328
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 2, February, 2007
Mukhanova et al.
a solution of 2ꢀformylꢀ5ꢀmethoxybenzofuran (12b) (1.76 g,
0 mmol) in a mixture of methanol (20 mL) and chloroform
10 mL). After the reduction was completed (1 h), the solvents
1H NMR, δ: 2.39 (s, 3 H, Me); 2.86, 3.04 (both s, 3 H each,
1
(
NMe ); 3.62 (s, 2 H, CH ); 3.92 (s, 3 H, OMe); 6.76, 7.02
2
2
(both m, 1 H + 2 H, H(4)—H(6)).
were removed and the residue was diluted with water. The preꢀ
cipitate that formed was filtered off, washed with water and light
petroleum, and dried. The yield of compound 9b was 1.6 g. IR,
N,NꢀDimethylꢀ(5ꢀbromoꢀ2ꢀmethylbenzofuranꢀ3ꢀyl)acetamide
(13d) was obtained analogously from alcohol 9d (1.8 g, 8 mmol)
and acetal 3 (2.6 mL, 16 mmol) in DMF (12 mL). The yield was
–
1
1
–1
•+
ν/cm : 3318, 3260 (OH). H NMR, δ: 3.76 (s, 3 H, OMe); 4.51
1.56 g. IR, ν/cm : 1638 (C=O). MS, m/z: 318 [M + Na]
296 [M + H] , 223 [M – C(O)NMe2] . H NMR, δ: 2.38 (s,
,
•+
•+ 1
(
5
4
d, 2 H, CH OH, J = 5.4 Hz); 5.45 (t, 1 H, CH OH, J =
2
2
3
.4 Hz); 6.67 (s, 1 H, H(3)); 6.84 (dd, 1 H, H(6), J = 8.8 Hz,
3 H, Me); 2.84, 3.06 (both s, 3 H each, NMe ); 3.70 (s, 2 H,
2
4
3
4
J = 2.4 Hz); 7.10 (d, 1 H, H(4), J = 2.4 Hz); 7.41 (d, 1 H,
CH ); 7.33 (dd, 1 H, H(6), J = 8.4 Hz, J = 2.1 Hz); 7.43 (d,
2
3
3
4
H(7), J = 8.8 Hz).
1 H, H(7), J = 8.4 Hz); 7.66 (d, 1 H, H(4), J = 2.1 Hz).
N,NꢀDimethylꢀ(5,7ꢀdichloroꢀ2ꢀmethylbenzofuranꢀ3ꢀyl)acetꢀ
amide (13e) was obtained analogously from alcohol 9e (0.5 g,
2.3 mmol) and acetal 3 (0.75 mL, 4.6 mmol) in DMF (4 mL).
The yield was 0.3 g. IR, ν/cm : 1638 (C=O). MS, m/z: 308
[M + Na] , 286 [M + H] , 213 [M – C(O)NMe2]
2
ꢀHydroxymethylꢀ7ꢀmethoxybenzofuran (9c) was obtained
analogously from 2ꢀformylꢀ7ꢀmethoxybenzofuran (12c) (1.76 g,
–
1
1
3
0 mmol). The yield of compound 9c was 1.7 g. IR, ν/cm :
1
–1
410, 3350 (OH). H NMR, δ: 3.93 (s, 3 H, OMe); 4.54 (d, 2 H,
•
+
•+
•+
CH OH, J = 5.4 Hz); 5.37 (t, 1 H, CH OH, J = 5.4 Hz); 6.66 (s,
.
2
2
1
1
H, H(3)); 6.71, 7.11 (both m, 1 H + 2 H, H(4)—H(6)).
ꢀBromoꢀ2ꢀhydroxymethylbenzofuran (9d) was obtained
analogously from 5ꢀbromoꢀ2ꢀformylbenzofuran (12d) (2.25 g,
H NMR, δ: 2.42 (s, 3 H, Me); 2.84, 3.07 (both s, 3 H each,
5
NMe ); 3.73 (s, 2 H, CH ); 7.44, 7.54 (both d, 1 H each, H(4),
2
2
4
H(6), J = 1.8 Hz).
–
1
1
3
6
7
0 mmol). The yield of compound 9d was 1.7 g. IR, ν/cm
:
N,NꢀDimethylꢀ3ꢀ(indolꢀ3ꢀyl)propanamide (14). A. The synꢀ
thesis was carried out as described for compound 13b. Amide 14
was obtained from 3ꢀ(hydroxymethyl)indole (10) (1.47 g,
10 mmol) and acetal 3 (3.2 mL, 20 mmol) in DMF (15 mL).
368, 3281 (OH). 1H NMR, δ: 4.57 (d, 2 H, CH OH, J =
2
.0 Hz); 5.53 (t, 1 H, CH OH, J = 5.4 Hz); 6.75 (s, 1 H, H(3));
2
3
4
.40 (dd, 1 H, H(6), J = 8.4 Hz, J = 2.1 Hz); 7.52 (d, 1 H,
3
4
–1
H(7), J = 8.8 Hz); 7.80 (d, 1 H, H(4), J = 2.1 Hz).
,7ꢀDichloroꢀ2ꢀhydroxymethylbenzofuran (9e) was obtained
analogously from 5,7ꢀdichloroꢀ2ꢀformylbenzofuran (12e)
0.80 g, 3.7 mmol). The yield of compound 9e was 0.76 g. IR,
The yield was 1 g. IR, ν/cm : 3210 (NH), 1634 (C=O).
•
+
•+
5
MS, m/z: 455 [2 M + Na] , 239 [M + Na] , 130
•
+
1
[M – CH C(O)NMe ]
.
H NMR, δ: 2.63, 2.90 (both t,
2
2
(
2 H each, (CH ) CONMe , J = J = 7.2 Hz); 2.81, 2.92 (both s,
2
2
2
1
2
–
1
1
ν/cm : 3188 (OH). H NMR, δ: 4.61 (d, 2 H, CH OH, J =
3 H each, NMe ); 6.96, 7.05, 7.32, 7.50 (all m, 1 H each,
2
2
4
6
7
.0 Hz); 5.64 (t, 1 H, CH OH, J = 5.4 Hz); 6.86 (s, 1 H, H(3));
H(4)—H(7)); 7.12 (d, 1 H, H(2), J
= 2.1 Hz); 10.76
NH,H(2)
2
3
4
.40 (dd, 1 H, H(6), J = 8.4 Hz, J = 2.1 Hz); 7.52 (d, 1 H,
(br.s, 1 H, NH).
4
H(7)); 7.52, 7.70 (both d, 1 H each, H(4), H(6), J = 1.8 Hz).
N,NꢀDimethylꢀ(2ꢀmethylbenzofuranꢀ3ꢀyl)acetamide (13a).
A mixture of 2ꢀhydroxymethylbenzofuran (9a) (1.04 g, 7 mmol)
and N,Nꢀdimethylacetamide dimethyl acetal (3) (2.3 mL,
B. A mixture of alcohol 10 (0.37 g, 2.5 mmol) and acetal 3
(0.5 mL, 3.1 mmol) was stirred in benzene (5 mL) at 20 °C
for 5 h. The solvent and the excess of acetal 3 were removed
in vacuo. The residue was diluted with ether (5 mL) and allowed
to crystallize at 0 °C. The precipitate was filtered off, washed
with light petroleum, and dried. The yield was 0.135 g; the
sample was identical with that obtained according to procedure A.
N,NꢀDimethylꢀ2ꢀ(6ꢀmethylꢀ1,2,3,4ꢀtetrahydrocarbazolꢀ1ꢀ
yl)acetamide (15). Acetal 3 (4 mL, 25 mmol) was added to a
suspension of 1ꢀhydroxyꢀ6ꢀmethylꢀ1,2,3,4ꢀtetrahydrocarbazole
1
4 mmol) was refluxed in DMF (8 mL) for 15 h. Volatile subꢀ
stances were removed in vacuo. Column chromatography of the
residue on silica gel eluted with benzene gave the starting alcoꢀ
–
1
hol 9a (0.38 g) and amide 13a (0.33 g). IR, ν/cm : 1640 (C=O).
•
+
•+
MS, m/z: 240 [M
[
+
Na]
,
218 [M
+
H]
, 145
•
+ 1
M – C(O)NMe2] . H NMR, δ: 2.38 (s, 3 H, Me); 2.85, 3.06
1
7
(
both s, 3 H each, NMe ); 3.69 (s, 2 H, CH ); 7.17, 7.44 (both m,
(11) (4 g, 20 mmol) in benzene (30 mL). The precipitate
dissolved rapidly and the resulting solution spontaneously heated
from 20 to 30 °C. The mixture was stirred for 30 min, the solvent
was removed, and the residue was dissolved in ether (20 mL) and
allowed to crystallize at 4 °C. The precipitate that formed was
filtered off and washed with ether (4 mL). Recrystallization
from MeCN (6 mL) gave amide 15 (2 g). MS, m/z: 309
2
2
2
H each, H(4)—H(7)).
N,NꢀDimethylꢀ(5ꢀmethoxyꢀ2ꢀmethylbenzofuranꢀ3ꢀyl)acetꢀ
amide (13b). A mixture of 2ꢀhydroxymethylꢀ5ꢀmethoxybenzoꢀ
furan (9b) (0.89 g, 5 mmol) and N,Nꢀdimethylacetamide diꢀ
methyl acetal (3) (1.6 mL, 10 mmol) was refluxed in DMF
(
8 mL) until the starting reagent 9b was completely consumed.
•
+
•+
•+
Volatile substances were removed in vacuo. The residue was
diluted with ether (10 mL) and allowed to crystallize at 0 °C.
The precipitate that formed was filtered off and dried. The yield
[M + K] , 293 [M + Na] , 271 [M + H] , 226
•
+
•+
1H NMR
[M – NMe2] , 184 [M – CH C(O)NMe ]
.
2
2
(CDCl ), δ: 1.66, 2.08 (both m, 1 H each, C(2)H ); 1.83 (m,
3
2
–
1
of amide 13b was 1 g. IR, ν/cm : 1647 (C=O). MS, m/z: 270
2 H, C(3)H ); 2.45 (s, 3 H, Me); 2.62 (d, 2 H, CH CO, J =
2
2
•
+
•+
•+
[
M + Na] , 248 [M + H] , 175 [M – C(O)NMe2]
.
6.7 Hz); 2.70 (m, 2 H, C(4)H ); 2.99, 3.04 (both s, 3 H each,
2
1
3
H NMR, δ: 2.34 (s, 3 H, Me); 2.83, 3.04 (both s, 3 H each,
NMe ); 3.66 (s, 2 H, CH ); 3.74 (s, 3 H, OMe); 6.77 (dd, 1 H,
H(6), J = 8.8 Hz, J = 2.4 Hz); 6.99 (d, 1 H, H(4), J =
NMe ); 3.46 (m, 1 H, H(1)); 6.94 (dd, 1 H, H(7), J = 8.2 Hz,
J = 1.6 Hz); 7.20 (d, 1 H, H(8), J = 8.2 Hz); 7.26 (m, 1 H,
H(5)); 9.18 (br.s, 1 H, NH).
2
4
3
2
2
3
4
4
3
2
.4 Hz); 7.32 (d, 1 H, H(7), J = 8.8 Hz).
N,NꢀDimethylꢀ(7ꢀmethoxyꢀ2ꢀmethylbenzofuranꢀ3ꢀyl)acetꢀ
References
amide (13c) was obtained analogously from alcohol 9c (1.2 g,
.7 mmol) and acetal 3 (2.3 mL, 14 mmol) in DMF (10 mL).
6
–
1
The yield was 1.34 g. IR, ν/cm : 1638 (C=O). MS (EI),
m/z (Irel (%)): 247 [M]•+ (65), 175 [M – C(O)NMe2]•+ (100).
1. K. Kanematsu, A. Nishiraki, Y. Sato, and M. Shiro, Tetraꢀ
hedron Lett., 1992, 33, 4967.