3360 J . Org. Chem., Vol. 61, No. 10, 1996
Bertolini et al.
5-P h e n yl-3-isop r op yl-2,3-d ih yd r o-1,3-oxa zin -4-on e
0.6H), 1.31 (d, 2.4H). Anal. Calcd for C12H15NO2: C, 74.58;
H, 7.82; N, 7.25. Found: C, 74.76; H, 7.72; N, 7.31.
3-Acetyl-1,3-oxa zolid in e (7c): yield 97%; Rf ) 0.30 (C-A
(5b): Rf ) 0.35 (H-E 8:2); mp 71-72 °C (hexane); IR (cm-1
KBr) 1655, 1615, 1605; 1H NMR (DMSO-d6) δ 7.62 (s, 1H),
,
7.54-7.25 (m, 5H), 5.26 (s, 2H), 4.59 (m, 1H), 0.62 (d, 6H); 13
C
8:2); oil; H NMR (DMSO-d6) δ 4.89 (s, 0.7H), 4.79 (s, 1.3H),
1
NMR (DMSO-d6) δ 161.6, 154.8, 133.4, 128.6, 128.2, 127.2,
116.7, 74.2, 42.9, 20.3. Anal. Calcd for C13H15NO2: C, 71.87;
H, 6.96; N, 6.45. Found: C, 72.14; H, 7.05; N, 6.39.
4.07 (t, 0.7H), 3.99 (t, 1.3H), 3.51 (t, 1.3H), 3.40 (t, 0.7H), 2.02
(s, 1.9H), 1.99 (s, 1.1H). Anal. Calcd for C5H9NO2: C, 52.11;
H, 7.88; N, 12.17. Found: C, 52.01; H, 7.93; N, 12.09.
Gen er a l P r oced u r e for th e Syn th esis of 3-(3-Hyd r oxy-
p r op -2-en oyl)-1,3-oxa zolid in es 8a -c. A solution of 7 (20
mmol) in THF (65 mL) was slowly added to a suspension of
NaH (530 mg, 22 mmol) in THF (65 mL) followed by ethyl
formate (8a and 8b) or ethyl benzoate (8c) (100 mmol). Then
the reaction mixture was refluxed for 5 h. After evaporation
of the solvent, the crude product was dissolved in aqueous HCl
(1 N) and extracted with AcOEt. The crude material was
purified to give pure 8.
3-(3-H yd r oxy-2-p h en ylp r op -2-en oyl)-1,3-oxa zolid in e
(8a ): yield 81%; Rf ) 0.35 (C-A 9:1); oil; 1H NMR (DMSO-d6)
δ 7.40-7.10 (m, 6H), 4.60 (m, 2H), 4.00-3.00 (m, 4H). Anal.
Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: C,
65.33; H, 5.71; N, 6.13.
5-P h en yl-3-cyclop r op yl-2,3-d ih yd r o-1,3-oxa zin -4-on e
(5c): Rf ) 0.30 (H-E 7:3); mp 91-93 °C (hexane); IR (cm-1
,
KBr) 1665, 1640, 1600; 1H NMR (DMSO-d6) δ 7.60 (s, 1H),
7.51 (m, 2H), 7.41-7.26 (m, 3H), 5.21 (s, 2H), 2.62 (m, 1H),
0.85-0.63 (m, 4H); 13C NMR (DMSO-d6) δ 163.9, 155.1, 133.2,
128.7, 128.1, 127.23, 116.3, 79.4, 26.6, 7.1. Anal. Calcd for
C13H13NO2: C, 72.54; H, 6.09; N, 6.51. Found: C, 72.56; H,
6.18; N, 6.59.
5-P h en yl-3-cycloh exyl-2,3-d ih yd r o-1,3-oxa zin -4-on e
(5d ): Rf ) 0.40 (H-E 8:2); mp 94-96 °C (hexane); IR (cm-1
,
KBr) 1640, 1620, 1605; 1H NMR (DMSO-d6) δ 7.61 (s, 1H),
7.53-7.24 (m, 5H), 5.25 (s, 2H), 4.18 (m, 1H), 1.83-1.03 (m,
10H); 13C NMR (DMSO-d6) δ 161.6, 154.8, 133.4, 128.6, 128.2,
127.2, 116.8, 74.8, 50.9, 30.3, 25.7, 25.1. Anal. Calcd for
C16H19NO2: C, 74.68; H, 7.44; N, 5.44. Found: C, 74.86; H,
7.51; N, 5.39.
2-Met h yl-3-(3-h yd r oxy-2-p h en ylp r op -2-en oyl)-1,3-ox-
1
a zolid in e (8b): yield 76%; Rf ) 0.40 (C-A 9:1); oil; H NMR
(DMSO-d6) δ 7.50-7.10 (m, 6H), 5.40-5.20 (m, 1H), 4.10-3.20
(m, 4H), 1.40-1.20 (m, 3H). Anal. Calcd for C13H15NO3: C,
67.50; H, 6.54; N, 6.06. Found: C, 67.42; H, 6.41; N, 6.01.
3-(3-H yd r oxy-3-p h en ylp r op -2-en oyl)-1,3-oxa zolid in e
(8c): yield 38%; Rf ) 0.40 (C-A 8:2); mp 73-78 °C (Et2O); 1H
NMR (DMSO-d6) δ 7.81 (d, 2H), 7.50 (m, 3H), 6.10 (m, 1H),
5.10-4.70 (m, 2H), 4.10-3.00 (m, 4H). Anal. Calcd for
C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: C, 65.53; H,
5.82; N, 6.26.
Gen er a l P r oced u r e for th e Syn th esis of 2,3-Dih yd r o-
3-(2-h yd r oxyeth yl)-1,3-oxa zin -4-on e (9a -c). A 2 N solu-
tion of HCl in ethyl ether (10 mL, 20 mmol) was added to a
solution of 8 (10 mmol) in AcOEt (50 mL). Then the mixture
was stirred for 8-24 h at room temperature. After evaporation
of the solvent, the crude product was purified to give pure 9.
2,3-Dih yd r o-3-(2-h yd r oxyeth yl)-5-p h en yl-1,3-oxa zin -4-
on e (9a ): yield 40%; Rf ) 0.30 (H-E 1:1); oil; 1H NMR
(DMSO-d6) δ 7.63 (s, 1H), 7.50 (d, 2H), 7.35 (m, 3H), 5.31 (s,
2H), 3.52 (m, 4H). Anal. Calcd for C12H13NO3: C, 65.74; H,
5.98; N, 6.39. Found: C, 65.85; H, 5.87; N, 6.43.
3,5-Dip h en yl-2,3-d ih yd r o-1,3-oxa zin -4-on e (5e): Rf
)
0.35 (H-E 8:2); mp 141-144 °C (hexane); IR (cm-1, KBr) 1660,
1620, 1600; 1H NMR (DMSO-d6) δ 7.82 (s, 1H), 7.58-7.25 (m,
10H), 5.69 (s, 2H); 13C NMR (DMSO-d6) δ 161.7, 156.0, 139.5,
133.0, 129.1, 128.8, 128.3, 127.5, 126.4, 125.4, 116.7, 80.4.
Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N, 5.57.
Found: C, 76.24; H, 5.05; N, 5.39.
5-P h en yl-3-ben zyl-2,3-d ih yd r o-1,3-oxa zin -4-on e (5f): Rf
) 0.25 (H-E 8:2); mp 83-85 °C; IR (cm-1, KBr) 1660, 1640,
1600; 1H NMR (DMSO-d6) δ 7.67 (s, 1H), 7.54 (m, 2H), 7.42-
7.26 (m, 8H), 5.31 (s, 2H), 4.66 (m, 2H); 13C NMR (DMSO-d6)
δ 162.2, 155.2, 137.8, 133.1, 128.9, 128.6, 128.2, 127.7, 127.5,
127.3, 116.4, 78.6, 47.1. Anal. Calcd for C17H15NO2: C, 76.95;
H, 5.70; N, 5.28. Found: C, 76.77; H, 5.58; N, 5.19.
5-P h en yl-3-h exyl-2,3-d ih yd r o-1,3-oxa zin -4-on e (5g): Rf
) 0.40 (H-E 8:2); oil; IR (cm-1, neat) 1660, 1640, 1600; 1H
NMR (DMSO-d6) δ 7.62 (s, 1H), 7.50 (m, 2H), 7.39-7.24 (m,
3H), 5.27 (s, 2H), 3.40 (m, 2H), 1.51 (m, 2H), 1.29 (m, 6H),
0.88 (t, 3H); 13C NMR (DMSO-d6) δ 162.0, 154.8, 133.3, 128.5,
128.2, 127.2, 116.5, 78.6, 43.8, 31.2, 28.2, 26.2, 22.3, 14.2.
Anal. Calcd for C16H21NO2: C, 74.10; H, 8.16; N, 5.40.
Found: C, 73.97; H, 8.24; N, 5.28.
2,3-Dih yd r o-3-(2-h yd r oxyeth yl)-2-m eth yl-5-p h en yl-1,3-
1
oxa zin -4-on e (9b): yield 36%; Rf ) 0.40 (H-E 1:1); oil; H
NMR (DMSO-d6) δ 7.50 (m, 3H), 7.31 (m, 3H), 5.62 (q, 1H),
3.68 (m, 1H), 3.57 (m, 2H), 3.31 (m, 1H), 1.64 (d, 3H). Anal.
Calcd for C13H15NO3: C, 67.50; H, 6.54; N, 6.06. Found: C,
67.65; H, 6.71; N, 6.12.
2-Met h yl-5-p h en yl-3-p r op yl-2,3-d ih yd r o-1,3-oxa zin -4-
on e (5h ): Rf ) 0.35 (H-E 8:2); oil; IR (cm-1, neat) 1660, 1645,
1
1610; H NMR (DMSO-d6) δ 7.48 (m, 2H), 7.46 (s, 1H), 7.32
(m, 3H), 5.59 (q, 1H), 3.33 (m, 2H), 1.58 (d, 3H), 1.54 (m, 2H),
0.87 (t, 3H); 13C NMR (DMSO-d6) δ 161.3, 152.4, 133.4, 128.5,
128.1, 127.1, 115.2, 85.4, 43.9, 21.7, 18.1, 11.5. Anal. Calcd
for C14H17NO2: C, 72.70; H, 7.41; N, 6.06. Found: C, 72.65;
H, 7.59; N, 6.16.
2,3-Dih yd r o-3-(2-h yd r oxyeth yl)-6-p h en yl-1,3-oxa zin -4-
on e (9c): yield 35%; Rf ) 0.25 (H-E 1:1); mp 97-101 °C
(Et2O); 1H NMR (DMSO-d6) δ 7.79 (d, 2H), 7.50 (m, 3H), 6.07
(s, 1H), 5.39 (s, 2H), 3.50 (m, 4H). Anal. Calcd for C12H13
-
NO3: C, 65.74; H, 5.98; N, 6.39. Found: C, 65.82; H, 5.92; N,
6.16.
Gen er a l P r oced u r e for th e Syn th esis of 3-Acyl-1,3-
oxa zolid in es 7a -c. A suspension of paraformaldehyde or
paraldehyde (80 mmol), N-(2-hydroxyethyl) amide 69 (20
mmol), and p-toluenesulfonic acid (380 mg, 2 mmol) in
toluene-THF 2:1 (60 mL) was refluxed for 1 h. The solid was
filtered off, and the organic phase was washed with aqueous
NaOH and water and finally dried. The crude product was
purified to give pure 7. 1H NMR spectra of compounds 7a -c
are characterized by two sets of peaks due to the configura-
tional isomers of the secondary amide.
Gen er a l P r oced u r e for th e Syn th esis of 2,3-Dih yd r o-
3-(2-ch lor oeth yl)-1,3-oxa zin -4-on e (10a -c). Thionyl chlo-
ride (700 µL, 9.6 mmol) was slowly added at 0 °C to a solution
of 9 (8 mmol) in CHCl3 (40 mL), and the solution was stirred
at room temperature for 3 h. The solvent was removed, and
the crude product was dissolved in fresh CHCl3 (50 mL) and
evaporated to dryness three times. Purification of the crude
product gave pure 10.
2,3-Dih yd r o-3-(2-ch lor oet h yl)-5-p h en yl-1,3-oxa zin -4-
on e (10a ): yield 92%; Rf ) 0.30 (H-E); oil; 1H NMR (DMSO-
d6) δ 7.63 (s, 1H), 7.50 (d, 2H), 7.35 (m, 3H), 5.33 (s, 1H), 3.79
(s, 4H). Anal. Calcd for C12H12ClNO2: C, 60.64; H, 5.09; Cl,
14.92; N, 5.89. Found: C, 60.35; H, 5.17; Cl, 14.73; N, 5.77.
2,3-Dih yd r o-3-(2-ch lor oet h yl)-2-m et h yl-5-p h en yl-1,3-
oxa zin -4-on e (10b): yield 96%; Rf ) 0.40 (H-E); oil; 1H NMR
(DMSO-d6) δ 7.57 (s, 1H), 7.50 (d, 2H), 7.33 (m, 3H), 5.80 (q,
1H), 3.90 (m, 1H), 3.79 (m, 2H), 3.55 (m, 1H), 1.64 (d, 3H).
Anal. Calcd for C13H14ClNO2: C, 62.03; H, 5.61; Cl, 14.09; N,
5.57. Found: C, 62.36; H, 5.47; Cl, 14.25; N, 5.67.
2,3-Dih yd r o-3-(2-ch lor oet h yl)-6-p h en yl-1,3-oxa zin -4-
on e (10c): yield 86%; Rf ) 0.35 (H-E); mp 124-127 °C (Et2O);
3-(P h en yla cetyl)-1,3-oxa zolid in e (7a ): yield 80%; Rf )
1
0.30 (C-A 9:1); oil; H NMR (DMSO-d6) δ 7.28 (m, 5H), 4.99
(s, 0.8H), 4.83 (s, 1.2H), 4.04 (t, 1.2H), 3.98 (t, 0.8H), 3.69 (s,
1.2H), 3.60 (s, 0.8H), 3.59 (t, 1.2 H), 3.40 (t, 0.8H). Anal. Calcd
for C11H13NO2: C, 69.09; H, 6.85; N, 7.33. Found: C, 68.85;
H, 6.81; N, 7.25.
2-Met h yl-3-(p h en yla cet yl)-1,3-oxa zolid in e (7b ): yield
1
52%; Rf ) 0.35 (C-A 9:1); oil; H NMR (DMSO-d6) δ 7.28 (m,
5H), 5.66 (q, 0.2H), 5.29 (q, 0.8H), 4.10-3.10 (m, 6H), 1.34 (d,
(9) Prepared by mixing the corresponding ethyl esters and ethanol-
amine at 70 °C for several hours.