A. E. Sparke et al. / Tetrahedron Letters 51 (2010) 4723–4726
4725
forms a part of our ongoing studies, in addition to anti-viral as-
says32,33 and chelator formation with these compounds.
Supplementary data
CCDC 772926 and 772927 contain the supplementary crystallo-
graphic data for compounds 4ꢀHCl and 5, respectively. These data
can be obtained free of charge from The Cambridge Crystallo-
Acknowledgements
We thank the University of Hull Clinical Biosciences Institute
(CMF, AES) and the EPSRC (REM) for funding and the EPSRC Na-
tional Mass Spectrometry Service for analyses. We also acknowl-
edge the use of the EPSRC Chemical Database Service at Daresbury.
Figure 1. The molecular structure of 1-(4-nitrobenzyl)-2-chloromethyl benzimi-
dazolium chloride 4ꢀHCl showing the atom labelling and 50% probability ellipsoids
for non-H atoms.
References and notes
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There is no clear
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18. 1-(4-Nitrobenzyl)phenylenediamine (2). Preferred method: 4-Nitrobenzyl
bromide (5 g, 0.023 mol) dissolved in MeOH (300 ml) was added dropwise to
similar to the crystal structure for 4ꢀHCl, although in this case
the chloride group is located in close proximity to the charged
pyridinium group. There are some slight differences in the bond
lengths and angles which may be attributed to the steric bulk of
the pyridyl group. The only X-ray structure of a similar nature
deposited at the CCDC has a pyrrolic group attached via a methyl
linker in the 2-position of the benzimidazole, but this is not a
charged species.31
In conclusion, 1-(4-nitrobenzyl)-2-chloromethyl benzimidazole
was synthesised via a robust route. A key reaction was between
1,2-phenylenediamine and 4-nitrobenzylbromide in the absence
of a base giving exclusively a mono-alkylated product in a single
step. Benzimidazole formation by the treatment of 2 with chloroace-
tic acidin 5 N hydrochloricacidwas unsatisfactory dueto theconsis-
tent presence of by-products, and this was similarly the case with
the alkylation of chloromethylbenzimidazole. Therefore, the most
reliable route to synthesise this compound was from 3. Subsequent
tothereactionofthechloromethylgroupthenitrogroupcouldbere-
ducedusing sulfurated borohydride offering thepotentialfor further
functionalisation at this position. Investigation of these reactions
a
stirred solution of 1,2-phenylenediamine (12.51 g, 0.12 mol) in MeOH
(400 ml) over 30 min. The reaction was stirred at room temperature for 4 h.
Evaporation of the solvent under reduced pressure gave a red solid, which was
dissolved in EtOH (250 ml) with heating, and then allowed to cool. The
resulting precipitate was collected and purified by column chromatography
using CH2Cl2 as the eluent to yield a red/orange solid. Rf: 0.37. Yield 3.92 g
(66%). 1H NMR (400 MHz, CD2Cl2): d 3.34 (s, 2H), 3.91 (s, 1H), 4.38 (s, 2H), 6.39
(d, 1H, J = 7.3 Hz), 6.65 (m, 3H), 7.49 (d, 2H, J = 8.7 Hz), 8.0 (d, 2H, J = 8.7 Hz).
LRMS (ES) m/z (rel int%): 244 ([M+H]+, 100).
19. Silversides, J. D.; Sparke, A. E.; Archibald, S. J. Acta Crystallogr., Sect. E Struct. Rep.
Online 2006, 62, o5944–o5946.
20. 1-(4-Nitrobenzyl)-2-hydroxymethyl benzimidazole (3). 1H NMR (400 MHz,
CD3OD): d 4.83 (s, 2H), 5.69 (s, 2H), 7.29 (m, 4H), 7.60 (d, 2H, J = 8.7 Hz), 8.10 (d,
2H, J = 8.7 Hz). 13C NMR (100 MHz, CD3OD): d 46.9, 57.0, 110.1, 119.3, 122.9,
123.6, 124.1, 127.5, 135.0, 141.3, 143.2, 147.7, 154.2. MS (ES) m/z (rel int %):
284 ([M+H]+, 100).
21. 1-(4-Nitrobenzyl)-2-chloromethyl benzimidazole (4). 1H NMR (400 MHz,
CD3OD): d 4.97 (s, 2H), 5.79 (s, 2H), 7.36 (m, 4H), 7.82 (d, 2H, J = 8.7 Hz),
8.19 (d, 2H, J = 8.7 Hz). 13C NMR (100 MHz, CD3OD): d 32.9, 48.9, 114.1, 116.3,
124.8, 127.0, 127.8, 129.4, 131.6, 133.2, 142.1, 148.9, 149.5. MS (ES) m/z (rel int
%): 302 ([M+H]+, 100). HRMS m/z: calcd for C15H13N3O2Cl 302.0692 ([M+H]+);
found 302.0696. Mp 257 °C dec.
22. Fletcher, D. A.; McMeeking, R. F.; Parkin, D. J. Chem. Inf. Comput. Sci. 1996, 36,
746–749.
23. Ping, G.-J.; Liu, Y.-Y.; Han, T.-T.; Ma, J.-F. Acta Crystallogr., Sect. E Struct. Rep.
Online 2007, 63, o4508.
24. Li, Q. X.; Luo, Q. H.; Li, Y. Z.; Duan, C. Y.; Tu, Q. Y. Inorg. Chim. Acta 2005, 358,
504–512.
Figure 2. The molecular structure of 1-(4-nitrobenzyl)-2-methylpyridinium benz-
imidazole chloride 5, showing the atom labelling and 50% probability ellipsoids for
non-H atoms.