) as a yellow solid, mp
102e104 ꢀC; [Found: C, 63.0; H, 2.8; N, 5.6. C13H6F2NS requires C,
63.15; H, 2.85; N, 5.66%]; dH (500 MHz, CDCl3) 8.05 (1H, dd, J 7.5,
4.5 Hz, ArH), 7.84e7.81 (2H, m, ArH), 7.62 (1H, dd, J 8.0, 2.5 Hz, ArH),
7.51e7.47 (1H, m, ArH), 7.27e7.20 (2H, m, ArH). dC (125 MHz, CDCl3)
165.7 (d, J 250 Hz), 163.4, 161.2 (d, J 265 Hz), 159.0, 150.2, 134.8 (d, J
8.8 Hz), 131.6 (d, J 8.8 Hz), 124.4 (d, J 10.0 Hz), 123.5, 118.3 (d, J
21.3 Hz),115.4 (d, J 23.8 Hz),113.5 (d, J 23.8 Hz),108.8 (d, J 27.5 Hz); dF
(471 MHz, CDCl3) 115.37, 111.92; m/z (EI) 247 (100, Mþ).
4.2. General procedure for the synthesis of substituted 2-
phenylbenzothiazoles
The appropriate 4- or 5-substituted 2-aminothiophenol disulfide
(0.86 mmol), substituted benzaldehyde (0.88 mmol) and sodium
metabisulfite (0.88 mmol) were dissolved in anhydrous DMSO
(5 mL). The resulting reaction mixture was stirred at 120 ꢀC and the
formation of the desired compound monitored by TLC analysis. On
completion of reaction (in most cases between 40 and 90 min) the
mixture was cooled to room temperature, water was added and the
resulting precipitate was collected by vacuum filtration. The pre-
cipitate was then washed with excess water, re-dissolved in
dichloromethane (25 mL) and the remaining traces of sodium
metabisulfite were removed by washing with brine (25 mL). The
organic layer was dried (MgSO4) and the solvent removed in vacuo.
In a minority of cases further purification was required, and the
product was either recrystallised or washed through a plug of silica
(using dichloromethane as eluent) and reduced to dryness.
4.3.3. 2-(3-Chlorophenyl)-6-fluorobenzothiazole (7ah). Bis(2-amino-
5-fluorophenyl)disulfide and 3-chlorobenzaldehyde were reacted to
give the title compound 7ah (210 mg, 91%) as a pale green solid, mp
101e103 ꢀC; [Found: C, 59.2; H, 2.8; N, 5.4. C13H7ClFNS requires C,
59.21; H, 2.68; N, 5.31%]; dH (500 MHz, CDCl3) 8.11 (1H, t, J 1.5 Hz, H-
20), 8.05 (1H, dd, J 9.0, 5.0 Hz, H-7), 7.93 (1H, dt, J 7.5, 1.5 Hz, H-4), 7.62
(1H, dd, J 8.0, 2.5 Hz, H-60), 7.50e7.40 (2H, m, H-40, H-50), 7.35e7.28
(1H, m, H-5); dC (125 MHz, CDCl3) 166.0, 161.7, 159.7, 150.6, 136.1 (d, J
11.3 Hz), 135.1 (d, J 28.8 Hz), 130.9, 130.3, 127.3, 125.6, 124.4 (d, J
8.8 Hz), 115.3 (d, J 23.8 Hz), 107.9 (d, J 26.3 Hz); dF (471 MHz, CDCl3)
115.10; m/z (EI) 263 (100, Mþ).
4.3. Spectroscopic and characterisation data for selected
representative new substituted 2-phenylbenzothiazoles
4.3.4. 2-(4-Bromophenyl)-6-fluorobenzothiazole (7ai). Bis(2-amino-
5-fluorophenyl)disulfide and 4-bromobenzaldehyde were reacted to
give the title compound 7ai (240 mg, 89%) as a pale green solid, mp
144e146 ꢀC; dH (500 MHz, CDCl3) 8.04 (1H, dd, J 9.0, 4.5 Hz, H-4), 7.96
(2H, d, J 8.5 Hz, H-30, H-50), 7.66 (2H, d, J 8.5 Hz, H-20, H-60), 7.61 (1H,
dd, J 7.5, 2.5 Hz, H-7), 7.27 (1H, dt, J 7.5, 2.5 Hz, H-5); dC (125 MHz,
CDCl3) 166.4 (d, J 3.8 Hz), 161.6,159.6,150.7,136.0 (d, J 11.3 Hz), 132.3,
4.3.1. 6-Fluoro-2-(3-methoxyphenyl)benzothiazole
(7ab). Bis(2-
amino-5-fluorophenyl)disulfide and m-anisaldehyde were reacted
to give the title compound 7ab (190 mg, 84%) as a pale green solid,
mp 84e86 ꢀC; [Found: C, 64.8; H, 4.0; N, 5.6. C14H10FNOS requires C,
64.85; H, 3.89; N, 5.40%]; dH (500 MHz, CDCl3) 8.04 (1H, dd, J 9.0,

A.A. Weekes et al. / Tetrahedron 67 (2011) 7743e7747
7747
128.8,125.5, 124.3 (d, J 8.8 Hz),115.2 (d, J 25.0 Hz),107.9 (d, J 26.3 Hz);
References and notes
dF (471 MHz, CDCl3) 115.31; m/z (EI) 307/309 (100, Mþ); HRMS (EI):
Mþ, found 306.9461. C13H7BrFNS requires 306.9467.
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4.3.5. 4-(6-Fluorobenzothiazol-2-yl)benzonitrile
(7aj). Bis(2-
amino-5-fluorophenyl)disulfide and 4-cyanobenzaldehyde were
reacted to give the title compound 7aj (190 mg, 86%) as a yellow
solid, mp 218e220 ꢀC; dH (500 MHz, CDCl3) 8.38 (2H, d, J 9.0 Hz, H-
20, H-60), 8.26 (2H, d, J 9.0 Hz, H-30, H-50), 8.10 (1H, dd, J 8.5, 5.0 Hz,
H-4), 7.66 (1H, dd, J 8.5, 2.5 Hz, H-7), 7.32 (1H, td, J 8.5, 2.5 Hz, H-5);
dC (125 MHz, DMSO-d6) 165.0, 161.2, 159.3, 150.4, 148.8, 138.1, 136.4
(d, J 12.5 Hz), 128.3, 124.9 (d, J 10.0 Hz), 124.6, 115.8 (d, J 25.0 Hz),
109.0 (d, J 27.5 Hz); dF (471 MHz, CDCl3) 113.79. m/z (EI) 254 (100,
Mþ); HRMS (EI): Mþ, found 254.0312. C14H7FN2S requires 254.0314.
4.3.6. 2-(4-Bromophenyl)-6-ethoxybenzothiazole
(7di). Bis(2-
amino-5-ethoxyphenyl)disulfide and 4-bromobenzaldehyde were
reacted to give the title compound 7di (270 mg, 93%) as a white
solid, mp 130e133 ꢀC; dH (500 MHz, CDCl3) 7.92 (1H, d, J 9.0 Hz, H-
4), 7.91 (2H, d, J 8.5 Hz, H-30, H-50), 7.61 (2H, d, J 8.5 Hz, H-20, H-60),
7.34 (1H, d, J 2.5 Hz, H-7), 7.10 (1H, dd, J 8.5, 2.5 Hz, H-5), 4.13 (2H, q,
J 7.0 Hz, OCH2), 1.49 (3H, t, J 7.0 Hz, CH3). dC (125 MHz, CDCl3)
164.03, 157.34, 148.56, 136.44, 132.76, 132.16, 128.59, 124.83, 123.80,
116.30, 104.87, 64.15, 14.82; m/z (EI) 333/335 (100, Mþ); HRMS (EI):
Mþ, found 332.9822. C15H12BrNOS requires 332.9823.
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We thank the Welsh School of Pharmacy, Cardiff University for
financial support in the form of a Ph.D. studentship (to A.A.W.), and
EPSRC National Mass Spectrometry Centre (Swansea, U.K.) for an-
alytical support.
Supplementary data
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Characterisation data (mp, NMR, MS) for previously reported
substituted 2-phenylbenzothiazole products (7aa, 7aceaf, 7ak,
7bcebk, 7caecl, 7daeah, 7djel, 7ec, 7faefi, 7gcegd). Supplementary
data associated with this article can be found, in the online version, at
doi:10.1016/j.tet.2011.08.004.
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