Trichloroisocyanuric Acid/Triphenylphosphine-Mediated Synthesis of Benzimidazoles, Benzoxazoles, and Benzothiazoles

Article abstract of DOI:10.1071/CH14037

A new and efficient method for preparation of benzimidazoles, benzoxazoles, and benzothiazoles from reactions of different carboxylic acids with o-phenylenediamine, o-aminophenol, and o-aminothiophenol in the presence of triphenylphosphine/trichloroisocyanuric acid system is presented. The desired products have been characterised on the basis of spectral (infrared, NMR, mass spectrometry) data, and the mechanism of their formation is proposed. The remarkable advantages are the inexpensive and readily available reagent, simple procedure, mild conditions, and good-to-excellent yields.

Full text of DOI:10.1071/CH14037

CSIRO PUBLISHING
Aust. J. Chem. 2015, 68, 145–155
Full Paper
http://dx.doi.org/10.1071/CH14037
Trichloroisocyanuric Acid/Triphenylphosphine-Mediated
Synthesis of Benzimidazoles, Benzoxazoles,
and Benzothiazoles
A
A B
,
A
Soodabeh Rezazadeh, Batool Akhlaghinia,
and Nasrin Razavi
A
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad,
Mashhad 9177948974, Iran.
B
Corresponding author. Email: akhlaghinia@um.ac.ir
A new and efficient method for preparation of benzimidazoles, benzoxazoles, and benzothiazoles from reactions of
different carboxylic acids with o-phenylenediamine, o-aminophenol, and o-aminothiophenol in the presence of
triphenylphosphine/trichloroisocyanuric acid system is presented. The desired products have been characterised on the
basis of spectral (infrared, NMR, mass spectrometry) data, and the mechanism of their formation is proposed. The
remarkable advantages are the inexpensive and readily available reagent, simple procedure, mild conditions, and good-to-
excellent yields.
Manuscript received: 26 January 2014.
Manuscript accepted: 24 April 2014.
Published online: 25 June 2014.
Introduction
Results and Discussion
Benzimidazoles, benzoxazoles, and benzothiazoles, as impor-
tant N-heterocyclic compounds, have always remained a major
source for therapeutic drugs and have received significant
attention.[1] They are considered as privileged structures in
the medicinal chemistry field[2] and are found in a large variety
of natural products.[3] They have been used as antiviral,[4]
antimicrobial,[5] anti-tumour,[6] antibiotic,[7] antifungal,[8]
anticonvulsant,[9] anti-inflammatory,[10] anti-ulcer,[11a] anti-
helminthic,[11a] antihypertensive,[11b] and anti-analgesic,[11c]
agents. Moreover, their application in the field of advanced
materials is worthy of note.[12] A thorough retrospect over the
reported routes for the synthesis of benzimidazoles, benzox-
azoles, and benzothiazoles reveals plenty of synthetic methods
that involve two common approaches. These involve reaction
between either an appropriate aromatic amine and an aldehyde,
followed by oxidative cyclisation of the imine intermediate, or
between o-phenylenediamine/o-aminophenol/o-aminothiophenol,
as the starting substrates, and a carboxylic derivative under
strong acidic conditions.[1b,1d,13–17] However, the above men-
tioned methods suffer from several disadvantages such as harsh
reaction conditions including the use of corrosive acids, toxic
catalysts, high catalyst costs (often not recoverable and reus-
able), occurrence of side reactions, additional oxidation step
(which leads to poor yield and difficulty in the work-up proce-
dure), low functional group tolerance, and the need to use
reagents in large excess and long reaction times.
In continuation of our interest to explore the use of trichloro-
isocyanuric acid/triphenylphosphine systems,[18] we decided to
study the synthesis of benzimidazoles, benzoxazoles, and
benzothiazoles from the reaction between o-phenylenediamine,
o-aminophenol, and o-aminothiophenol and a variety of
substituted carboxylic acids using the trichloroisocyanuric acid/
triphenylphosphine system (Scheme 1).
In order to establish the optimum conditions for the
preparation of benzimidazoles, various molar ratios of tri-
chloroisocyanuric acid:PPh3 (triphenylphosphine):PhCOOH:
o-phenylenediamine were examined for the synthesis of
2-phenyl-1H-benzimidazole in using different solvents and
temperatures as a model reaction (Table 1). As observed, based
on the data, CH3NO2, THF, toluene, and DMF are not appropri-
ate solvents for this transformation (Table 1, entries 1–5). We
observed that very low yields of the desired product were
obtained under reflux in CH2Cl2, acetone, CHCl3, and 1,2-
dichloroethane (Table 1, entries 6–9). Applying 0.3 : 1 :1 : 1
and 0.3 : 1 : 1 : 1.5 molar ratios of trichloroisocyanuric acid:
PPh3 : PhCOOH : o-phenylenediamine under reflux in CH3CN
produced 2-phenyl-1H-benzimidazole in 80 % isolated yield
after 4 h (Table 1, entries 10 and 11). Using anisole as solvent
at 1308C resulted in the desired product in 80 % yield after 3 h
(Table 1, entry 12). The best yield of 2-phenyl-1H-benzimidazole
was obtained under reflux in 1,4-dioxane. Interestingly, increas-
ing the molar ratio of o-phenylenediamine under reflux in 1,4-
dioxane has no influences on the reaction rate (Table 1, entries
13 and 14). The effect of reaction temperature on the yield of the
product is another important factor that was studied. The
reaction yield decreased to 10 % when the temperature was
decreased to room temperature (Table 1, entry 15).
Therefore, because of the wide range of pharmacological
properties, commercial and synthetic applications of these hetero
cycles, in addition to overcoming all of the above mentioned
problems, investigating an efficient and straightforward proce-
dure for the synthesis of 1, 3-benzazoles is highly sought after.
Journal compilation Ó CSIRO 2015
www.publish.csiro.au/journals/ajc

146
S. Rezazadeh, B. Akhlaghinia, and N. Razavi
O
Cl
Cl
N
N
O
Cl
N
O
NH2
XH
PPh3,
N
R
X
O
R
ꢀ
1, 4-dioxane, reflux or 190ꢁC
HO
X ꢂ NH, O, S
R ꢂ aryl, alkyl, heteroaryl
Scheme 1. Synthesis of benzimidazoles, benzoxazoles, and benzothiazoles.
Table 1. Conversion of benzoic acid into 2-phenyl-1H-benzimidazole using the TCCA/TPP/benzoic acid/o-phenylenediamine
system under different reaction conditions
Entry
Trichloroisocyanuric acid : PPh3 :
Solvent
Temperature [8C]
Time [h]
Isolated yield [%]
PhCOOH : o-phenylenediamine
1
0.3 : 1 : 1 : 1
CH3NO2
CH3NO2
THF
reflux
reflux
reflux
reflux
150
24
24
24
18
22
18
24
24
24
4
0
0
2
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1
3
0
4
Toluene
DMF
0
5
0
6
CH2Cl2
reflux
reflux
reflux
reflux
reflux
reflux
130
10
10
30
40
80
80
80
90
90
10
7
Acetone
CHCl3
8
9
1,2-C2H4Cl2
CH3CN
10
11
12
13
14
15
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1
CH3CN
4
PhOMe
3
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
reflux
reflux
rtA
1
1
0.3 : 1 : 1 : 1
24
ART: room temperature
After establishing the methodology for benzimidazoles, we
next focussed our attention on the synthesis of another important
N-heterocycle benzoxazoles. We examined the reaction between
benzoic acid and o-aminophenol as the model reaction in the
presence of the trichloroisocyanuric acid/triphenylphosphine
(TCCA/TPP) system using the same reaction conditions as
above (Table 2). Based on the proposed mechanism in Scheme 2
and the results obtained from Table 2, formation of VII by
intramolecular cyclisation of V and subsequent dehydration of
VI was considered as a difficult step towards the construction of
N-heterocyclic compounds. In the presence of CH3NO2 and
DMF, II was formed in low concentrations, and did not have any
tendency to react with o-aminophenol (Table 2, entries 1 and 2).
No product formation was observed when the reaction was carried
out in 1,2-dichloroethane, acetone, CH3CN, CHCl3, CH2Cl2,
THF, toluene, and anisole using a 0.3 : 1 : 1 : 1.5 molar ratio
of trichloroisocyanuric acid : PPh3 : PhCOOH : o-aminophenol
(Table 2, entries 3–10). After long periods of time, only V was
formed in the above-mentioned solvents with different isolated
yields. As observed from Tables 1 and 2, 1,4-dioxane seemed to
bea bettersolvent intermsofobtaining the desiredN-heterocyclic
compound. Under reflux in 1,4-dioxane, only the amide inter-
mediate V was obtained with 95 % isolated yield. However, at
this temperature formation of VII from cyclisation and dehy-
dration of V were not observed (Table 2, entry 11). Hence, the
results obtained from Table 2 lead us to conclude that cyclisation
and dehydration steps are strongly dependent on temperature.
To achieve good yields of the desired product, the reaction was
performed in 1,4-dioxane at various temperatures. According to
the results obtained from Table 2, increasing the reaction
temperature benefited the yield of 2-phenyl-benzoxazole. For
example, when the reaction was performed at 1308C and 1608C
(the reaction was performed in a sealed tube), the desired
product was obtained after an extended reaction period in
30 % and 85 % isolated yields, respectively (Table 2, entries
12 and 13). The rate of reaction was efficiently increased when
the reaction was carried out at 1908C, producing 97 % isolated
yield of 2-phenyl-benzoxazole (Table 2, entry 14). It seems that
the choice of temperature was crucial for cyclisation of the
amide intermediate V. To investigate the effect of molar ratio of
o-aminophenol, the reaction was carried out in 1,4-dioxane in
the presence of 0.3 : 1 : 1 : 1 molar ratio of trichloroisocyanuric
acid : PPh3 : PhCOOH : o-aminophenol at 1908C. According to
this study, decreasing the molar ratio of o-aminophenol leads to
80 % yield of the desired product and 10 % of the amide
intermediate V (Table 2, entry 15).
To widen the applicability of the present protocol, we
investigated the synthesis of thia-analogues of benzimidazoles:
benzothiazoles (whose structures are found in various bioactive
molecules) using the TCCA/TPP system. Under the optimised
reaction conditions established for preparation of benzimida-
zoles and benzoxazoles, 2-phenylbenzothiazole was synthesised
from the reaction between benzoic acid and o-aminothiophenol
under reflux in 1,4-dioxane, using a 0.3 : 1 : 1 : 1 molar ratio of

Synthesis of 1,3-Benzazoles
147
Table 2. Conversion of benzoic acid into 2-phenylbenzoxazole using the TCCA/TPP/benzoic acid/o-aminophenol
system under different reaction conditions
Entry
Trichloroisocyanuric acid : PPh3 :
Solvent
Temperature [8C]
Time [h]
Isolated yield
of V/VII [%]A
PhCOOH : o-aminophenol
1
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1.5
0.3 : 1 : 1 : 1
CH3NO2
DMF
reflux
150
24
24
15
20
21
22
22
15
15
22
15
21
8
0/0
0/0
2
3
1,2-C2H4Cl2
Acetone
reflux
reflux
reflux
reflux
reflux
reflux
reflux
130
20/0
60/0
80/0
90/0
90/0
90/0
95/0
95/0
95/0
60/30
10/85
0/97
10/80
4
5
CH3CN
6
CHCl3
7
CH2Cl2
8
THF
9
Toluene
10
11
12B
13B
14B
15B
PhOMe
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
reflux
130
160
190
4
190
6
AV and VII correspond to amide intermediate V and final product in Scheme 2.
BReactions were performed in a sealed tube.
ꢀ
PPh3Cl
ꢃO
O
N
O
Cl
Cl
N
N
N
N
ꢀ
ꢃ
3 RCOOH
3 PPh3
Cl
O
N
O
ꢀ
PPh3Cl
ꢃO
ꢀ
PPh3Cl
I
HO
N
H
N
O
ꢀ
R
N
N
PPh3
Clꢃ
3
R
O
OH
3 O ꢂ PPh3
ꢀ
3 HCl
ꢀ
ꢀ
O
HX
HO
H2N
HX
V
III
II
O
HN
O
H
N
NH
OH
R
O
NH
IV
X
N
X
VI
ꢃH2O
R
VII
X ꢂ NH, O, S
Scheme 2. Synthesis mechanism of 1,3-benzazoles.
trichloroisocyanuric acid : PPh3 : PhCOOH : o-aminothiophenol,
in high yields (Table 3).
products in good-to-excellent yields. o-Aminophenol showed
a lower reactivity than that of o-phenylenediamine and
o-aminothiophenol towards carboxylic acids. Most probably,
because of the low nucleophilicity of the attached hydroxyl
group to the phenyl ring in o-aminophenol, the nucleophilic
attack of OH on amide intermediate V (Scheme 2) was per-
formed at a higher reaction temperature and also a longer
reaction time was used when compared with the reactions
Under the optimised reaction conditions established, as
observed in Table 4, heterocyclisations of differently substituted
aromatic carboxylic acids, hetero-aromatic, and aliphatic
carboxylic acids with o-phenylenediamine, o-aminophenol,
and o-aminothiophenol were carried out. In general, most of
the reactions proceeded smoothly to give corresponding

148
S. Rezazadeh, B. Akhlaghinia, and N. Razavi
Table 3. Conversion of benzoic acid into 2-phenylbenzothiazole using the TCCA/TPP/benzoic acid/o-aminothiophenol
system under different reaction conditions
Entry
Trichloroisocyanuric acid : PPh3 :
Solvent
Temperature [8C]
Time [min]
Isolated yield [%]
PhCOOH : o-aminothiophenol
1
0.3 : 1 : 1 : 1
0.3 : 1 : 1 : 1
0.3 : 1 : 1 : 1
0.3 : 1 : 1 : 1
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
rtA
2 h
1 h
5
80
80
90
90
2
60
3
4B
reflux
150
5
ART: room temperature.
BThe reaction was performed in a sealed tube.
Table 4. Synthesis of different structurally benzimidazoles, benzoxazoles, and benzothiazoles using the TCCA/TPP system
Entry
1
Substrate
Product
Time [h]/Isolated yield [%]
1/90
X ¼ NH (1a)
X
N
4/97
X ¼ O (1b)
Benzoic acid
5(min)/90
X ¼ S (1c)
2/70
2/90
2/85
X ¼ NHA (2a)
X ¼ O (2b)
X
N
NO2
2
3
4-Nitrobenzoic acid
3-Nitrobenzoic acid
X ¼ SA (2c)
2/90
4/95
3/80
X ¼ NHA (3a)
NO2
X ¼ O (3b)
X
N
X ¼ SA (3c)
40(min)/95
5/95
X ¼ NH (4a)
X ¼ O (4b)
X ¼ S (4c)
Cl
X
4
5
6
3,5-Dichlorobenzoic acid
4-Chlorobenzoic acid
2-Chlorobenzoic acid
15(min)/95
Cl
Cl
N
1/97
X ¼ NH (5a)
X ¼ O (5b)
X ¼ S (5c)
X
N
5/95
5(min)/95
Cl
2/80
X ¼ NH (6a)
X ¼ O (6b)
X ¼ S (6c)
X
N
7/70
5(min)/80
1.5/95
X ¼ NH (7a)
X ¼ O (7b)
X ¼ S (7c)
X
N
5/90
Br
7
8
4-Bromobenzoic acid
4-Methylbenzoic acid
15(min)/95
2/85
5/95
3/80
X ¼ NH (8a)
X ¼ O (8b)
X ¼ S (8c)
X
N
X
N
2.5/80
6/90
X ¼ NH (9a)
X ¼ O (9b)
X ¼ S (9c)
9
3,5-Dimethylbenzoic acid
3/95
3/90
6/95
2/80
X ¼ NH (10a)
X ¼ O (10b)
X ¼ S (10c)
X
N
OMe
10
11
4-Methoxybenzoic acid
3/80
6/95
3/70
X ¼ NH (11a)
X ¼ O (11b)
X ¼ S (11c)
X
(E)-Cinnamic acid
N
(Continued)

Synthesis of 1,3-Benzazoles
149
Table 4. (Continued)
Entry
12
Substrate
Product
Time [h]/Isolated yield [%]
1/95
6/90
2/75
X ¼ NH (12a)
X
N
X ¼ O (12b)
4-Chlorocinnamic acid
X ¼ S (12c)
Cl
X
N
1/70
6/85
3/90
X ¼ NHA (13a)
X ¼ O (13b)
X ¼ S (13c)
13
14
Phenylacetic acid
X
N
4-Methoxyphenylacetic acid
6/85
X ¼ O (14b)
OMe
X ¼ NHA (15a)
X ¼ O (15b)
X ¼ S (15c)
X
N
2/85
7/65
2/80
15
Diphenyl acetic acid
X
N
CH2(CH2)6CH ꢂ CH(CH2)7CH3
16
17
18
19
20
Oleic acid
6/85
X ¼ O (16b)
2.5/98
6/90
X ¼ NH (17a)
X ¼ O (17b)
X ¼ S (17c)
X
CH2(CH2)15CH3
N
Stearic acid
1/90
1/80
5/70
1/90
X ¼ NH (18a)
X ¼ O (18b)
X ¼ S (18c)
X
S
3-Thiophene carboxylic acid
4-Pyridine carboxylic acid
Benzoic acid
N
0.5/80
2/90
X ¼ NH (19a)
X ¼ O (19b)
X
N
N
O
N
1/95
X ¼ O (20b)
AMolar ratio of RCOOH/o-phenylenediamine (1 : 1.5).
involving the two other nucleophiles (NH and SH groups) in
o-phenylenediamine and o-aminothiophenol. Based on the
results from Table 4 and the proposed mechanism in Scheme 2,
amide intermediates V and VI can be referred as two key
intermediates of the heterocyclisation reaction. In all reactions,
amide intermediate V was formed by nucleophilic attack of
NH of the corresponding amine on II, regardless of the type
of carboxylic acids. Cinnamic acid and aliphatic carboxylic
acids, as well as benzoic acid and substituted benzoic acids
reacted smoothly with o-phenylenediamine, o-aminophenol,
and o-aminothiophenol, and produced the corresponding hetero-
cycle compounds (Table 4, compare entries 1–10 with entries
11–17). Heteroaromatic carboxylic acids were converted readily
into the corresponding heterocycle compounds when compared
with the other mentioned carboxylic acids (Table 4, entries
18 and 19).
To further expand the scope of the reaction, substituted
o-phenylenediamine and o-aminophenol were employed as
substrates to react with benzoic acid in the presence of the
TCCA/TPP system. The reaction was significantly affected by
the substituents on the aromatic ring of o-phenylenediamine
and o-aminophenol. When 4-chlorobenzene-1,2-diamine was
reacted with benzoic acid, amide intermediate V and corre-
sponding benzimidazole were obtained after 1 h with a yield of
50/50 %. Considerable progress was not achieved at 1908C in
1,4-dioxane after 21 h. Under optimised conditions, no desired
benzoxazole was detected from the reaction between 2-amino-
5-chlorophenol and benzoic acid. The amide intermediate V was
formed in 30 % yield, which remained unchanged following
reaction at 1908C in 1,4-dioxane for 20 h. It must be pointed out
that the presence of an electron-deficient substituent slowed the
reactions and decreased the yields.

150
S. Rezazadeh, B. Akhlaghinia, and N. Razavi
The presence of an electron-donating substituent (CH3) on
Conclusion
the para-position of the phenyl ring accelerates the formation of
amide intermediate V that leads to formation of the desired
product in shorter reaction times (Table 4, entry 20).
We have developed a simple, practical, highly efficient, and
convenient method for the synthesis of benzimidazoles,
benzoxazoles, and benzothiazoles via the condensation of
o-phenylenediamine, o-aminophenol, and o-aminothiophenol
with various carboxylic acids. By using carboxylic acids as the
starting materials, we have eliminated the need for toxic oxi-
dants that are necessary for the reaction to proceed when either
alcohols or aldehydes are used. Moreover, the present protocol
affords several significant advantages (i) good-to-excellent
product yields, (ii) high level of generality and applicability to
a broad range of substrates, (iii) mild reaction conditions
requirements in the absence of harsh activating reagents, (iv)
the use of inexpensive and readily available reagents and
promoters, thereby increasing the level of usefulness of
the reaction, and (v) easy purification procedure. Owing to the
advantages of the current method, the latter presents a valid
contribution to the existing methodologies.
In our experiments, completion of the reaction was con-
firmed by the disappearance of the carboxylic acids and then
amide intermediate V on TLC, followed by the disappearance of
acidic OH stretching frequency at 3400–2400 cmꢀ1 in the
Fourier transform infrared (FTIR) spectra. The resulting
N-heterocycle compounds, after purification via either crystal-
lisation or column chromatography were characterised using
FTIR, NMR, and mass spectrometry (MS). Absorption bands at
3395–2400, 1679–1590, and 1388–1306 cmꢀ1, corresponding
to NH, C¼N, and C–N groups of benzimidazoles, respectively
confirmed the formation of benzimidazoles. Formation of
benzoxazoles were also confirmed by the appearance of absorp-
tion bands at 1639–1597 and 1250–1225 cmꢀ1 that correspond
to C¼N and C–O groups of benzoxazoles, respectively.
Absorption band at 1748–1511 cmꢀ1 confirmed the presence
of C¼N group of benzothiazoles. In the 1H NMR spectrum, the
NH proton of benzimidazoles showed a downfield shift at
12.70–12.38 ppm. In the 13C NMR spectrum, signals around
150.9–148.6, 165–159, and 168.60–164.90 ppm that were
assigned to the quaternary carbon atom of benzimidazole,
benzoxazole, and benzothiazole, respectively, were observed.
All of the products obtained were known compounds and
characterised by comparison of their melting points with those
of reported compounds.
According to the above observations and previous report in
the literature,[18] a pathway for the overall process was
proposed, as shown in Scheme 2. The initial attack at the
halogen in TCCA by triphenylphosphine leads to the halogen–
phosphonium salt I. The reaction between the halogen–
phosphonium salt and carboxylic acid yields the activated
carboxylic acid species II and [1,3,5]triazine-2,4,6-triol (III),
which is in equilibrium with [1,3,5]triazinane-2,4,6-trione
(IV). As soon as II is formed, a nucleophilic attack occurs
between II and the corresponding amine to form triphenylpho-
sphine oxide and amide intermediate V (at room temperature).
Upon heating the reaction mixture (101–1908C), amide inter-
mediate V may be gradually transformed into VI by intra-
molecular cyclisation. Subsequently thermal dehydration of VI
gives the corresponding N-heterocyclic compound VII. To
elucidate the reaction path more clearly, we attempted to
isolate and identify III, IV, and V.
Experimental
General
The products were purified by column chromatography.
Determination of the product purity was accomplished by TLC
on silica gel poly gram STL G/UV 254 plates. The melting
points of products were determined with an Electrothermal Type
9100 melting point apparatus. The FTIR spectra were recorded
on an Avatar 370 FT-IR Thermal Nicolet spectrometer. The
NMR spectra were recorded on a Brucker Avance 400 MHz
instrument in [D6]DMSO and CDCl3. All of the products were
known compounds and characterised by the IR, and 1HNMR and
13CNMR spectroscopies, and comparison of their melting points
with those of known compounds. Elemental analyses were
performed using a Thermo Finnegan Flash EA 1112 Series
instrument. Mass spectra were recorded with a CH7A V aria mat
Bremem instrument at 70 eV.
Typical Procedure for the Preparation of
2-Phenyl-1H-benzimidazole
To a cold solution of triphenylphosphine (0.262 g, 1 mmol)
in 1,4-dioxane (6 mL), trichloroisocyanuric acid (0.076 g,
0.3 mmol) was added with continuous stirring. Benzoic acid
(0.122 g, 1 mmol) was added, and stirring was continued for
30 min. The temperature was raised to room temperature.
o-Phenylenediamine (0.108 g, 1 mmol) was added, and stirring
of the pale yellow suspension was continued for 1 h under
refluxing conditions. The progress of the reaction was monitored
by TLC. Upon completion of the reaction, the crude product was
filtered, washed with CHCl3 (10 mL), and re-crystallised from
ethanol. 2-Phenyl-1H-benzimidazole was obtained in 90 % yield
(0.174 g).
FTIR spectra of the two tautomeric forms [1,3,5]triazine-
2,4,6-triol (III) and [1,3,5]triazinane-2,4,6-trione (IV) showed a
broad absorption band at 3350–3100 cmꢀ1, owing to OH and
NH stretching vibration of III and IV. The presence of C¼N and
C¼O was confirmed by the appearance of absorption bands at
1613 and 1755–1713 cmꢀ1, respectively.
Amide intermediate V was also isolated, purified, and
identified by melting point analysis and FTIR spectroscopy.
Absorption bands at 3272/3056–2594/3360 (X ¼ NH/O/S) and
1644/1644/1598 (X ¼ NH/O/S) cmꢀ1, corresponding to NH and
C¼O groups, confirmed the formation of the amide linkages of
amide intermediate V. In addition, two absorption bands,
corresponding to the stretching vibration of NH2 (X ¼ NH),
were observed at 3444 and 3370 cmꢀ1. A broad absorption at
3411 (X ¼ O) and a weak absorption band at 2586 (X ¼ S) cmꢀ1
confirmed the respective presence of OH and SH groups of the
corresponding amide intermediate V. Further investigation of
the reaction mechanism is ongoing in our group.
Typical Procedure for the Preparation of 2-Phenyl-
benzoxazole
To a cold solution of triphenylphosphine (0.262 g, 1 mmol) in
1,4-dioxane (6 mL), trichloroisocyanuric acid (0.076 g,
0.3 mmol) was added with continuous stirring. Benzoic acid
(0.122 g, 1 mmol) was added, and stirring was continued for
30 min. The temperature was raised to room temperature.
o-Aminophenol (0.164 g, 1.5 mmol) was added, and stirring was
continued in a sealed tube for 4 h at 1908C. The progress of the
reaction was monitored by TLC. Upon completion of the

Synthesis of 1,3-Benzazoles
151
reaction, the reaction mixture was cooled and the resulting
mixture was purified by thin layer chromatography using ethyl
acetate/n-hexane (1 : 1, v/v) as eluent; 2-phenyl-benzoxazole
was obtained in 97 % yield (0.188 g).
1634 (C¼N), 1530, 1486, 1348 (C–N), 1233, 1123, 918, 811,
739, 703, 620, 540. dH ([D6]DMSO, 400 MHz) 9.03 (1H, s, Ph),
8.64 (1H, d, J 7.6, Ph), 8.32 (1H, d, J 8.0, Ph), 7.84 (1H, t, J 8.0,
Ph), 7.65 (2H, dd, J 6.0, 3.2, Ar), 7.24 (2H, dd, J 4.4, 3.2, Ar). dC
([D6]DMSO, 100 MHz) 149.6 (–C¼N), 148.8 (¼C–NO2),
139.1 (¼C–N), 132.9, 132.3, 131.1, 124.6, 123.0, 121.3, 115.9.
2-(3-Nitrophenyl) benzo[d]oxazole (3b): mp 205–2078C (lit.
2078C[25]). nmax (KBr)/cmꢀ1 3096, 2921, 2859, 1609 (C¼N),
1528, 1472, 1451, 1351, 1245 (C–O), 1098, 1053, 807, 765, 743,
705, 665. dH (CDCl3, 400 MHz) 9.12 (1H, t, J 1.6, Ph), 8.61 (1H,
dt, J 7.6, 1.2, Ph), 8.40 (1H, dt, J 7.2, 1.2, Ph), 7.85–7.83 (1H, m,
Ar), 7.76 (1H, t, J 8.0, Ph), 7.67–7.65 (1H, m, Ar), 7.47–7.41
(2H, m, Ar). m/z (EI) 240 (12 %, [M]þ).
Typical Procedure for the Preparation
of 2-Phenyl-benzothiazole
To a cold solution of triphenylphosphine (0.262 g, 1 mmol) in
1,4-dioxane (6 mL), trichloroisocyanuric acid (0.076 g,
0.3 mmol) was added with continuous stirring. Benzoic acid
(0.122 g, 1 mmol) was added, and stirring was continued for
30 min. The temperature was raised to room temperature.
o-Aminothiophenol (0.125 g, 1 mmol) was added and stirring
was continued for 5 min at reflux. The progress of the reaction
was monitored by TLC. Upon completion of the reaction, the
reaction mixture was cooled and the resulting mixture was
purified by thin layer chromatography using ethyl acetate/
n-hexane (1 : 3, v/v) as eluent; 2-phenyl-benzothiazole was
obtained in 90 % yield (0.190 g).
2-Phenyl-1H-benzo[d]imidazole (1a): mp 287–2888C (lit.
287–2888C[19]). nmax (KBr)/cmꢀ1 3150–2530 (NH), 1625
(C¼N), 1510, 1460, 1379 (C–N), 1231, 872, 752, 698, 622,
527. dH ([D6]DMSO, 400 MHz) 8.21–8.18 (2H, m, Ar), 7.75–
7.71 (2H, m, Ph), 7.68–7.62 (3H, m, Ph), 7.41–7.37 (2H, m, Ar).
m/z (EI (electron impact)) 194 (62.5 %, [M]þ).
2-Phenyl benzo[d]oxazole (1b): mp 102–1038C (lit. 102–
1038C[14b]). nmax (KBr)/cmꢀ1 3060, 1617 (C¼N), 1552, 1472,
1446, 1343, 1241 (C–O), 1200, 1052, 1022, 924, 804, 745, 687.
dH (CDCl3, 400 MHz) 8.28 (2H, dd, J 6.4, 4, Ph), 7.82–7.79 (1H,
m, Ar), 7.60–7.57 (1H, m, Ar), 7.54–7.50 (3H, m, Ph), 7.39–7.34
(2H, m, Ar). dC (CDCl3, 100 MHz) 163.0 (–C¼N), 150.7
(¼C–O), 142.1 (¼C–N), 131.5, 128.9, 127.6, 127.1, 125.1,
124.5, 120.0, 110.6. m/z (EI) 195 (87 %, [M]þ).
2-Phenyl benzo[d]thiazole (1c): mp 113–1148C (lit. 112–
1148C[20]). nmax (KBr)/cmꢀ1 3060, 3019, 2929, 2847, 1511
(C¼N), 1477, 1432, 1313, 1224, 1160, 1074, 963, 764, 730,
688, 624. dH (CDCl3, 400 MHz) 8.13–8.11 (1H, m, Ph), 8.11–
8.09 (2H, m, Ar), 7.93 (1H, d, J 8.0, Ar), 7.54–7.50 (4H, m, Ph),
7.41 (1H, td, J 8.4, 1.2, Ar). m/z (EI) 211 (63 %, [M]þ). Anal.
Calc. for C13H9NS: C 73.90, H 4.29, N 6.63, S 15.18. Found:
C 73.62, H 4.06, N 6.36, S 15.06 %.
2-(4-Nitrophenyl)-1H-benzo[d]imidazole (2a): mp 302–
3058C (lit. 304–3068C[21]). nmax (KBr)/cmꢀ1 3141–2400 (NH),
1629 (C¼N), 1605, 1525, 1450, 1401, 1381 (C–N), 1351, 1229,
1111, 1000, 868, 853, 754, 702, 617, 544, 493. dH ([D6]DMSO,
400 MHz) 8.67 (2H, d, J 8.8, Ph), 8.37 (2H, d, J 8.8, Ph), 7.85
(2H, dd, J 6.4, 3.2, Ar), 7.54 (2H, dd, J 6.0, 3.2, Ar). m/z (EI) 239
(78 %, [M]þ).
2-(4-Nitrophenyl) benzo[d]oxazole (2b): mp 269–2728C (lit.
271–2738C[22]). nmax (KBr)/cmꢀ1 3113, 3092, 1597 (C¼N),
1554, 1521, 1450, 1347, 1225 (C–O), 1106, 1056, 855, 752,
706, 493. dH (CDCl3, 400 MHz) 8.46 (2H, dt, J 9.2, 2.0, Ph), 8.41
(2H, dt, J 9.2, 2.0, Ph), 7.86–7.84 (1H, m, Ar), 7.67–7.65 (1H, m,
Ar), 7.49–7.42 (2H, m, Ar).
2-(4-Nitrophenyl) benzo[d]thiazole (2c): mp 229–2308C (lit.
228–2308C[23]). nmax (KBr)/cmꢀ1 3060, 1599 (C¼N), 1521,
1425, 1343, 1313, 1108, 970, 855, 766, 728, 686. dH (CDCl3,
400 MHz)8.36 (2H, dt, J 8.8, 2.0,Ph), 8.27(2H, dt, J 8.8, 2.0, Ph),
8.15 (1H, d, J 7.8, Ar), 7.97 (1H, d, J 7.8, Ar), 7.57 (1H, td, J 7.2,
1.2, Ar), 7.48 (1H, td, J 7.2, 1.2, Ar). m/z (EI) 256 (11 %, [M]þ).
2-(3-Nitrophenyl)-1H-benzo[d]imidazole (3a): mp185–
1878C (lit. 185–1878C[24]). nmax (KBr)/cmꢀ1 3313–2500 (NH),
2-(3-Nitrophenyl) benzo[d]thiazole (3c): mp185–1868C (lit.
185–1868C[23]). nmax (KBr)/cmꢀ1 3092, 1580 (C¼N), 1529,
1433, 1346, 1315, 1225, 1102, 984, 886, 761, 739, 671. dH
(CDCl3, 400 MHz) 8.96 (1H, t, J 2.0, Ph), 8.44 (1H, dt, J 7.6, 1.4,
Ph), 8.37–8.34 (1H, m, Ph), 8.14 (1H, d, J 8.0, Ar), 7.97 (1H, dd,
J 4.6, 0.4, Ar), 7.71 (1H, t, J 8.0, Ph), 7.57 (1H, td, J 8.0, 1.2, Ar),
7.48 (1H, td, J 8.0, 1.2, Ar). dC (CDCl3, 100 MHz) 164.9
(–C¼N), 153.9 (¼C–N), 148.7 (C–NO2), 135.3 (¼C–S),
135.1, 133.0, 130.1, 126.8, 126.0, 125.2, 123.7, 122.3, 121.8.
2-(3,4-Dichlorophenyl)-1H-benzo[d]imidazole (4a): mp
225–2278C (lit. 2298C[26]). nmax (KBr)/cmꢀ1 3395–2520 (NH),
1629 (C¼N), 1515, 1464, 1447, 1428, 1229, 1325 (C–N), 1141,
1030, 894, 820, 738, 677, 506 cmꢀ1. dH ([D6]DMSO, 400 MHz)
8.47 (1H, s, Ph), 8.19 (1H, d, J 8.4, Ph), 7.90 (1H, d, J 8.4, Ph),
7.69 (2H, s, Ar), 7.35 (2H, s, Ar). dC ([D6]DMSO, 100 MHz)
148.6 (–C¼N), 140.0 (¼C–N), 137.3, 133.9, 132.4, 131.9,
129.0, 127.4, 124.2, 115.5, 115.4. m/z (EI) 263 (98 %, [M]þ),
265 (28 %, [Mþ2]þ).
2-(3,4-Dichlorophenyl) benzo[d]oxazole (4b): mp 143–
1458C (lit. 144–1458C[1d]). nmax (KBr)/cmꢀ1 3084, 3051, 1621
(C¼N), 1546, 1465, 1453, 1394, 1377, 1241 (C–O), 1134, 1064,
1029, 886, 820, 741, 676, 440. dH (CDCl3, 400 MHz) 8.38 (1H,
d, J 2.0, Ph), 8.10 (1H, dd, J 8.4, 2.0, Ph), 7.81–7.79 (1H, m, Ar),
7.64 (1H, s, Ph), 7.62–7.60 (1H, m, Ar), 7.42–7.38 (2H, m, Ar).
m/z (EI) 264 (34 %, [M]þ), 266 (3 %, [Mþ2]þ).
2-(3,4-Dichlorophenyl) benzo[d] thiazole (4c): mp 122–
1238C (lit. 123–1248C[20]). nmax (KBr)/cmꢀ1 3101, 1555
(C¼N), 1504, 1463, 1432, 1374, 1310, 1229, 1136, 1028, 984,
865, 824, 757, 725, 692, 669, 432. dH (CDCl3, 400 MHz) 8.23
(1H, d, J 2.0, Ar), 8.10 (1H, d, J 8.2, Ar), 7.94 (1H, d, J 0.4, Ph),
7.91 (1H, dd, J 8.4, 2.4, Ph), 7.58 (1H, d, J 8.4, Ph), 7.54 (1H, td,
J 7.8, 1.2, Ar), 7.44 (1H, td, J 8.0, 1.2, Ar).
2-(4-Chlorophenyl)-1H-benzo[d]imidazole (5a): mp 281–
2848C (lit. 282–2858C[27]). nmax (KBr)/cmꢀ1 3313–2529 (NH),
1627 (C¼N), 1602, 1489, 1458, 1379 (C–N), 1232, 1092, 1012,
837, 749, 616, 528, 501. dH ([D6]DMSO, 400 MHz) 8.38 (2H,
dd, J 4.8, 2.0, Ar), 7.84–7.81 (4H, m, Ph) 7.53 (2H, dd, J 6.2, 2.8,
Ar). m/z (EI) 228 (90 %, [M]þ), 229 (11 %, [M þ 1]þ).
2-(4-Chlorophenyl) benzo[d]oxazole (5b): mp 150–1528C
(lit. 150–1528C[28]). nmax (KBr)/cmꢀ1 3092, 3060, 1617 (C¼N),
1484, 1452, 1405, 1343, 1244 (C–O), 1091, 1056, 1011, 927,
832, 758, 739, 497. dH (CDCl3, 400 MHz) 8.21 (2H, dt, J 8.8,
2.4, Ar), 7.80–7.77 (1H, m, Ph), 7.61–7.58 (1H, m, Ph), 7.52
(2H, dt, J 8.8, 2.4, Ar), 7.41–7.36 (2H, m, Ph).
2-(4-Chlorophenyl) benzo[d]thiazole (5c): mp 113–1148C
(lit. 114–1168C[20]). nmax (KBr)/cmꢀ1 3056, 2925, 2851, 1585
(C¼N), 1474, 1433, 1398, 1315, 1233, 1089, 1008, 969, 828,
756, 730, 691, 482. dH (CDCl3, 400 MHz) 8.09 (1H, d, J 8.0, Ar),
8.05 (2H, dt, J 8.8, 2.0, Ph), 7.92 (1H, d, J 8.0, Ar), 7.55–7.53
(1H, m, Ar), 7.49 (2H, dt, J 8.8, 2.0, Ph), 7.42 (1H, td, J 8.0, 1.2,

152
S. Rezazadeh, B. Akhlaghinia, and N. Razavi
Ar). m/z (EI) 245 (82.5 %, [M]þ), 247 (27.5 %, [Mþ2]þ). Anal.
Calc. for C13H8ClNS: C 63.54, H 3.28, N 5.70, S 13.05. Found:
C 63.26, H 3.18, N 5.61, S 12.95 %.
(NH), 1626 (C¼N), 1564, 1515, 1458, 1369 (C–N), 1258, 1229,
874, 751, 624, 559. dH ([D6]DMSO, 400 MHz) 10.00 (1H, br s,
NH), 7.66 (1H, dd, J 6.0, 3.6, Ph), 7.56 (4H, s, Ar), 7.29 (1H, dd,
J 6.2, 3.6, Ph), 7.23 (1H, s, Ph), 2.32 (6H, s, 2Me). m/z (EI) 222
(12 %, [M]þ).
2-(3,5-Dimethylphenyl) benzo[d]oxazole (9b): mp 119–
1218C (lit. 121–1228C[35]). nmax (KBr)/cmꢀ1 3051, 2921,
2855, 1601 (C¼N), 1551, 1472, 1450, 1376, 1242 (C–O),
1173, 1002, 928, 861, 742, 681, 534, 493. dH (CDCl3,
400 MHz) 7.91 (2H, s, Ar), 7.80–7.77 (1H, m, Ph), 7.61–7.58
(1H, m, Ph), 7.38–7.35 (2H, m, Ar), 7.16 (1H, s, Ph), 2.44 (6H, s,
2Me). m/z (EI) 223 (67 %, [M]þ).
2-(3,5-Dimethylphenyl) benzo[d]thiazole (9c): mp 74–768C.
nmax (KBr)/cmꢀ1 3072, 3011, 2908, 2855, 1772, 1748, 1683,
1601(C¼N), 1506, 1458, 1431, 1309, 1277, 1184, 1162, 877,
842, 754, 724, 685. dH (CDCl3, 400 MHz) 8.10 (1H, dd, J 8.0,
0.4, Ar), 7.92 (1H, dd, J 8.0, 0.4, Ar), 7.73 (2H, s, Ph), 7.51 (1H,
td, J 8.0, 1.2, Ar), 7.40 (1H, td, J 7.8, 1.2, Ar), 7.15 (1H, d, J 0.8,
Ph), 2.43 (6H, s, 2Me). dC (CDCl3, 100 MHz) 168.6 (C¼N),
154.0 (C–N), 138.7, 134.9 (C–S), 133.4, 132.7, 126.2, 125.3,
125.0, 123.1, 121.6, 21.2. m/z (EI) 239 (67 %, [M]þ). Anal. Calc.
for C15H13NS: C 75.28, H 5.47, N 5.85, S 13.40. Found: C 75.23,
H 5.20, N 5.40, S 13.04 %.
2-(4-Methoxyphenyl)-1H-benzo[d]imidazole (10a): mp
228–2298C (lit. 228–2308C[36]). nmax (KBr)/cmꢀ1 3325–2400
(NH), 1634 (C¼N), 1608, 1506, 1461, 1306 (C–N), 1263, 1189,
1021, 839, 750, 616. dH ([D6]DMSO, 400 MHz) 8.31 (2H, dd, J
6.8, 2.0, Ar), 7.79–7.76 (2H, m, Ph), 7.51–7.47 (2H, m, Ar), 7.27
(2H, d, J 9.2, Ph), 3.90 (3H, s, OMe).
2-(4-Methoxyphenyl) benzo[d]oxazole (10b): mp 95–97 (lit.
96–988C[37]). nmax (KBr)/cmꢀ1 3051, 2982, 2839, 1618 (C¼N),
1605, 1589, 1503, 1453, 1327, 1255, 1243 (C–O), 1169, 1061,
1019, 923, 831, 741, 729, 518. dH (CDCl3, 400 MHz) 8.21 (2H,
dd, J 7.2, 2.0, Ph), 7.77–7.75 (1H, m, Ar), 7.58–7.56 (1H, m, Ar),
7.37–7.32 (1H, m, Ar), 7.04 (2H, dd, J 6.8, 2.0, Ph), 3.91 (3H, s,
OMe). m/z (EI) 225 (78 %, [M]þ).
2-(4-Methoxyphenyl) benzo[d]thiazole (10c): mp 123–
1248C (lit. 123–1248C[20]). nmax (KBr)/cmꢀ1 2991, 2934,
2836, 1603 (C¼N), 1518, 1482, 1434, 1308, 1258, 1223,
1171, 1110, 1027, 967, 832, 759, 626, 551. dH (CDCl3,
400 MHz) 8.06–8.04 (3H, d, J 8.4, Ar, Ph), 7.90 (1H, d, J 8.0,
Ph), 7.49 (1H, t, J 7.6, Ar), 7.37 (1H, t, J 7.2, Ar), 7.02 (2H, d,
J 8.4, Ph), 3.90 (3H, s, OMe). m/z (EI) 241 (21 %, [M]þ). Anal.
Calc. for C14H11NOS: C 69.68, H 4.59, N 5.80, S 13.29. Found:
C 69.33, H 4.50, N 5.42, S 12.95 %.
(E)-2-Styryl-1H-benzo[d]imidazole (11a): mp 2008C (dec.)
(lit. 2008C[38]). nmax (KBr)/cmꢀ1 3329–2500 (NH), 1644
(C¼N), 1624, 1560, 1447, 1384, 1311 (C–N), 1225, 974, 758,
701, 616. dH ([D6]DMSO, 400 MHz) 12.45 (1H, br s, NH), 8.00
(2H, d, J 7.2, Ar), 7.70–7.30 (5H, m, Ph), 7.18 (2H, d, J 3.2, Ar),
6.87 (1H, d, J 13.2, CH), 6.58 (1H, d, J 13.2, CH). dC ([D6]
DMSO, 100 MHz) 149.6 (–C¼N), 136.1 (¼C–N), 135.8, 134.8,
130.4, 129.4, 128.9, 128.5, 127.4, 123.1, 118.1.
(E)-2-Styryl benzo[d]oxazole (11b): mp 74–768C (lit. 77.5–
788C[39]). nmax (KBr)/cmꢀ1 3060, 3031, 1639 (C¼N), 1575,
1532, 1449, 1352, 1234 (C–O), 1176, 964, 931, 861, 840, 761,
740, 702, 681, 498. dH (CDCl3, 400 MHz) 7.82 (1H, d, J 16.4,
CH), 7.75–7.73 (1H, m, Ph), 7.62 (2H, d, J 8.4, Ar), 7.56–7.53
(1H, m, Ph), 7.47–7.40 (3H, m, Ph), 7.39–7.33 (2H, m, Ar), 7.11
(1H, d, J 16, CH).
2-(2-Chlorophenyl)-1H-benzo[d]imidazole (6a): mp 226–
2288C (lit. 227–2298C[24]). nmax (KBr)/cmꢀ1 3100–2500 (NH),
1590 (C¼N), 1443, 1404, 1373, 1316 (C–N), 1274, 1054, 973,
751, 731. dH ([D6]DMSO, 400 MHz) 2.7 (1H, br s, NH), 7.72–
7.24 (8H, m, Ph, Ar). m/z (EI) 228 (32 %, [M]þ), 229 (6 %,
[M þ 1]þ).
2-(2-Chlorophenyl) benzo[d]oxazole (6b): mp 68–708C (lit.
69–708C[29]). nmax (KBr)/cmꢀ1 3068, 1609 (C¼N), 1568, 1535,
1452, 1430, 1343, 1311, 1249 (C–O), 1086, 1021, 918, 813, 761,
746, 729, 461. dH (CDCl3, 400 MHz) 8.17 (1H, dd, J 7.4, 2.0,
Ph), 7.89–7.86 (1H, m, Ph), 7.65–7.62 (1H, m, Ph), 7.59 (1H, dd,
J 8.0, 1.6, Ph), 7.49–7.38 (4H, m, Ar).
2-(2-Chlorophenyl) benzo[d]thiazole (6c): mp 80–828C (lit.
80–828C[20]). nmax (KBr)/cmꢀ1 3056, 1556 (C¼N), 1479, 1427,
1315, 1270, 1221, 1059, 1036, 967, 865, 758, 729, 684. dH
(CDCl3, 400 MHz) 8.23 (1H, dd, J 5.6, 3.6, Ph), 8.16 (1H, d,
J 8.4, Ar), 7.98 (1H, d, J 8.0, Ar), 7.57–7.53 (2H, m, Ar), 7.48–
7.43 (3H, m, Ph). m/z (EI) 245 (41 %, [M]þ) 247 (7 %, [Mþ2]þ).
2-(4-Bromophenyl)-1H-benzo[d]imidazole (7a): mp 291–
2938C (lit. 292–2938C[30]). nmax (KBr)/cmꢀ1 3325–2528 (NH),
1626 (C¼N), 1599, 1490, 1456, 1378 (C–N), 1231, 1073, 1010,
830, 739, 616. dH ([D6]DMSO, 400 MHz) 8.26 (2H, d, J 8.8,
Ar), 7.94 (2H, d, J 8.8, Ar), 7.81–7.78 (2H, m, Ph), 7.50 (2H, dd,
J 6.0, 3.2, Ph). m/z (EI) 273 (50 %, [M]þ), 275 (33 %, [Mþ2]þ).
2-(4-Bromophenyl) benzo[d]oxazole (7b): mp 157–1588C
(lit. 157–1588C[1b]). nmax (KBr)/cmꢀ1 3084, 3051, 1614 (C¼N),
1591, 1548, 1483, 1451, 1400, 1343, 1244 (C–O), 1180, 1069,
1052, 1008, 925, 830, 740, 716, 494. dH (CDCl3, 400 MHz) 8.14
(2H, dt, J 8.8, 2.0, Ar), 7.80–7.78 (1H, m, Ph), 7.69 (2H, dt, J 8.8,
2.0, Ar), 7.61–7.59 (1H, m, Ph), 7.41–7.37 (2H, m, Ph). m/z (EI)
274 (90 %, [M]þ), 272 (100 %, [M–2]þ).
2-(4-Bromophenyl) benzo[d]thiazole (7c): mp 128–1298C
(lit. 127–1298C[31]). nmax (KBr)/cmꢀ1 3064, 3031, 2913, 2851,
1589 (C¼N), 1503, 1475, 1401, 1319, 1221, 1070, 1008, 969,
826, 752, 721, 681, 481. dH (CDCl3, 400 MHz) 8.09 (1H, dd,
J 8.0, 0.4, Ar), 7.98 (2H, dt, J 8.4, 2.4, Ph), 7.93 (1H, dd, J 8.2,
0.4, Ar), 7.65 (2H, dt, J 8.4, 2.4, Ph), 7.53 (1H, td, J 8.0, 1.2, Ar),
7.42 (1H, td, J 7.6, 1.2, Ar).
2-p-Tolyl-1H-benzo[d]imidazole (8a): mp 274–276 (lit.
274–2768C[32]). nmax (KBr)/cmꢀ1 3056–2500 (NH), 1621
(C¼N), 1500, 1447, 1430, 1398, 1369 (C–N), 1274, 1229,
1123, 964, 821, 746, 726, 545, 489. dH ([D6]DMSO,
400 MHz) 12.81 (1H, br s, NH), 8.07 (2H, d, J 8.0, Ph), 7.58
(2H, m, Ar), 7.35 (2H, d, J 8.0, Ph), 7.18 (2H, dd, J 6.3, 2.8, Ar),
2.38 (3H, s, Me). m/z (EI) 208 (100 %, [M]þ).
2-p-Tolyl benzo[d]oxazole (8b): mp 103–1058C (lit.105–
1068C[33]). nmax (KBr)/cmꢀ1 3060, 3023, 2917, 2851, 1621
(C¼N), 1555, 1501, 1451, 1409, 1348, 1243 (C–O), 1172,
1115, 1055, 1016, 820, 746, 726, 501. dH (CDCl3, 400 MHz)
8.17 (2H, d, J 8.0, Ph), 7.79–7.77 (1H, m, Ph), 7.60–7.58 (1H, m,
Ph), 7.38–7.34 (4H, m, Ar), 2.46 (3H, s, Me).
2-p-Tolyl benzo[d]thiazole (8c): mp 83–848C (lit. 80–
848C[20]). nmax (KBr)/cmꢀ1 3060, 3023, 2908, 1609 (C¼N),
1527, 1484, 1433, 1407, 1312, 1226, 1181, 959, 817, 761, 729,
691, 622, 482. dH (CDCl3, 400 MHz) 8.08 (1H, d, J 8.0, Ar), 8.01
(2H, d, J 8.4, Ph), 7.91 (1H, d, J 7.6, Ar), 7.50 (1H, td, J 8.4, 1.2,
Ar), 7.39 (1H, td, J 8.4, 1.2, Ar), 7.32 (2H, d, J 8.0, Ph), 2.45 (3H,
s, Me). m/z (EI) 225 (57 %, [M]þ).
(E)-2-Styryl benzo[d]thiazole (11c): mp 106–1078C (lit.
106–1088C[40]). nmax (KBr)/cmꢀ1 3056, 3031, 2921, 2847,
1621 (C¼N), 1495, 1432, 1312, 1188, 958, 939, 853, 758,
2-(3,5-Dimethylphenyl)-1H-benzo[d]imidazole (9a): mp
259–2618C (lit. 260–2638C[34]). nmax (KBr)/cmꢀ1 3382–2504

Synthesis of 1,3-Benzazoles
153
725, 689, 666, 433. dH (CDCl3, 400 MHz) 8.02 (1H, d, J 8.0, Ar),
7.87 (1H, d, J 8.0, Ar), 7.62–7.53 (3H, m, Ph), 7.50 (1H, td,
J 8.2, 1.2, Ar), 7.46–7.38 (5H, m, Ar, Ph, 2CH). m/z (EI) 237
(65 %, [M]þ).
(E)-2-(4-Chlorostyryl)-1H-benzo[d]imidazole (12a): mp
227–229 (lit. 228–2298C[41]). nmax (KBr)/cmꢀ1 3358–2500
(NH), 1646 (C¼N), 1571, 1462, 1409, 1311 (C–N), 1229,
1086, 973, 817, 755, 624, 502. dH ([D6]DMSO, 400 MHz)
8.21 (1H, d, J 16.4, CH), 7.81–7.77 (2H, m, Ar), 7.76 (2H, d,
J 8.8, Ph), 7.59 (2H, d, J 8.4, Ph), 7.54–7.50 (2H, m, Ar), 7.36
(1H, d, J 16.4, CH). m/z (EI) 253 (3 %, [M–1]þ).
(E)-2-(4-Chlorostyryl) benzo[d]oxazole (12b): mp 142–
1448C (lit. 144–1458C[42]). nmax (KBr)/cmꢀ1 3051, 1639
(C¼N), 1593, 1527, 1487, 1449, 1348, 1286, 1239 (C–O),
1176, 1086, 968, 928, 811, 739, 719, 501. dH (CDCl3,
400 MHz) 7.76–7.72 (2H, m, CH, Ph), 7.55–7.52 (3H, m, Ph),
7.42–7.33 (4H, m, Ar), 7.06 (1H, d, J 16.4, CH).
(E)-2-(4-Chlorostyryl) benzo[d]thiazole (12c): mp 177–
1788C (lit. 177–1788C[43]). nmax (KBr)/cmꢀ1 3051, 3027,
2990, 1625 (C¼N), 1589, 1493, 1454, 1403, 1313, 1234,
1189, 1089, 1009, 957, 942, 811, 756, 723, 657, 491. dH (CDCl3,
400 MHz) 8.02 (1H, d, J 8, Ar), 7.87 (1H, dd, J 8, 0.4, Ar), 7.52–
7.46 (4H, m, Ar, Ph), 7.42–7.36 (4H, m, CH, Ph).
2-Benzyl-1H-benzo[d]imidazole (13a): mp 172–1748C (lit.
1758C[44]). nmax (KBr)/cmꢀ1 3234–2851 (NH), 1679 (C¼N),
1646, 1600, 1540, 1496, 1453, 1339 (C–N), 1290, 1180, 972,
744, 696, 563. dH ([D6]DMSO, 400 MHz) 9.53 (1H, m, Ar), 7.47
(1H, t, J 3.2, Ar), 7.32 (5H, m, Ph), 7.26 (1H, d, J 5.6, Ar), 7.14
(1H, t, J 4, Ar), 3.61 (2H, s, CH2). m/z (EI) 208 (2 %, [M]þ).
2-Benzyl benzo[d]oxazole (13b): mp 27–288C (lit. 288C[45]).
nmax (neat)/cmꢀ1 3084, 3062, 3031, 2929, 1666, 1614 (C¼N),
1569, 1495, 1455, 1425, 1348, 1273, 1241 (C–O), 1140, 1104,
1002, 955, 841, 747, 765, 721, 695. dH (CDCl3, 400 MHz) 7.72–
7.70 (1H, m, Ar), 7.50–7.47 (1H, m, Ar), 7.42–7.40 (2H, m, Ar),
7.39–7.35 (2H, m, Ph), 7.33–7.30 (3H, m, Ph), 4.30 (2H, s, CH2).
2-Benzyl benzo[d]thiazole (13c): mp 157–1588C (lit. 158–
1608C[46]). nmax (KBr)/cmꢀ1 3061, 3029, 2949, 2923, 2847,
1723, 1601(C¼N), 1516, 1494, 1454, 1435, 1311, 1242, 1107,
1061, 861, 759, 729, 703, 639, 436. dH (CDCl3, 400 MHz) 8.21
(1H, d, J 8.0, Ar), 7.82 (1H, d, J 8.0, Ar), 7.49–7.45 (1H, m, Ar),
7.41–7.30 (6H, m, Ph, Ar), 4.46 (2H, s, CH2).
2-(4-Methoxybenzyl) benzo[d]oxazole (14b): mp 43–458C.
nmax (KBr)/cmꢀ1 3035, 3007, 2966, 2928, 2904, 2833, 1899,
1772, 1736, 1612 (C¼N), 1566, 1512, 1455, 1441, 1303, 1247
(C–O), 1179, 1140, 1029, 816, 743, 551. dH (CDCl3, 400 MHz)
7.70 (dd, 1H, J 6.2, 4, Ar), 7.48 (dd, 1H, J 5.8, 4, Ar), 7.33–7.28
(4H, m, Ar, Ph), 6.91 (2H, d, J 8.4, Ph), 4.23 (2H, s, CH2), 3.81
(3H, s, OMe). dC (CDCl3, 100 MHz) 165.0 (–C¼N), 158.8
(¼C–OMe), 150.6 (¼C–O), 141.3 (¼C–N), 130.0, 126.7,
124.6, 124.1, 119.8, 114.2, 110.4, 55.2 (OCH3), 34.4 (CH2).
m/z (EI) 239 (62 %, [M]þ). Anal. Calc. for C15H13NO2: C 75.30,
H 5.48, N 5.85. Found: C 74.90, H 5.18, N 5.19 %.
(1H, m, Ar), 7.53–7.51 (1H, m, Ar), 7.39–7.29 (12H, m, Ar, Ph),
5.81 (1H, s, CH). m/z (EI) 285 (12 %, [Mþ]).
2-Benzhydryl benzo[d] thiazole (15c): mp 78–798C (lit.
78–798C[48]). nmax (KBr)/cmꢀ1 3060, 3023, 2921, 2851, 1956,
1593 (C¼N), 1492, 1448, 1431, 1310, 1248, 1180, 1140, 1127,
1025, 887, 762, 723, 702, 600. dH (CDCl3, 400 MHz) 8.06 (1H,
d, J 8.4, Ar), 7.84 (1H, d, J 8.4, Ar), 7.49 (1H, td, J 8.0, 1.2, Ar),
7.40–7.28 (11H, m, Ar, 10Ph), 5.99 (1H, s, CH). m/z (EI) 301
(40 %, [M]þ).
2-(Heptadec-8-enyl) benzo[d]oxazole (16b): Liquid (lit.[47]).
nmax (neat)/cmꢀ1 3056, 3004, 2925, 2853, 1615 (C¼N), 1572
(C¼C), 1456, 1374, 1242 (C–O), 1147, 1002, 928, 837, 744. dH
(CDCl3, 400 MHz) 7.70–7.67 (1H, m, Ar), 7.50–7.48 (1H, m,
Ar), 7.32–7.30 (2H, m, Ar), 5.37–5.34 (2H, m, –CH¼CH–), 2.94
(2H, t, J 8, a to benzoxazole ring), 2.03–2.02 (4H, m,
–CH2CH¼CHCH2–), 1.94–1.87 (2H, m, b to benzoxazole ring),
1.44–1.28 (20H, m, chain CH2), 0.89 (3H, t, J 6.8, CH3).
2-Heptadecyl-1H-benzo[d]imidazole (17a): mp 87–888C
(lit. 88–908C[49]). nmax (KBr)/cmꢀ1 3317–2508 (NH), 1648
(C¼N), 1531, 1470, 1370 (C–N), 1225, 894, 857, 744, 624. dH
([D6]DMSO, 400 MHz) 12.17 (1H, br s, NH), 7.44 (2H, s, Ar),
7.09 (2H, s, Ar), 2.77 (2H, t, J 6.8, a benzoimidazole ring), 1.76–
1.72 (2H, m, b benzoimidazole ring), 1.28–0.95 (28H, m, CH2
chain), 0.83 (3H, t, J 6.8, CH3). m/z (EI) 356 (20 %, [M]þ).
2-Heptadecyl benzo[d]oxazole (17b): mp 53–558C (lit.
558C[50]). nmax (KBr)/cmꢀ1 3056, 2953, 2920, 2849, 1614
(C¼N), 1569, 1470, 1456, 1385, 1241 (C–O), 1142, 1111,
1008, 943, 898, 836, 746, 719. dH (CDCl3, 400 MHz) 7.70–
7.67 (1H, m, Ar), 7.51–7.47 (1H, m, Ar), 7.33–7.28 (2H, m, Ar),
2.94 (2H, t, J 7.6, a benzoxazole ring), 1.94–1.86 (2H, m, b
benzoxazole ring), 1.46–1.27 (28H, m, CH2 chain), 0.90 (3H, t,
J 6.4, CH3). m/z (EI) 357 (27 %, [M]þ).
2-Heptadecylbenzo[d]thiazole (17c): mp 52–538C (lit.
538C[51]). nmax (KBr)/cmꢀ1 3076, 2956, 2918, 2848, 2553,
1704 (C¼N), 1506, 1466, 1315, 1237, 1160, 1090, 890, 764,
728, 628. dH (CDCl3, 400 MHz) 8.00 (1H, d, J 8.0, Ar), 7.85 (1H,
d, J 8.0, Ar), 7.46 (1H, td, J 8.0, 1.2, Ar), 7.36 (1H, td, J 8.0, 1.2,
Ar), 3.13 (2H, t, J 7.6, a benzothiazole ring), 1.93–1.85 (2H, m,
b benzoimidazole ring), 1.49–1.27 (28H, m, CH2 chain), 0.90
(3H, t, J 6.8, CH3). m/z (EI) 373 (19 %, [M]þ).
2-(Thiophen-3-yl)-1H-benzo[d]imidazole (18a): mp 298–
3008C (lit. 3008C[52]). nmax (KBr)/cmꢀ1 3272–2528 (NH),
1649 (C¼N), 1597, 1528, 1448, 1428, 1315 (C–N), 1272,
1115, 988, 878, 742, 604. dH ([D6]DMSO, 400 MHz) 12.87
(1H, br s, NH), 8.26–8.25 (1H, m, thiophen), 7.79–7.78 (1H, m,
thiophen), 7.74–7.72 (1H, m, thiophen), 7.56 (2H, m, Ar), 7.19–
7.17 (2H, m, Ar). m/z (EI) 200 (85 %, [M]þ).
2-(Thiophen-3-yl) benzo[d]oxazole (18b): mp 107–1088C
(lit. 1088C[53]). nmax (KBr)/cmꢀ1 3088, 1616 (C¼N), 1576,
1450, 1405, 1276, 1241 (C–O), 1176, 1055, 1008, 935, 863,
801, 742, 714, 600. dH (CDCl3, 400 MHz) 8.22 (1H, dd, J 3.2,
1.2, thiophen), 7.82 (1H, dd, J 5.0, 1.2, thiophen), 7.78–7.76
(1H, m, Ar), 7.59–7.56 (1H, m, Ar), 7.48 (1H, dd, J 5.0, 3.2,
thiophen), 7.39–7.34 (2H, m, Ar). dC (CDCl3, 100 MHz) 159.7
(–C¼N), 150.3 (¼C–O), 141.9 (¼C–N), 129.2, 128.0, 127.0,
126.6, 125.0, 124.6, 119.9, 110.4.
2-(Thiophen-3-yl) benzo[d]thiazole (18c): mp 98–998C (lit.
99–1008C[46]). nmax (KBr)/cmꢀ1 3080, 3051, 2917, 2851, 1540
(C¼N), 1474, 1432, 1372, 1312, 1238, 1188, 1164, 1075, 995,
892, 870, 839, 785, 766, 731, 652. dH (CDCl3, 400 MHz) 8.06
(1H, d,J8.4,Ar),8.04(1H,dd, J2.8,1.2,Ar),7.90(1H,d,J8,Ar),
7.73 (1H, dd, J 5, 1.2, Ar), 7.50 (1H, td, J 8, 1.2, thiophen), 7.45
(1H, dd, J 5.2, 3.2, thiophen), 7.40 (1H, td, J 7.6, 0.8, thiophen).
2-Benzhydryl-1H-benzo[d]imidazole (15a): mp 209–2118C
(lit. 210–2128C[17a]). nmax (KBr)/cmꢀ1 3252–2500 (NH), 1728,
1679, 1609 (C¼N), 1491, 1454, 1425, 1388 (C–N), 1270, 1172,
1070, 1029, 753, 743, 701. dH ([D6]DMSO, 400 MHz) 12.38
(1H, br s, NH), 7.54–7.52 (1H, m, Ar), 7.43 (1H, m, Ar),
7.36–7.31 (8H, m, Ar, Ph), 7.27–7.22 (2H, m, Ph), 7.16–7.13
(2H, m, Ph), 5.74 (1H, s, CH).
2-Benzhydryl benzo[d]oxazole (15b): mp 67–698C (lit.
69.5–70.58C[47]). nmax (KBr)/cmꢀ1 3060, 3031, 2921, 1605
(C¼N), 1563, 1492, 1449, 1236 (C–O), 1154, 1033, 1004,
933, 867, 744, 696, 645, 473. dH (CDCl3, 400 MHz) 7.79–7.76

154
S. Rezazadeh, B. Akhlaghinia, and N. Razavi
2-(Pyridin-4-yl)-1H-benzo[d]imidazole (19a): mp 206–
[11] (a) A. T. Mavrova, K. K. Anichina, D. I. Vuchev, J. A. Tsenov,
P. S. Denkova, M. S. Kondeva, M. K. Micheva, Eur. J. Med. Chem.
2006, 41, 1412. doi:10.1016/J.EJMECH.2006.07.005
(b) Y. Kohara, K. Kubo, E. Imamiya, T. Wada, Y. Inada, T. Naka,
J. Med. Chem. 1996, 39, 5228. doi:10.1021/JM960547H
(c) G. I. Elmer, J. O. Pieper, S. R. Goldberg, F. R. George, Psycho-
pharmacology (Berl.) 1995, 117, 23. doi:10.1007/BF02245094
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doi:10.1002/CJOC.201180310
2088C (lit. 207.3–2088C[54]). nmax (KBr)/cmꢀ1 3382–2524
(NH), 1634, 1614 (C¼N), 1544, 1429, 1318 (C–N), 1237,
1015, 967, 835, 767, 750, 698, 559. dH ([D6]DMSO,
400 MHz) 12.70 (1H, br s, NH), 8.76 (2H, d, J 6, Py), 8.11
(2H, d, J 6 Hz, Py), 7.66 (2H, dd, J 5.6, 3.2, Ar), 7.26 (2H, dd,
J 6.0, 3.2, Ar). dC ([D6]DMSO, 100 MHz) 150.9 (–C¼N), 149.2
(–C¼N pyridine ring), 137.6 (¼C–N), 123.3, 120.7, 119.1.
2-(Pyridin-4-yl) benzo[d]oxazole (19b): mp 125–1278C (lit.
127–1288C[55]). nmax (KBr)/cmꢀ1 3047, 2958, 2929, 2851,
1728, 1687, 1614 (C¼N), 1594, 1540, 1449, 1411, 1346, 1250
(C–O), 1057, 927, 833, 811, 751, 703, 690, 516. dH (CDCl3,
400 MHz) 8.85 (2H, s, Py), 8.12 (2H, d, J 6, Py), 7.86–7.84 (1H,
m, Ar), 7.67–7.65 (1H, m, Ar), 7.48–7.42 (2H, m, Ar).
6-Methyl-2-phenyl benzo[d]oxazole (20b): mp 90–928C (lit.
90–938C[56]). nmax (KBr)/cmꢀ1 3060, 3023, 2855, 1736, 1616
(C¼N), 1553, 1484, 1447, 1336, 1290, 1249 (C–O), 1172, 1127,
1051, 1020, 922, 832, 808, 700, 686, 604. dH (CDCl3, 400 MHz)
8.27–8.24 (2H, m, Ph), 7.66 (1H, d, J 8.0, Ar), 7.55–7.52 (3H, m,
Ph), 7.40 (1H, s, Ar), 7.19 (1H, d, J 8.0, Ar), 2.53 (3H, s, Me). m/z
(EI) 209 (13 %, [M]þ).
[13] X. Wen, J. El Bakali, R. Deprez-Poulain, B. Deprez, Tetrahedron Lett.
2012, 53, 2440. doi:10.1016/J.TETLET.2012.03.007
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(b) H. M. Bachhav, S. B. Bhagat, V. N. Telvekar, Tetrahedron Lett.
2011, 52, 5697. doi:10.1016/J.TETLET.2011.08.105
(c) A. J. Blacker, M. M. Farah, M. I. Hall, S. P. Marsden, O. Saidi,
J. M. Williams, Org. Lett. 2009, 11, 2039. doi:10.1021/OL900557U
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Supplementary Material
Details of analysis of 1,3-benzazoles derivatives are available
on the Journal’s website.
(b) J. A. Seijas, T. Vazquez, M. Pilar, R. Carballido, M. Raquel,
C. J. Crecente, L. Romar-Lopez, Synlett 2007, 313. doi:10.1055/S-
2007-967994
Acknowledgements
(c) M. B. Maradolla, S. K. Allam, A. Mandha, G. V. P. Chandramouli,
ARKIVOC 2008, 15, 42. doi:10.3998/ARK.5550190.0009.F05
[18] (a) A. Kiani, B. Akhlaghinia, H. Rouhi-Sadabad, M. Bakavoli,
J. Sulfur Chem. 2014, 35, 119. doi:10.1080/17415993.2013.801476
(b) B. Akhlaghinia, H. Rouhi-Sadabad, Can. J. Chem. 2013, 91, 181.
doi:10.1139/CJC-2011-0493
The authors gratefully acknowledge partial support of this study by Ferdowsi
University of Mashhad Research Council (Grant No. p/3/25246).
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