SYNTHESIS, STRUCTURE, AND HECK CYCLIZATION
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mixture was heated for 10 h under reflux. When the
initial amine disappeared (TLC), the mixture was
cooled to room temperature, a solution of 10 g of
sodium hydroxide in 100 ml of water was added, and
the mixture was thoroughly stirred and treated with
100 ml of benzene. The organic phase was separated,
dried over KOH, and evaporated under reduced pres-
sure, and the residue was subjected to column chroma-
tography on silica gel using benzene as eluent. Yield
2.31 g (55%), viscous material, Rf 0.52 (C6H6).
1H NMR spectrum, δ, ppm: 1.85 q (3H, CH3, J =
2.0 Hz), 2.18 s (3H, CH3), 2.23 s (3H, CH3), 3.93–
4.27 m (6H, 6-H, 2-H, 3-H, NH), 5.61–5.68 m (1H,
3-H), 6.84 s (1H, 3′-H), 7.36 s (1H, 5′-H). 13C NMR
spectrum, δC, ppm: 19.7, 19.8, 21.2 (CH3); 54.2 (C5);
65.6, 67.8 (C2′, C6′), 94.8 (C2); 123.3, 132.4, 137.9 (C3′,
C5′, C3); 130.6, 133.2; 134.0, 144.3 (C1′, C4′, C6′, C4).
Found, %: C 48.84; H 5.18; I 36.85; N 3.99.
C14H18INO. Calculated, %: C 48.99; H 5.29; I 36.98;
N 4.08.
(PhH–EtOAc, 9:1). H NMR spectrum, δ, ppm: 1.43 s
(3H, CH3), 1.85 s (3H, CH3), 2.25 s (3H, CH3), 2.37 s
(3H, CH3), 3.23 d.d (1H, 2-HA, J = 4.0, 11.0 Hz),
3.62 d.d.d (1H, 2-HB, J = 1.0, 2.6, 11.0 Hz), 3.84 d.d
(1H, 3-H, J = 3.8, 11.0 Hz), 3.95 d.t (1H, 6-HA, J = 2.9,
11.0 Hz), 4.20 t (1H, 6-HB, J = 10.9 Hz), 7.03 br.s (1H,
5-H), 7.10 s (1H, 5′-H), 7.64 s (1H, 3′-H). Found, %:
C 49.79; H 5.14; I 32.82; N 3.55. C16H20INO2. Calcu-
lated, %: C 49.88; H 5.23; I 32.94; N 3.64.
N-(2-Iodo-4,6-dimethylphenyl)-N-(4-methyl-3,6-
dihydro-2H-pyran-3-yl)-4-nitrobenzamide (syn-
VIIb). 4-Nitrobenzoyl chloride, 0.52 g (2.8 mmol),
was added under stirring to a solution of 0.74 g
(2.16 mmol) of amine VI in 3 ml of anhydrous pyri-
dine. The mixture was stirred for 4 h, 20 ml of water
and 200 ml of methylene chloride were added, the
mixture was stirred, the organic phase was separated,
washed in succession with 4% aqueous HCl (170 ml),
water (50 ml), and a saturated solution of NaHCO3,
dried over Na2SO4, and evaporated under reduced
pressure, and the residue was subjected to column
chromatography on silica gel. From the first fractions
we isolated 0.178 g (24%) of unreacted amine VI
(conversion 76%). The subsequent elution gave 0.21 g
(26% calculated on the 76% conversion) of syn-VIIb
as an amorphous material, Rf 0.7 (PhH–EtOAc, 9:1).
1H NMR spectrum, δ, ppm: 1.64 s (3H, CH3), 2.16 s
(3H, CH3), 2.55 s (3H, CH3), 3.76 d.d (1H, 2-HA, J =
3.7, 12.0 Hz), 4.07–4.39 m (2H, 2-HB, 6-HA), 4.48 d.d
(1H, 6-HB, J = 3.7, 12.0 Hz), 4.61 br.s (1H, 3-H),
5.61 br.s (1H, 5-H), 6.97 s (1H, 5′-H), 7.34 s (1H,
N-(2-Iodo-4,6-dimethylphenyl)-N-(4-methyl-3,6-
dihydro-2H-pyran-3-yl)acetamide (syn-VIIa). Acetyl
bromide, 1.12 ml (16 mmol), was added under stirring
to a solution of 2.74 g (8 mmol) of amine VI in 5 ml of
anhydrous methylene chloride in the presence of 2.2 g
(16 mmol) of potassium carbonate. The mixture was
stirred for 4 h, treated with 20 ml of a saturated solu-
tion of sodium hydrogen carbonate, stirred, and ex-
tracted with 100 ml of methylene chloride. The organic
phase was separated, washed with water (2×20 ml),
dried over Na2SO4, and evaporated under reduced
pressure, and the residue was subjected to column
chromatography on silica gel using benzene to ben-
zene–ethyl acetate (4:1) as eluents (gradient elution) to
isolate 1.79 g (73% calculated on the 80% conversion)
of a mixture of syn-VIIa and anti-VIIa. From the
preceding fractions we also isolated 0.55 g (20%) of
unreacted initial amine VI. The isomer mixture was
separated by HPLC. Yield of syn-VIIb 0.59 g (24%),
transparent glassy material, Rf 0.45 (PhH–EtOAc,
3′-H), 7.65 d (2H, Harom, J = 9.0 Hz), 8.02 d (2H, Harom
,
J = 9.0 Hz). Found, %: C 51.08; H 4.20; I 25.64;
N 5.58. C21H21IN2O4. Calculated, %: C 51.23; H 4.30;
I 25.78; N 5.69.
N-(2-Iodo-4,6-dimethylphenyl)-N-(4-methyl-3,6-
dihydro-2H-pyran-3-yl)-4-nitrobenzamide (anti-
VIIb) was isolated by further elution. Yield 0.37 g
(46% for the 76% conversion), Rf 0.6 (PhH–EtOAc,
9 : 1), mp 119°C (from tert-butyl methyl ether).
1H NMR spectrum, δ, ppm: 2.01 s (3H, CH3), 2.17 s
(3H, CH3), 2.44 s (3H, CH3), 3.67 d.d (1H, 2-HA, J =
4.3, 12.6 Hz), 3.97 d.d (1H, 2-HB, J = 5.0, 12.6 Hz),
4.04–4.11 m (2H, 6-HA, 6-HB), 5.14 br.s (1H, 3-H),
5.66 br.s (1H, 5-H), 6.95 s (1H, 5′-H), 7.35 s (1H,
1
9:1). H NMR spectrum, δ, ppm: 1.61 s (3H, CH3),
1.77 s (3H, CH3), 2.26 s (3H, CH3), 2.29 s (3H, CH3),
3.45 d.d (1H, 2-HA, J = 3.7, 10.6 Hz), 3.52–3.61 m
(2H, 2-HB, 3-H), 3.90 d.t (1H, 6-HA, J = 2.4, 10.9 Hz),
4.05 d.d (1H, 6-HB, J = 9.7, 10.9 Hz), 6.43 br.s (1H,
5-H), 7.10 s (1H, 5′-H), 7.65 s (1H, 3′-H). Found, %:
C 49.77; H 5.16; I 32.85; N 3.49. C16H20INO2. Cal-
culated, %: C 49.88; H 5.23; I 32.94; N 3.64.
3′-H), 7.61 d (2H, Harom, J = 8.9 Hz), 8.01 d (2H, Harom
,
J = 8.9 Hz). Found, %: C 51.11; H 4.22; I 25.67;
N 5.59. C21H21IN2O4.Calculated, %: C 51.23; H 4.30;
I 25.78; N 5.69.
N-(2-Iodo-4,6-dimethylphenyl)-N-(4-methyl-3,6-
dihydro-2H-pyran-3-yl)acetamide (anti-VIIa). Yield
0.34 g (14%), transparent glassy material, Rf 0.35
N-(2,4-Dimethylphenyl)-N-(4-hydroxy-4-methyl-
tetrahydro-2H-pyran-3-yl)acetamide (X). Com-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 10 2013