Synthesis of 2-substituted 4,5-diphenyloxazoles under solvent-free microwave irradiation conditions

Article abstract of DOI:10.1080/00397910701392244

A novel method for the direct conversion of deoxybenzoin into 2-alkyl-4,5-diphenyloxazoles and 2-aryl-4,5-diphenyloxazoles has been developed using treatment of HTIB and nitriles under solvent-free microwave irradiation conditions. Copyright Taylor & Fran

Full text of DOI:10.1080/00397910701392244

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Synthesis of 2‐Substituted
4,5‐Diphenyloxazoles under Solvent‐Free
Microwave Irradiation Conditions
Jong Chan Lee a , Jang‐Woo Seo a & Jong Wook Baek a
a Department of Chemistry , Chung‐Ang University , Seoul, South Korea
Published online: 03 Jul 2007.
To cite this article: Jong Chan Lee , Jang‐Woo Seo & Jong Wook Baek (2007) Synthesis of 2‐Substituted
4,5‐Diphenyloxazoles under Solvent‐Free Microwave Irradiation Conditions, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:13, 2159-2162, DOI:
10.1080/00397910701392244
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Synthetic Communicationsw, 37: 2159–2162, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701392244
Synthesis of 2-Substituted
4,5-Diphenyloxazoles under Solvent-Free
Microwave Irradiation Conditions
Jong Chan Lee, Jang-Woo Seo, and Jong Wook Baek
Department of Chemistry, Chung-Ang University, Seoul, South Korea
Abstract: A novel method for the direct conversion of deoxybenzoin into
2-alkyl-4,5-diphenyloxazoles and 2-aryl-4,5-diphenyloxazoles has been developed
using treatment of HTIB and nitriles under solvent-free microwave irradiation
conditions.
Keywords: hypervalent iodine, microwave, oxazole, solvent-free
Oxazoles, important heterocycles in organic chemistry, have received great
attention because of their useful, biologically important properties.[1–3] In
particular, in the past decade, synthesis of 2,4,5-trisubstituted oxazoles
received increasing attention because of their common existence in naturally
occurring compounds.[4,5] Among other 2,4,5-trisubstituted oxazoles, 2-sub-
stituted 4,5-diphenyloxazoles recently received substantial interest because
of thier usefulness as synthetic scaffolds. The preparation of 2-substituted
4,5-diphenyloxazoles can be achieved by various methods, which include
the reaction of benzoins with nitriles in the presence of triflic acid/
H2SO4,[6] the reaction of benzoin carboxylates with formamide in the presence
of H2SO4,[5] the coupling reaction of 2-methylthio-4,5-diphenyloxazole with
Grignard reagents/nickel-bidentate phosphine complexes,[7] and the reaction
of oxazolone template with aromatic solvents in the presence of aluminum
chloride and triflic acid.[8] However, all of these methods generally use very
strong acidic or basic conditions, which limit their further practical
Received in Japan September 6, 2006
Address correspondence to Jong Chan Lee, Department of Chemistry, Chung-Ang
University, Seoul 156-756, South Korea. E-mail: jclee@cau.ac.kr
2159

2160
J. C. Lee, J.-W. Seo, and J. W. Baek
applications. Furthermore, there have been far fewer methods that describe the
preparation of multisubstituted oxazoles starting directly from ketones.[6,9]
Recently, we reported the successful results of the preparation of
multisubstituted oxazoles by the reaction of ketones with [hydroxyl(2,4-dini-
trobenzenesulfonyloxy)iodo]benzene (HDNIB) and amides under microwave
irradiation conditions.[10] However, in this method, replacement of amides by
nitriles mostly gave far inferior yields of oxazoles, and a majority of undesir-
able side products was obtained. In the course of our program, we needed an
efficient method for the direct preparation of 2-substituted 4,5-diphenyloxa-
zoles using the reaction of deoxybenzoin with easily available nitrile
reagents. To the best of our knowledge, there was no report utilizing nitriles
in the direct preparation of oxazoles from ketones under solvent-free
microwave irradiation conditions. The Koser’s reagent, [hydroxy(tosyloxy)io-
do]benzene (HTIB), is one of the most versatile and readily available hyper-
valent iodine compounds, and its use in organic transformations is well
documented.[11,12] Therefore, it is highly desirable to develop a new method
for the synthesis of oxazoles starting from ketones using a reagent combi-
nation of HTIB and nitriles. Herein, we report a novel and facile method
for the synthesis of 2-substituted 4,5-diphenyl oxazoles from the reaction of
deoxybenzoin with HTIB and various nitriles under microwave irradiation
conditions. Thus, sequential treatment of deoxybenzoin with HTIB (1.2
equiv.) and nitriles (1.0 equiv.) for 2–5 min under microwave irradiation
in solvent-free conditions provided the corresponding 2-substituted 4,5-
disubstituted oxazoles in high yields (Scheme 1). Both aliphatic and
aromatic nitriles gave satisfactory yields of 2-alkyl-4,5-diphenyloxazoles
and 2-aryl-4,5-diphenyloxazoles as shown in Table 1. The yields obtained
in this study are comparable or superior to the previous results obtained
from the reported methods for the direct synthesis of oxazoles from
ketones. Therefore, this method can serve as a useful alternative to the
existing methods because of the rapid, neutral, and ecofriendly nature of the
reaction conditions. Apparently, the present protocol proceeded by the
Ritter-type reactions of a-tosyloxydeoxybenzoin intermediates with nitriles
lead to smooth formation of substituted oxazoles. Application of this
protocol to the other ketones such as acetophenone and propiophenone
provided only a-tosyloxy ketones without formation of oxazoles.
In summary, we have developed a new and efficient method for the prep-
aration of 2-substituted 4,5-diphenyloxazoles from the microwave-promoted
reactions of deoxybenzoin with HTIB/nitriles.
Scheme 1.

2-Substituted 4,5-Diphenyloxazoles
2161
Table 1. Preparation of 2-substituted 4,5-diphenyloxazoles
Entry
Nitriles
Oxazoles
Yield (%)a
1
2
3
4
5
6
7
8
9
CH3CN
CH3CH2CN
R ¼ CH3
72
82
60
75
67
66
83
92
71
R ¼ CH3CH2
R ¼ CH3CH2CH2
R ¼ C6H5
CH3CH2CH2CN
C6H5CN
p-CH3C6H4CN
p-CH3OC6H4CN
p-BrC6H4CN
p-ClC6H4CN
p-FC6H4CN
R ¼ p-CH3C6H4
R ¼ p-CH3OC6H4
R ¼ p-BrC6H4
R ¼ p-ClC6H4
R ¼ p-FC6H4
aIsolated yield.
EXPERIMENTAL
A commercial domestic microwave oven (Samsung RE-21C) with an 850-W
power output was used for the all reactions.
General Procedure for 2-Substituted 4,5-Diphenyloxazoles
Deoxybenzoin (1.0 mmol) and HTIB (1.2 mmol) were mixed thoroughly and
placed in a 50 mL glass tube. The reaction mixture was placed in a domestic
microwave oven and irradiated three times for a period of 30 s with 10-s
intervals. Then nitrile (1.0 mmol) was added to the reaction mixture, which
was irradiated one to seven times for a period of 30 s with 10-s intervals.
The reaction mixture was extracted with dichloromethane (2 Â 30 mL) and
washed with water. The organic layer was dried with magnesium sulfate.
After evaporation of the solvent, the residue was purified by silica-gel
column chromatography using dichloromethane as eluent to give the pure
2-substituted 4,5-diphenyloxazole.
ACKNOWLEDGMENTS
This research was supported by Chung-Ang University Research Grant in
2007.
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