1326
M. R. Aouad, N. Rezki, and E. S. H. El Ahsry
Vol 45
Microwave and solid support method. A mixture of
(m, 5H, Ar-H), 12.57 (s, 1H, D2O exchangeable, NH). Anal.
Calcd. for C18H16N2S (292.40): C, 73.94; H, 5.52; N, 9.58.
Found: C, 73.71; H, 5.29; N, 9.42.
compound 1 (0.5 mmol) and epichlorohydrin (2) (0.55 mmol)
were adsorbed on the surface of activated bentonite, alumina or
silica gel (0.3 g) and mixed uniformly in a closed Teflon vessel
and then irradiated by MW for 2 min. After cooling, the product
was extracted by boiling ethanol. The ethanol was evaporated
and the product was recrystallized from ethanol to give 4.
General procedure for the alkylation of the S-alkylated
thioimidazoles 6-8.
Conventional method (CM). To a solution of S-alkylated 6-8
(1 mmol) in DMF (25 mL), potassium carbonate (2.2 mmol) was
added followed by allyl bromide and/or epichlorohydrin (2.2
mmol). The mixture was heated under reflux for 4-6 h, then
cooled and poured onto crushed ice. The products were washed
with water, dried and recrystallized from ethanol (Table 2).
Microwave method (MW). A mixture of S-alkylated 6-8 (1
mmol), DMF (5 mL), potassium carbonate (2.2 mmol) and allyl
bromide and/or epichlorohydrin (2.2 mmol) in a closed Teflon
vessel was irradiated by MW for 2-3.5 min. The obtained
reaction mixture was treated as described above (Table 2).
6,7-Diphenyl-2H,3H,4H-3-hydroxytetrahydroimidazo[2,1-
b][1,3]thiazine (3). This compound [24,25] was obtained as
colorless crystals, mp 210-212 ºC, lit. mp 219-220 °C, lit. mp
210-212 °C; ir (KBr): 1574 (C=C), 1625 (C=N) and 3215 (NH)
1
cm-1; H nmr (DMSO-d6): ꢀ 3.11 (dd, 1H, J = 6.9, J = 12.6 Hz,
SCH2), 3.26 (dd, 1H, J = 6.3, Jgem = 12.6 Hz, SCH2), 3.55 (dd,
1H, J = 6.3, Jgem = 13.0 Hz, NCH2), 3.76 (dd, 1H, J = 3.4, Jgem
=
13.0 Hz, NCH2), 4.26-4.30 (m, 1H, CHO), 5.61 (s, 1H, D2O
exchangeable, OH), 7.18-7.27 (m, 6H, Ar-H), 7.31-7.41 (m, 4H,
Ar-H). Anal. Calcd. for C18H16N2SO (308.40): C, 70.10; H, 5.23;
N, 9.08. Found: C, 69.92; H, 5.39; N, 9.36.
1-Allyl-2-thioallyl-4,5-diphenylimidazole
compound was obtained as colorless crystals, mp 122 ºC; ir
(9).
This
4,5-Diphenyl-2-thiomethyloxiraneimidazole (4). This
compound was obtained as colorless crystals, mp 265-266 ºC; ir
1
(KBr): 1535 (C=C), 1685 (C=N) cm-1. H nmr (DMSO-d6): ꢀ
1
(KBr): 1565 (C=C), 1610 (C=N) and 3198 (NH) cm-1. H nmr
3.95 (d, 2H, J3.2 = 6.9 Hz, SCH2-allyl), 4.80 (d, 2H, J3,2 = 5.3 Hz,
NCH2-allyl), 5.16 (d, 1H, J1,2 = 9.9 Hz, =CH2(S)), 5.28 (d, 1H,
J1',2 = 17.6 Hz, =CH2(S)), 5.32 (d, 1H, J1,2 = 10.7 Hz, =CH2(N)),
5.36 (d, 1H, J1',2 = 17.6 Hz, =CH2(N)), 5.59-6.01 (m, 2H, -CH=
(S), -CH= (N)), 7.17-7.26 (m, 3H, Ar-H), 7.32-7.37 (m, 2H, Ar-
H), 7.40-7.50 (m, 5H, Ar-H). Anal. Calcd. for C21H20N2S
(332.46): C, 75.87; H, 6.06; N, 8.43. Found: C, 75.58; H, 5.97;
N, 8.13.
(CDCl3): ꢀ 3.32 (dd, 1H, J = 6.1, Jgem = 15.3 Hz, SCH2), 3.41
(dd, 1H, J = 2.3, Jgem = 15.3 Hz, SCH2), 3.65 (d, 2H, J = 2.3 Hz,
OCH2), 4.22-4.26 (m, 1H, CHO), 7.26-7.30 (m, 6H, Ar-H),
7.41-7.43 (m, 4H, Ar-H); 13C nmr ꢀ 37.5 (SCH2), 48.8 (OCH2),
70.2 (CHO), 126.7, 127.9, 128.8, 129.0, 129.7, 131.2, 140.7 (Ar-
C). Anal. Calcd. for C18H16N2SO (308.40): C, 70.10; H, 5.23; N,
9.08. Found: C, 70.21; H, 4.99; N, 9.26.
1-Allyl-2-thiomethyl-4,5-diphenylimidazole (10). This
compound was obtained as yellow crystals, mp 205-206 ºC; ir
General procedure for the preparation of the S-alkyalted
derivatives (6-8).
1
(KBr): 1515 (C=C), 1672 (C=N) cm-1. H NMR (DMSO-d6): ꢀ
Conventional method (CM). To a mixture 1 (1 mmol) and
triethylamine (1.1 mol) in ethanol (50 mL), the appropriate
alkyl halide (1.1 mmol) was added. The mixture was heated
under reflux for 0.5-2 h. The ethanol was removed under
reduced pressure and the product was recrystallized from
ethanol. (Table 2)
2.70 (s, 3H, CH3), 4.40 (d, 2H, J3,2 = J3',2 = 3.1 Hz, NCH2-allyl),
4.93 (d, 1H, J1,2 = 17.3 Hz, =CH2), 5.18 (d, 1H, J1',2 = 10.7 Hz,
=CH2), 5.77-5.80 (m, 1H, -CH=), 7.11-7.20 (m, 3H, Ar-H),
7.31-7.35 (m, 2H, Ar-H), 7.41-7.49 (m, 5H, Ar-H). Anal. Calcd.
for C19H18N2S (306.43): C, 74.47; H, 5.92; N, 9.14. Found: C,
74.29; H, 5.65; N, 9.03.
Microwave method (MW). A mixture of 1 (1 mmol),
triethylamine (1.1 mol), ethanol (5 mL) and the appropriate alkyl
halide (1.1 mmol) in a closed Teflon vessel was irradiated by
MW. The obtained mixture was treated as described above
(Table 2).
4,5-Diphenyl-2-thiomethylimidazole (6). This compound
[28,29] was obtained as colorless crystals, mp 190-191 ºC; ir
(KBr): 1575 (C=C), 1660 (C=N), 3210 (NH) cm-1. 1H nmr
(CDCl3): ꢀ 2.53 (s, 3H, CH3), 7.18-7.30 (m, 5H, Ar-H), 7.34-
7.51 (m, 5H, Ar-H), 12.50 (s, 1H, D2O exchangeable, NH).
Anal. Calcd. for C16H14N2S (266.36): C, 72.15; H, 5.30; N,
10.52. Found: C, 72.39; H, 5.41; N, 10.79.
1-Allyl-2-thiobenzyl-4,5-diphenylimidazole (11). This
compound was obtained as colorless crystals, mp 218-219 ºC; ir
1
(KBr): 1529 (C=C), 1682 (C=N) cm-1. H nmr (CDCl3): ꢀ 4.11
(d, 2H, J3.2 = J3',2 = 7.6 Hz, NCH2-allyl), 4.34 (s, 2H, CH2Ph),
4.75 (d, 1H, J1,2 = 17.6 Hz, =CH2), 5.04 (d, 1H, J1,2 = 10.7 Hz,
'
=CH2 ), 5.55-5.62 (m, 1H, -CH=), 7.13-7.27 (m, 10H, Ar-H),
7.40-7.52 (m, 5H, Ar-H). Anal. Calcd. for C25H22N2S (382.15):
C, 78.50; H, 5.80; N, 7.32. Found: C, 78.39; H, 5.46; N, 7.54.
1-(3-Chloro-2-hydroxyprop-1-yl)-2-thiomethyl-4,5-diphen-
ylimidazole (12). This compound was obtained as colorless
1
syrup; ir (KBr): 1583 (C=C), 1637 (C=N), 3345 (O-H) cm-1. H
nmr (CDCl3): ꢀ 2.65 (s, 3H, CH3), 3.50 (dd, 1H, J = 4.6, Jgem
=
13.7 Hz, NCH2), 3.60 (d, 2H, J= 8.1 Hz, CH2Cl), 3.73 (dd, 1H,
J= 4.6, Jgem= 13.7 Hz, NCH2), 4.08-4.12 (m, 1H, CH), 4.20-4.26
(m, 1H, D2O exchangeable, OH), 7.20-7.29 (m, 5H, Ar-H), 7.35-
7.48 (m, 5H, Ar-H). Anal. Calcd. for C19H19ClN2OS (358.89): C,
63.59; H, 5.34; N, 7.81. Found: C, 63.23; H, 5.45; N, 8.02.
1-(3-Chloro-2-hydroxyprop-1-yl)-2-thiobenzyl-4,5-diphenyl-
imidazole (13). This compound was obtained as colorless syrup;
ir (KBr): 1587 (C=C), 1640 (C=N) and 3337 (O-H) cm-1. 1H nmr
(CDCl3): ꢀ 3.46 (dd, 1H, J = 6.1, Jgem= 13.0 Hz, NCH2), 3.54 (d,
2H, J = 8.4 Hz, CH2Cl), 3.68 (dd, 1H, J= 6.1, Jgem= 13.0 Hz,
NCH2), 4.06-4.10 (m, 1H, CH), 4.18-4.25 (m, 1H, D2O
exchangeable, OH), 4.37 (s, 2H, CH2Ph), 7.22-7.30 (m, 5H, Ar-
H), 7.37-7.47 (m, 5H, Ar-H). Anal. Calcd. for C25H23Cl N2OS
4,5-Diphenyl-2-thiobenzyl-imidazole (7). This compound
[26,27] was obtained as colorless crystals, mp 184-185 ºC, lit.
mp 185-186 °C, lit. [30] mp 183 °C; ir (KBr): 1540 (C=C), 1690
(C=N), 3218 (NH) cm-1. 1H nmr (CDCl3): ꢀ 4.35 (s, 2H, CH2Ph),
7.17-7.29 (m, 8H, Ar-H), 7.34-7.44 (m, 7H, Ar-H), 12.59 (s, 1H,
D2O exchangeable, NH). Anal. Calcd. for C22H18N2S (342.46):
C, 77.16; H, 5.30; N, 8.18. Found: C, 76.89; H, 5.42; N, 8.06.
4,5-Diphenyl-2-thioallylimidazole (8). This compound
[26,27] was obtained as colorless needles, mp 174 ºC, lit. mp
181-182 °C; ir (KBr): 1580 (C=C), 1642 (C=N), 3194 (NH)
1
cm-1. H nmr (CDCl3): ꢀ 3.73 (d, 2H, J3.2 = 6.1 Hz, SCH2-allyl),
5.05 (d, 1H, J1,2 = 9.9 Hz, =CH2), 5.22 (d, 1H, J1,2 = 16.9, =CH2),
5.89-5.97 (m, 1H, -CH=), 7.16-7.29 (m, 5H, Ar-H), 7.35-7.50