REACTION OF 3-ALKYL(ARYL)-5-CHLOROMETHYLISOXAZOLES
1533
%: C 71.75; H 6.48; N 13.97. C12H14N2O. Calculated,
%: C 71.29; H 6.93; N 13.86.
3-Methylisoxazol-5-ylmethyl acetate (IVa). Yield
76%, bp 106–108°C (3 mm), nD20 = 1.4650, d420
=
1.1146. IR spectrum, ν, cm–1: 3150 (=C–H), 1760
(C=O), 1626, 1540 (C=C, C=N), 1203 (C–O). 1H NMR
spectrum, δ, ppm: 1.98 s (3H, 3-CH3), 2.17 s (3H,
COCH3), 4.96 s (2H, OCH2), 6.02 s (1H, 4-H). Found,
%: C 54.72; H 5.50; N 9.55. C7H9NO3. Calculated, %:
C 54.19; H 5.81; N 9.03.
2-(3-Methylisoxazol-5-ylmethylamino)ethanol
(IIIa). Yield 74%, bp 126–127°C (3 mm), Rf 0.70,
nD20 = 1.5180, d420 = 1.1020. IR spectrum, ν, cm–1: 3430
(OH), 3340 (NH), 3248 (=C–H), 1619, 1570 (C=C,
1
C=N). H NMR spectrum, δ, ppm: 2.10 s (3H, CH3),
2.63 t (2H, OCH2), 3.53 t (2H, NCH2), 3.70 s (2H,
5-CH2), 3.90 s (1H, OH), 5.36 (1H, NH), 5.90 s (1H,
4-H). Found, %: C 53.41; H 7.99; N 17.53.
C7H12N2O2. Calculated, %: C 53.85; H 7.69; N 17.95.
3-Ethylisoxazol-5-ylmethyl acetate (IVb). Yield
73%, bp 120–122°C (3 mm), nD20 = 1.4620, d420
=
1.0830. IR spectrum, ν, cm–1: 3144 (=C–H), 1758
(C=O), 1620, 1560 (C=C, C=N), 1205 (C–O). 1H NMR
spectrum, δ, ppm: 1.65 t (3H, CH3), 1.97 s (3H,
COCH3), 2.60 q (2H, CH3CH2), 4.99 s (2H, OCH2),
6.10 s (1H, 4-H). Found, %: C 57.32; H 6.25; N 8.79.
C8H11NO3. Calculated, %: C 57.83; H 6.63; N 8.43.
2-(3-Ethylisoxazol-5-ylmethylamino)ethanol
(IIIb). Yield 71%, bp 136–137°C (3 mm), Rf 0.68,
nD20 = 1.5090, d420 = 1.0980. IR spectrum, ν, cm–1: 3435
(OH), 3337 (NH), 3250 (=C–H), 1625, 1590 (C=C,
1
C=N). H NMR spectrum, δ, ppm: 1.19 t (3H, CH3),
2.50 m (2H, CH2), 2.70 t (2H, OCH2), 3.59 t (2H,
NCH2), 3.84 s (2H, 5-CH2), 3.35 s (1H, OH), 5.34 s
(1H, NH), 5.96 s (1H, 4-H). Found, %: C 56.98;
H 8.74; N 16.91. C8H14N2O2. Calculated, %: C 56.47;
H 8.24; N 16.47.
3-Phenylisoxazol-5-ylmethyl acetate (IVd). Yield
68%, bp 157–159°C (4 mm), nD20 = 1.5090, d420
=
1.1195. IR spectrum, ν, cm–1: 3147 (=C–H), 3081
(C–Harom), 1767 (C=O), 1618, 1579, 1573 (C=C,
C=N), 1208 (C–O). 1H NMR spectrum, δ, ppm: 1.70 s
(3H, COCH3), 4.60 s (2H, OCH2), 6.15 s (1H, 4-H),
7.10–7.85 m (5H, Harom). Found, %: C 66.74; H 5.27;
N 6.87. C12H11NO3. Calculated, %: C 66.34; H 5.07;
N 6.45.
2-(3-Phenylisoxazol-5-ylmethylamino)ethanol
(IIId). Yield 67%, bp 175–177°C (3 mm), nD20
=
1.5670, d420 = 1.1650. IR spectrum, ν, cm–1: 3418 (OH),
3328 (NH), 3241 (=C–H), 1615, 1585 (C=C, C=N).
1H NMR spectrum, δ, ppm: 2.70 t (2H, OCH2), 3.64 t
(2H, NCH2), 3.80 s (2H, 5-CH2), 3.98 s (1H, OH),
5.36 s (1H, NH), 5.96 s (1H, 4-H), 7.10–7.40 m (5H,
3-(4-Methylphenyl)isoxazol-5-ylmethyl acetate
(IVe). Yield 67%, bp 150–152°C (3 mm), nD20 = 1.5060,
d240 = 1.1086. IR spectrum, ν, cm–1: 3154 (=C–H), 3090
(C–Harom), 1760 (C=O), 1610, 1584, 1570 (C=C,
C=N), 1195 (C–O). 1H NMR spectrum, δ, ppm: 1.36 s
(3H, CH3), 2.31 s (3H, COCH3), 4.10 s (2H, OCH2),
6.51 s (1H, 4-H), 7.17 d and 7.58 d (2H each, Harom).
Found, %: C 67.98; H 5.79; N 6.58. C13H13NO3. Cal-
culated, %: C 67.53; H 5.63; N 6.06.
H
arom). Found, %: C 66.50; H 6.89; N 12.35.
C12H14N2O2. Calculated, %: C 66.05; H 6.42; N 12.84.
2-[3-(4-Methylphenyl)isoxazol-5-ylmethyl-
amino]ethanol (IIIe). Yield 63%, bp 172–173°C
(3 mm), nD20 = 1.5730, d420 = 1.1620. IR spectrum, ν,
cm–1: 3422 (OH), 3291 (NH), 3238 (=C–H), 1620,
1
1575 (C=C, C=N). H NMR spectrum, δ, ppm: 2.59 t
3-Alkyl(aryl)-5-(methoxymethyl)isoxazoles Va,
Vb, and Vd (general procedure). Metallic sodium,
2.3 g (0.1 mol), was dissolved in 50 ml of anhydrous
methanol cooled to –5°C, a solution of 0.1 mol of
isoxazole Ia, Ib, or Id in 20 ml of anhydrous methanol
was added dropwise at 20–25°C, and the mixture was
stirred for 3 h at 25–30°C and treated with a saturated
aqueous solution of sodium carbonate. The organic
phase was separated and washed with water, the aque-
ous phase was extracted with diethyl ether, the extract
was combined with the organic phase, dried over
MgSO4, and evaporated, and the residue was subjected
to vacuum distillation in a stream of nitrogen.
(2H, OCH2), 3.47 t (2H, NCH2), 3.56 s (2H, 5-CH2),
3.85 s (1H, OH), 5.30 s (1H, NH), 5.85 s (1H, 4-H),
7.16 d and 7.68 d (2H each, Harom). Found, %: C 67.70;
H 6.59; N 12.39. C13H16N2O2. Calculated, %: C 67.24;
H 6.70; N 12.07.
3-Alkyl(aryl)-5-acetoxymethylisoxazoles IVa,
IVb, IVd, and IVe (general procedure). Isoxazole Ia,
Ib, Id, or Ie, 0.1 mol, was added dropwise under
stirring to a solution of 16.4 g (0.2 mol) of sodium
acetate in 150 ml of water. The mixture was heated for
5 h under reflux, cooled, and extracted with diethyl
ether. The extract was washed with water, dried over
MgSO4, and evaporated, and the residue was distilled
under reduced pressure in a stream of nitrogen.
5-Methoxymethyl-3-methylisoxazole (Va). Yield
77%, bp 61–62°C (3 mm), Rf 0.70, nD20 = 1.4560,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011