F. Aldabbagh, M. P. Carty et al.
6,9-Dimethoxy-1,2,3,4-tetrahydropyrido
Bu3SnH (1.15 g, 3.95 mmol) and ACN (1.54 g, 6.32 mmol) in PhMe
(55 mL) were added over 18 h by syringe pump to 11 (0.62 g,
A
(12):
1.70 ppm (m, 2H; 3’-CH2); 13C NMR: d=142.9 (C), 142.2 (Im-2-CH),
133.0 (PhCH), 132.1 (C), 131.0 (C), 130.0 (C), 129.2 (PhCH), 127.2
(PhCH), 120.5 (Ar-4-CH), 109.9 (Ar-7-CH), 42.5 (NCH2), 29.7 (2’-CH2),
27.3 (3’-CH2, CH2SePh), 20.7 (Me), 20.4 ppm (Me); IR (neat): n˜ =1023,
1215, 1326, 1436, 1473, 1493, 1570, 2933 cmÀ1; HRMS (CI): m/z: calcd for
C19H23N2Se: 359.1021; found: 359.1015 [M+H]+; HRMS (EI): m/z (%):
358 (20) [M]+, 201 (100), 200 (37), 159 (95), 91 (50), 78 (78).
1.58 mmol) and CSA (0.36 g, 1.58 mmol) in PhMe (95 mL) heated at
reflux. Further ACN (0.58 g, 2.37 mmol) in 10 mL of PhMe was divided
into three equal portions, and added after 1, 5 and 9 h to the reaction
mixture. The reaction was stirred at reflux for an additional 1 h, and
cooled. The diazole products were extracted with 2m HCl (75 mL), and
KF was added. The solution was gravity filtered, and further KF was
added until no more precipitate of Bu3SnF was formed. Na2CO3 was
added to the filtrate until it was pH 8. The free diazole was extracted
with CHCl3, dried (MgSO4) and evaporated to dryness and the residue
purified by column chromatography using silica gel as absorbent with
gradient elution of hexane and EtOAc to give 12 (0.26 g, 70%) as an
orange oil. Rf =0.23 (EtOAc); 1H NMR: d=6.49 (s, 2H; ArH), 4.42 (t,
J=5.9 Hz, 2H; 1-CH2), 3.94 (s, 3H; Me), 3.86 (s, 3H; Me), 3.06 (t, J=
6.4 Hz, 2H; 4-CH2), 2.04, 1.96 ppm (m, 4H; 2-CH2, 3-CH2); 13C NMR:
d=150.1 (4a-C), 145.4 (C), 141.8 (C), 134.5 (C), 125.3 (C), 102.2 (ArCH),
101.4 (ArCH), 55.7 (2Me), 45.3 (1-CH2), 25.4 (all CH2), 23.0, 20.4 ppm;
IR (neat): n˜ =1091, 1157, 1193, 1260, 1311, 1402, 1424, 1449, 1523, 2837,
2932 cmÀ1; HRMS (EI): m/z: calcd for C13H16N2O2: 232.1212; found:
232.1215 [M]+; HRMS (EI): m/z (%): 232 (80) [M]+, 231 (100), 217 (97),
203 (25).
5,6-Dimethyl-1-[5-(phenylseleno)pentyl]-1H-benzimidazole (16): The
procedure given for the preparation of 14 was followed; 5,6-dimethyl-
1H-benzimidazole (1.67 g, 11.42 mmol), sodium hydride (0.41 g,
17.11 mmol) and 5-iodo-1-(phenylselanyl)pentane (3.03 g, 8.58 mmol) in
DMF (200 mL) gave 16 (2.37 g, 74%) as a yellowsolid after column
chromatography. Rf =0.27 (EtOAc); m.p. 67–698C; 1H NMR: d=7.72 (s,
1H; Im-2-H), 7.56 (s, 1H; Ar-4-H), 7.44 (m, 2H; PhH), 7.24 (m, 3H;
PhH), 7.12 (s, 1H; Ar-7-H), 4.08 (t, J=7.1 Hz, 2H; NCH2), 2.85 (t, J=
7.3 Hz, 2H; CH2SePh), 2.38 (d, J=2.9 Hz, 6H; Me), 1.84 (m, 2H; 2’-
CH2), 1.71, 1.43 ppm (m, 4H; 3’-CH2, (4’)-CH2); 13C NMR: d=142.7 (C),
142.3 (Im-2-CH), 132.7 (2C), 132.1 (PhCH), 131.1 (C), 131.0 (C), 129.2
(PhCH), 127.0 (PhCH), 120.4 (Ar-4-CH), 109.9 (Ar-7-CH), 44.9 (NCH2),
29.7 (4’-CH2), 29.4 (2’-CH2), 27.5 (CH2SePh), 27.0 (3’-CH2), 20.8 (Me),
20.4 ppm (Me); IR (neat): n˜ =1020, 1223, 1326, 1446, 1493, 1580, 2860,
2926, 3086 cmÀ1
found: 371.1108 [M]+; HRMS (EI): m/z (%): 189 (94), 156 (39), 68 (40).
6,7-Dimethyl-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazole (17a): Bu3SnH
; HRMS (EI): m/z: calcd for C20H24N2Se: 372.1105;
1,2,3,4-Tetrahydropyrido
A
ACHTREUNG
(1.36 g, 4.66 mmol) and ACN (1.82 g, 7.46 mmol) in PhMe (60 mL) were
added over 18 h by a syringe pump to 14 (0.64 g, 1.86 mmol) and CSA
(0.43 g, 1.86 mmol) in PhMe (60 mL) heated at reflux. Further ACN
(0.68 g, 2.79 mmol) in 9 mL of PhMe was divided into three equal por-
tions and added after 1, 5 and 9 h to the reaction mixture. The solution
was stirred at reflux for an additional 1 h, cooled and evaporated to dry-
ness to give a brown residue, which was purified by column chromatogra-
phy with 10% w/w of finely ground KF and 90% w/w silica gel as absorb-
ent and gradient elution with hexane and EtOAc to give in order of elu-
tion 6,7-dimethyl-1-propyl-1H-benzimidazole 17b (0.19 g, 54%), as a
yellowsolid and 17a (0.11 g, 32%) as a yellowpowder.
12 (0.57 g, 2.45 mmol) in 48% hydrobromic acid (20 mL) was heated at
reflux for 3 h. The reaction was cooled and evaporated to dryness. FeCl3
aq (0.7m, 20 mL) was added to the residue and stirred at room tempera-
ture overnight. The solution was extracted with CHCl3, the combined or-
ganic extracts dried (MgSO4) and evaporated to dryness to give a red
solid, which was purified by column chromatography using silica gel as
absorbent with gradient elution of hexane and EtOAc to yield 6 (0.43 g,
87%) as a yellowsolid. Rf =0.26 (EtOAc); m.p. 153–1558C; 1H NMR:
d=6.60 (ABq, J=10.5 Hz, 2H; 7-H, 8-H), 4.33 (t, J=6.1 Hz, 2H; 1-CH2),
3.01 (t, J=6.3 Hz, 2H; 4-CH2), 2.05, 1.98 ppm (m, 4H; 3-CH2, 2-CH2);
13C NMR: d=181.3 (C=O), 178.3 (C=O), 151.9 (4a-C), 141.4 (C), 136.2
(ArCH), 136.0 (ArCH), 130.1 (C), 45.5 (1-CH2), 25.0 (all CH2), 22.3,
19.8 ppm; IR (neat): n˜ =965, 1035, 1058, 1074, 1157, 1205, 1244, 1302,
1354, 1376, 1409, 1429, 1458, 1483, 2919, 1510, 1590, 1650 cmÀ1 (C=O);
HRMS (ESI): m/z: calcd for C11H11N2O2: 203.0815; found: 203.0818
[M+H]+; elemental analysis calcd (%) for C11H10N2O2: C 65.1, H 5.0, N
13.8; found: C 65.0, H 4.9, N 13.8.
Product 17a: Rf =0.10 (EtOAc); m.p. 159–1618C (lit[26] m.p. 177–1798C);
1H NMR: d=7.42 (s, 1H; Ar-5-H), 7.04 (s, 1H; Ar-8-H), 4.00 (m, 2H; 1-
CH2), 2.99 (m, 2H; 3-CH2), 2.66 (m, 2H; 2-CH2), 2.34 ppm (s, 6H; Me);
13C NMR: d=160.5 (Ar-3a-C), 147.6 (C), 131.0 (C), 130.7 (C), 130.4 (C),
119.8 (Ar-5-CH), 109.9 (Ar-8-CH), 42.8 (1-CH2), 26.2 (2-CH2), 23.6 (3-
CH2), 20.5 (Me), 20.4 ppm (Me); IR (neat): n˜ =1000, 1130, 1293, 1300,
1446, 1523, 1410, 2940 cmÀ1
.
5,6-Dimethyl-1-[3-(phenylseleno)propyl]-1H-benzimidazole (14): 5,6-Di-
methyl-1H-benzimidazole (1.50 g, 10.26 mmol) and sodium hydride
(0.40 g, 16.67 mmol) in DMF (120 mL) were heated at 808C for 0.5 h. 1-
Iodo-3-phenylselanylpropane (2.69 g, 8.27 mmol) was added and heating
continued for an additional 2.5 h. The reaction was cooled, filtered
through Celite and evaporated to dryness. The resultant brown residue
was purified by column chromatography using silica gel as absorbent
with gradient elution of hexane and EtOAc to give 14 (1.93 g, 68%) as a
Product 17b: Rf =0.33 (EtOAc); m.p. 81–838C; 1H NMR: d=7.74 (s,
1H; Im-2-H), 7.55 (s, 1H; Ar-4-H), 7.14 (s, 1H; Ar-7-H), 4.06 (t, J=
6.9 Hz, 2H; NCH2), 2.37 (d, J=8.2 Hz, 6H; Me), 1.85 (m, 2H; 2’-CH2),
0.91 ppm (t, J=7.3 Hz, 3H; CH2CH3); 13C NMR: d=142.4, 142.3, 132.1
(C), 132.0 (C), 130.9 (C), 120.3 (Ar-4-CH), 109.9 (Ar-7-CH), 46.8
(NCH2), 23.2 (2’-CH2), 20.8 (Me), 20.5 (Me), 11.5 ppm (CH2CH3); IR
(neat): n˜ =986, 1055, 1137, 1215, 1351, 1374, 1449, 1486, 1500, 1676, 2876,
2926 cmÀ1; elemental analysis calcd (%) for C12H16N2: C 76.5, H 8.6, N
14.9; found: C 76.2, H 8.5, N 14.7.
1
yellowoil. Rf =0.23 (EtOAc); H NMR: d=7.71 (s, 1H; Im-2-H), 7.54 (s,
1H; Ar-4-H), 7.46 (m, 2H; PhH), 7.25 (m, 3H; PhH), 7.10 (s, 1H; Ar-7-
H), 4.24 (t, J=6.7 Hz, 2H; NCH2), 2.80 (t, J=6.8 Hz, 2H; CH2SePh),
2.36 (s, 6H; Me), 2.20 ppm (m, 2H; 2’-CH2); 13C NMR: d=142.7 (C),
142.4 (Im-2-CH), 133.2 (PhCH), 132.2 (C), 131.2 (C), 129.4 (PhCH),
129.1 (C), 127.5 (PhCH), 120.5 (Ar-4-CH), 109.9 (Ar-7-CH), 44.2
(NCH2), 29.6 (2’-CH2), 24.3 (CH2SePh), 20.7 (Me), 20.4 ppm (Me); IR
(neat): n˜ =903, 1020, 1216, 1326, 1366, 1436, 1493, 1576, 1740, 2206,
2926 cmÀ1; HRMS (EI): m/z: calcd for C18H20N2Se: 344.0792; found:
344.0796 [M]+; HRMS (EI): m/z (%): 344 [M]+, 147 (34), 190 (100).
7,8-Dimethyl-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazole (18a): The
A
procedure given for the preparation of 17a was followed; Bu3SnH
(1.26 g, 4.33 mmol), ACN (2.33 g, 9.51 mmol) CSA (0.40 g, 1.73 mmol)
and 15 (0.62 g, 1.73 mmol) in PhMe (170 mL) gave 18a (0.24 g, 69%) as
an off-white powder after column chromatography. Rf =0.23 (EtOAc);
m.p. 161–1638C; 1H NMR: d=7.41 (s, 1H; Ar-6-H), 7.01 (s, 1H; Ar-9-
H), 3.97 (t, J=6.0 Hz, 2H; 1-CH2), 3.01 (t, J=6.3 Hz, 2H; 4-CH2), 2.34
(d, J=4.6 Hz, 6H; Me), 2.05 (m, 2H; 2-CH2), 1.96 ppm (m, 2H; 3-CH2);
13C NMR: d=150.9 (Ar-4a-C), 141.4 (C), 133.2 (C), 130.7 (C), 130.6 (C),
119.0 (Ar-6-CH), 109.2 (Ar-9-CH), 42.4 (1-CH2), 25.5 (4-CH2), 22.8 (3-
CH2), 20.9, 20.5, 20.4 ppm; IR (neat): n˜ =900, 1003, 1253, 1314, 1363,
1413, 1455, 1516, 1723, 2863, 2937 cmÀ1; HRMS (EI): m/z: calcd for
C13H16N2: 200.1388; found: 200.1106 [M]+; HRMS (EI): m/z (%): 200
[M]+ (100), 185 (99), 157 (40), 171 (41), 121 (9).
5,6-Dimethyl-1-[4-(phenylseleno)butyl]-1H-benzimidazole (15): The pro-
cedure given for the preparation of 14 was followed; 5,6-dimethyl-1H-
benzimidazole (1.46 g, 10.00 mmol), sodium hydride (0.36 g, 15.00 mmol)
and 4-iodo-1-(phenylselanyl)butane (2.56 g, 7.55 mmol) in DMF
(180 mL) gave 15 (1.54 g, 57%) as a yellowsolid after column chromo-
tography. Rf =0.28 (EtOAc); m.p. 74–768C; 1H NMR: d=7.70 (s, 1H;
Ar-2-H), 7.54 (s, 1H; Ar-4-H), 7.43 (m, 2H; PhH), 7.24 (m, 3H; PhH),
7.13 (s, 1H; Ar-7-H), 4.09 (t, J=7.1 Hz, 2H; NCH2), 2.88 (t, J=7.1 Hz,
2H; CH2SePh), 2.38 (d, J=2.9 Hz, 6H; Me), 1.99 (m, 2H; 2’-CH2),
2,3-Dimethyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole (19a):
T
The procedure given for the preparation of 17a was followed; Bu3SnH
(0.98 g, 3.38 mmol), ACN (1.81 g, 7.7 mmol), CSA (0.31 g, 1.35 mmol)
3224
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 3218 – 3226