A. Dhawan, S. Balwani, A. K. Prasad, B. Ghosh, and V. S. Parmar
Vol 000
0
0
0
+
(
(
J = 3.8 Hz, C-5 ), 132.47 (C-6 ), 134.96 (J = 9.06Hz, C-4 ), 143.19
HRMS m/z Calcd for C H O [M + Na] 319.1305, found
19 20 3
[M+ Na] 319.1297.
0
+
C-9), 151.85 (C-6), 161.90 (d, J = 209.1 Hz, C-2 ), 163.98 (C═O);
HRMS m/z Calcd for C18
M+ Na] 323.1046.
,2-Dimethylchroman-6-yl 3-fluorobenzoate (6f).
obtained as a yellowish waxy solid (240 mg, 80% yield); IR
Nujol): 2933, 1727, 1491, 1264, 1194, 1142, 1070, 893,
62 cm ; H NMR (300 MHz, CDCl
.81 (t, 2 H, J = 6.8 Hz, C–3H), 2.79 (t, 2H, J = 6.8 Hz, C–4H),
.78–6.81 (m, 1H, C–8H), 6.88–6.92 (m, 2H, C–5H and C–7H),
.14–7.19 (m, 2H, C–4 H and C–5 H), 8.17–8.22 (m, 2H, C–2
+
H17FO
3
[M+ Na] 323.1054, found
General procedure for the synthesis of amides 7a–7i. To
a solution of 2,2-dimethyl-6-aminochroman 4 (177 mg, 10mmol)
and triethylamine (101 mg, 10mmol) in dichloromethane (5mL), a
solution of the acid chloride (5a–5i, 10mmol) in dichloromethane
+
[
2
It was
ꢀ
(
(1 mL) was added slowly at 0 C. After the addition of acid
ꢂ1
1
7
1
6
7
3
):d 1.34 (s, 6H, 2 ꢃ CH
3
),
chloride, the reaction mixture was stirred at RT until TLC showed
complete disappearance of 4. After the completion of reaction, the
reaction mixture was extracted with brine solution, followed by
extraction with water. The organic layer was then dried over
0
0
0
0
13
and C–6 H); C NMR (CDCl
3
, 75.5 MH
Z
):d 22.62 (C-4), 26.85
2 4
anhydrous Na SO and evaporated under reduced pressure to
(
1
1
2ꢃ CH
3
), 32.51 (C-3), 74.38 (C-2), 115.56, 115.85, 117.88,
obtain the crude product, which was purified by column
chromatography over silica gel using ethyl acetate–petroleum
ether (1:99 to 1:19) as eluent to afford the pure amides 7a–7i in
72–90% yields. The structures of all the amides 7a–7i were
unambiguously established from the analysis of their spectral data
0 0 0
20.33, 121.66, 121.90 (C-5, C-7, C-8, C-10, C-2 C-4 and C-6 ),
0
0
26.07 (d, J = 3.0 Hz, C-1 ), 132.69 (d, J = 9.8 Hz, C-5 ), 143.35
(
C-9), 151.83 (C-6), 164.70 (C═O), 166.07 (d, J = 255.2 Hz,
0
+
C-3 ); HRMS m/z Calcd for C18
found [M + Na] 323.1040.
H
17FO
3
[M + Na] 323.1054,
+
1
13
(IR, H NMR, C NMR, and mass spectra).
2
,2-Dimethylchroman-6-yl 4-fluorobenzoate (6g).
It was
N-(2,2-Dimethylchroman-6-yl)benzamide (7a).
It was
ꢀ
obtained as a yellowish waxy solid (228 mg, 76% yield); IR
Nujol): 2926, 1739, 1490, 1268, 1193, 1159, 1070, 891,
50 cm ; H NMR (300 MHz, CDCl
.81 (t, 2H, J = 6.6 Hz, C–3H), 2.79 (t, 2H, J = 6.6 Hz, C–4H),
.76–6.85 (m, 1H, C–8H), 6.87–6.97 (m, 2H, C–5H and C–7H),
.27–7.39 (m, 1H, C–5 H), 7.41–7.54 (m, 1H, C–3 H), 7.86 (d,
H, J = 7.2 Hz, C–6 H), 7.97 (d, 1H, J = 7.8 Hz, C–2 H); C
NMR (75.5 MHz, CDCl
2.50 (C-3), 74.41 (C-2), 116.97 (d, J = 22.7 Hz, C-3 ), 117.90
C-8), 120.25 (C-7), 120.49(d, J = 21.1 Hz, C-5 ), 121.69
C-10), 121.83 (C-5), 125.83 (d, J = 3.8 Hz, C-1 ), 130.16 (d,
J = 7.6 Hz, C-6 ), 132.00 (d, J = 7.6 Hz, C-2 ), 143.28 (C-9),
51.90 (C-6), 162.61 (d, J = 247.6 Hz, C-4 ) 164.52 (C═O);
obtained as an off-white solid (233 mg, 83% yield), mp:150–152 C,
ꢂ1
(
IR: (Nujol)/cm :3255, 2938, 1643, 1498, 1267, 1122, 1030, 829,
ꢂ1
1
1
7
1
6
7
1
3
):d 1.35 (s, 6H, 2 ꢃ CH
3
),
703; H NMR (300 MHz, CDCl
3
):d 1.33 (s, 6H, 2 ꢃ CH
3
), 1.80 (t,
2H, J=6.7Hz, C–3H), 2.79 (t, 2H, J=6.7Hz, C–4H), 6.76 (d, 1H,
J = 8.7Hz, C–8H), 7.15–7.18 (m, 1H, C–7H), 7.44–7.53 (m, 4H,
0
0
0 0 0
C–5H, C–3 H, C–4 H, and C–5 H), 7.70 (br s, 1H, NH), 7.84 (d,
0
0
13
0
0
13
2H, J = 6.9 Hz, C–2 H and C–6 H); C NMR (75.5 MHz,
CDCl ), 32.69 (C-3), 74.28
): d 22.63 (C-4), 26.79 (2 ꢃ CH
(C-2), 117.46 (C-8), 120.17 (C-5), 121.39 (C-10), 122.01 (C-7),
3
):d 22.62 (C-4), 26.85 (2 ꢃ CH
3
),
3
3
0
3
(
(
0
0 0 0 0
126.93 (C-3 and C-5 ), 128.71 (C-2 and C-6 ), 129.90(C-6),
0
0
0
131.60 (C-4 ), 135.14 (C-1 ), 153.15 (C-9), 165.55 (C═O);
+
0
0
HRMS m/z Calcd for C18
H19NO
2
[M+ Na] 304.1308, found
0
+
+
1
[M+ Na] 304.1303.
HRMS m/z Calcd for C18
H
17FO
3
[M + Na] 323.1054, found
2-Chloro-N-(2,2-dimethylchroman-6-yl)benzamide (7b). It
+
[
M + Na] 323.1039.
,2-Dimethylchroman-6-yl 3-methoxybenzoate (6h). It was
was obtained as an off-white solid (249 mg, 78% yield); mp:
ꢀ
2
120–121 C; IR: (Nujol): 3317, 2931, 1654, 1498, 1206, 1123,
ꢂ1
1
obtained as a colorless solid (250 mg, 80% yield) by following the
general procedure. mp: 85–88 C; IR (Nujol): 2928, 1729, 1490,
275, 1195, 1145, 1082, 891, 747 cm ; H NMR (300 MHz,
1049, 815, 749 cm ; H NMR (300 MHz, CDCl
3
): d 1.34 (s,
ꢀ
6H, 2 ꢃ CH
3
), 1.81 (t, 2H, J = 6.9 Hz, C–3H), 2.80 (t, 2H,
J = 6.9Hz, C–4H), 6.77 (d, 1H, J = 8.7 Hz, C–8H), 7.17 (dd, 1H,
ꢂ1
1
1
0
CDCl ):d 1.34 (s, 6H, 2 ꢃ CH ), 1.81 (t, 2H, J = 6.6 Hz, C–3H),
J = 2.4 and 8.7 Hz, C–7H), 7.34–7.46 (m, 3H, C–5H, C–4 H
3
3
0
0
2
6
.79 (t, 2H, J = 6.6 Hz, C–4H), 3.87 (s, 3H, OCH ),
and C–5 H), 7.52 (br s, 1H, NH), 7.71–7.76 (m, 2H, C–3 H and
3
0
13
.78–6.81 (m, 1H, C–8H), 6.89–6.92 (m, 2H, C–5H and
C–7H),7.14–7.18 (m, 1H, C–4 H),7.37–7.42 (m, 1H,
C–5 H),7.68–7.69 m, 1H, C-6 ), 7.77–7.78 (m, 1H, C–2 H);
C
C–6 H); C NMR (75.5MHz, CDCl
(2ꢃ CH ), 32.65 (C-3), 74.31 (C-2), 117.46, 120.03, 121.38 and
121.81 (C-5, C-7, C-8, and C-10), 127.19, 128.34, 129.54,
3
):d 22.61 (C-4), 26.76
0
3
0
0
0
1
3
0 0 0 0
130.26, and 130.58 (C-6, C-3 , C-4 , C-5 , and C-6 ), 131.44
NMR (75.5 MHz, CDCl3):
d
22.62 (C-4), 26.85
0
0
(
1
2 ꢃ CH ), 32.53 (C-3), 55.50 (OCH ), 74.36 (C-2), 117.45,
(C-1 ), 135.37 (C-2 ), 151.31 (C-9), 164.27 (C═O); HRMS m/z
+ +
3
3
17.85, 120.00, 120.37, 121.63, 121.94, 122.53, (C-5, C-7,
2
Calcd for C18H18ClNO [M + Na] 338.0918, found [M+ Na]
0
0
0
0
0
C-8, C-10, C-2 , C-4 , and C-6 ), 129.53 (C-5 ), 131.11 (C-1 ),
43.49 (C-9), 151.77 (C-6), 159.67 (C-3 ), 165.54 (C═O); HRMS
m/z Calcd for C H O [M + Na] 335.1254, found [M + Na]
35.1239.
338.0908.
0
1
3-Chloro-N-(2,2-dimethylchroman-6-yl)benzamide (7c). It
+
+
was obtained as an off-white solid (261 mg, 83% yield); mp:
1
9 20 4
ꢀ
3
145–146 C; IR: (Nujol): 3269, 2927, 1643, 1497, 1261, 1121,
ꢂ1
1
2
,2-Dimethylchroman-6-yl 4-methylbenzoate (6i).
It was
1094, 823, 707 cm ; H NMR (300 MHz, CDCl
3
): d 1.34 (s, 6H,
ꢀ
obtained as a colorless solid (222 mg, 75% yield); mp: 109–111 C;
IR: (Nujol): 2975, 1725, 1490, 1272, 1197, 1143, 1074, 892,
2 ꢃ CH
3
), 1.79 (t, 2H, J = 6.7 Hz, C–3H), 2.77 (t, 2H, J = 6.7 Hz,
C–4H), 6.75 (d, 1H, J = 8.7 Hz, C–8H), 7.16 (dd, 1H, J = 2.1
ꢂ1
1
0
7
1
50 cm ; H NMR (300 MHz, CDCl ): d 1.34 (s, 6H, 2 ꢃ CH ),
and 8.7 Hz, C–7H),7.36–7.53 (m, 3H, C–5H, C–5 H, and
3
3
0
0
0
.80 (t, 2H, J= 6.6Hz, C–3H), 2.44 (s, 3H, CH
3
), 2.79 (t, 2H,
C–6 H),7.69–7.75 (m, 2H, C–2 H and C–4 H), 7.82 (br s, 1H,
1
3
J= 6.6Hz, C–4H), 6.77–6.81 (m, 1H, C–8H), 6.90–6.92 (m, 2H,
C–5H and C–7H), 7.26–7.30 (m, 2H, C–3 H and C–5 H),8.06 (d,
H, J= 8.1Hz, C–2 H and 6 H); C NMR (75.5 MHz, CDCl ): d
NH); C NMR (CDCl
(2ꢃ CH ), 32.68 (C-3), 74.37 (C-2), 117.52, 120.32, 121.43,
122.13 (C-5, C-7, C-8, and C-10), 125.05, 127.37, 129.54,
3 Z
, 75.5MH ): d 22.63 (C-4), 26.81
0
0
3
0
0
13
2
2
7
(
5
3
0 0 0 0
130.02, 131.61 (C-6, C-2 , C-4 , C-5 , and C-6 ), 134.90
1.73 (CH ), 22.62 (C-4), 26.85 (2 ꢃ CH ), 32.54 (C-3),
3
3
0
0
4.33 (C-2), 117.81 (C-8), 120.44 (C-7), 121.58 (C-10), 122.00
(C-1 ), 136.95 (C-3 ), 151.41 (C-9), 164.24 (C═O); HRMS
+
0
0
0
0
C-5), 127.06 (C-1 ), 129.22 (C-2 and C-6 ), 130.15 (C-3 and C-
), 143.54 (C-9), 144.18 (C-4 ), 151.68 (C-6), 165.74 (C═O);
m/z Calcd for C18
H
18ClNO
2
[M + Na] 338.0918, found
0
0
+
[M + Na] 338.0905.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet