Indian Journal or Chemistry
Vol. 428, September 2003, pp. 2115-2118
Note
Syntheses of 1-alkyl -2-(substituted-2-
pyridyl)benzimidazoles
P K Dubey*, C Ravi Kumar & P V V Prasada Reddy,
Dept. of Chemistry, College or Engg .. J. N. T. University,
Kukatpally. Hyderabad, (AP)- 500 072. India.
Recei1·ed 16 Nm·emher 2001: accepted (rel'i.l'ed) 5 Nm·ember 2023
1-a-Pyridinium acetophenone chloride 2 on reaction with
2-cinnamoylbenzimidazoles 3 followed by alkylation yields 1-
alkyl-2-(substituted-2-pyridyl) benzimidazolcs 5. The latter could
also be synthesized by direct reaction of 2 with 1-alkyl-2-
cinnamoylbcnzimidawles 6 in accordance with the Kriihnke's
pyridine synthesis.
2-Substitutedbenzimidazoles represent a variety of
biologically active compounds 1• In continuation of
2
our earlier work in this direction, we report herein
our studies on syntheses of 1-alkyl-2-(substituted-2-
pyridy I)benzimidazoles.
Heating a mixture of 2-chloroacetophenone 1 and
pyridine gave 1-a-pyridiniumacetophenone chloride
2, which on treatment with benzimidazole-2-~-p­
methoxyphenylvinylketone3 3a 1 (i.e. 3a, R'=OMe-p)
in the presence of ammonium acetate gave a product
characterized as I H- 2-( 4-p- methox yphen y 1-6-pheny 1-
2-pyridyl)benzimidazole 4a 1 (i.e, 4a, R'=OMe-p) on
the basis of spectral and analytical data. Thus, its IR
(KBr) spectrum showed a strong broad band at= 3000
1 bromide salt Sb.The latter on treatment with simple
cm· assignable to imidazole -NH- stretching. Its 1H
NMR (COCI 3ffMS) spectrum showed signals at 8
3.85 (s. 3H, -OCH 3), 7.0 and 7.8 (AB quartet, 4H,
1=6Hz, four p-methoxyphenyl protons), 7.2-7.4 (m,
3H), 7.4 -7.6 (m, 4H), 8.0-8.2 (d, 2H), (nine protons
accounting for five phenyl and four benzimidazole
aryl protons), 7.9 (s, I H) and 8.6 (s, 1H) [~. Wprotons
of the pyridine ring) 10.65 (broad s, IH, -NH-
proton). Its mass spectrum showed peaks at mlz (%1):
378 (13, M+l), 377 (51, M+), 280 (5), 253 (14), 251
(4), 189 (6), 134 (16), 120 (42), 118 (100), 91 (17), 90
(13), 77 (15) (Scheme 1).
The above reaction of 2 was extended to different 3
and the products, thus obtained were assigned
structure 4 by analogy and on the basis of their
analytical and spectral data (Table 1).
Treatment of 4a 1 with dimethyl sulfate (OMS)
gave a product, which was characterized as !-methyl-
2-(4-p-methoxyphenyl-6-phenyl-2-pyridyl)benzimida-
zole Sb 1 (i.e. Sb, R=Me, R'=OMe-p). Its IR (KBr)
spectrum showed the absence of strong broad band at
= 3000 cm· 1 assigned earlier to imidazole -NH-
stretching. Its 1H NMR (COCI 3ffMS) spectrum
showed signals at 8 2.35 (s, 3H, -OCH 3), 4.25 (s, 3H.
-NCH 3), 7.1-7.8 (complex m, ISH, two protons due
to pyridine ring, five phenyl protons, four p-
methoxyphenyl protons and four aryl protons of the
benzimidazole ring system). Its mass spectrum
showed peaks at m/z (%1): 391 (5, M+ ), 379 (6), 378
(34 ), 377 ( 100), 362 (9), 334 (4 ), 300 (II), 252 (20),
186 (9), 118 (30), 90 (10).
Similar reactions of 4a with benzyl chloride under
the same conditions yielded the corresponding N-
benzyl derivative, Sc 1 (i.e. Sc, R= CH 2Ph) (Table II).
Sb was also synthesized by direct reaction of 2
with N-methylbenzimidazole-2-~-arylvinylketone 6b
4
(i.e. 6, R=Me) in the presence of ammonium acetate.
The product, thus obtained, was found to be identical
in m.p, m.m.p., co-TLC and superimposable IR with
Sb obtained earlier by alkylation of 4a with OMS, in
the route 3a---74a~Sa. The above reaction of 6b with
2 was extended to other 6 to obtain various 5.
Alternatively, N- meth y 1-a-bromo- 2-acety Ibenzi mid-
azote 7b (i.e. 7, R = Me) was treated with pyridine to
obtain N-methylbenzimidazole-2-acetylpyridinium
chalcone 9a (i.e. 9, R'=OMe) gave a product identical
in all respects with Sb. This reaction has been extended
to other 9, which were prepared by using reported
procedure5 . All the above reactions are summarized in
Scheme I. The reactions can be explained on the basis
of the mechanism shown in Scheme II.
Experimental Section
Spectroscopic data were recorded with JASCO FT-
IR 5300, VARIAN 200 ( 1H NMR, 200MHz), Hewlet
Packard (El-MS 70 eV) instruments. Melting points
were determined in open capillary tubes in sulfuric
acid bath and are uncorrected. TLC analyses were
done on glass plates coated with silicagel-G and
spotting was done using iodine or U V Light.
Preparation of 2/8 from 117 (General procedure).
A mixture of 117 (10 m mole) and pyridine ( 10 mL)
was heated on a steam bath at 100°C with stirring for
2116 INDIAN Jo CHEMO. SEC 8, SEPTEMBER 2003

~NO.c,
0
~C_I_Py_ri_di_nc_l_!::._ _ _

( 2)
(I )

0
o=:~ ,~N~ In·
H 0 H 0
AcOHt6

~ UU
7

( 3a) R' ( 2)

DMS or PhCH 2CI

TEBAC I K 2C0 1 I CHCJ 1 1 RT

H4NOOCCH 1
AcOHi/:::,.
H"NOOCCH,
,>.cOHi/:::,. .
R 0 H

o=:~
~ u
r
R'
( 6)

H~NOOCCH 1
AcOHi/:::,.

~
U ~ U+ R'
0 Br
0

( 9) (II)

~~HJO
~N'~Br _I_'y_rid_in_c_IR_T_---1•0=)--CN~
CH3 0 I.B'
( 7 h) (8b)

Scheme 1
 NOTES 2117

Table I --Characterization data of compounds 4

1
SI Starting Reagent Product Yield m.p. H-NMR
No material used obtained (%) (IC) ( 8, ppm)
I 3a 1 2 4a 1 (R'=OMe) 72 225 Data given in text
2 3a 2 2 4a 2(R'=H) 68 248 7.0 and 7.85 (m, 5H, five phenyl protons), 7.2-7.4 {m, 3H), 7.4 -7.6
(m, 4H), 8.0-8.2 (d. 2H). (nine protons accounting for rive phenyl
four benzimidazole aryl protons), 7.9 {s, I H) and 8.6 {s, I H) (8. B'
protons of the pyridine ring), 10.65 (broads. I H. -NH- proton).
3 Ja.1 2 69 >260 7.0 and 7.80 (A8 quartet, 4H, J=6Hz, p-chlorophenyl protons), 7.2-
7.4 (m, 3H). 7.4 -7.6 (m, 4H), 8.0-8.2 (d. 2H), (nine proiOns
accounting for five phenyl. four benzimidazole aryl protons). 7.9 (s.
I H) and 8.6 (s. I H) (8. 8' protons of the pyridine ring), 10.65 (broad
s. I H. -NH- proton).
2 65 >260 3.95 (s, 3H, -SCH~). 7.2 and 7.9 (A8 quartet, 4H, J=6Hz, four p-
thiomethylphenyl protons), 7.3-7.4 (m. 3H). 7.5 -7.7 (m. 4H). 8.0-8.2
(d. 2H), (nine protons accounting for five phenyl, four
benzimidazole aryl protons). 7.92 (s. IH) and 8.5 (s. IH) (B. B'
protons of the pyridine ring), I 0.63 (broad singlet, I H. -NH- proton).
5 3as 2 4a 5(R'=Me) 71 >260 3.00 (s, 3H, -CH~). 7.0 and 7.38 (A8 quartel. 4H, J=6Hz.
p-methylphenyl protons). 7.2-7.4 (m, 3H). 7.4 -7.6 (m. 4H). 8.0-8.2
(d, 2H), (nine protons accounting for five phenyl four benzimidazole
aryl protons), 7.9 (s, I H) and 8.6 (s. I H) (8. 8' protons of the
pyridine ring), 10.62 (broad s, I H, NH- proton).
Table II -Characterization data of compound 5
1
Sl. Starting Reagent Reaction Product Yield m.p. H-NMR
No. material used condition' obtained (%) (oC) ( 8, ppm)
4a 1 OMS A Sb1 62 190-3 Data given in text
(R=Me, 55 192
2 B R'=OMe) 52 192
Sb B
2 OMS A Sb 2 68 248 4.25 (s, 3H, -NCH~). 7.1-7.8 (complex m, 16H, two
(R=Me, protons due to pyridine ring, 2xfive phenyl protons and
2 8 R'=H) 70 249 four aryl protons of the benzimidazole system).
Sb 8 45 246-9
3 OMS A Sb_1 69 260 4.29 (s, 3H, -NCH~). 7.5-7.83 (complex m. 15H, five
(R=Me, phenyl protons, four p-chlorophenyl protons and four
6b.l 2 8 R'=Cl) 71 259 aryl protons of the benzimidazole system and two
9c Sb B 56 260 pyridine ring protons).
4 4as OMS A Sbs 68 245
(R=Me,
2 B R'=Me) 65 245
Sb 8 62 245-6
5 2 B sc. 65 235 1.5 (t, 3H, -CH~). 3.9 (s, 3H. -OCH 1), 4.75 (q, 2H, -CH 2).
(R=Et, 6.85-S.l(complex m, 15H. two protons due to pyridine ring.
R'=OMe) live phenyl protons, four p-methoxyphenyl protons and
four aryl protons of benzimidazole moiety).
6 A Sd1 69 250 3.75 (s, 3H, -OCH 1 ), 5.9 (s, 2H, -CH 2Ph), 7.0-8.4 (complex
(R=CH 2Ph, m, 20H, two protons due to pyridine ring, five phenyl
2 8 R'=OMe) 72 250 protons, four p-methoxyphenyl protons, live benzylic
protons and four aryl protons of benzimidazole moiety).
7 A Sd 2 71 240 5.85 (s, 2H, -CH 2 Ph), 7.0-8.42 (complex m, 21 H. two
(R=CH2Ph, protons due to pyridine ring, 2xfive phenyl protons, five
2 B R'=H) 70 240 benzylic protons and four aryl protons of benzimidazole
moiety).
A Sd 3 67 210 5.9{s, 2H, -CH 2 Ph), 7.0-8.4 (complex m, 20H, two
(R=CH2Ph. protons due to pyridine ring, five phenyl protons, four p-
6d.l 2 B R'=Cl) 64 210 chlorophenyl protons. five benzylic protons and four
aryl protons of benzimidazole moiety).
*A: RT. B: Reflux (IIX 0 C).
Satisfactory IR's were obtained for all compounds in the Tables I and II in accordance with structures assigned.
2118 INDIAN J. CHEM., SEC B. SEPTEMBER 2003
1.5 and 0.5 hr respectively. At the end of this period,
the reaction mixture was cooled. and the separated
product was filtered, washed with ethyl acetate and
then dried to obtain pure 2/8 (yield of 2 is 94 % and
that or 8 is 80% ).
Spectral data of 2: IR (KBr): 3029 (s, -CH- str),
1697 (vs, with a shoulder at 1709, -CO- str), 1635 (m,
-C=N- str), 1579 (w), 1486 (vs). 1469 (s) cm· 1 etc. 1H
NMR (0~0): 8 4.15 (s, 2H, -CH]- ). 7.45-9.0 (complex
rn. IOH, five phenyl and five pyridyl protons) and
rn.p. >300" C.
Spectral data of 8: IR (KBr): 3136 (w, -CH str),
3032 (m), 1693 (vs, -CO- str), 1636 (m, -C=N-), 1594
(m). 1578 (m), 1494 (m) cm· 1 etc. 1H NMR (0]0): 8
2.3 (s, 3H,-NCH~). 4.2 (s, 2H, -CH 2 - ), 7.0-7.3
(complex m, 9H, five pyridyl protons and four aryl
protons of benzimidazole moiety) and m.p. >300" C.
Preparation of 4 from 3 (General procedure). To
a solution of 3 ( 10 m mole) and ammonium acetate
(30m mole) in acetic acid (15 mL) was added solid 2
( 12 m mole) as one lot and the mixture refluxed at
II8°C for I hr. Then, the reaction mixture was poured
into icc-cold water (I 00 mL) and the separated solid
was filtered, washed with water and dried to obtain
crude 4. The latter was recrystallized from methanol-
chloroform to obtain pure 4 (Table 1).
Preparation of 5/6 from 4a/3a (General
procedure). A mixture of 4 (10 m mole). K]CO~
(0.83 g. 6 111 mole). TEBAC (0.113 g, 0.5 m mole)
and the alkylating agent OMS I PhCH 2Cl ( 12 111
mole) in chloroform (25 mL) was stirred at RT for
2.5 hr. The reaction mixture was filtered and the
chloroform filtrate was washed with water (2x20
111L), dried over anhyd. MgS0 4 , filtered and
evaporated to dryness yielding a residue, which was
crude 5/6. The latter were recrystallized to obtain
pure 5/6 (Table II).
Preparation of 5 from 2/9 and 6/8 (General
procedure). A mixture of 6/8 (1 0 IT: mole). 2/9 (12 m
mole), ammonium acetate (30m moie) and acetic acid
(15 mL) was retluxed atll8° C for I hr., the reaction
mixture was cooled to RT and poured into icc-cold
water ( 100 mL). The separated solid was filtered,
washed with water (2x50 111L) and dried to obtain a
crude 5. The latter was recrystallized from methanol-
chloroform to give pure 5 (Table II).
Preparation of 1,5-diketone. Treatment of 2 ( 12
m mole) with 3a 1(10 m mole) (i.e. 3a. R'=OMc) in
retluxing acetic ac£d for 4 hr, gave I ,5-diketone 2"a 1
(i.e., 2", R=H, R'=OMe-p), m.p. 167-70"C. IR (KBr):
3000 (vb, imidazole -NH-). 1688, 1686 (vs, doublet,
with a shoulder at 1670, -CO- str), 1625 (vs. -C=C-,
str), 1591 (vs), 1490(m), 1420(s)crn· 1ctc.
Acknowledgement
The authors are deeply indebted to U G C, New
Delhi, for financial support.
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