Methyl 4-benzyl-2-ethoxycarbonylmethylene-2,3-dihydro-6-
methyl-6H-1,3-thiazine-5-carboxylate 5
NH); δC(C2HCl3; 125.7 MHz) 13.9 (CH3CH2O), 15.8 and 16.4
(2 × CH CH᎐), 49.8 and 49.9 (2 × CH C᎐S), 51.8 (CH O), 61.6
᎐
᎐
3
2
2
Freshly prepared methyl 2-ethylidene-3-oxo-4-phenylbutyrate 9
(2.07 g, 9.50 mmol) and ethoxycarbonylthioacetamide 11 (1.39
g, 9.50 mmol) were dissolved in dry 1,4-dioxane (25 cm3) and
the solution was saturated with dry hydrogen chloride gas at
0 ЊC. The solution was left overnight at room temperature and
the solvent was removed in vacuo to give an orange gum. Chro-
matographic purification (silica gel, dichloromethane) gave the
dihydrothiazine 5 as a yellow solid, which was recrystallised
from ethanol to afford yellow crystals (2.35 g, 71%); mp 80–
81 ЊC (Found: C, 62.38; H, 6.38; N, 3.71. C18H21NO4S requires
and 61.7 (2 × CH3O), 127.7, 128.1, 128.3, 128.5 and 128.6
(aromatic carbons), 130.4 [HN᎐C᎐C(H)Ph], 130.6 [HN᎐C᎐
᎐
᎐
C(H)Ph], 139.4 (CH CH᎐C᎐CO CH ), 143.8 (CH CH᎐C᎐
᎐
᎐
3
2
3
3
CO CH ) 166.1 and 168.9 (2 × O᎐C᎐O), 193.1 (C᎐S).
᎐
᎐
2
3
Ethyl 2-ethylidene-3-oxo-3-phenylpropanoate 1011
Ethyl benzoylacetate (19.20 g, 0.1 mol) was cooled to Ϫ20 ЊC
and freshly distilled acetaldehyde (4.40 g, 0.1 mol) was added
with stirring. Piperidine (0.15 g) was added dropwise over a
period of 10 min keeping the temperature below Ϫ10 ЊC. The
reaction mixture was left at Ϫ10 ЊC for 24 h. The reaction mix-
ture was dissolved in diethyl ether washed with dilute aqueous
acetic acid followed by water and the organic extract was dried.
The solvent was removed in vacuo to give a clear oil which was
C, 62.22; H, 6.10; N, 4.03%); m/z 345 [(M Ϫ 2)ϩ ], 256
ؒ
[(M Ϫ C6H7)ϩ]; λmax(MeOH)/nm 194 (ε/dm3 molϪ1 cmϪ1 891),
338 (ε 31 520); νmax(Nujol mull)/cmϪ1 1709 and 1697 (O᎐C᎐O),
᎐
1660 (conjugated double bond), 1578 (NH bend); δH(C2HCl3;
500 MHz) 1.24 (3H, t, J 7.16, CH3CHaHbO), 1.41 (3H, d, J 6.95
CH3CH), 3.77 (3H, s, CH3O), 4.11 (2H, dq, J 7.16 for CHaHbO,
1H, q partially hidden, CH CH᎐), 4.17 and 4.28 (2H, 2 × d, J
1
distilled to give a clear liquid. The H NMR spectrum showed
both the Z- and E-isomers in a ratio of 17:83 (14.02 g, 64%);
bp 136–138 ЊC/2 mmHg; m/z 219 [(M ϩ H)ϩ ], 145
ؒ
᎐
3
14.86, CH Ph), 5.02 (1H, s, C᎐CH), 7.29 (5H, m, aromatic pro-
[(M Ϫ C2H5CO2)ϩ], 172 [(M Ϫ EtOH)ϩ]; δC(C2HCl3; 500 MHz)
Z-isomer (minor), 1.09 (3H, t, J 7.50, CH3CH2O), 2.14 (3H, d,
J 7.50, CHCH3), 4.14 (2H, q, J 7.50, CH2O), 6.75 (1H, q, J 7.50,
CH3CH), 7.68 (5H, m, aromatic protons); E-isomer (major),
1.21 (3H, t, J 7.50, CH3CH2O), 1.75 (3H, d, J 7.50, CHCH3),
4.14 (2H, q, J 7.50, CH2O), 7.31 (1H, q, J 7.50, CH3CH), 7.68
(5 H, m, aromatic protons). Some starting material was also
present.
᎐
2
tons), 10.97 (1H, br s, NH); δC(C2HCl3; 125.7 MHz) 14.35
(CH3CH2O), 22.59 (CHCH3), 32.91 (CHCH3), 38.51 (CH2Ph),
51.61 (CO CH ), 59.56 (CH O), 90.82 (exocyclic C᎐C᎐H),
᎐
2
3
2
105.65 (ring HN᎐C᎐C), 126.88 (aromatic meta and para car-
᎐
bons), 128.75 (aromatic ortho carbons), 136.85 (aromatic ipso
carbons), 147.49 (ring BnC᎐C), 151.41 (N᎐C᎐S), 166.08 and
᎐
168.59 (2 × O᎐C᎐O).
᎐
2-(Ethoxycarbonylthioacetamido)-3-methoxycarbonyl-1-phenyl-
penta-2,4-dienes 15–18
Ethyl 2-ethoxycarbonylmethylene-2,3-dihydro-6-methyl-4-
phenyl-6H-1,3-thiazine-5-carboxylate 6
The dihydrothiazine 5 (0.39 g, 1.13 mmol) was photolysed in a
similar manner to compound 3. The reaction was monitored by
following reduction of the absorption at λmax 338 nm in the UV
spectrum due to the dihydrothiazine 5. TLC showed the reac-
tion to be complete within 3 h and the solvent was removed in
vacuo to give a dark oil which, after column chromatography
(silica gel, diethyl ether–light petroleum, 60–80 ЊC, 1:1) gave
two different components 18 and 15–17 both as pale oils which
failed to crystallise.
Freshly prepared ethyl 2-ethylidene-3-oxo-3-phenylpropanoate
10 (1.67 g, 7.66 mmol) and ethoxycarbonylthioacetamide 11
(1.13 g, 7.69 mmol) were dissolved in dry 1,4-dioxane (25 cm3)
and the solution was saturated with dry hydrogen chloride gas
at 0 ЊC. The solution was left to stand overnight at room tem-
perature and the solvent was removed in vacuo to give an orange
gum. Chromatographic purification (silica gel, dichlorometh-
ane) gave the dihydrothiazine 6 as a yellow solid, which was
recrystallised from ethanol to afford yellow crystals (2.04 g,
77%); mp 86–87 ЊC (Found: C, 62.23; H, 5.87; N, 3.84.
C18H21NO4S requires C, 62.22; H, 6.10; N, 4.03%); m/z 347
Isomer 18 (0.035 g, 9%); m/z 347 [(M)ϩ ], 315 [(M Ϫ
ؒ
CH3OH)ϩ], 302 [(M Ϫ OEt)ϩ], 269 [(M Ϫ C6H6)ϩ], 242 {[M Ϫ
(Ph ϩ C2H5)]ϩ}; λmax(MeOH)/nm 208 (ε/dm3 molϪ1 cmϪ1 9170),
270 (ε 8450) this chromophore also showed a considerable
shoulder; νmax(CCl4 liquid film)/cmϪ1 3270–2950 (NH), 1722
(Mϩ ), 314 {[M Ϫ (H2O ϩ CH3)]ϩ}, 301 {[M Ϫ (C2H4 ϩ
ؒ
H2O)]ϩ}, 242{[M Ϫ (Ph ϩ C2H5)]ϩ}; λmax(MeOH)/nm 222 (ε/
dm3 molϪ1 cmϪ1 7255), 344 (ε 21 229); νmax(Nujol mull)/cmϪ1
(O᎐C᎐O), 1634 (conjugated double bond), 1575 (aromatic
1690 (O᎐C᎐O), 1661 (conjugated double bond), 1573 (NH
᎐
᎐
C᎐C), 1029 (C᎐S); δ (C2HCl ; 500 MHz) 1.28 (3H, t, J 7.50,
bend); δH(C2HCl3; 500 MHz) 0.87 and 1.26 (2 × 3H, 2 × t,
J 7.15, 2 × CH3CHaHbO), 1.55 (3H, d, J 6.97, CH3CH), 3.92
(2H, q, J 7.12, exocyclic CH2O), 4.12 (2H, d × q, J 7.15 and
᎐
᎐
H
3
CH CH O), 1.69 (3H, d, J 7.50, CH CH᎐), 3.81 (3H, s, CH O),
᎐
3
2
3
3
3.92 (2H, s, CH C᎐S), 4.23 (2H, q, J 7.50, CH O), 7.15 (1H, q,
᎐
2
2
J 7.50, CH CH), 7.27 (5H, m, Ph᎐CH᎐), 7.45 (1H, s, Ph᎐CH᎐),
6.97 CH H O and 1H, q, J 6.97 CH CH), 5.13 (1H, s, C᎐CH),
᎐
a b 3
᎐
᎐
3
10.40 (1H, br s, hydrogen bonded NH); δC(C2HCl3; 125.7 MHz)
13.9 (CH3CH2O), 16.1 (CH CH᎐), 50.2 (CH C᎐S), 52.1
7.35–7.44 (aromatic protons), 10.92 (1H, br s, NH); δC(C2HCl3;
125.7 MHz) 13.56 and 14.36 (2 × CH3CH2O), 22.71 (CHCH3),
33.39 (CHCH3), 59.60 and 60.12 (2 × CH2O), 90.83 (exocyclic
᎐
᎐
2
3
(CH2O), 61.7 (CH3O), 127.6 (aromatic meta and para carbons),
128.3 (aromatic ortho carbons), 128.5 (aromatic ipso carbon),
C᎐C᎐H), 105.47 (ring HN᎐C᎐C), 128.35 (aromatic meta
᎐
᎐
129.0 [HN᎐C᎐C(H)Ph], 130.4 [HN᎐C᎐C(H)Ph], 134.9 (CH -
and para carbons), 129.49 (aromatic ortho protons), 137.11
(aromatic ipso protons), 146.68 (ring PhC᎐C), 151.33 (N᎐C᎐S),
᎐
᎐
3
CH᎐C᎐CO CH ), 145.5 (CH CH᎐C᎐CO CH ), 166.4 and
᎐
᎐
᎐
2
3
3
2
3
169.8 (2 × O᎐C᎐O), 191.4 (C᎐S).
166.39 and 168.76 (2 × O᎐C᎐O).
᎐
᎐
᎐
Isomers 15–17 (0.13 g, 33% isolated); m/z 347 [(M)ϩ ], 315
[(M Ϫ CH3OH)ϩ], 302 [(M Ϫ OEt)ϩ], 269 [(M Ϫ C6H6)ϩ];
λmax(MeOH)/nm 212 (ε/dm3 molϪ1 cmϪ1 15 903), 270 (ε 15 758)
this chromophore also showed a slight shoulder; νmax(CCl4
ؒ
Ethyl 2-ethoxycarbonylmethylene-5,6-dihydro-5-methyl-4-
phenyl-2H-1,3-thiazine-6-carboxylate 20
The dihydrothiazine 6 (0.31 g, 0.89 mmol) was photolysed in
a similar manner to compound 3. The reaction was moni-
tored by the gradual disappearance of the absorption at λmax
344 nm in the UV spectrum due to the dihydrothiazine 6.
After the reaction was complete (3 h) the solvent was
removed in vacuo to give a dark oil which after column
chromatography (silica gel, diethyl ether–light petroleum 60–
80 ЊC, 1:1) gave a pale oil which failed to crystallise (0.16 g,
liquid film)/cmϪ1 3273–2908 (NH), 1725 (O᎐C᎐O), 1636 (con-
᎐
jugated double bond), 1048 and 1028 (C᎐S); δ (C2HCl ; 500
᎐
H
3
MHz) 1.29 (2 × 3H, 2 × t, J 7.50, 2 × CH3CH2O), 2.05, 2.10
and 2.15 [3 × 3H (isomer ratio 15:16:17, 20:9:1), 3 × d,
J 7.50, 3 × CH CH᎐], 3.80 [5H (isomer ratio 15:16:17,
᎐
3
20:9:1), 6 × s, 3 × CO CH ϩ 3 × 2H, s, CH C᎐S], 4.19 (4H,
᎐
2
2
3
2 × q, J 7.50, 2 × CH2O), 6.33, 6.50 and 6.65 (3 × 1H, 3 × s,
3 × PhCH᎐), 6.43 (1H, q, J 7.50, minor isomer 16 CH CH),
46%); m/z 347 (Mϩ ), 302 [(M Ϫ OEt) ], 274 [(M Ϫ CO2Et) ];
λmax(MeOH)/nm 208 (ε/dm3 molϪ1 cmϪ1 1332), 230 (ε 1367),
290 (ε 1799), 338 (ε 1490); νmax(CH3Cl2 liquid film)/cmϪ1
ϩ
ϩ
ؒ
᎐
3
7.20 (1H, q, J 7.50, major isomer 15 CH3CH), 7.34 (5H, m,
Ph᎐CH᎐), 10.0 and 10.1 (2H, 2 × br s, 2 × hydrogen bonded
᎐
J. Chem. Soc., Perkin Trans. 1, 1998
573