Indian Journ al of Chemistry
Vol. 42B, December 2003, pp. 3128-3130
Note
Solid phase synthesis of benzimidazole
ketones and benzimidazole chalcones
under solvent-free conditions
P K Dubey*, C Ravi Kumar & Balaji Babu
Department of Chemistry, JNTU College of Engi neerin g,
Kukatpally, Hyderabad 500072.
Received 20 AugusT 2002; accepTed (revised) 25 AugusT 2003
Oxidation of I-alkyl/aralky 1-2-( a-hydrox yalky l/ary I)benzimid-
azo les 1 with KMn04 on neutral alumina under solid phase condi-
tion s gives the corresponding ketones, l -alkyl/aralkyl-2 -acy l-
benzimidazoles 2. Compound 2a (R 2 = CH 3 ) on condensation
with aromatic aldehydes in the presence of solid NaOH under
solvent-free conditions, yields the corresponding chalcones, 1-
alkyl/aralkyl-2-benzimidazole ary l vinyl keto ne 3 .
Aldehydes and ketones are found to be very good re-
active intermediates. Numerous methods have been
reported I in the literature to synthesize carbonyl com-
pounds from primary and secondary alcohols. One of
2
these methods involves solid phase oxidation using
either supported or unsupported KMn04. 2-
Acetylbenzimidazoles are very useful reactive inter-
mediates and can be converted into a variety of 2-
substituted benzimidazoles. A good number of these
latter compounds are found 3 to be biologi cally active.
Earlier, we have prepared4 2-acetylbenzimidazoles by
oxidation with K2Cr20 7 under aqueous acidic condi-
tion s in connection with our work on benzimidazoles.
We, now, wish to report the sy nthesis of the same
compounds under solvent-free conditions, a method
which is eco-friendly in nature. The 2-acetylbenzi-
midazoles, thus obtained, were further used for con-
den sation with aromatic aldehydes, once again under
solvent-free conditions to obtain benzimidazolyl chal-
N II
Rl
))
//: NR
I
)-CH(OH)'R2
1
o o
II
£I
N
I ) - C - C HJ
Ar-CHO
,,;::. NR NaOH
Rl
2a
Scheme I
cones 3. It may be mentioned here th at 0 Villemin
5
and co-workers first reported the preparation of
ferrocene chalcones by condensing 3-acetylferrocene
with various aromatic aldehydes using solid NaOH
pellets under so lvent-free conditions.
2-(a-Hydroxyethyl)benzimidazole (la, i.e. , R=H
I 2 '
R =H, R =CH 3 ) was added to KMn04 supported on
finely powdered alumina. The mixture was ground
with a pestle for 5 min at room temperature. Immedi-
ate TLC examination of the resulting mixture showed
the disappearance of the starting material, la. The
reaction mixture was then taken in acetone and fil-
tered. The acetone filtrate was evaporated to obtain a
residue of 2-acetylbenzimidazole (2a, i.e., 2, R2=CH 3)
(Scheme I), which was found to be crude on compari-
so n with an authentic sample (mp, mmp and TLC).
The use of alumina seems to be essential. This is
~ hown by the fact that the reaction did not proceed
with KMn04 in the absence of alumina. The starting
material remained as such on TLC examination even
after several hours . The same reaction did not proceed
when KMn04 was rep laced with Mn02 or K2Cr 207.
The reason for thi s seems to be inactivity of these
oxidants in the presence of neutral alumina. The reac-
tion seems to be selective as is evident in the forma-
tion of only carbonyl compound as shown by TLC
examination of crude reaction mixtures. Normal oxi-
dation of the alcoho ls with KMn04 in so lution phase
yields the carboxylic acid not the carbonyl com-
pound 6 .
The above reaction has been extended to other 1-
alkyl/aralkyl-2- (a-hydroxyalkyl/ary\)benzimidazoles
I and in all the cases, the reaction was completed in
about 5 min as shown by TLC examination . All the
products were found to be l-alkyl/aralkyl-2-acyl
o
Rl M I
//
2
N
} - C - R2
NR
II
£I
N
I }- C - CH=CH·Ar
,,;::. NR
Rl
3
 NOTES 3129

Table I---Oxidati on of alcohol 1 to carbonyl compounds 2'

SI Alcohols R RI RZ Reaction Product Yie ld m.p.

No. Time Obtained (%) (0C)
(min)
I. la H H CH 3 7 2a 91 180-8 1
2. Ib CH 3 H CH 3 5 2b 89 71-3
3. Ie CH 2CH 3 H CH 3 6 2e 86 72-3
4. Id CH 2Ph H CH 3 8 2d 88 102-4
5. Ie H H Ph 7 2e 90 165-67
6. If H H H 8 2f 86 190-93
' Structures of products were confimled by comparison with authentic samples4

Table II - Physical data of compounds 3

Starting R Reage nt Product Time in Yield m.p. Litt.

material Ar= (min ) (%) (0C) (0C)

2a H -Ph 3a 5- 10 87 201 -05 205 7

2a. H p-Cl-Ph 3a. 5-10 90 225-27 225 8
2a2 H p -N0 2-Ph 3az 5-10 80 230-32 232 8
H p -MeO-Ph 5-10 91 190-92 7
2aJ 3aJ 189
2a4 H p -F-Ph 3a4 5-10 94 174-76
2as H o-Cl-Ph 3as 5- 10 88 190-92
2a6 H p-CH r Ph 3a6 15-20 89 2 10- 12 2 127
2a7 H p-N( Meh-Ph 3a7 15-20 90 11 8-20
2aH H poOH- Ph 3ax 5- 10 93 110- 14
2b Clh -Ph 3b 5- 10 92 195-97 195-97 7
2b . CH, p-Cl-Ph 3h. 5- 10 92 145-47 147 8
2b ~ C ~h p- NOr Ph 3h z 5- 10 89 2 10- 12 2 12M
2b , p-McO-Ph 5- 10 94 126-28 7
Clh 3bJ 128
2h4 C H, p -F-Ph 3h4 5- 10 90 94-6
2b, H, o-Cl -Ph 3b s 5- 10 91 110-14
2b 6 C H, p-CH,-Ph 3b" 5- 10 95 104-6 105-77
2e Cz H ~ -Ph 3e 5-10 86 150-52 1488
2e. C 2HS p-Cl- Ph 3e. 5- 10 88 159-6 1 160 8
2e2 C, II ~ p- NOr Ph 3e2 5- 10 84 208- 11 2 11 8
2d CHzPh -Ph 3d 5-10 86 110- 12 109-128
2d. C HzPh p -Cl-Ph 3d. 5- 10 88 154-56 156 8
2d 2 CHzPh p-NOr Ph 3d z 5- 10 84 150-52 152 8

It may bc mentioned here that the com pounds 2as,2a6,2bs & 2b 6 are not reported in literature. They
have, however, been adeq uately cha racte ri zed by their elemental analysis and ·H NMR data. The ·H
NMR of thcse compounds is as follows:
2a4 - (in 8) 7.1 -8.0 (Complex m, 10H, four aryl proto ns of thc benzimidazole ring. four aryl protons
of the p-f1uorophenyl ring and two protons of the et hylenic part.), 10.4 (broad s, I H, -NH)
2as - (in 8) 7.3-8.0 (Complex m, 8H, four aryl protons of the benzimidazole ring and four protons
of the a-ch iaro-phenyl ring), 8. 18 (d, I H, J = 18Hz) and 8.58 (d, 1H, J=18Hz)(Trans ethylenic pro-
tons), 10.3 (broad s, I H, -NH)
2b4 - (in 8) 4.2 (s,3 H, -N-CH 3), 7.0-8.2 (Complex m, IOH, four aryl protons of the benzimidazole
ring, four ary l protons of the p-f1uorophenyl ring and two protons of the ethylenic moiety)
2bs - (in 8) 4.2 (s, 3H, -N-CH 3), 7.2-8.3 (Complex m, 10H, four aryl protons of the benzimidazole
ring, four aryl protons of the p-f1uorophenyl ring and two protons of the ethylenic link).
3130 INDIAN J. CHEM., SEC B, D ECEMBER 2003
ben zimidazoles 2 on comparison with authentic sam-
ples. The results are shown in Table I.
]n another sequence of reactions, 2-acetylbenzimid-
azole (2a, R=CH 3 ) and NaOH pellets were ground to
a fine powder in a mortar and pestle. To this an aro-
matic aldehyde was added and ground at room tem-
perature for a few more min, ti ll the condensation was
complete as shown by TLC, which is not more than
10 min. The reaction proceeds at room temperature in
a short duration giving high purity and yields of the
benzimidazolyl chalcones 3. The above reaction was
extended to other 2-acylbenzimidazoles 2. The com-
pounds obtained were ass igned the structures by com-
pari son with authentic samples. The results are shown
in Table II. All the above reaction s are summari zed
in the Scheme I.
Experimental Section
Melting points were determined in open capillaries
in sulphuric acid bath and are uncorrected. TLC
analyses were done on glass plates coated with silica
gel-G and spotting was done using Iodine blower or
UY lamp. IR spectra were recorded in KBr on a
JASCO-FfIR 5300 spectrometer, IH NMR spectra on
a Y ARIAN 200 MHz instrument using TMS as inter-
nal standard. All the yield s refer to isolated products.
(i) Preparation of 2 from 1. General procedure.
The alumina supported permanganate was prepared
by mixing solid KMn04 (2 g, 12.65 mmoles) and
so lid alumina (2.5 g) in a mortar and ground with a
pestl e until a fine homogeneou s purple powder was
obtai ned. Later, l-alky lIaral ky 1-2-( a-hydrox yalky lIary 1)-
ben zimidazole 1 (5 mmoles) was added to the above
mixture and ground with a pestle for some more time
at roo m temperature. Examination of the mixture by
TLC showed complete di sappearance of starting
material which requires approximately a few minutes
as indicated in Table I. Then acetone (20 mL) was
added to the reaction mixture and after vigorou s
stirring the mixture was filtered and the acetone
fi ltrate was evaporated to obtain a crude residue. The
latter was taken up in chloroform (15 mL) and washed
with water (3 0 mL) to remove any occluded inorganic
matter and dried over anhyd.Na 2S04' The crude
product thus obtained was recrystallised from hot
hexane to get the pure products 2 (Table I) .
(ii) Preparation of 3 from 2a. General Proce-
dure. NaOH pellets (l g, 25 mmo les) and 2a (5
mmoles) were ground in a mortar to a fine powder at
room temperature . To this aromatic aldehyde (7.5
mmoles) was added and the mixture was ground by
pestle at room temperatu re for a few more minutes (=
5-10 min) till t e condensation was co mpl ete as
shown by TLC. The solid mixture was then suspended
in water to remove inorganic impu rities and filtered.
The residue was washed with water and dri ed. The
crude compound was recrystalli zed from a suitable
organic so lvent to get the pure product 3a (Table II).
Acknowledgement
The authors are hi ghly indebted to UGC, New
Delhi for financial support and to JNT University,
Hyderabad for providing laboratory faci lities.
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