Simple and efficient one-pot synthesis of 2-substituted benzoxazole and benzothiazole

Article abstract of DOI:10.1080/00397910902906602

2-Substituted benzoxazole and benzothiazole were synthesized from condensation of aldehyde and 2-aminophenol or 2-aminothiophenol via a one-pot process using diethyl bromo phoshonate and tert-butyl hypochlorite.

Full text of DOI:10.1080/00397910902906602

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Simple and Efficient One-Pot Synthesis
of 2-Substituted Benzoxazole and
Benzothiazole
Sachin S. Patil a & Vivek D. Bobade a
a Department of Chemistry, Hansraj Pragji Thakersi Arts and Raojisa
Yamasa Kshatriya Science College, Nasik, India
Version of record first published: 29 Dec 2009
To cite this article: Sachin S. Patil & Vivek D. Bobade (2009): Simple and Efficient One-Pot Synthesis
of 2-Substituted Benzoxazole and Benzothiazole, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 40:2, 206-212
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Synthetic Communications1, 40: 206–212, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902906602
SIMPLE AND EFFICIENT ONE-POT SYNTHESIS OF
2-SUBSTITUTED BENZOXAZOLE
AND BENZOTHIAZOLE
Sachin S. Patil and Vivek D. Bobade
Department of Chemistry, Hansraj Pragji Thakersi Arts and Raojisa Yamasa
Kshatriya Science College, Nasik, India
2-Substituted benzoxazole and benzothiazole were synthesized from condensation of alde-
hyde and 2-aminophenol or 2-aminothiophenol via a one-pot process using diethyl bromo
phoshonate and tert-butyl hypochlorite.
Keywords: 2-Aminophenol; 2-aminothiophenol; benzoxazole; diethyl bromo phoshonate; tert-butyl
hypochlorite
INTRODUCTION
Benzoxazole and benzothiazole are molecules that possess an array of biologi-
cal properties.[1] Benzoxazoles are heterocycles that are encountered in number of
natural products as well as a variety of other purposes such as H2-antagonist,[2] anti-
parasitics,[3] and UK-1[4] and elastase inhibitors.[5] benzothiazoles are widely used as
in Caþ2 channel antagonists[6] and antitumor agents.[7] Because of their numerous
applications, there is a demand for the development of simple, efficient, and envir-
onmentally benign synthesis. Classical methods for synthesis of benzoxazoles and
benzothiazoles involve condensation of 2-aminophenol and 2-aminothiophenol with
carboxylic acid derivatives respectively in strong acid at high temperature,[8,9] oxidat-
ive cyclization using barium manganate,[10] lead tetra-acetate,[11] nickel oxide,[12] thi-
anthrene cation radical,[13] diacetoxyiodobenzene,[14] manganese(III) acetate,[15]
MnO2=silica,[16] pyridinium chlorochromate,[17] and copper-catalyzed[18] approaches.
All these methods involve multistep synthesis, use of toxic reagents, metal ions (Ni, Pb,
Ba, Mn, Cr), and drastic reaction conditions. In the case of metal-containing reac-
tions, mostly metal scavengers are required for the removal of metals from the reaction
mixture. Solid-supported reactions require an additional separation–purification step.
All these methods have limited application for the synthesis of benzoxazole and
benzothiazole. In pursuit of a simple and environmentally benign process, we herein
report a new method for the synthesis of benzoxazole and benzothiazoles using two
different oxidants, diethyl bromophosphonate and tert-butyl hypochlorite.
Received December 18, 2008.
Address correspondence to Vivek D. Bobade, Department of Chemistry, HPT Arts and RYK
Science College, Nasik, India. E-mail: v_bobade31@rediffmail.com
206

2-SUBSTITUTED BENZOXAZOLE AND BENZOTHIAZOLE
207
RESULTS AND DISCUSSION
Diethyl bromophosphonate[19] and tert-butyl hypochlorite[20] are widely used
in oxidation processes. They have been used for oxidative cyclization and intramol-
ecular cyclization. We have extended this idea of oxidative cyclization of Schiff’s
base prepared from condensation of various aldehydes with 2-aminophenol and
2-aminothiophenol using diethyl bromophosphonate and tert-butyl hypochlorite in
acetonitrile, which leads to formation of benzoxazole and benzothiazole as shown
in Scheme 1. Reaction conditions were optimized by carrying out experiments at dif-
ferent molar ratios in different solvents. Reactions proceeded well with 2 equivalents
of both the oxidants in acetonitrile.
Synthesis of benzoxazole and benzothiazole using diethyl bromophosphonate
(A) and tert-butyl hypochlorite (B) are given in Table 1.
EXPERIMENTAL
1H NMR spectra were recorded on a Brucker 300-MHz spectrometer, and 13
C
NMR were recorded on a 125-MHz spectrometer. Mass spectra (MS) were recorded
on a MS-3200Q trap spectrometer. The reaction monitoring was accomplished by
thin-layer chromotography (TLC) on silica-gel plates.
General Experimental Procedure Using Diethyl Bromophosphonate
(Method A): Application to the Synthesis of Compound 3f
The mixture of benzaldehyde (1.06 g, 1.0 mmol) and 2-amino phenol (1.09 g,
1.0 mmol) in acetonitrile (10 ml) was refluxed for 1 h. The reaction mixture was
cooled to room temperature, and then diethyl bromophosphonate (4.34 g, 2.0 mmol)
was added. The reaction mixture was stirred at room temperature, and the reaction
was monitored by TLC (hexane–ethyl acetate 9:1). After completion of the reaction,
the solvent was evaporated. The reaction was quenched in water and neutralized by
aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate
(3 ꢀ 10 ml), dried over sodium sulfate, filtered, concentrated, and purified by column
chromatography on silica gel using hexane–ethyl acetate (98:2).
An identical procedure was employed to prepare benzoxazole and benzothia-
zole as shown in Table 1.
General Experimental Procedure Using tert-Butyl Hypochlorite
(Method B): Application to the Synthesis of Compound 3f
The mixture of benzaldehyde (1.06 g, 1.0 mmol) and 2-amino phenol (1.09 g,
1.0 mmol) in acetonitrile (10 ml) was refluxed for 1 h. The reaction mixture was
Scheme 1. Synthesis of benzoxazole and benzothiazole using reagents A and B. R is alkyl or aryl, X is O or
S, A is diethyl bromophosphonate, and B is tert-butyl hypochlorite.

208

209

210
S. S. PATIL AND V. D. BOBADE
cooled to room temperature, and tert-butyl hypochlorite (2.16 g, 2.0 mmol) was
added. The reaction mixture was stirred at room temperature and monitored by
TLC (hexane–ethyl acetate, 9:1). After completion, the solvent was evaporated
and quenched in 1% aq. sodium metabisulfite solution, extracted with ethyl acetate
(3 ꢀ 10 ml), dried over sodium sulfate, filtered, concentrated, and purified by column
chromatography on silica gel using hexane-ethyl acetate (98:2). An identical pro-
cedure was employed to prepare benzoxazole and benzothiazole as shown in Table 1.
Spectral (1H NMR, 13C NMR) Data of Representative Benzoxazoles
1
2-Methyl-1,3-benzoxazole (3a). Colorless liquid; bp 177–178ꢁC; H NMR
(300 MHz, CDCl3): d 7.66 (dd, 2 H), 7.55 (t, 1 H), 7.34 (m, 1 H), 2.59 (s, 3 H). 13C
NMR (125 MHz, CDCl3): d 162.78, 155.0, 129.76, 123.19, 122.22, 121.18, 109.76,
10.05. MS (EI): m=z ¼ 133 (Mþ1 ¼ 134).
1
2-Phenyl-1,3-benzoxazole (3f). Yellowish solid; mp 102–105ꢁC; H NMR
(300 MHz, CDCl3): d 7.92 (d, 2 H), 7.61 (m, 1 H), 7.53 (m, 1 H), 7.20 (m, 3 H),
7.09 (d, 1 H), 6.93 (t, 1 H). 13C NMR (125 MHz, CDCl3): d 163.0, 150.8, 142.0,
131.4, 128.8, 127.5, 127.0, 125.0, 124.5, 119.9, 110.5. MS (EI): m=z ¼ 195
(Mþ1 ¼ 196).
2-(4-Chlorophenyl)-1,3-benzoxazole (3h). Pale yellow solid; mp
1
150–152ꢁC; H NMR (300 MHz, CDCl3): d 8.15–8.01 (m, 2 H), 7.8–7.25 (m, 1 H),
7.70–7.62 (m, 2 H), 7.61–7.53 (m, 1 H), 7.43–7.32 (m, 2 H). MS (EI): m=z ¼ 230
(Mþ1 ¼ 231, Mþ2 ¼ 232).
2-(3-Pyridyl)-1,3-benzoxazole (3j). Colorless solid; mp 112–113ꢁC; 1H
NMR (300 MHz, CDCl3): d 8.95 (s, 1 H), 8.29 (d, 1 H), 8.20 (d, 2 H), 7.58–7.51
(m, 4 H). MS (EI): m=z ¼ 196 (Mþ1 ¼ 197).
2-(2-Chlorophenyl)-1,3-benzothiazole. Colorless solid; mp 71–73ꢁC; 1H
NMR (300 MHz, CDCl3): d 8.21–8.19 (m, 1 H), 8.11 (d, 1 H), 7.93 (d, 1 H),
7.55–7.51 (m, 2 H), 7.44–7.36 (m, 3 H). 13C NMR (125 MHz, CDCl3): d 164.3,
152.6, 136.2, 132.8, 132.3, 131.5, 131.1, 130.4, 126.9, 126.2, 124.8, 123.4, 121.4.
MS (EI): m=z ¼ 245 (Mþ2 ¼ 247).
ACKNOWLEDGMENTS
The author thanks Mr. Pravin Patil and Mr. Sachin Narkhede for their
valuable suggestions.
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