Gas-phase pyrolysis of benzimidazole derivatives: novel route to condensed heterocycles

Article abstract of DOI:10.1016/j.tet.2010.03.061

Gas-phase pyrolysis of N-(1H-benzimidazol-2-yl)-N′-arylidenehydrazines 1a-e gave the corresponding arylnitriles 2a-e, 2-aminobenzimidazole 3, 2,4,5-triphenylimidazole 4, 1,3-diphenyl-8H-2,3a,8-triazacyclopenta[a]indene 5, and 5,11-diphenyl-6H,12H-dibenzimidazo[1,2-a];1',2'-d]pyrazine 6. The kinetics and analysis of the products of reaction are reported and used to elucidate the mechanism of the elimination process.

Full text of DOI:10.1016/j.tet.2010.03.061

Tetrahedron 66 (2010) 4243–4250
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Gas-phase pyrolysis of benzimidazole derivatives: novel route to condensed
heterocycles
,
Maher R. Ibrahim a, Talal F. Al-Azemi a, Alya Al-Etabi b, Osman M.E. El-Dusouqui a
,
*
Nouria A. Al-Awadi a
a Chemistry Department, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait
b Natural Science Department, College of Health Science, Public Authority for Applied Education and Training, Kuwait
a r t i c l e i n f o
a b s t r a c t
Gas-phase pyrolysis of N-(1H-benzimidazol-2-yl)-N0-arylidenehydrazines 1a–e gave the corresponding
arylnitriles 2a–e, 2-aminobenzimidazole 3, 2,4,5-triphenylimidazole 4, 1,3-diphenyl-8H-2,3a,8-tri-
azacyclopenta[a]indene 5, and 5,11-diphenyl-6H,12H-dibenzimidazo[1,2-a];1’,2’-d]pyrazine 6. The ki-
netics and analysis of the products of reaction are reported and used to elucidate the mechanism of the
elimination process.
Article history:
Received 4 January 2010
Received in revised form 23 February 2010
Accepted 15 March 2010
Available online 20 March 2010
Ó 2010 Published by Elsevier Ltd.
Keywords:
Benzimidazol-2-yl-N0-arylidenehydrazine
2-Aminobenzimidazole
Triazacyclopenta[a]indene
Azaindino[1,2-b]fluorine
Gas-phase pyrolysis
Mechanism
1. Introduction
Earlier, we have used N-substituted cyclic amides, thioamides,
and related nitrogen heterocycles as substrates in thermal gas-
Gas-phase pyrolysis is a useful alternative synthetic strategy
offering an important route for the preparation of novel condensed
heterocycles. Many valuable heterocyclic compounds of synthetic
importance and potential biological, pharmaceutical and industrial
application have been prepared using the two major gas-phase
pyrolysis methodologies: static (sealed-tube) pyrolysis (STP) and
flash vacuum pyrolysis (FVP).1–7 Both processes are conducted at
low pressure, while FVP is further characterized by relatively short
(millisecond) substrate residence time.2,5,8 Our pioneering use of
STP in the study of the kinetics of gas-phase pyrolysis reactions
gave extensive data on thermal reactivity, which was used in
combination with product analysis to provide added support for
proposed mechanisms of thermal gas-phase elimination re-
actions.3–5 It is to be noted that no reagents, solvents or catalysts
are used in these reactions, and hence these reactions: (a) are
deemed reasonably economic and environmentally benign;8,9 (b)
are increasingly being employed as models for theoretical in-
vestigations of thermal gas-phase reactivity, transition states and
reaction mechanisms.10–13
phase elimination reactions to prepare condensed heterocyclic
compounds, in which the reactions of N-arylidenaminohetero-
cycles were found to proceed via a six-membered transition state
(TS) with elimination of arylnitriles.14–17 However, the rates and
products of the reaction were affected by structural factors and the
nature of the heterocyclic ring. Here, we report the results of a ki-
netic and mechanistic investigation of the FVP and STP reactions of
substituted benzimidazolylarylidinehydrazine compounds in
which the arylidene diaza substituent is on a ring carbon atom of
the nitrogen heterocycle. This feature and the nature of the benz-
imidazole ring account for the interesting condensed heterocyclic
compounds obtained in the elimination process.
2. Results and discussion
2.1. Products and mechanism
Reaction products from the complete gas-phase pyrolysis of
N-(1H-benzimidazol-2-yl)-N0-arylidenehydrazines 1a–e were obtained
at optimal STP reaction conditions of temperature, pressure
(0.045 Torr), and substrate residence time (ca. 900 s) compatible
with ꢀ98% reaction as evidenced by HPLC analysis of the pyrolysate
in kinetic runs. The products of FVP of 1a–e at 700 ꢁC and 0.02 Torr
* Corresponding author. Tel.: þ965 24985575; fax: þ965 24816482; e-mail
address: osman.eldusouqui@ku.edu.kw (O.M.E. El-Dusouqui).
0040-4020/$ – see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tet.2010.03.061

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M.R. Ibrahim et al. / Tetrahedron 66 (2010) 4243–4250
pressure (ca. 10 ms residence time) were separated and directly
collected in a U-shaped trap cooled in liquid nitrogen, and analyzed
by 1H NMR spectroscopy and LCMS. The elimination products from
FVP consist of arylnitriles 2a–e and 2-aminobenzimidazole 3 in
yields of ca. 75% and 80% (ꢂ10%), respectively (Table 1). A plausible
mechanism to explain the elimination products of FVP is shown in
Scheme 1. It is suggested that the amine tautomer (A, B) of the
substrates 1a–e pyrolyzes to give the two major elimination frag-
ments via a six-membered TS, suggested earlier for the FVP of
compatible heterocycles.3 An alternative pathway involves the
fragmentation at the N–N bond of the amine tautomer to give re-
active radical intermediates, which exchange hydrogen atoms and
form the elimination fragments.3–5 This pathway is evident from
analysis of the mechanism proposed for the STP process and the
results of both the kinetic and products of pyrolysis. Besides, for-
mation of radicals during FVP has been reported for a wide range of
reactions.3,6,10,17,18
1H and 13C NMR and 2D NMR spectroscopy. Thus, substrate 1a
pyrolyzed to give (Table 1): benzonitrile 2a (15%), 2-amino-
benzimidazole 3 (20%), 2,4,5-triphenylimidazole 4 (21%), 1,3-
diphenyl-8H-2,3-a,8-triazacyclopenta[a]indene 5 (15%), and 5,11-
diphenyl-6H,12H-dibenzimidazo[1,2-a];1’,2’-d]pyrazine
6 (18%),
as shown in Scheme 2.
Assignment of the heterocyclic ring protons and carbons of
compound 5 are shown in Figure 1. These assignments were made
based on 1H, H-COSY, HMQC, HMBC, and HSQC experiments. The
numbering used and the important HMBC correlation of the het-
erocyclic proton/carbon cross peaks: H9 at 7.25 correlates with C7,
C
11 at 136.5, 123.4; H10 at 7.04 correlates with C8, C12 at 125.6, 112.5;
H11 at 7.28 correlates with C7, C9 at 136.5, 111.6; H12 at 7.43 corre-
lates with C8, C10 at 125.6, 119.6; H14 at 7.68 correlates with C1, C16
at
118.2, 128.36; H15 at 7.36 correlates with C13 at 134.8; H16 at
7.49 correlates with C14 at 130.4; H18 at 7.72 correlates with C3,
20 at 137.8, 127.0; H19 at 7.54 correlates with C17 at
130.6, and
20 at 7.30 correlates with C18 at
127.5.
Scheme 3 illustrates plausible mechanistic routes to explain the
d
d
d
d
C
H
d
d
d
d
d
Table 1
formation of the products of pyrolysis (2–6) in the STP reaction of
compound 1a. It has already been shown in Scheme 1 that the
amine tautomer B of substrates 1a pyrolyzes into radical in-
termediates 10 and 11 (as labeled in Scheme 3), which undergo
intermolecular H exchange to give the observed fragmentation
products 2 and 3, respectively. On the other hand, elimination of H2
and extrusion of molecular nitrogen from the substrate 1a under
the conditions of pyrolysis yield intermediate 8 followed by the
diradical 9. This diradical reacts further with the benzonitrile 2a
present in the reaction mixture to produce the condensed hetero-
cycle 5. Besides, colligation of two units of the diradical 9 leads to
the formation of the heterocycle 6.
Products of FVP of 1a–e, STP of 1a and 16, and % yield
Substrate
X
Condition % Yield of pyrolysis products
2a–e
3
4
5
6
17 18 2a
a
b
a
a
a
a
b
1a
1a
1b
1c
1d
1e
16
H
H
78
15
85
86
65
58
d
73
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
10
d
20 21 15 18
OCH3
CH3
Cl
NO2
H
78
85
67
65
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
48 38
a
FVP, 700 ꢁC, 0.02 Torr.
STP, 280 ꢁC, 0.045 Torr, 15 min.
b
Evidence for the mechanism was obtained in part from the STP
reaction (280 ꢁC/15 min) of the substrate 1a in the presence of
p-tolunitrile. Analysis of the pyrolysate using LCMS confirmed the
presence of a methyl substituent in the aryl derivative 5, while
compound 6 remained unchanged. On the other hand, when
compound 6 was pyrolyzed at higher temperature (310 ꢁC) and
The products of complete pyrolysis from the STP reaction of
the substrates under study were collected and separated by col-
umn chromatography using silica gel and ethyl acetate/petroleum
ether (60–80) as eluent (5–25% ethyl acetate). The pyrolysates
were analyzed qualitatively and quantitatively by GC–MS, LCMS,
H
H
N
N
CN
FVP/700 o
0.02 Torr
C
N
N
NH
N
N
H
N
N
NH
+
2
H
N
H
H
X
imine
1a-e
3
2a-e
(65-85)
(58-86)
X
X
amine A
.
H
N
N
FVP/700 o
0.02 Torr
C
NH
N
N
H
2a-e
3
+
+
.
N
H
N
H
NH
X
X
amine B
X; a, H; b, OCH ; C, CH ; d, Cl; e, NO
2
3
3
Scheme 1. Pathway of FVP of benzimidazolylarylidenehydrazine 1a–e.

M.R. Ibrahim et al. / Tetrahedron 66 (2010) 4243–4250
4245
N
H
N
H
N
N
H
Ph
1a
STP
280 oC / 15 min
CN
H
N
Ph
N
Ph
Ph
H
N
N
N
N
Ph
N
H
NH
2
N
N
Ph
H
N
H
N
Ph
Ph
5
3
4
6
2a
(20)
(18)
(15)
(21)
(15)
Scheme 2. Products of STP of substrate 1a.
128.39
7.36
149.8
15
7.43
H
16
H
134.8
12
9
H
14
112.5
7.49
128.36
6
H
N
136.5
H
7
8
H
H
H
11
10
5
H
7.28
123.4
7.04
H
N
H
H
H
13
N
1
2
N
4
N
N
H
130.4
7.68
N
N
H
3
H
N
17
118.2
137.8
18
119.6
125.6
H
H
111.6
H
7.25
19
H
130.6
7.72
H
20
H
127.5
129.9
7.54
7.30
H
127.0
Figure 1. Assignment of heterocyclic protons and carbons of compound 5.
longer residence time (30 min), to ascertain the route of formation
of 5, it was found that compound 6 had isomerized by 1,3-H shift to
yield the 5H, 11H-dihydroderivative 7. The LCMS data of these two
compounds were, respectively, 412 at Rt 5.5 and Rt 9.5. Besides,
compound 5 when heated at higher temperature (310 ꢁC) and
longer time (30 min) it remained unchanged.
The STP reaction mechanism (Scheme 3) shows two routes open
for the formation of 2,4,5-triphenylimidazole 4, a feature, which
indicates a convergence of the reaction pathways and thus an
added confirmation of the mechanism suggested for the pyrolysis
of the substrate under study. According to one route (Scheme 4),
conversion of radical 10 into the amarine derivative 12 proceeds
through intermediate 13. Formally, the reaction involving three
moles of 10 yields one mole of 13 in addition to nitrogen, and the
generation of two molecules of 13 would be associated with the
extrusion of molecular nitrogen. Subsequent dehydrogenation of 12
gives compound 4. It is noteworthy that reaction of the radical
intermediate 10 with hydrogen leads to the formation of the cor-
responding arylimine, which has been reported to yield 13 by
elimination of ammonia.19
turn undergoes consecutive 1,3-H shifts to yield 15; and the latter
by 1,3-H shift and loss of an NH3 unit yields the 2,4,5-triphenyli-
midazole 4 (Scheme 4). This argument is supported by the results of
two experiments. In one experiment, compound 5 was reacted
under the conditions of STP in the presence of hydrogen from an
external source (cyclohexene); the result was the formation of
2,4,5-triphenylimidazole 4. In a separate experiment, substrate 1a
was pyrolyzed after reaction with methyl iodide (to remove imid-
azole hydrogen from the substrate molecule), as a consequence of
which neither compound 4 nor any of the other condensed het-
erocycles (5, 6) could be obtained. Instead, STP of 16 at the same
reaction conditions (280 ꢁC, 15 min.) gave only 3-phenyl-9H-ben-
zo[4,5]imidazo[2,1-c][1,2,4]triazole 17, and 9-methyl-3-phenyl-9H-
benzo[2,1-c][1,2,4]triazole 18 as the major products of reaction
(Scheme 5). Further, it is of interest to note that the data shown in
Table 1 seem to provide additional support for the proposed
mechanism, in that the formation of compounds 4–6 appears to
come at the expense of the elimination fragments 2 and 3.
From Table 1, it is evident that FVP of substrate 1a gave similar
products to those obtained from STP except for compounds 4, 5, 6.
This could be explained by further fragmentation during the longer
residence time of the STP reaction (15 min, 280 ꢁC compared with
10 ms and 700 ꢁC for FVP).
The alternative route to 4 involves the pyrolysis of compound 5
obtained from the diradical intermediate 9. It is argued that during
STP, compound 5 reacts with H2 to yield intermediate 14, which in

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M.R. Ibrahim et al. / Tetrahedron 66 (2010) 4243–4250
.
N
CN
H
H
N
N
STP
N
+
+
280 oC
.
NH
N
N
H
N
H
NH
2
N
H
NH
2a
10
11
3
Ph
1a
STP
-N
2
280 oC
-H
Ph
Ph
2
Ph
N
-H
N
2
N
N
H
Ph
Ph
Ph
N
H
N
N
4
12
N
Ph
+H
2
-NH
8
3
H
N
Ph
-N
Ph
N
H
2
+PhCN
N
N
N
Ph
N
5
N
N
.
310 o
30 min
C
H
Ph
N
.
Ph
H
N
7
Ph
N
1,3-H shift
N
2 mol
9
N
H
Ph
6
Scheme 3. Mechanism and STP products of 1a.
.
H
N
Ph
Ph
Ph
H
H
N
3 mol
N
N
H
-H
Ph
2
N
H
Ph
Ph
Ph
Ph
N
13
12
10
N
H
Ph
4
H
N
H
N
Ph
N
H
N
1,3-H
shift
H
1,3-H shift
-NH
3
Ph
N
STP
N
Ph
N
H
N
H
N
Ph
Ph
Ph
15
5
14
Scheme 4. Two routes to compound 4.

M.R. Ibrahim et al. / Tetrahedron 66 (2010) 4243–4250
4247
H
N
NCH
NCH
3
3
STP
STP
N
N
N
N
N
N
N
N
N
H
280 oC
15 min
280 oC
15 min
H C
3
H
H
H
H
Ph
Ph
Ph
-H
2
-CH
4
16
H
N
NCH
3
N
N
N
N
N
N
Ph
Ph
18
17
Scheme 5. STP reaction products of 16.
2.2. Kinetic analysis and thermal reactivity
this temperature lies within the range over which the kinetic
measurements were made; (ii) rates calculated at this temperature
allow comparisons to be made with data for other compatible het-
erocycles.3,4,6,7,14–17
The rates of pyrolysis of the substrates under study 1a–e shown
in Table 2 were measured over a temperature range of 57ꢂ8 K
between 453 and 558 K, a condition deemed necessary for reliable
kinetic analysis of thermal gas-phase elimination reactions.3,5b,11 The
rate constant at each reaction temperature is an average from at least
three kinetic runs in agreement to within ꢂ2% rate spread. Rate is
obtained by monitoring thedisappearance of the substrate duringthe
reaction, and using the relation for a first-order rate equation:
log k¼log AꢃEa/4.57 T. The values of the Arrhenius log A/sꢃ1 and
energyofactivation (Ea/kJ molꢃ1)alsoshowninTable 2 were obtained
from Arrhenius plots that were strictly linear over ꢀ92% reaction and
with correlation coefficients of the order of 0.997ꢂ0.002. The limits
of error in the table represent the correlation statistical values. The
rate constant data used for comparing the thermal reactivity of
the substrates were calculated at 500 K for two valid reasons: (i)
The kinetic data in Table 2 show all the substituted compounds
under investigation to be more reactive than the parent heterocycle
1a. The relative rates (k¼3ꢂ0.03) of 1b–d though moderate are
nevertheless significant, while krel of the nitro compound 1e is
six-fold higher. Both the electron-withdrawing and the electron-
donating groups in these substrates appear to enhance the
molecular reactivity of compounds 1b–e in their thermal gas-phase
elimination reactions. This pattern of substituent effect associated
with the arylidinehydrazine group has been observed, and the
different behaviour of the nitro group in gas-phase pyrolysis has
also been reported.3,5 The present kinetic results support a reaction
mechanism in which both a six-membered transition (TS) and
radical reactive intermediate pathways (Schemes 1 and 3) contribute
Table 2
Rate constant (k/sꢃ1), Arrhenius log A, and Ea, and rate constant at 500 K of gas-phase pyrolysis of compounds (1a–e)
Cpd
X
T/K
104k/sꢃ1
log A/sꢃ1
Ea/kJ molꢃ1
159.0ꢂ6.3
104k500K/sꢃ1
1a
H
502.05
516.25
530.10
544.25
558.15
1.087
3.619
8.933
25.73
48.11
12.6ꢂ0.62
1.01
1b
OCH3
489.95
513.85
525.75
537.75
549.65
1.691
5.389
9.658
14.41
25.47
6.97ꢂ0.23
100.7ꢂ2.3
2.80
1c
CH3
Cl
487.95
503.05
518.05
553.25
1.911
3.783
7.019
28.62
6.23ꢂ0.08
9.90ꢂ0.54
93.00ꢂ0.85
128.9ꢂ5.3
3.29
2.76
1d
497.75
507.75
517.75
537.75
547.55
2.573
4.481
7.099
23.23
44.43
1e
NO2
453.25
466.45
479.15
492.10
504.95
3.574
5.275
8.989
15.06
21.60
4.42ꢂ0.31
68.50ꢂ2.9
18.6

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M.R. Ibrahim et al. / Tetrahedron 66 (2010) 4243–4250
to the observed overall thermal gas-phase reactivity of compounds
1a–e. The three molecular sites in the TS (Fig. 2) leading to its
development are bonds a, b, and d.8,11 An electron-withdrawing
group (x) in the arylidinehydrazine moiety would enhance reacti-
vity by an effect on the protophilic character of the hydrogen of bond
(a) and the polarization of the (N–N) bond (b), and through the
stabilization of any partial negative charge being developed at the
incipient cyano moiety.
133 (20%). 1H NMR (DMSO-d6)
7.81 (d, 2H, J 7.8 Hz), 7.44 (t, 2H, J 7.6 Hz), 7.36 (t, 1H, J 7.8 Hz), 7.25
(m, 2H), 6.97 (m, 2H). 13C NMR (DMSO-d6)
153.4, 140.6, 135.2,
128.8, 128.6, 126.4, 119.9, 113.4, 109.4. Anal. Calcd for C14H12N4
(236.3): C, 71.17; H, 5.12; N, 23.71. Found: C, 71.01; H, 5.21; N, 23.73.
d 11.61 (br, 2H, 2NH), 8.03 (s, 1H),
d
4.2.2. N-1H-Benzimidazol-2-yl-N0-p-methoxybenzylidenehydrazine
1b. Yield (2.0 g, 75%) as a colorless solid from DMF, mp 210–212 ꢁC
(lit.22b mp 212 ꢁC). IR: 3395, 3061, 2981,1656,1609,1510,1460,1247,
1168, 1163, 1106, 1027, 733. LCMS: m/z¼267 (Mþ1). MS: m/z¼266
H
N
H
N
(Mþ, 75%),133 (100%).1H NMR (DMSO-d6)
d 11.45 (br, 2H, 2NH), 7.99
H
N
(s, 1H), 7.75 (d, 2H, J 8.8 Hz), 7.24 (m, 2H), 7.00 (d, 2H, J 8.8 Hz), 6.97
d
.
(m, 2H), 3.81 (s, 3H, OCH3). 13C NMR (DMSO-d6)
d
160.0,153.4,140.7,
N
NH
b
NH
136.4, 127.9, 127.7, 119.6, 114.1, 112.4, 55.2. Anal. Calcd for C15H14N4O
(266.3): C, 67.65; H, 5.30; N, 21.04. Found: C, 67.59; H, 5.21; N, 21.03.
;
H
N
N
a
X
4.2.3. N-1H-Benzimidazol-2-yl-N0-p-methylbenzylidenehydrazine
1c. Yield (2.0 g, 80%) as a colorless solid from DMF mp 275–276 ꢁC
(lit.22b mp 277 ꢁC). IR: 3445, 3060, 2916, 1654, 1586, 1517, 1460, 1267,
1129, 1034, 809, 737. LCMS: m/z¼251 (Mþ1). MS: m/z¼250 (Mþ,
10
11
Ar
Six-membered TS
Free radical intermediates
Figure 2.
85%), 221 (20%), 133 (100%). 1H NMR (DMSO-d6)
d 11.52 (br, 1H, NH),
11.42 (br, 1H, NH), 8.0 (s, 1H), 7.70 (d, 2H, J 7.6 Hz), 7.24 (m, 4H), 6.96
The radical pathway is initiated by the thermolysis of the polar
(N–N) bond (b). The important electronic effect associated with this
pathway would be the resonance stabilization of radical (11) due to
the conjugative interaction of the nitrogen free radical centre with
the benzimidazole ring system.3,20 The electron-donating sub-
stituents could exert their observed moderate effect by stabilizing
the arylnitrile fragment (10).
(m, 2H), 2.34 (s, 3H). 13C NMR (DMSO-d6)
d
153.5, 140.7, 138.4, 132.4,
129.2,126.4,119.3,114.9,109.4, 21.0. Anal. Calcd for C15H14N4 (250.3):
C, 71.98; H, 5.64; N, 22.38. Found: C, 71.91; H, 5.52; N, 22.30.
4.2.4. N-1H-Benzimidazol-2-yl-N0-p-chlorobenzylidenehydrazine
1d. Yield (2.3 g, 85%) as colorless crystals from DMF, mp 267–69 ꢁC.
(lit.22b 270 ꢁC). IR: 3432, 3053, 1651, 1585, 1516, 1491, 1268, 1087,
1013, 826, 738. LCMS: m/z¼273 (Mþ2), 271 (Mþ1). MS: m/z¼270
3. Conclusion
(Mþ,100%), 241 (10%),133 (100%). 1H NMR (DMSO-d6)
d 11.65 (br, 2H,
2NH), 8.03 (s, 1H), 7.85 (d, 2H, J 8.4 Hz), 7.50 (d, 2H, J 8.4 Hz), 7.27 (m,
The present study offers interesting new routes towards het-
erocyclic compounds, some of which are novel. The study also
provides comparison between FVP and static pyrolysis of arylhy-
drazinobenzimidazole, which shows that FVP gave similar products
to those obtained from static pyrolysis (STP), except for products of
further pyrolysis arising from longer residence time in STP.
2H), 7.00 (m, 2H). 13C NMR (DMSO-d6)
d
153.0, 140.0, 137.2, 134.1,
133.2, 128.7, 128.1, 120.3, 112.2. Anal. Calcd for C14H11ClN4 (270.7): C,
62.11; H, 4.10; N, 20.70. Found: C, 62.09; H, 4.21; N, 20.63.
4.2.5. N-1H-Benzimidazol-2-yl-N0-p-nitrobenzylidenehydrazine
1e. Yield (2.5 g, 89%) as red crystals from DMF, mp 280–82 ꢁC.
(lit.22b 283 ꢁC). IR: 3417, 3060, 1641, 1586, 1508, 1333, 1267, 1149,
1107, 826, 738. MS: m/z¼281 (Mþ, 100%), 252 (10%), 133 (70%). 1H
4. Experimental
4.1. General
NMR (DMSO-d6) d 11.79 (br, 2H, 2NH), 8.26 (d, 2H, J 8.8 Hz), 8.13 (s,
1H), 8.06 (d, 2H, J 8.8 Hz), 7.25 (m, 2H), 7.01 (m, 2H). 13C NMR
(DMSO-d6) 153.8, 146.6, 142.1, 138.7, 132.9, 120.9, 119.9, 114.4,
d
Melting points were recorded on a Gallenkamp apparatus. IR
spectra in KBr were recorded on a Perkin–Elmer System 2000 FT-
IR spectrophotometer. 1H and 13C NMR spectra were recorded on
Bruker DPX 400, 600 MHz super-conducting NMR spectrometers.
LCMS were measured using an Agilent 1100 series LC/MSD with
an API-ES/APCI ionization mode. Mass spectra were recorded on
VG Auto-spec-Q (high resolution, high performance, tri-sector
GC/MS/MS). Microanalyses were performed on LECO CH NS-
932 Elemental Analyzer.
109.5. Anal. Calcd for C14H11N5O2 (281.3): C, 59.78; H, 3.94; N, 24.90.
Found: C, 59.69; H, 3.91; N, 24.83.
4.2.6. N-Benzylidene-N0-1-methylbenzimidazol-2-yl-hydrazine
16. General procedure: A mixture of 1-methylbenzimidazole-2-yl-
hydrazine23 (1.62 g, 10 mmol), benzaldehyde (1.27 g, 12.0 mmol),
and sodium acetate (1.2 g, 15 mmol) in glacial acetic acid (20.0 mL)
was heated under reflux for 2 h. After cooling, ice water (50 mL) was
added to the reaction mixture; the precipitate so formed was
collected by filtration and crystallized from DMF to give 16 (2.1 g,
75%) as a colorless solid, mp 283–85 ꢁC (lit.24 mp 280–282 ꢁC). IR:
3428, 3055, 1660, 1560, 1488, 1381, 1239, 1116, 1089, 953, 743. LCMS:
m/z¼251 (Mþ1). MS: m/z¼250 (Mþ, 100%), 1147 (30%). 1H NMR
4.2. Preparation of starting compounds 1a–e
General procedure: A mixture of 2-hydrazinobenzimidazole21a,b
(1.48 g, 10 mmol), the appropriate aromatic aldehyde (12.0 mmol),
and sodium acetate (1.2 g, 15 mmol) in glacial acetic acid (20.0 mL)
was heated under reflux for 1 h. After cooling, ice water (50 mL) was
added tothe reactionmixture;theprecipitatesoformed was collected
by filtration and crystallized from the proper solvent to give 1a–e.
(DMSO-d6)
1.2 Hz), 7.49–7.40 (m, 4H), 7.32 (m, 1H), 7.20 (m, 2H), 3.60 (s, 3H,
CH3). 13C NMR (DMSO-d6)
151.8, 147.7, 134.8, 132.2, 130.2, 129.5,
d 12.08 (br, 1H, NH), 8.33 (s, 1H), 7.89 (dd, 2H, J 8.4,
d
128.6, 127.1, 122.4, 122.1, 110.4, 109.0, 28.9. Anal. Calcd for C15H14N4
(250.3): C, 71.98; H, 5.64; N, 22.38. Found: C, 71.79; H, 5.51; N, 22.23.
4.2.1. N-1H-Benzimidazol-2-yl-N0-benzylidenehydrazine 1a. Yield
(2.0 g, 85%) as a colourless solid from DMF, mp 286–287 ꢁC (lit.22a,b
mp 290 ꢁC). IR: 3432, 3056, 1657, 1589, 1523, 1461, 1433, 1351, 1269,
1136, 932, 733. LCMS: m/z¼237 (Mþ1). MS: m/z¼236 (Mþ, 25%),
4.3. Pyrolysis product
4.3.1. Flash vacuum pyrolysis of 1a–e. The apparatus used was
similar to the one, which has been described in our recent

M.R. Ibrahim et al. / Tetrahedron 66 (2010) 4243–4250
4249
publications.25a–c The substrate was volatilized from a tube in
a Bu¨chi Kugelrohr oven through a 30ꢄ2.5 cm horizontal fused
quartz tube. This was heated externally by a Carbolite Eurotherm
tube furnace MTF-12/38A to a temperature of 700 ꢁC, the temper-
ature being monitored by a Pt/Pt-13%Rh thermocouple situated at
the center of the furnace. The products were collected in a U-sha-
ped trap cooled in liquid nitrogen. The whole system was main-
tained at a pressure of 010ꢃ2 Torr by an Edwards Model E2M5 high
capacity rotary oil pump, the pressure being measured by a Pirani
gauge situated between the cold trap and pump. Under these
conditions the contact time in the hot zone was estimated to be ca.
10 ms. The different fractions of the product collected in the
U-shaped trap were analyzed by 1H, 13C NMR spectroscopy, IR, and
GC–MS. Relative and percent yields were determined from NMR.25c
7.43 (d, 2H, J 7.8 Hz), 7.38 (dt, 2H, J 7.8, 1.2 Hz), 7.30 (t, 2H, J 7.8 Hz),
7.22 (t, 1H, J 7.2 Hz). 13C NMR (DMSO-d6)
145.9, 137.5, 135.6, 131.5,
130.8, 129.2, 129.1, 128.9, 128.73, 128.71, 128.6, 128.3, 127.5, 126.9,
125.6. Anal. Calcd for C21H16N2 (296.4): C, 85.11; H, 5.44; N, 9.45.
Found: C, 85.09; H, 5.31; N, 9.45.
d
4.3.10. 1,3-Diphenyl-8H-2,3a,8-triazacyclopenta[a]indene 5. Yield
(36 mg, 15%), white crystals from ethyl acetate, mp 310–312 ꢁC.
LCMS: m/z¼310 (Mþ1). MS: m/z¼309 (Mþ, 100%), 281 (10%), 165
(20%). IR: 3395, 3061, 1656, 1609, 1510, 1460, 1247, 1168, 1027, 733.
1H NMR (CDCl3)
d 7.72 (dd, 2H, J 7.4, 1.2 Hz), 7.68 (dd, 2H, J 7.6,
1.6 Hz), 7.54 (tt, 2H, J 7.2, 1.2 Hz), 7.49 (tt, 1H, J 7.6, 1.5 Hz), 7.43 (dd,
1H, J 7.2, 0.8 Hz), 7.36 (t, 2H, J 7.8 Hz), 7.30 (tt, 1H, J 7.2, 1.2 Hz), 7.28
(tt, 1H, J 7.2, 1.2 Hz), 7.25 (dd, 1H, J 7.2, 1.2 Hz), 7.04 (dt, 1H, J 7.2,
1.2 Hz), 3.31 (br, 1H, NH). 13C NMR (CDCl3)
d 149.8, 137.8, 136.5,
4.3.2. Static pyrolysis of 1a, 16. A sample of the substrate (1 mmol),
was introduced in the reaction tube (1.5ꢄ12 cm Pyrex), cooled in
liquid nitrogen, sealed under vacuum (0.045 Torr) and placed in the
pyrolyzer for 15 min at 280 ꢁC, a temperature that is required for
complete pyrolysis of the substrate as indicated by preliminary
HPLC studies. The reaction products were separated by column
chromatography using Merck Al-silica gel 60 F254 with ethyl ace-
tate/petroleum ether (60–80) to give successively 2, 3, 4, 5, and 6
from substrate 1a and give 17, 18 from 16. The static sealed-tube
(STP) pyrolysis was conducted in a custom-made Chemical Data
System (CDS) pyrolyser consisting of an aluminum block with
a groove to accommodate the Pyrex sealed-tube reactor, and fitted
with a platinum-resistance thermometer and thermocouple con-
nected to a Comark microprocessor thermometer. The block tem-
perature was controlled by a Eurothem 093 precision temperature
regulator. Aluminum was chosen for its low temperature gradient
and resistance to elevated temperatures. Maximum pyrolysis for
product analysis was conducted at temperatures equal to or ex-
ceeding those recorded for complete pyrolysis during kinetic runs.
134.8, 130.6, 130.4, 129.0, 128.39, 128.36, 127.5, 127.0, 125.6, 123.4,
119.6, 118.2, 112.5, 111.6. Anal. Calcd for C21H15N3 (309.4): C, 81.53;
H, 4.89; N, 13.58. Found: C, 81.49; H, 4.81; N, 13.45.
HRMS¼309.1261 (C21H15N3 requires 309.1260).
4.3.11. 5,11-diphenyl-6H,12H-dibenzimidazo[1,2-a];1’,2’-d]pyrazine (6);
5,11-diphenyl-5H,11H-dibenzimidazo[1,2-a;1’,2’-d]pyrazine (7). Yield
(43 mg, 18%), white crystals from ethyl acetate, mp 301–303 ꢁC
(lit.29a,b mp 301 ꢁC). LCMS: m/z¼413 (Mþ1). MS: m/z¼412 (Mþ,
100%), 308 (10%), 205 (20%). IR: 3059, 3032, 2955, 2928, 2857, 1725,
1584, 1540, 1341, 1370, 1272, 1124, 1070, 916, 739. 1H NMR (DMSO-
d6)
d
13.21 (br, 2H, 2NH), 7.84 (m, 2H), 7.69 (m, 2H), 7.55–7.24 (m,
152, 142.2, 136.9, 130.1, 128.6, 128.2,
14H). 13C NMR (DMSO-d6)
d
123.9,123.4,119.5,111.1. Anal. Calcd for C28H20N4 (412.5): C, 81.53; H,
4.89; N, 13.58. Found: C, 81.50; H, 5.00; N, 13.50. HRMS¼412.1682
(C28H20N4 requires 412.1682).
4.3.12. 3-Phenyl-9H-benzo[4,5]imidazo[2,1-c][1,2,4]triazole
17. Colourless crystals from ethanol/water, yield (120 mg, 48%),
mp 267–268 ꢁC (lit.22b mp 270 ꢁC). LCMS m/z¼235 (Mþ1). MS:
m/z¼234 (Mþ, 100%), 205 (10%), 104 (25%). 1H NMR (DMSO-d6)
4.3.3. Benzonitrile 2a. LCMS: m/z¼104 (Mþ1). 1H NMR spectro-
scopic data identical to that reported in the literature.26a
d 7.95 (dd, 2H, J 7.8, 1.6 Hz), 7.71 (d, 1H, J 8.0 Hz), 7.68 (t, 2H J 7.6 Hz),
7.61 (t, 1H, J 7.8), 7.51 (d, 1H, J 8.0 Hz), 7.42 (dt, 1H, J 8.0, 1.2 Hz), 7.21
4.3.4. p-Methoxybenzonitrile 2b. LCMS: m/z¼134 (Mþ1). 1H NMR
(dt, 1H, J 8.0, 1.2 Hz), 3.4 (br, 1H, NH). 13C N MR (DMSO-d6)
d
155.8,
spectroscopic data identical to that reported in the literature.26b
142.7, 130.1,129.3, 127.4, 127.0, 125.4, 122.9,120.3, 113.4,112.6,112.4.
Anal. Calcd for C14H10N4 (234.3): C, 71.78; H, 4.30; N, 23.92. Found:
C, 71.69; H, 4.21; N, 23.93.
4.3.5. p-Tolunitrile 2c. LCMS: m/z¼118 (Mþ1). 1H NMR spectro-
scopic data identical to that reported in the literature.27
4.3.13. 9-Methyl-3-phenyl-9H-benzo[4,5]imidazo[2,1-c][1,2,4]tri-
azole 18. Colourless crystals from ethanol, yield (96 mg, 38%), mp
202–204 ꢁC. IR: 3060, 2930, 1705, 1599, 1492, 1447, 1170, 1112, 914.
LCMS: m/z¼249 (Mþ1). MS: m/z¼248 (Mþ, 100%), 105 (30%). 1H
4.3.6. p-Chlorobenzonitrile 2d. LCMS: m/z¼139, 138 (Mþ2, Mþ1).
1H NMR spectroscopic data identical to that reported in the
literature.26c
NMR (CDCl3)
d 7.98 (dd, 2H, J 8.0, 1.6 Hz), 7.86 (d, 1H, J 8.4 Hz), 7.68
4.3.7. p-Nitrobenzonitrile 2e. LCMS: m/z¼149 (Mþ1). 1H NMR
(t, 3H, J 7.4 Hz), 7.56 (t, 1H, J 8.0 Hz), 7.41 (m, 2H), 3.73 (s, 3H). 13C
NMR (CDCl3) 157.1, 144.9, 138.9, 133.2, 129.9, 129.1, 128.4, 127.6,
spectroscopic data identical to that reported in the literature.26d
d
125.6, 120.6, 112.8, 109.9, 53.4. Anal. Calcd for C15H12N4 (248.3): C,
72.56; H, 4.87; N, 22.57. Found: C, 72.49; H, 4.81, N, 22.56.
HRMS¼248.1056 (C15H12N4 requires 248.1056).
4.3.8. 2-Aminobenzimidazole 3. Colourless crystals from ethanol,
yield static (48 mg, 20%), FVP (65–85%, Table 1), mp 222–24 ꢁC
(lit.28 mp 225 ꢁC). IR: 3431, 1651, 1567, 1463, 1049, 1025, 1002, 826,
764. LCMS m/z¼134 (Mþ1). MS: m/z¼133 (Mþ, 100%), 105 (30%). 1H
Acknowledgements
NMR (DMSO-d6)
d 7.10 (m, 2H), 6.88 (m, 2H), 6.11 (br, 3H, NH, NH2).
13C NMR (DMSO-d6)
d
155.1, 136.4, 119.2, 111.5. Anal. Calcd for
The support of the University of Kuwait received through re-
search grant #. Sc 03/06 and the facilities of ANALAB and SAF
(grants #. GS01/01, GS02/01, GS01/04) are gratefully acknowledged.
C7H7N3 (133.2): C, 63.14; H, 5.30; N, 31.56. Found: C, 63.09; H, 5.21;
N, 31.43.
4.3.9. 2,4,5-Triphenylimidazole 4. Yield (50 mg, 21%), white crystals
from ethyl acetate, mp 274–276 ꢁC (lit.19 mp 274–75). LCMS:
m/z¼297 (Mþ1). MS: m/z¼296 (Mþ, 100%), 190 (10%), 165 (85%). IR:
3395, 3061, 2928, 1756, 1639, 1503, 1435, 1240, 1148, 1034, 736. 1H
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