608
R. Islam, Y. Takikawa, and K. T. Lim
Vol 51
2,6-Di-tert-butyl-4-(p-chlorophenyl)-6H-1,3,5-oxathiazine (1b).
Lewis acid-induced thermal reaction of 6H-1,3,5-oxathiazine
S,S-dioxides (3). A toluene solution (20 mL) of 6H-1,3,5-
Colorless crystals, mp 95.5–96.1 ꢀC (decomp.) (Lit. [14],
95.4–96.0 ꢀC decomp.).
oxathiazine S,S-dioxide (3, 1.0 mmol) was treated with Lewis acid
(silica gel or TsOH) (2.0 equiv) at refluxing temperature. The
reaction mixture was quenched with aqueous Na2SO3 solution and
was extracted with chloroform. The mixture was then subjected to
the usual work-up. After removing the solvent in vacuo, the
products 6 and 7 were separated by the silica gel chromatography.
Benzamide (6a). White powder, mp 127–132 ꢀC; (Lit. [18],
130–131 ꢀC).
2,6-Di-tert-butyl-4-(p-fluorophenyl)-6H-1,3,5-oxathiazine (1c).
Colorless plates, mp 55.4–56.6 ꢀC (decomp.) (Lit. [14], 55.5–
56.5 ꢀC decomp.).
2,6-Di-tert-butyl-4-(p-methoxyphenyl)-6H-1,3,5-oxathiazine (1d).
Colorless needles, mp 101.2ꢀC; (Lit. [14], 101ꢀC decomp.).
2,6-Diisopropyl-4-phenyl-6H-1,3,5-oxathiazine (1e). Pale yellow
1
oil, (Lit. [14]); H NMR (CDCl3): d 1.04 (6H, dd, J= 6.2, 6.1 Hz),
1.09 (6H, dd, J= 6.3, 6.2 Hz), 2.06 (1H, quint, J= 6.5 Hz), 2.17
(1H, quint, J= 6.5 Hz), 5.00 (1H, d, J= 1.5 Hz), 5.02 (1H, d,
J= 2.5 Hz), 7.36–7.42 (3H, m), 7.82–7.84 (2H, m).
4-Chloro-benzamide (6b). White powder, mp 176–180 ꢀC (Lit.
[18], 177–181 ꢀC).
2,6-Dimethyl-4-phenyl-6H-1,3,5-oxathiazine (1f). Pale yellow
oil, (Lit. [14]); 1H NMR (CDCl3): d 1.61 (3H, d, J = 6.1 Hz), 1.62
(3H, d, J = 6.2 Hz),5.28(1H,q,J = 6.2 Hz),5.36(1H,q,J = 6.1 Hz),
7.35–7.43(3H,m),7.78–7.81(2H,m).
Preparation of 2,4,6-trisubstituted 6H-1,3,5-oxathiazine
S,S-dioxides (3) by m-CPBA oxidation of 6H-1,3,5-oxathiazines
(1). A chloroform solution (20 mL) of 6H-1,3,5-oxathiazine
(1, 1.0 mmol) was treated with m-CPBA (2.2 equiv) at 0 ꢀC in
the presence of NaHCO3 (2 equiv). The reaction mixture was
quenched with aqueous Na2SO3 solution and was extracted
with chloroform. The mixture was then subjected to the usual
work-up. After removing the solvent in vacuo, the products 3
were purified by the silica gel chromatography in moderate
4-Fluoro-benzamide, (6c). White powder, mp 155–159 ꢀC (Lit.
[18], 154–158 ꢀC).
4-Methoxy-benzamide (6d). collette White powder, mp 163–168 ꢀC
(Lit. [18], 164–167 ꢀC).
Benzonitrile (7a). collette Clear liquid, (Lit. [19]); H NMR
1
(CDCl3) d 7.49 (2H, t), 7.62 (1H, t), 7.66 (2H, d).
4-Chloro-benzonitrile (7b). collette Pale yellow crystalline
solid, mp 92–96 ꢀC (Lit. [19], 92–94 ꢀC).
4-Fluoro-benzonitrile (7c). Colorless solid, mp 32–36 ꢀC
(Lit. [20], 33–36 ꢀC).
4-Methoxy-benzonitrile (7d). White crystalline powder, mp
55–62 ꢀC (Lit. [19], 60–62 ꢀC).
Preparation of 2,4,6-trisubstituted 6H-1,3,5-oxathiazine S-oxides
(2) by m-CPBA oxidation of 6H-1,3,5-oxathiazines (1).
A
yield as single epimers (3a–d).
chloroform solution (20 mL) of 6H-1,3,5-oxathiazine (1, 1.0 mmol)
was treated with m-CPBA (1.1 equiv) at 0 ꢀC in the presence of
NaHCO3 (2equiv). The reaction mixture was quenched with
aqueous Na2SO3 solution and was extracted with chloroform. The
mixture was then subjected to the usual work-up. After removing
the solvent in vacuo, product 2 was found in almost quantitative
yield as single epimers (2a–d).
2,6-Di-tert-butyl-4-phenyl-6H-[1,3,5]oxathiazine S,S-dioxide (3a).
Colorless needles; mp 135–137 ꢀC (decomp.); MS m/z 238 (M+ À
tBuCHO + 1; 6%), 70 (M+ À C6H5CN À tBuCHO À SO2; 100%);
IR (KBr): 2977, 1661, 1625, 1478, 1364, 1309, 1201, 1131, 1093,
1062, 999, 766 cmÀ1; 1H NMR (CDCl3): d 1.10 (9H, s), 1.25 (9H,
s), 4.48 (1H, s), 4.83 (1H, s), 7.38–7.53 (3H, m), 8.01–8.04 (2H,
m); 13C NMR (CDCl3): d 25.3 (q), 25.9 (q), 36.3 (s), 37.3 (s), 98.2
(d), 98.4 (d), 128.4 (d), 128.5 (d), 129.7 (s), 131.7 (d), 158.8 (s);
Calcd for C17H25NO3S: C, 63.13; H, 7.79; N, 4.33%; Found: C,
63.22; H, 7.81; N, 4.36%.
2,6-Di-tert-butyl-4-phenyl-6H-1,3,5-oxathiazine S-oxide (2a).
1
Pale yellow oil, (Lit. [14]); H NMR (CDCl3) d 1.02 (9H, s),
1.22 (9H, s), 4.25 (1H, s), 4.99 (1H, s), 7.41–7.48 (3H, m),
7.91–7.94 (2H, m).
2,6-Di-tert-butyl-4-(4-chlorophenyl)-6H-[1,3,5]oxathiazine S,
S-dioxide (3b). Colorless needles; mp 135–137 ꢀC (decomp.);
MS m/z 155 (M+ À ClC6H4CN-SO2 À 1; 63%), 139 (M+ À tBu-
CHO À SO2-tBuCH+ 2; 100%); IR (KBr) 2977, 1622, 1489,
2,6-Di-tert-butyl-4-(p-chlorophenyl)-6H-1,3,5-oxathiazine S-oxide
(2b). Pale yellow oil, (Lit. [14]); 1H NMR (CDCl3) d 1.01 (9H, s),
1.18 (9H, s), 4.24 (1H, s), 4.98 (1H, s), 7.43 (2H, br d, J =8.0 Hz),
7.87 (2H, br d, J = 8.0Hz).
1
1306, 1134, 1095cmÀ1; H NMR (CDCl3) d 1.09 (9H, s), 1.25
(9H, s), 4.48 (1H, s), 4.83 (1H, s), 7.41 (2H, d, J = 6.8 Hz), 8.00
(2H, d, J = 6.8 Hz); 13C NMR (CDCl3) d 25.3 (q), 25.9 (q), 36.3
(s), 37.3 (s), 98.4 (d), 98.5 (d), 128.1 (s), 128.9 (d), 129.7 (d),
158.0 (s), 170.3 (s); Calcd for C17H24ClNO3S: C, 57.05; H, 6.76;
N, 3.91%; Found: C, 57.21; H, 6.79; N, 3.96%.
2,6-Di-tert-butyl-4-(p-fluorophenyl)-6H-1,3,5-oxathiazine S-
oxide (2c). Pale yellow oil, (Lit. [14]); 1H NMR (CDCl3) d 1.01
(9H, s), 1.19 (9H, s), 4.25 (1H, s), 4.98 (1H, s), 7.12 (2H, t,
J = 8.7 Hz), 7.96 (2H, dd, J = 8.7, J = 5.4 Hz).
2,6-Di-tert-butyl-4-(p-methoxyphenyl)-6H-1,3,5-oxathiazine
S-oxide (2d). Colorless prisms, mp 85–86ꢀC; (Lit. [14], 84–85ꢀC
decomp.).
2,6-Di-tert-butyl-4-(4-fluorophenyl)-6H-[1,3,5]oxathiazine S,
S-dioxide (3c). Colorless needles; mp 143–145 ꢀC (decomp.);
MS m/z 325 (M+ À O; 5%), 204 (M+ À FC6H4CNO; 100%); IR
Thermal reaction of 6H-1,3,5-oxathiazine S-oxides (2).
A
1
(KBr) 2977, 1623, 1485, 1307, 1131, 1094, 1001 cmÀ1; H NMR
benzene solution (20 mL) of 6H-1,3,5-oxathiazine S-oxide (2,
1.0 mmol) was heated at refluxing temperature for 4–6 h, and
the reaction mixture was cooled to room temperature. After
removing the solvent in vacuo, 5H-1,2,4-oxathiazoles 4a–d
were obtained as pure products in high yields.
(CDCl3) d 1.05 (9H, s), 1.25 (9H, s), 4.48 (1H, s), 4.82 (1H, s), 7.11
(2H, t, J= 8.6 Hz), 8.03–8.07 (2H, m); 13C NMR (CDCl3) d 25.4 (q),
25.9 (q), 36.4 (s), 37.4 (s), 98.4 (d), 98.5 (d), 115.7 (d), 115.9 (d),
130.7 (s), 130.8 (s), 157.8 (s), 165.5 (d, J= 254.3 Hz); Calcd for
C17H24FNO3S: C, 59.80; H, 7.08; N, 4.10%; Found: C, 59.92; H,
7.11; N, 4.12%.
5-tert-Butyl-3-phenyl-5H-1,2,4-oxathiazole (4a). Pale yellow
1
oil, (Lit. [14]); H NMR (CDCl3) d 1.08 (9H, s), 5.89 (1H, s),
2,6-Di-tert-butyl-4-(p-methoxyphenyl)-6H-1,3,5-oxathiazine S,
S-dioxide (3d). Colorless crystals; mp 121–123 ꢀC (decomp.); MS
m/z 233 (M+ À tBuCHOS À 2; 12%), 201 (M+ À MeOC6H4CN À
tBuCH À 2; 100%); IR (KBr) 2978, 1621, 1488, 1305, 1137,
7.40–7.46 (3H, m), 7.46–7.57 (2H, m).
5-tert-Butyl-3-(p-chlorophenyl)-5H-1,2,4-oxathiazole (4b). Pale
yellow oil, (Lit. [14]); 1H NMR (CDCl3) d 1.09 (9H, s), 5.87 (1H, s),
7.42 (2H, br d, J= 8.0 Hz), 7.51 (2H, br d, J=8.0Hz).
1097 cmÀ1 1H NMR (CDCl3): d 1.04 (9H, s), 1.12 (9H, s),
;
5-tert-Butyl-3-(p-fluorophenyl)-5H-1,2,4-oxathiazole (4c). Pale
yellow oil, (Lit. [14]); 1H NMR (CDCl3) d 1.09 (9H, s), 5.86
(1H, s), 7.12 (2H, t, J = 8.6 Hz), 7.58 (2H, dd, J = 8.6, J = 5.3 Hz).
5-tert-Butyl-3-(p-methoxyphenyl)-5H-1,2,4-oxathiazole (4d). Pale
yellow oil, (Lit. [14]); 1H NMR (CDCl3) d 1.06 (9H, s), 3.83 (3H, s),
5.85 (1H, s), 6.92(2H, d, J= 8.7 Hz), 7.52 (2H, d, J=8.5Hz).
3.86 (3H,s), 4.09 (1H,s), 5.42 (1H,s), 6.94 (2H,d, J = 8.9 Hz),
7.58 (2H, d, J = 8.9 Hz); 13C NMR (CDCl3):d 24.4 (q) 26.2
(q), 33.0 (s), 34.0 (s), 55.5 (q), 88.8 (d), 104.1 (d), 114.7
(d), 114.8 (s), 120.3 (s), 133.9 (d), 162.8 (s); Calcd for
C18H27NO4S: C, 61.16; H, 7.70; N, 3.96%; Found: C,
61.24; H, 7.74; N, 3.98%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet