1450
L. Oresmaa, H. Taberman, M. Haukka, P. Vainiotalo, P. Aulaskari
Vol 44
1,3-Dibenzylimidazolium chloride 2.
Benzyl chloride 1.5 eq, reaction time 24h at RT, yield 43%,
1
products 6a 30%, 6b 70%. H nmr (DMSO-d6): ꢀ=6a 5.39 (s,
Method A: Benzyl chloride 2 eq, reaction time 24h at RT,
chloroform was used instead of acetone to wash the product
2H); 7.25-7.46 (m); 7.88 (s, 1H); 8.28 (s, 1H) in agreement with
literature [16], 6b 5.29 (s, 2H); 7.25-7.46 (m); 8.07 (s, 1H); 8.23
(s, 1H).
1
from KF-alumina, yield 50%. H nmr (CDCl3) ꢀ=5.55 (s,4H);
7.24-7.34 (m, 12 H); 10.66 (s, 1H) in agreement with literature
[29].
1-Methyl imidazole-5-carbaldehyde 7a and 1-methyl
imidazole-4-carbaldehyde 7b.
1-Benzyl imidazole-5-carbaldehyde 5a and 1-benzyl-
imidazole-4-carbaldehyde 5b.
Method A: Methyl iodide 1 eq, reaction time 24 h at RT,
yield 50%, products 7a 26%, 7b 74%. Method E: Methyl iodide
1.5 eq, reaction time 96 h at RT, yield 35%, products 7a 66%,
7b 34%.Method LA: Methyl iodide 1.5eq, reaction time 96 h at
Method A: Benzyl chloride 1 eq, reaction time 27 h at RT,
yield 68%, products 5a 30%, 5b 70%; benzylchloride 1 eq,
reaction time 5 h at 50 oC, yield 50%, products 5a 26%, 5b 74%
Method B: Benzyl chloride 1 eq, reaction time 94 h at RT, yield
50% products 5a 37%, 5b 63%. Method C but with alumina
1
RT, yield 39%, products 7a 64%, 7b 36%. H nmr (CDCl3): 7a
ꢀ=3.95 (s, 3H); 7.62 (s, 1H); 7.79 (s, 1H) in agreement with
literature [22], 7b ꢀ= 3.78 (s, 3H); 7.54 (s, 1H); 7.53 (s, 1H) in
agreement with literature [22].
o
dried at 300 C in vacuum for 20 h. Benzyl chloride 1.5 eq,
reaction time 94 h at RT, yield 60%, products 5a 52%, 5b 48%.
Method C: Benzyl chloride 1.5 eq, reaction time 94 h at RT,
yield 54%, products 5a 53%, 5b 47%. Method D: Benzyl
chloride 1 eq, reaction time 96 h at RT, yield 44%, products 5a
45%, 5b 55%. Method E: Benzyl chloride 1.5 eq, reaction time
48 h at RT, yield 50%. Products 5a 69%, 5b 31%. Benzyl
chloride 1.5 eq, reaction time 22h at 50oC, yield 38%. Products
5a 68%, 5b 32%.
1-Methyl-5-cyano-imidazole 8a and 1-methyl-4-cyano-
imidazole 8b.
Method A: Methyl iodide 1 eq, reaction time 24 h at RT,
yield 48%, products 8a 30%, 8b 70%. Method E: Methyl
iodide 1.5 eq, reaction time 96 h at RT, yield 34%, products 8a
50%, 8b 50%. Method LA: Methyl iodide 1.5 eq, reaction time
1
96 h at RT, yield 60%, products 8a 39%, 8b 61%. H nmr
Small scale preparations: Benzyl chloride 1.5 eq, silica 0.5
g, Et3N 2 eq, reaction time 96h at RT. Products 5a 53%, 5b
47%. No solid support, benzyl chloride1.5 eq, Et3N 2 eq
Products 5a 45%, 5b 55%. Product ratio is from partly reacting
mixture, according to nmr spectra measured after two weeks in
RT. Benzyl chloride 1.5 eq, carbon nanotubes 0.1 g, Et3N 2 eq,
products 5a 49%, 5b 51%. Product ratio is from partly reacting
mixture, according to nmr spectra measured after 10 days in RT.
Benzyl chloride 1eq, Pr3N 2 eq, ZnO 0.5g, reaction time 17 days
at RT . Products 5a 77%, 5b 23%. Benzyl chloride 1.5 eq, ZnO
0.5g, pyridine 2 eq, reaction time 48h at RT. Products 5a 68%,
5b 32%. Benzyl chloride 1.5 eq, acidic alumina 0.5g, Et3N 2 eq,
reaction time 96h at RT. Products 5a 54%, 5b 46%. Benzyl
chloride1.5 eq, N,N-dimethylpropyl amine 2 eq, ZnO 0.5 g,
reaction time 48h at RT. Products 5a 67%, 5b 33%.
(CDCl3): 8a ꢀ=3.83 (s, 3H); 7.62 (s, 1H); 7.66 (s, 1H) in
agreement with literature [31], 8b ꢀ=3.78 (s, 3H); 7.48 (s, 1H);
7.50 (s, 1H) in agreement with literature [31].
REFERENCES AND NOTES
[1] Begtrup, M.; Larsen P. Acta Chem. Scand. 1990, 44, 1050.
[2] Chen, B- C.; Skoumbourdis, A. P.; Sundeen, J. E.; Rovnyak,
G. C.; Traeger, S. C. Org. Proc. Res. Dev. 2000, 4, 613.
[3] Ohkanda, J.; Lockman, J. W.; Kothare, M. A.; Qian, Y.;
Blaskovich, M. A.; Sebti, S.M.; Hamilton, A.D. J. Med. Chem. 2002,
45, 177.
[4] Daninos-Zeghal, S.; Al Mourabit, A.; Ahond, A.; Poupat, C.;
Potier, P. Tetrahedron 1997, 53, 7605.
[5] Millet, R.; Domarkas, J.; Houssin, R.; Gilleron, P.; Goossens,
J-F.; Chavatte, P.; Logé,C.; Pommery, N.; Pommery, J.; Hénichart, J-P.
J. Med. Chem. 2004, 47, 6821.
[6] Grimmet, M. R. in Comprehensive Heterocyclic Chemistry,
Eds. Katritzky, A. R.; Rees, C.W. Pergamon Press, London, 1984, vol.
5, pp. 345.
[7] Benjes, P.A.; Grimmett, M. R. N-Alkylation of nitrogen
azoles. Advances in Detailed Reaction Mechanisms. Reactions of
Importance in Synthesis. 1994, 3, 199.
Method LA: 1 eq ZnCl2, alumina, after a 7 days no products
were seen in nmr spectra. 0.2 eq ZnCl2, alumina, reaction time
96 h at RT, yield 44%, products 5a 69%, 5b 31%; 0.2 eq ZnCl2,
no solid support, reaction time 48 h at RT, yield 48%, products
5a 68%, 5b 32%; 0.2 eq ZnCl2, K2CO3 was used instead of Et3N,
alumina, reaction time 96 h at RT, the reaction was made in
small scale, using ꢀ amounts of the starting materials, products
5a 45 %, 5b 55%; 0.2 eq AlCl3, reaction time 96 h at RT, the
reaction was made in small scale, using ꢀ amounts of the
starting materials, products 5a 55%, 5b 45%.
[8] He,Y.; Chen, Y.; Du, H.; Scmid, L.A.; Lovely, C. L.
Tetrahedron Lett. 2004, 45, 5529.
[9] Tanaka, K.; Toda F. Chem. Rev. 2000, 100, 1025.
[10] Varma, R. S. Green Chem. 1999, 43.
[11] Kabalka, G. W.; Pagni, R. M. Tetrahedron 1997, 53, 7999.
[12] Blass, B. E. Tetrahedron 2002, 58, 9301.
1H nmr (DMSO-d6): ꢀ= 5a: 5.52 (s, 2H); 7.20-7.41 (m); 7.94
(s, 1H); 8.27 (s, 1H); 9.71 (s, 1H), in agreement with literature
1
[30]. 5b H nmr (DMSO-d6): ꢀ= 5.29 (s, 2H); 7.20-7.41 (m);
8.02 (s, 1H); 8.14 (s, 1H); 9.69 (s, 1H).
[13] Hosseini Sarvari, M.; Sharghi, H. J. J. Org. Chem. 2004,
69,6953.
1-Benzyl-5-cyano-imidazole 6a and 1-benzyl-4-cyano-
imidazole 6b
[14] Tamaddon, F.; Amrollahi, M. A.; Sharafat, L. Tetrahedron
Lett. 2005, 46,7841.
[15] Oresmaa, L.; Kotikoski, H.; Haukka, M.; Salminen, J.;
Oksala, O.; Pohjala, E.; Moilanen, E.; Vapaatalo, H.; Vainiotalo, P.;
Aulaskari, P. J. Med. Chem. 2005, 48, 4231.
[16] Oresmaa, L.; Kotikoski, H.; Haukka, M.; Oksala, O.; Pohjala,
E.; Moilanen, E.; Vapaatalo, H.; Vainiotalo, P.; Aulaskari, P Eur. J.
Med. Chem. 2006, 41, 1073
Method A: Benzyl chloride 1 eq, reaction time 48 h at RT,
yield 49%, products 6a 24%, 6b 76 % Method C: Benzyl
chloride 1.5 eq, reaction time 72 h at RT, yield 60%, products 6a
29%, 6b 71%. Method E: Benzyl chloride 1.5 eq, reaction time
72 h at RT, yield 41 %, products 6a 50%, 6b 50 %.Method LA: