November 2010
A Facile Solvent-Free Synthesis of 1-Alkyl/Aralkyl-2-(1-arylsulfonyl alkyl)
Benzimidazoles Using ‘‘TBAB’’ as Surface Catalyst
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ACH3), 4.45 (q, J ¼ 16 Hz, 2H, ACH2ACH3), 4.85 (s,
2H,ACH2), 7.15–7.70 (m, 8H, Ar-H); Mþ þ 1: 315; Anal.
Calcd. for (C17H18N2O2S) requires: C, 64.94; H, 5.77; N,
8.91%; Found: C, 64.90; H, 5.72; N, 8.86%.
4c. IR (KBr): showed the absence of a strong broad band at
ꢂ3000 cmꢁ1 assigned to benzimidazole (ANH); 1H NMR
(CDCl3): d 2.45 (s, 3H, ACH3), 4.72 (s, 2H, ACH2), 5.65 (s,
2H, ANACH2APh), 7.10–7.80 (m, 13H, Ar-H); Mþ þ 1: 377;
Anal. Calcd. for (C22H20N2O2S) requires: C, 70.19; H, 5.35;
N, 7.44%; Found: C, 70.15; H, 5.30; N, 7.42%.
4d. IR (KBr): showed the absence of a strong broad band at
ꢂ3000 cmꢁ1 assigned to benzimidazole (ANH); 1H NMR
(CDCl3): d 1.85 (d, J ¼ 7.18 Hz, 3H, ACH2ACH3), 2.40 (s,
3H, AC6H4ACH3A(p)), 3.95 (s, 3H, ANCH3), 4.70 (q, J ¼
7.0 Hz, 1H, ACHACH3), 7.20–7.70 (m, 8H, Ar-H); Mþ þ 1:
315; Anal. Calcd. for (C17H18N2O2S) requires: C, 64.94; H,
5.77; N, 8.91%; Found: C, 64.90; H, 5.75; N, 8.86%.
4e. IR (KBr): showed the absence of a strong broad band at
ꢂ3000 cmꢁ1 assigned to benzimidazole (ANH); 1H NMR
(CDCl3): d 1.50 (t, J ¼ 18.0 Hz, 3H, ACH2ACH3), 1.75 (d,
J ¼ 12 Hz, 3H, ACHACH3), 2.45 (s, 3H, ACH3) 4.35 (q, J ¼
14.6 Hz, 1H, ACHACH3), 4.65 (q, J ¼ 16.0 Hz, 2H,
ACH2ACH3), 7.15–7.65 (m, 8H, Ar-H); Mþ þ 1: 329; Anal.
Calcd. for (C18H20N2O2S) requires: C, 65.83; H, 6.14; N,
8.53%; Found: C, 65.78; H, 6.10; N,8.50%.
5a. IR (KBr): showed the absence of a strong broad band at
1
ꢂ3000 cmꢁ1 assigned to benzimidazole; H NMR (CDCl3): d
3.95 (s, 3H, ANCH3), 4.95 (s, 2H, ACH2), 7.15–7.80 (m, 4H,
Ar-H); Mþ þ 1: 181; Anal. Calcd. for (C9H9ClN2) requires: C,
59.84; H, 5.02; N, 15.51%; Found: C, 59.82; H, 5.0; N,
15.47%.
5b. IR (KBr): showed the absence of a strong broad band at
1
ꢂ3000 cmꢁ1 assigned to benzimidazole; H NMR (CDCl3): d
4.96 (s, 2H, ACH2), 5.60 (s, 2H, ACH2Aph), 7.15–7.80 (m,
9H, Ar-H); Mþ þ 1: 257; Anal. Calcd. for (C15H13ClN2)
requires: C, 70.18; H, 5.10; N, 10.91%; Found: C, 70.15; H,
5.07; N, 10.89%.
5c. IR (KBr): showed the absence of a strong broad band at
1
ꢂ3000 cmꢁ1 assigned to benzimidazole; H NMR (CDCl3): d
2.15 (d, J ¼ 7.16Hz, 3H, ACHACH3), 3.90 (s, 3H, ANCH3),
5.30 (q, J ¼ 7.12 Hz, 1H, ACHACH3), 7.10–7.80 (m, 4H, Ar-
H); Mþ þ 1: 195; Anal. Calcd. for (C10H11ClN2) requires: C,
61.70; H, 5.70; N, 14.39%; Found: C, 61.68; H, 5.66; N,
14.36%.
5d. IR (KBr): showed the absence of a strong broad band at
1
ꢂ3000 cmꢁ1 assigned to benzimidazole; H NMR (CDCl3): d
2.10 (d, J ¼ 7.12Hz, 3H, ACHACH3), 5.10 (q, J ¼ 7.0 Hz, 1H,
ACHACH3), 5.55 (s, 2H, ACH2APh), 7.05–7.80 (m, 9H, Ar-
H); Mþ þ 1: 271; Anal. Calcd. for (C16H15ClN2) requires: C,
70.98; H, 5.58; N, 10.35%; Found: C, 70.94; H, 5.56; N, 10.33%.
4f. IR (KBr): showed the absence of a strong broad band at
ꢂ3000 cmꢁ1 assigned to benzimidazole (ANH); 1H NMR
(CDCl3): d 1.68 (d, J ¼ 14.2 Hz, 3H, ACHACH3), 2.45 (s,
3H, ACH3), 4.45 (q, J ¼ 14.4 Hz, 1H, ACHACH3), 5.55–
5.90 (dd, 2H, ANACH2APh), 7.0–7.65 (m, 13H, Ar-H); Mþ
þ 1: 391; Anal. Calcd. for (C23H22N2O2S) requires: C, 70.74;
H, 5.68; N, 7.17%; Found: C, 70.72; H, 5.64; N, 7.13%.
4g. IR (KBr): showed the absence of a strong broad band at
ꢂ3000 cmꢁ1 assigned to benzimidazole (ANH); 1H NMR
(CDCl3): d 1.70 (d, J ¼ 7.18 Hz, 3H, ACHACH3), 3.85 (s,
3H, ANCH3), 5.10 (q, J ¼ 7.0 Hz, 1H, ACHACH3), 7.2–7.87
(m, 9H, Ar-H); Mþ þ 1: 301; Anal. Calcd. for (C16H16N2O2S)
requires: C, 63.98; H, 5.37; N, 9.33%; Found: C, 63.95; H,
5.33; N, 9.29%.
4h. IR (KBr): showed the absence of a strong broad band at
ꢂ3000 cmꢁ1 assigned to benzimidazole (ANH); 1H NMR
(CDCl3): d 1.65 (d, J ¼ 7.12 Hz, 3H, ACHACH3), 4.60 (q, J
¼ 7.16 Hz, 1H, ACHACH3), 5.50–5.70 (dd, 2H, ACH2APh),
6.95–7.65 (m, 14H, Ar-H); Mþ þ 1: 377; Anal. Calcd. for
(C22H20N2O2S) requires: C, 70.19; H, 5.35; N, 7.44%; Found:
C, 70.15; H, 5.31; N, 7.42%.
Typical procedure for 4 from 5. A mixture of 5 (10
mmol), 2 (10.1 mmol), and TBAB catalytic amount 10 mol %
were ground together in a mortar at RT till the reaction was
complete, as shown by TLC. The solid mixture was then sus-
pended in water to remove inorganic impurities and the insolu-
ble product was filtered, washed with water, and dried. The
crude product was recrystallized from hot benzene to get the
pure product 4 (Table 2).
Typical procedure for 5. A mixture of 1 (10 mmol), alkyl-
ating agent (10.2 mmol), K2CO3 (11 mmol), and TBAB cata-
lytic amount 10 mol % were ground together in a mortar and
pestle at RT till the completion of reaction, as shown by TLC.
The solid mixture was then suspended in water to remove
inorganic impurities and the insoluble product was filtered,
washed with water, and dried, gave a pure 5 (Table 2).
Acknowledgments. The authors are highly indebted to CSIR,
Govt. of. India, New Delhi, for the award of Senior Research Fel-
lowship (SRF) to Mr. K. Srinivas and financial support. They are
also thankful to the authorities of Jawaharlal Nehru Technologi-
cal University (Hyd.) for providing laboratory facilities.
REFERENCES AND NOTES
[1] (a) Erhardt, P. W. J Med Chem 1987, 30, 231; (b) Tomc-
zuk, B. E.; Taylor, C. R., Jr.; Moses, L. M.; Sutherland, D. B.; Lo, Y.
S.; Johnson, D. N.; Kinnier, W. B.; Kilpatrick, B. F. J Med Chem
1991, 34, 2993; (c) Spasov, A. A.; Yozhitsa, I. N.; Bugaeva, L. I.;
Anisimova, V. A. Pharm Chem J 1999, 33, 232; (d) Preston, P. N.
Chem Heterocycl Compd 1980, 40, 531; (e) Zimmer, C.; Wahnert, U.
Prog Biophys Mol Biol 1986, 47, 31; (f) Gravatt, G. L.; Baguley, B.
C.; Wilson, W. R.; Denny, W. A. J Med Chem 1994, 37, 4338; (g)
Soderlind, K.-J.; Gorodetsky, B.; Singh, A. K.; Bachur, N.; Miller, G.
G.; Lown, J. W. Anti-cancer Drug Design 1999, 14, 19.
[2] As inhibitors of DNA topoisomerases: (a) Kim, J. S.; Gatto,
B.; Yu, C.; Liu, A.; Liu, L. F.; LaVoie, E. J. J Med Chem 1996, 39,
992; (b) Chen, A. Y.; Yu, C.; Gatto, B.; Liu, L. F. Proc Natl Acad
Sci USA 1993, 90, 8131; (c) Woynarowski, J. M.; McHugh, M. M.;
Sigmud, R. D.; Beerman, T. A. Mol Pharmacol 1989, 35, 177.
[3] As HIV-reverse transcriptase inhibitors: Roth, T.; Morning-
star, M. L.; Boyer, P. L.; Hughes, S. H.; Buckheit, R. W., Jr.;
Michejda, C. J. J Med Chem 1997, 40, 4199.
[4] Bergmann, E. D.; Lavie, D. J Am Chem Soc, 1952, 74,
4948.
[5] Popoff, I. C.; Engle, A. R.; Whitaker, R. L.; Singhal, G. H.
J Med Chem 1971, 14, 1166.
[6] Boundy, R. E. Burger’s Medicinal Chemistry, Part II; Wolf,
M. E., Ed.; John Wiley: New York, 1979.
[7] Bhingolikar, V. E.; Mahalle, S. R.; Bondge, S. P.; Mane, R.
A. Indian J Chem B 2005, 44, 2589.
[8] Pandeya, S. N.; Ojha, T. J.; Srivastava, V. J Scient Ind Res
1985, 44, 150.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet