Iodine-mediated cyclisation of thiobenzamides to produce benzothiazoles and benzoxazoles

Article abstract of DOI:10.1016/j.tet.2007.07.076

Synthesis of benzothiazoles by reaction of iodine with thiobenzamides, which do not possess an ortho alkoxy or ester group, is described. The unlikely synthesis of benzoxazoles from reaction of 2-alkoxythiobenzamides with iodine is also reported.

Full text of DOI:10.1016/j.tet.2007.07.076

Tetrahedron 63 (2007) 10276–10281
Iodine-mediated cyclisation of thiobenzamides to produce
benzothiazoles and benzoxazoles
*
Nadale K. Downer-Riley and Yvette A. Jackson
Department of Chemistry, University of the West Indies, Mona, Kingston 7, Jamaica
Received 26 March 2007; revised 7 July 2007; accepted 20 July 2007
Available online 29 July 2007
Abstract—Synthesis of benzothiazoles by reaction of iodine with thiobenzamides, which do not possess an ortho alkoxy or ester group, is
described. The unlikely synthesis of benzoxazoles from reaction of 2-alkoxythiobenzamides with iodine is also reported.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
alternative to liquid bromine in the cyclisation of arylthio-
ureas to 2-aminobenzothiazoles has since been reported, in
which these disadvantages are eliminated.5
Synthesis of 2-substituted benzothiazoles is of interest due to
their cyctotoxicity as well as their possible use as precursors
to pharmacologically active natural products.1,2 Among the
methods of synthesis of these benzothiazoles, cyclisation of
the corresponding thiobenzamides has received much atten-
tion, and varying reagents—Dess–Martin periodinane, man-
ganese triacetate, radiation, tributyltin hydride and AIBN,
NaH and NMP, potassium carbonate in acetone, palladium,
copper, butyllithium, potassium ferricyanide with base—
have been used.3
Iodine, which is available as a crystalline solid, is easier to
handle and less toxic than liquid bromine. The ability of
iodine to act as an oxidant as well as a Lewis acid has
been exploited in the cyclisation of thiols and disulfides to
produce benzothiophenes, dihydronaphthothiophenes, dihy-
dronaphthopyrans and thiazinones.6–8 The use of iodine in
cyclisation of thiobenzamides to benzothiazoles, however,
has not been reported. We set out to investigate this.
Bromine has also been used to good effect for this cyclisa-
tion, and in this case the reaction is thought to occur via a
sulfenyl bromide, which is subsequently attacked by the
p-system of the aromatic ring , similar to the pathway shown
in Scheme 1.4 Bromine is, however, a toxic and corrosive re-
agent. Furthermore, the measurement of stoichiometric
amounts for small scale reactions is difficult and there is
therefore a high risk of forming brominated side products.
The use of benzyltrimethylammonium tribromide as an
2. Results and discussion
We first explored the reaction of 2-methoxythiobenzamides
with iodine. This reaction was expected to occur via the sul-
fenyl iodide, as in the reaction with bromine (Scheme 1).
Cyclisation of arylthioureas with bromine in chloroform
was found to require heating at reflux for 2.5 h.5 After stir-
ring a mixture of thiobenzamides 1–3 and iodine (2 mol
OMe
OMe
OMe
H
N
H
N
Ph
N
Ph
Br
Ph
-HBr
Br2
S
S
S
Br Br
OMe
OMe
N
Ph
N
S
Ph
S
H
Br
Scheme 1.
Keywords: Benzoxazoles; Benzothiazoles; Iodine-mediated cyclisation; Thiobenzamides.
* Corresponding author. E-mail: yvette.jackson@uwimona.edu.jm
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.07.076

N. K. Downer-Riley, Y. A. Jackson / Tetrahedron 63 (2007) 10276–10281
10277
Br
equiv) in refluxing chloroform, benzene or toluene for up to
OMe
H
N
H
N
Ph
Ph
a day, however, only the starting material was recovered.
This was thought to be due to lack of formation of the sul-
fenyl iodide. In order to promote formation of the sulfenyl
iodide, NaH was added to a solution of each thiobenzamide
in benzene followed by addition of iodine. Reaction of thio-
carbonyls with a halogen in the presence of hydroxide ions is
known to produce the corresponding carbonyl compound.9
Scrupulously dry conditions were therefore maintained. In
each case, a mixture of thiobenzamide 1a–c and NaH
(1.2 mol equiv) in dry benzene was heated at reflux for
15 min. Addition of iodine (2 mol equiv) to this mixture,
and heating at reflux for a further 2 h, surprisingly, yielded
the corresponding 2-phenylbenzoxazoles 2a–c as the major
product (Scheme 2).
O
O
R1
R2
3a R1 = R2 = H
3d
3b R1 = H, R2 = OMe
3c R1 = R2 = OMe
These reactions, however, yielded only the starting material
in the case of compounds 3b–d, whereas 2-methoxybenz-
amide (3a) gave 2-phenylbenzoxazole (1a, 25%—identical
to a sample prepared by condensation of o-aminophenol
with benzoyl chloride), possibly via an addition–elimination
reaction (Scheme 4).12 The reluctance of 2-bromobenz-
amide (3d) to cyclise under these conditions indicated that
the imidol radical was not being generated. It is also clear
that reaction of 1a–c as outlined in Scheme 2 does not
involve initial conversion to the corresponding benzamide.
OMe
H
R2
R1
N
Ph
N
O
NaH, I2
Ph
S
R1
benzene, reflux
R2
It seems, then, that in the NaH/I2 cyclisation of thiobenz-
amides 1a–c to benzoxazoles 2a–c, the oxygen atom of the
benzoxazole moiety is from the methoxy group ortho to
the thiobenzamide functionality. Thiolate ions are known
to effect demethylation of aryl alkyl ether.2 If the thiolate
anion, produced by reaction of thiobenzamide with base,
was capable of demethylating the ortho methoxy group,
the phenolate anion thus produced could go on to form the
benzoxazole (Scheme 5).
1a R1 = R2 = H
2a (95 %)
2b (80 %)
2c (39 %)
1b R1 = H, R2 = OMe
1c R1 = R2 = OMe
Scheme 2.
In our experience, the reaction of o-methoxythiobenzamides
with AIBN brought about cyclisation to benzothiazoles, with
loss of a methoxy group as a radical.10 Reaction of thiobenz-
amides 1a–c to produce benzoxazoles 2a–c (Scheme 2),
with loss of methoxy radical could occur via the imidol
radical as shown in Scheme 3, but would suggest initial
formation of the corresponding benzamide. Irradiation of
2-halogenobenzamides in alkaline solution has also been
reported to yield benzoxazoles via an imidol radical.11
H3C
N
O
Ph
O
N
O
Ph
H
N
Ph
S
S
CH3
S
CH3
N
O
N
O
OMe
OMe
OMe
Ph
S
H
N
H
N
Ph
Ph
Ph
N
Ph
CH3
R
R
R
S
O
O
Scheme 5.
imidolate anion
In order to avoid the formation of thiolate anion, thiobenz-
amides 1a–c were treated with iodine in the absence of
base. Heating a solution of the thiobenzamides 1a–c in chlo-
robenzene with 2 mol equiv iodine at reflux for 12 h
produced, as in the case of the reaction with NaH/I2 in benz-
ene (Scheme 2), benzoxazoles 2a–c in yields of 42–81%
(Table 1). No reaction was observed when benzene or tolu-
ene was used as solvent.
OMe
N
Ph
N
Ph
R
R
O
O
imidol radical
Scheme 3.
Benzamide formation should have been precluded by the
dry reaction conditions. This was, however, investigated
by treatment of benzamides 3a–d with NaH/I2 under similar
conditions as for 1a–c.
Thiolate anion formation and demethylation, therefore,
were not necessary for benzoxazole formation. A rational
mechanism for the iodine-mediated cyclisation of
H
Ph
N
N
Ph
N
O
N
O
NaH
-[OMe]
Ph
Ph
O
O
OMe
OMe
3a
OMe
1a
Scheme 4.

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N. K. Downer-Riley, Y. A. Jackson / Tetrahedron 63 (2007) 10276–10281
Table 1. Thiobenzamide cyclisation using iodine
alkylated by reaction with the respective alkyl iodide and
potassium carbonate in acetone and tosylated by reaction
with p-toluenesulfonyl chloride in pyridine. The nitro com-
pounds were then reduced using hydrogen and catalyst, con-
densed with benzoyl chloride and the resultant benzamide
thionated using Lawesson’s reagent. Attempted reaction of
o-nitrophenol with tert-butyl iodide in a bid to synthesise
o-tert-butoxythiobenzamide was unsuccessful.
R1
R1
H
N
Ph
N
O
N
S
R2
R2
Ph
R2
Ph
or
S
9
10
2
R1
R2
H
NaH, I2/benzene I2/chlorobenzene I2/nitrobenzene
(% yield)
(% yield)
(% yield)
1a OMe
2a (95)
2b (80)
1c OMe 4,5-OMe 2c (39)
2a (73)
2b (81)
2c (42)
2a (83)
2a (68)
2a (40)
10a (56)
10b (70)
—
OH
OR
OR
1b OMe 4-OMe
2b (83)
2c (51)
—
NO2
NO2
NH2
i or ii
iii
8a OEt H
8b O-i-Pr H
8c OTs
2a (96)
2a (70)
2a (76)
—
—
—
—
5a R = Et
5b R = i-Pr
5c R = Ts
4
H
6
9a2
H
H
H
H
H
3-OMe 10a (67)
4-OMe 10b (27)
3,4-OMe 10c (87)
2-Br
H
9b2
9c2
iv
10c (73)
10c (84)
a
a
a
9d12
9e14
a
a
a
OR
H
OR
H
N
N
Ph
N
Ph
a
v
vi
Starting material was recovered from the reaction mixture.
Ph
S
O
O
1b
7
o-methoxythiobenzamides has therefore been proposed. The
sulfenyl iodide produced by reaction of iodine with thio-
benzamide is probably attacked by the oxygen atom of the
methoxy group, producing benzoxazole with loss of hydro-
gen iodide, methyl iodide and sulfur (Scheme 6).
8
Scheme 7. Reagents: (i) MeI or i-PrI, K2CO3, acetone, reflux; (ii) p-TsCl,
pyridine, 90 ꢀC; (iii) H2, Pd/C, MeOH; (iv) benzoyl chloride, pyridine, tol-
uene, reflux; (v) Lawesson’s reagent, toluene, reflux; (vi) NaH, I2, benzene,
reflux or I2, chlorobenzene, reflux.
Reaction of the o-ethoxythiobenzamide 8a and o-isopropoxy-
thiobenzamide 8b with iodine/chlorobenzene or iodine/NaH/
benzene resulted in formation of 2-phenylbenzoxazole (2a)
(68–96% yield). The iso-propoxy group did not hinder
benzoxazole formation. Reaction of thiobenzamide 8c
with iodine/chlorobenzene and iodine/NaH/benzene also
resulted in benzoxazole 2a (76 and 40%, respectively,
Table 1).
Reaction with chlorobenzene/I2 in benzene effected cyclisa-
tion in 12 h. Using chlorobenzene/TFA (4:1) or nitrobenzene
as solvent lessened the reaction time to 2 h. Use of K2CO3 in
place of NaH resulted only in conversion to the correspond-
ing benzamides.
We also explored the reaction of 2-ethoxy- and 2-isoprop-
oxythiobenzamides 8a,b as well as o-thiobenzamide tosyl
ester 8c with iodine. Based on the mechanism proposed
for benzoxazole formation from o-methoxythiobenzamides
(Scheme 6), bulky alkyl groups (such as tert-butyl and
isopropyl) could deter benzoxazole formation by preventing
attack of the sulfenyl iodide by the ortho oxygen. In addition
to being bulky, the tosyl group also reduces the nucleophilic
nature of the oxygen, rendering the ortho oxygen less
likely to attack the sulfenyl iodide. o-Ethoxythiobenzamide
8a was expected to react similarly to o-methoxy-
thiobenzamide 1.
We considered this reaction of tosyl ester 8c to be unusual,
and thus subjected various tosyl esters, which do not possess
the o-thiobenzamide moiety, to similar reaction with iodine.
In all cases, only the starting material was recovered, indi-
cating that detosylation was not a factor in formation of
benzoxazoles from compound 8c.
Based on these findings, it is apparent that cyclisation of
thiobenzamides will not occur to give benzothiazoles when
an ortho alkoxy or ester group is in place. We next explored
the reaction of known thiobenzamides 9a–e, which do
not possess the ortho methoxy group, with iodine. The
The desired thiobenzamides were synthesised from 2-nitro-
phenol (4) as shown in Scheme 7. o-Nitrophenol (4) was
H
N
H
N
H
Ph
N
Ph
Ph
S
I2
I
I
S
O
S
O
I
O
CH3
CH3
CH3
I
N
O
Ph
MeI + HSI
HI + S
Scheme 6.

N. K. Downer-Riley, Y. A. Jackson / Tetrahedron 63 (2007) 10276–10281
10279
corresponding benzothiazoles 10a–c were obtained from
thiobenzamides 9a–c in yields of up to 87% after heating
overnight with iodine in refluxing chlorobenzene or heating
with sodium hydride and iodine in refluxing benzene for 2 h
(Table 1). Treatment of thiobenzamides 9d and 9e with NaH
and iodine in benzene, however, yielded the unconverted
starting material. The primary rings of thiobenzamides 9d
and 9e possess low electron densities and as such are un-
likely to be involved in nucleophilic attack of the sulfenyl
halide.
3.4.1. 2-Ethoxyaniline (6a). Isolated as a purple oil (lit.17
bp, 224–229 ꢀC).
3.4.2. 2-Isopropoxyaniline (6b). Isolated as purple needles;
mp 137–139 ꢀC (lit.18 134–135 ꢀC).
3.4.3. 2-Aminophenyl 4-methylbenzenesulfonate (6c).
Isolated as light brown cubes; mp 94–96 ꢀC; nmax/cmꢁ1
3509, 3413, 1622; (Found: C, 59.00; H, 5.00; N, 5.32%.
Calcd for C13H13NO3S: C, 59.30; H, 4.98; N, 5.25%.) dH
2.46 (3H, s, CH3), 3.54 (2H, s, NH2), 6.60 (1H, m, 6-H),
6.75 (2H, m, 4,5-H), 7.02 (1H, m, 3-H), 7.32 (2H, d, J 8.3,
tosyl), 7.78 (2H, d, J 8.2, tosyl); dC 21.7, 117.2, 118.3,
122.9, 127.8, 128.5, 129.8, 132.7, 137.0, 139.6, 145.5.
In conclusion, iodine has been found to be useful for the for-
mation of benzothiazoles from thiobenzamides without an
ortho alkoxy or ester group and formation of benzoxazoles
from ortho alkoxythiobenzamides.
3.5. Preparation of benzamides
3. Experimental
3.1. General
To a solution of the aniline (1.0 g) in dry toluene (6 mL) and
pyridine (5 mL) was added benzoyl chloride (1.1 mol
equiv). The mixture was heated at reflux for 1 h then poured
into water (100 mL) and extracted with ethyl acetate
(30 mL). The organic solution was washed with 1 M HCl
(50 mL), 5% aqueous sodium bicarbonate (50 mL) then
water (50 mL), dried (Na2SO4) and concentrated in vacuo.
IR spectra were obtained on a Perkin–Elmer 735B FTIR
spectrometer as KBr discs. NMR spectra (Bruker 200 and
500 MHz) were obtained in CDCl3 solution and the reso-
nances are reported in d units downfield from TMS as an in-
ternal standard; J values are given in hertz. Elemental
analyses were carried out by MEDAC Ltd., Egham, Surrey,
UK. Column chromatography was carried out using silica
gel as adsorbent.
3.5.1. N-(2-Ethoxyphenyl)benzamide (7a). Isolated as
a yellow-brown oil, which was purified by column chroma-
tography using CH2Cl2 as the eluent (85%, lit.19 mp 104 ꢀC);
Rf (CH2Cl2) 0.73; nmax/cmꢁ1 1656, 1605; dH 1.44 (3H, t,
J 6.9, CH3), 4.13 (2H, q, J 7.1, CH2), 6.93 (1H, m, 3-H),
7.02 (1H, m, 5-H), 7.15 (1H, m, 4-H), 7.44 (3H, m,
30,40,50-H), 7.83 (2H, m, 20,60-H), 9.18 (1H, m, 6-H), 9.73
(1H, s, N–H); dC 14.8, 64.5, 111.3, 120.3, 121.4, 126.4,
126.7, 128.6, 128.8, 130.9, 144.1, 149.2.
3.2. Alkylation of 2-nitrophenol (4)
To a solution of 2-nitrophenol (3.77 g, 27.1 mmol) in ace-
tone (50 mL) was added potassium carbonate (3.77 g,
27.3 mmol) followed by alkyl iodide (1.2 mol equiv). The
mixture was heated at reflux for 4 h, cooled and then filtered.
The filtrate was poured into water (100 mL) and extracted
with dichloromethane (100 mL). The organic extract was
then dried (Na2SO4) and concentrated in vacuo to yield
a light yellow oil: 2-ethoxynitrobenzene (5a)15 (69%);
2-isopropoxynitrobenzene (5b)15 (82%).
3.5.2. N-(2-Isopropoxyphenyl)benzamide (7b). Isolated as
a yellow-brown oil, which was purified by column chroma-
tography using CH2Cl2 as the eluent (98%); (Found: C,
75.20; H, 6.58; N, 5.27%. Calcd for C16H17NO2: C, 75.27;
H, 6.71; N, 5.49%.) Rf (CH2Cl2) 0.80; nmax/cmꢁ1 3426,
1788; dH 1.39 (6H, d, J 6.0, CH3), 4.63 (1H, m, CH), 7.02
(1H, m, 3-H), 7.52 (3H, m, 30,40,50-H), 7.88 (2H, m, 20,60-
H), 8.14 (2H, m, 4,5-H), 8.57 (1H, m, 6-H), 8.69 (1H, s,
N–H); dC 22.3, 71.5, 112.7, 119.9, 121.1, 123.8, 127.0,
128.9, 130.6, 131.7, 134.6, 146.4, 165.0.
3.3. 2-Nitrophenyl 4-methylbenzenesulfonate (5c)
To a solution of 2-nitrophenol (4.05 g, 29.1 mmol) in pyri-
dine (10 mL) was added p-toluenesulfonyl chloride
(5.73 g, 30.0 mmol). The mixture was heated at 90 ꢀC for
20 min after which the mixture was poured into cold water
(200 mL). The resultant white solid was collected by filtra-
tion, washed with 3 M HCl (50 mL) followed by 5% aque-
ous NaOH (50 mL) and recrystallised from acetone/
hexanes as white needles (6.40 g, 75%), mp 78–79 ꢀC (ace-
tone/hexanes) (lit.16 81–82 ꢀC).
3.5.3. 2-(Benzoylamino)phenyl 4-methylbenzenesulfo-
nate (7c). Isolated as light brown cubes (87%), mp 105–
106 ꢀC (ethyl acetate/hexanes); (Found: C, 65.59; H, 4.61;
N, 3.77%. Calcd for C20H17NO4S: C, 65.38; H, 4.66; N,
3.81%.) nmax/cmꢁ1 3328, 1677; dH 2.36 (3H, s, CH3), 6.98
(2H, m, tosyl), 7.22 (3H, m, 3,4,5-H), 7.52 (3H, m,
30,40,50-H), 7.68 (2H, m, tosyl), 7.83 (2H, m, 20,60-H), 8.38
(2H, m, 6-H and N–H); dC 21.7, 122.9, 123.1, 124.6,
127.1, 127.9, 128.4, 128.8, 130.1, 131.3, 131.5, 132.2,
134.1, 139.3, 146.3, 165.0.
3.4. Reduction of nitro compounds
To a solution of the nitro compound (5.0 g) in methanol
(150 mL) was added 10% Pd/C (0.25 g). The mixture was
shaken in a Parr apparatus under an atmosphere of hydro-
gen (15 psi) for 4 h, filtered through Celite and concen-
trated to provide the corresponding aniline in quantitative
yield. The aniline was recrystallised from ethyl acetate/
hexanes.
3.6. Thionation of benzamides
To a solution of the benzamide (1.0 g) in dry toluene
(40 mL) was added Lawesson’s reagent (0.6 mol equiv).
The mixture was heated at reflux under an atmosphere of ni-
trogen for 2 h, after which it was concentrated and purified

10280
N. K. Downer-Riley, Y. A. Jackson / Tetrahedron 63 (2007) 10276–10281
by column chromatography or recrystallised from methanol
as yellow needles.
benzoxazole was then recrystallised from methanol as white
needles.
3.6.1. N-(2-Ethoxyphenyl)thiobenzamide (8a). Yield:
72%, mp 88–89 ꢀC (methanol); (Found: C, 70.17; H, 5.88;
N, 5.40%. Calcd for C15H15NOS: C, 70.01; H, 5.87; N,
5.45%.) nmax/cmꢁ1 1607, 928; dH 1.44 (3H, t, J 6.9, CH3),
4.13 (2H, q, J 7.0, CH2), 6.93 (1H, m, 3-H), 7.02 (1H, m,
5-H), 7.15 (1H, m, 4-H), 7.44 (3H, m, 30,40,50-H), 7.83
(2H, m, 20,60-H), 9.18 (1H, m, 6-H), 9.73 (1H, s, N–H); dC
14.8, 64.5, 111.3, 120.3, 121.4, 126.4, 126.7, 128.6, 128.8,
130.9, 144.1, 149.2.
3.7.1. 2-Phenylbenzoxazole (2a).12
(a) Yield: 95 and 73% from 1a using methods 1 and 2,
respectively.
(b) Yield: 96 and 83% from 8a using methods 1 and 2,
respectively.
(c) Yield: 70 and 68% from 8b using methods 1 and 2,
respectively.
(d) Yield: 76 and 40% from 8c using methods 1 and 2,
respectively.
(e) Yield: 25% from 3a using method 1.
3.6.2. N-(2-Isopropoxyphenyl)thiobenzamide (8b). Yield:
67%, mp 79–80 ꢀC (methanol); (Found: C, 70.75; H, 6.32;
N, 5.15%. Calcd for C16H17NOS: C, 70.81; H, 6.31; N,
5.16%.) nmax/cmꢁ1 3354, 2973; dH 1.35 (6H, d, J 5.7,
CH3), 4.62 (1H, m, CH), 6.96 (2H, m, 4,5-H), 7.14 (1H, d,
J 8.3, 3-H), 7.43 (3H, m, 30,40,50-H), 7.85 (2H, m, 20,60-H),
9.24 (1H, d, J 8.0, 6-H), 9.82 (1H, s, N–H); dC 22.3, 71.8,
112.8, 120.3, 121.3, 126.4, 126.7, 128.7, 131.1, 144.1,
148.1, 195.3.
3.7.2. 5-Methoxy-2-phenylbenzoxazole (2b). Yield: 80, 81
and 83% from 1b using methods 1, 2 and 3, respectively.
Mp 82–84 ꢀC (ethanol); (Found: C, 74.58; H, 4.87; N,
6.05%. Calcd for C14H11NO2: C, 74.65; H, 4.92; N,
6.22%.) nmax/cmꢁ1 2361, 1479; dH 3.85 (3H, s, OCH3),
6.94 (1H, dd, J 8.8 and 3.1, 6-H), 7.41 (1H, d, J 3.0, 4-H),
7.48 (4H, m, 30,40,50-H and 7-H), 8.21 (2H, m, 20,60-H); dC
55.9, 102.9, 110.7, 113.7, 127.3, 127.5, 128.9, 131.4,
142.9, 145.4, 157.4, 163.8.
3.6.3. 2-[(Phenylcarbonothioyl)amino]phenyl 4-methyl-
benzenesulfonate (8c). Yield: 73%, mp 121–123 ꢀC (meth-
anol); (Found: C, 62.62; H, 4.22; N, 3.58%. Calcd for
C20H17NO3S2: C, 62.64; H, 4.47; N, 3.65%.) nmax/cmꢁ1
3344, 1595, 1367; dH 2.43 (3H, s, CH3), 7.03 (1H, m,
4-H), 7.17 (1H, m, 3-H), 7.25 (2H, m, tosyl), 7.33 (1H, m,
5-H), 7.47 (3H, m, 30,40,50-H), 7.67 (2H, m, tosyl), 7.83
(2H, m, 20,60-H), 8.49 (1H, s, N–H), 9.43 (1H, m, 6-H); dC
21.8, 126.4, 126.9, 127.3, 127.4, 128.4, 128.6, 130.1,
131.5, 132.6, 146.3.
3.7.3. 5,6-Dimethoxy-2-phenylbenzoxazole (2c). Yield:
39, 42 and 51% from 1c using methods 1, 2 and 3, respec-
tively. Mp 114–115 ꢀC (ethanol); (Found: C, 70.73; H,
5.24; N, 5.32%. Calcd for C15H13NO3: C, 70.58; H, 5.13;
N, 5.49%.) nmax/cmꢁ1 3001, 1617; dH 3.95 (3H, s, OCH3),
3.96 (3H, s, OCH3), 7.14 (1H, s, 4-H), 7.26 (1H, s, 7-H),
7.48 (3H, m, 30,40,50-H), 8.19 (2H, m, 20,60-H); dC 56.4,
56.5, 94.3, 101.8, 127.0, 127.5, 128.9, 130.9, 134.9, 145.1,
147.8, 148.4, 162.3.
3.7. Cyclisation of thiobenzamides using iodine
3.7.4. 5-Methoxy-2-phenylbenzothiazole (10a).10 Yield:
67 and 56% from 9a using methods 1 and 2, respectively.
Method 1: to a mixture of thiobenzamide (0.10 g) and NaH
(1.2 mol equiv) under an atmosphere of nitrogen was added
dry benzene (5 mL). The mixture was heated at reflux for
15 min after which a saturated solution of iodine (2 mol
equiv) in dry benzene was added and the mixture heated at
reflux for 2 h. The mixture was then poured into 15% aque-
ous sodium hydrogen sulfite solution (20 mL) and extracted
with benzene (20 mL). The organic solution was then
washed with water (20 mL), dried over Na2SO4, concen-
trated and purified by column chromatography (CH2Cl2/hex-
anes 3:7) and recrystallised from methanol as white needles.
3.7.5. 6-Methoxy-2-phenylbenzothiazole (10b).2 Yield: 27
and 70% from 9b using methods 1 and 2, respectively.
3.7.6. 5,6-Dimethoxy-2-phenylbenzothiazole (10c).2
Yield: 87, 73 and 84% from 9c using methods 1, 2 and 3,
respectively.
Acknowledgements
Method 2: to a mixture of the thiobenzamide (0.10 g) and
iodine (1.5 mol equiv) under an atmosphere of nitrogen
was added chlorobenzene (3 mL). The mixture was heated
at reflux for 12 h then poured into 15% aqueous sodium bi-
sulfite solution (20 mL) and extracted with dichloromethane
(20 mL). The organic solution was then washed with water
(20 mL), dried over Na2SO4, concentrated and recrystallised
from methanol.
We gratefully acknowledge the support of NDR from
UWI and thank Professor Vernon Box (CUNY) for useful
discussions.
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