1802 Journal of Medicinal Chemistry, 2005, Vol. 48, No. 6
Ulmschneider et al.
The resulting alcohol was transformed into the phospho-
nium salt. Amounts of 40 mmol of the alcohol and 13.7 g of
triphenylphosphonium bromide (40 mmol) were suspended in
25 mL of benzene and refluxed for 12 h under nitrogen. The
precipitate was filtered off and dried. The solid was suspended
in dry diethyl ether and stirred for 10 min. The phosphonium
salt was filtered off and washed with acetone.
1.92 (m, 2H, H-3), 2.47-2.51 (m, 2H, H-2), 2.88-2.90 (m, 2H,
H-4), 6.37 (s, 1H, H-9), 7.19 (s, 1H, H-14), 7.36 (d, 3J ) 8.0
Hz, 1H, H-5), 7.58 (dd, 3J ) 8.0 Hz, 4J ) 1.6 Hz, 1H, H-6),
7.95 (s, 1H, H-8), 8.13 (s, 1H, H-12). IR (KBr) cm-1: νmax 2840,
2240, 1600, 1600, 1000, 940, 930, 850, 820, 710. Anal.
(C15H13N3‚C2H2O4) C, H, N.
(5Z)-5-(1H-Imidazol-5-ylmethylene)-5,6,7,8-tetrahy-
dronaphthalene-2-carbonitrile Oxalate (4b). From com-
pound 4i. Purification: FCC (CHCl3/DMF, 9:2). Yield 3%,
white solid, mp 206 °C. 1H NMR (400 MHz, DMSO-d6) δ 1.86-
1.93 (m, 2H, H-3), 2.47-2.50 (m, 2H, H-2), 2.83-2.86 (m, 2H,
A sodium ethanolate solution was prepared by dissolving
0.5 g of sodium (22 mmol) in 20 mL of ethanol. An amount of
2.1 g of imidazole-4(5)-carbaldehyde (22 mmol) was added to
this solution. The solution was warmed for some minutes until
it became clear. In a second flask, 20 mmol of the phosphonium
salt were suspended in 14 mL of ethanol and refluxed under
nitrogen atmosphere. The imidazolide solution was added in
portions through a septum within 2 h, and the reaction
mixture was refluxed for another 12 h. The mixture was cooled
to room temperature, and the solid was filtered off and
discarded. The solution was concentrated, and the residue was
diluted with 100 mL of water and was extracted several times
by diethyl ether. The combined organic phases were filtered
through Celite, dried over MgSO4, and evaporated. After
purification, the free base was dissolved in acetone and an
excess of oxalic acid in acetone was added to get the oxalate
salt, or it was dissolved in dry diethyl ether and an excess of
HCl in diethyl ether was added to get the hydrochloride.
5-[(E)-3,4-Dihydronaphthalen-1(2H)-ylidenemethyl]-
1H-imidazole (1a). Purification: FCC (acetone) and recrys-
tallization (acetone). Yield 14%, colorless crystals, mp 136-
138 °C. 1H NMR (400 MHz, DMSO-d6, free base) δ 1.72-1.82
(m, 2H, H-3), 2.68-2.73 (m, 2H, H-2), 2.77-2.82 (m, 2H, H-4),
6.94 (s, 1H, H-9), 7.10-7.22 (m, 4H, H-5, H-7, H-14), 7.66 (d,
3J ) 7.8 Hz, 1H, H-8), 7.69 (s, 1H, H-12). IR (KBr, free base)
cm-1: νmax 3110, 3055, 3020, 2935, 2865, 2830, 1666, 1621,
1597, 1481, 1453, 1441, 1430, 951, 943, 765. Anal. (C14H14N2,
free base) C, H, N.
3
H-3), 6.41 (s, 1H, H-9), 7.18 (s, 1H, H-14), 7.45 (dd, J ) 8.1
4
Hz, J ) 1.6 Hz, 1H, H-7), 7.66-7.68 (m, 2H, arom-H5, H-8),
8.12 (s, 1H, H-12). IR (KBr) cm-1: νmax 2220, 1610, 850, 710.
Anal. (C15H13N3‚C2H2O4) C, H, N.
(1E)-1-(1H-Imidazol-5-ylmethylene)indane-5-carboni-
trile Oxalate (5a). From compound 5i. Purification: FCC
(CHCl3/DMF, 9:2). Yield 39%, white solid, mp 217 °C. 1H NMR
(400 MHz, DMSO-d6) δ 2.96-2.99 (m, 2H, H-2), 3.14-3.17 (m,
2H, H-3), 7.16 (s, 1H, H-8), 7.72-7.79 (m, 3H, H-4, H-6, H-7),
7.83 (s, 1H, H-13), 9.17 (s, 1H, H-11). IR (KBr) cm-1: νmax 3080,
2220, 1600, 830. Anal. (C14H12N3‚HCl) C, H. N: calcd, 16.31;
found, 15.71.
(1Z)-1-(1H-Imidazol-5-ylmethylene)indane-5-carboni-
trile Oxalate (5b). From compound 5i. Purification: FCC
(CHCl3/DMF, 9:2). Yield 10%, white solid, mp 207 °C. 1H NMR
(400 MHz, DMSO-d6) δ 2.89-2.99 (m, 4H, H-2, H-3), 6.57 (s,
1H, H-8), 7.36 (s, 1H, H-4), 7.60 (d, 3J ) 8.2 Hz, 1H, H-6),
7.72 (s, 1H, H-13), 8.02 (s, 1H, H-11), 9.13 (d, 3J ) 8.2 Hz, 1H,
H-7). IR (KBr) cm-1: νmax 2220, 1620, 890, 830, 780, 720. Anal.
(C14H12N3‚0.8C2H2O4) C, H, N.
5-[(E)-(6-Chloro-3,4-dihydronaphthalen-1(2H)-ylidene)-
methyl]-1H-imidazole Hydrochloride (6a). Prepared via
compound 6i. Purification: FCC (CHCl3/DMF, 9:2). Yield 35%,
pearly crystals, mp 203 °C. 1H NMR (400 MHz, DMSO-d6, free
base) δ 1.73-1.80 (m, 2H, H-3), 2.67-2.70 (m, 2H, H-2), 2.80-
2.84 (m, 2H, H-4), 6.99 (s, 1H, H-9), 7.16-7.25 (m, 3H, H-5,
H-6, H-14), 7.67 (s, 1H, H-8), 7.76 (s, 1H, H-12). IR (KBr, free
base) cm-1: νmax 3060, 2940, 2840, 1590, 1120, 950, 870, 850,
840, 800. Anal. (C14H13ClN2‚0.2H2O) C, H, N.
5-[(Z)-3,4-Dihydronaphthalen-1(2H)-ylidenemethyl]-
1H-imidazole Oxalate (1b). Purification: FCC (CHCl3/DMF,
9:2). Yield 5%, white solid, mp 187 °C. 1H NMR (400 MHz,
DMSO-d6) δ 1.87-1.94 (m, 2H, H-3), 2.46-2.50 (m, 2H, H-2),
2.81-2.84 (m, 2H, H-4), 6.24 (s, 1H, H-9), 7.00-7.20 (m, 4H,
3
H-5, H-6, H-7, H-14), 7.37 (d, J ) 7.8 Hz, 1H, H-8), 8.31 (s,
5-[(E)-(5-Fluoro-2,3-dihydro-1H-inden-1-ylidene)me-
1H, H-12). IR (KBr) cm-1: νmax 1610, 1480, 1450, 920, 850,
760. Anal. (C14H14N2‚C2H2O4) C, H, N.
thyl]-1H-imidazole Hydrochloride (7a). Purification: FCC
1
(CHCl3/DMF, 9:2). Yield 49%, beige crystals, mp 245 °C. H
5-[(E)-2,3-Dihydro-1H-inden-1-ylidenemethyl]-1H-imi-
dazole (2a). Purification: FCC (acetone). Yield 28%, white
solid, mp 148-151 °C. 1H NMR (400 MHz, DMSO-d6, free base)
NMR (400 MHz, DMSO-d6) δ 2.96-3.01 (m, 2H, H-2), 3.10-
3.13 (m, 2H, H-3), 6.91 (s, 1H, H-8), 7.11-7.16 (m, 1H, H-6),
7.21 (d, 3J(H,F) ) 9.0 Hz, 1H, H-4), 7.64 (dd, 3J ) 8.5 Hz,
4J(H,F) ) 5.3 Hz, 1H, H-7), 7.69 (s, 1H, H-13), 9.14 (s, 1H,
H-11). IR (KBr) cm-1: νmax 3080, 1600, 1590, 1090, 940, 870.
Anal. (C13H11FN2‚HCl) C, H, N.
4
δ 2.89-2.96 (m, 2H, H-2), 3.00-3.08 (m, 2H, H-3), 6.92 (t, J
) 2.5 Hz, 1H, H-8), 7.13-7.25 (m, 3H, H-5, H-6, H-13), 7.30
3
3
(d, J ) 6.5 Hz, 1H, H-4), 7.57 (d, J ) 6.8 Hz, 1H, H-7), 7.69
(s, 1H, H-11). IR (KBr, free base) cm-1: νmax 3055, 3020, 2960,
2920, 2840, 1643, 1601, 1460, 985, 757. Anal. (C13H12N2‚
C2H2O4) C, H, N.
5-[(Z)-(5-Fluoro-2,3-dihydro-1H-inden-1-ylidene)meth-
yl]-1H-imidazole Oxalate (7b). Purification: FCC (CHCl3/
1
DMF, 9:2). Yield 15%, white solid, mp 205 °C. H NMR (400
5-[(Z)-2,3-Dihydro-1H-inden-1-ylidenemethyl]-1H-imi-
dazole Oxalate (2b). Purification: FCC (CHCl3/DMF, 9:2).
Yield 10%, white solid, mp 196 °C. 1H NMR (400 MHz, DMSO-
d6) δ 2.85-2.94 (m, 4H, H-2, H-3), 6.36 (s, 1H, H-8), 7.14 (t, 3J
MHz, DMSO-d6) δ 2.88-2.93 (m, 4H, H-2, H-3), 6.33 (s, 1H,
3
H-8), 6.98 (m, 1H, H-6), 7.14 (d, J(H,F) ) 9.1 Hz, 1H, H-4),
7.39 (s, 1H, H-13), 8.27-8.31 (m, 2H, H-7, H-11). IR (KBr)
cm-1: νmax 1600, 1480, 1220, 930, 860, 830, 720. Anal. (C13H11-
FN2‚C2H2O4) H, N. C: calcd, 59.21; found, 59.70.
3
3
) 7.4 Hz, 1H, H-5), 7.24 (t, J ) 7.4 Hz, 1H, H-6), 7.31 (d, J
3
) 7.4 Hz, 1H, H-4), 7.37 (s, 1H, H-13), 8.13 (d, J ) 7.4 Hz,
5-[(E)-(5-Chloro-2,3-dihydro-1H-inden-1-ylidene)me-
thyl]-1H-imidazole Hydrochloride (8a). Purification: FCC
(CHCl3/DMF, 9:2). Yield 37%, white solid, mp 238 °C. 1H NMR
1H, H-7), 8.30 (s, 1H, imidazole-H-11). IR (KBr) cm-1: νmax
1610, 1450, 750, 720. Anal. (C13H12N2‚0.75C2H2O4) C, H, N.
(8E)-8-(1H-Imidazol-5-ylmethylene)-5,6,7,8-tetrahy-
dronaphthalene-2-carbonitrile Hydrochloride (3a). From
compound 3i. Purification: FCC (CHCl3/DMF, 9:2). Yield 11%,
(400 MHz, DMSO-d
6) δ 2.95-2.97 (m, 2H, H-2), 3.10-3.13 (m,
2H, H-3), 6.94 (s, 1H, H-8), 7.34 (d,
3J ) 8.3 Hz, 1H, H-6),
7.46 (s, 1H, H-4), 7.64 (d,
3J ) 8.3 Hz, 1H, H-7), 7.72 (s, 1H,
1
green crystals, mp 217 °C. H NMR (400 MHz, DMSO-d6) δ
H-13), 9.11 (s, 1H, H-11). IR (KBr) cm-1
: νmax 3080, 1600, 1470,
1.80-1.84 (m, 2H, H-2), 2.71-2.74 (m, 2H, H-2), 2.81-2.84
(m, 2H, H-4), 7.10 (s, 1H, H-9), 7.42 (d, 3J ) 7.9 Hz, 1H, H-5),
7.68 (d, 3J ) 7.9 Hz, 1H, H-6), 7.82 (s, 1H, H-14), 8.13 (s, 1H,
H-8), 9.11 (s, 1H, H-12). IR (KBr, free base) cm-1: νmax 2940,
2220, 1620, 1600,1490, 1000, 900, 880, 840, 820. Anal.
(C15H13N3, free base) C, H, N.
(8Z)-8-(1H-Imidazol-5-ylmethylene)-5,6,7,8-tetrahy-
dronaphthalene-2-carbonitrile Oxalate (3b). From com-
pound 3i. Purification: FCC (CHCl3/DMF, 9:2). Yield 3%,
white solid, mp 197 °C. 1H NMR (400 MHz, DMSO-d6) δ 1.90-
1290, 1200, 1110, 1070, 830, 610. Anal. (C
H, N.
13H11ClN2‚HCl) C,
5-[(Z)-(5-Chloro-2,3-dihydro-1H-inden-1-ylidene)me-
thyl]-1H-imidazole Oxalate (8b). Purification: FCC (CHCl3/
1
DMF, 9:2). Yield 17%, white solid, mp 218 °C. H NMR (400
MHz, DMSO-d6) δ 2.87-2.96 (m, 4H, H-2, H-3), 6.39 (s, 1H,
3
4
H-8), 7.20 (dd, J ) 8.4 Hz, J ) 2.0 Hz, 1H, H-6), 7.37-7.38
3
(m, 2H, H-4, H-13), 8.24 (s, 1H, H-11), 8.50 (d, J ) 8.4 Hz,
1H, H-7). IR (KBr) cm-1: νmax 1600, 1470, 1210, 880, 860, 830,
710. Anal. (C13H11ClN2‚C2H2O4) C, H, N.