754
S. Pandey et al. / European Journal of Medicinal Chemistry 40 (2005) 751–756
followed by aqueous KOH solution (1.12 gm, 20 mmol in
0 ml water) and the resulting reaction mixture was stirred at
To a solution of 1,1-bis(methylthio)-pent-1-en-3-one
(2.43 gm, 15 mmol) in methanol (50 ml) was added 8a
(2.09 gm, 15 mmol) followed by aqueous KOH solution
(1.65 gm, 30 mmol in 15 ml water) and the resulting reaction
mixture was stirred at room temperature for 12 h. It was con-
centrated in vacuo, poured into water and extracted with
dichloromethane (50 ml × 3). The combined extract was
washed with water (3 × 75 ml), brine solution (2 × 50 ml),
dried (Na SO ) and the solvent was removed in vacuo. The
1
room temperature for 12 h. It was concentrated in vacuo,
poured into water (100 ml) and extracted with dichlo-
romethane (50 ml × 3). The combined extract was washed
with water (100 ml × 2), brine (2 × 50 ml), dried (Na SO )
2
4
and the solvent was removed in vacuo. The crude product
was column chromatographed (SiO , 60–120 mesh). Elution
2
with 25% ethyl acetate in hexane furnished 6c as a pale yel-
2
4
low crystalline solid (1.92 gm, 56.47%); m.p. 130–131 °C;
IR (KBr, cm ) 1704, 1600, 1488; H NMR (200 MHz,
crude product was purified by column chromatography (SiO2,
60–120 mesh). Elution with 20% ethyl acetate in hexane fur-
nished 9a as a yellow crystalline solid (2.7 gm, 51%); m.p.
–
1
1
CDCl ) d 2.50 (s, 6H), 3.75 (s, 3H), 3.80 (s, 6H), 6.20 (s,
3
–
1
1
H), 6.65 (d, J = 16.00 Hz, 1H), 6.70 (s, 2H), 7.55 (d,
148–150 °C; IR (KBr, cm ) 2938, 1640, 1587, 1438, 1239,
1
3
1
J = 16.00 Hz, 1H); C NMR (200 MHz, CDCl ) d 15.49 (q),
1119; H NMR (200 MHz, CDCl ) d 1.90 (m, 6H), 2.50 (s,
3
3
1
1
1
7.65 (q), 2 × 56.53 (q), 61.19 (q), 105.17 (d), 105.67 (d),
6H), 3.70 (m, 1H), 3.90 (m, 1H), 5.45 (m, 1H), 6.20 (s, 1H),
13.65 (d), 127.13 (d), 131.17 (s), 140.22 (s), 141.50 (d), 2 ×
6.70 (d, J = 16.00 Hz, 1H), 7.05 (d, J = 8.00 Hz, 2H), 7.50 (d,
+
13
53.75 (s), 165.77 (s), 184.06 (s); MS (m/e) 340 (M ), 324
J = 8.00 Hz, 2H), 7.60 (d, J = 16.00 Hz, 1H); C NMR
+
(M -CH ). Anal. Calcd. for C H O S : C, 56.45; H, 5.92;
(200 MHz, CDCl ) d 15.49 (q), 17.65 (q), 19.01 (t), 25.52 (t),
3
16 20
4
2
3
S, 18.83. Found: C, 57.1; H, 6.21; S, 19.36%.
30.61 (t), 62.42 (t), 96.61 (d), 114.03 (d), 2 × 130.00 (d),
1
41.39 (d), 159.01 (s), 164.83 (s) 184.48 (s); MS (m/e) 351
5
.4. 5-(4-Benzyloxyphenyl)-1,1-bis(methylthio)-penta-1,4-
+
+
(M + 1), 267 (M -THP). Anal. Calcd. for C H O S : C,
18 22 3 2
dien-3-one (6d)
6
1.60; H, 6.32; S, 18.3. Found: C, 60.61; H, 6.06; S, 18.01%.
To a solution of 5 (1.62 gm, 10 mmol) in methanol (40 ml)
was added aqueous KOH solution (1.12 gm, 20 mmol in 10 ml
water) and stirred it for 15 min. To the above reaction mix-
ture was added p-benzyloxybenzaldehyde (2.12 gm, 10 mmol)
and stirred the reaction mixture for 12 h at room temperature.
Solvent was removed in vacuo poured into water (100 ml)
and extracted it with dichloromethane (50 ml × 3). The com-
bined extract was washed with water (2 × 100 ml) brine solu-
5.6. 5-(4-Hydroxyphenyl)-1,1-bis(methylthio)-penta-1,4-
dien-3-one (10a)
To a solution of 9a (0.35 gm, 1 mmol) in methanol (25 ml)
was added ppts (0.02 gm, 0.1 mmol) and stirred it for 3 h at
room temperature. Water (3–4 drops) was added to the above
reaction mixture and further stirred for 3 h. Solvent was
removed in vacuo, poured into water and extracted with
dichloromethane (50 ml × 3). The combined extract was
washed with aqueous sodium bicarbonate solution (5 × 50 ml).
It was dried (Na SO ), solvent was removed in vacuo. The
tion (2 × 50 ml) dried (Na SO ) and the solvent was removed
2
4
in vacuo. The crude product thus obtained was chromato-
graphed (SiO , 60–120 mesh). Elution with 20% ethyl acetate
2
2
4
in hexane furnished 6d as a yellow crystalline solid (0.8 gm,
crude product was chromatographed (SiO , 60–120 mesh).
2
–
1
4
1
6
7
1
1
5%); m.p. 115–117 °C; IR (KBr, cm ) 1643, 1592, 1485,
Elution with 20% ethylacetate in hexane furnished 10a as a
1
250, 1172, 1128; H NMR (200 MHz, CDCl ) d 2.48 (s,
H), 5.10 (s, 2H), 6.20 (s, 1H), 6.70 (d, J = 16.00 Hz, 1H),
.00 (d, 1H), 7.60 (m, 9H); C NMR (200 MHz, CDCl ) d
5.50 (q), 17.67 (q), 70.51 (t), 114.05 (d), 2 × 115.62 (d),
25.76 (d), 2 × 127.86 (d), 128.51 (d), 2 × 128.68 (d), 129.04
3
yellow crystalline solid (0.2 gm, 96%); m.p. 169–170 °C; IR
–
1
1
(
KBr cm ) 3447, 1600, 1559, 1465, 1237, 1140; H NMR
13
3
(200 MHz, CDCl ): d 2.51 (s, 6H), 5.80 (s, 1H), 6.20 (s, 1H),
3
6
.70 (d, J = 16.00 Hz, 1H), 6.90 (d, J = 8.00 Hz, 2H), 7.50 (d,
1
3
J = 8.00 Hz, 2H), 7.60 (d, J = 16.00 Hz, 1H); C NMR
200 MHz, DMSO) d 14.67 (q), 17.10 (q), 114.12 (d), 2 ×
16.18 (d), 125.12 (d), 126.39 (s), 2 × 130.40 (d), 140.82 (d),
(
(
s), 2 × 130.17 (d), 136.98 (s), 141.33 (d), 160.73 (s), 164.91
s), 184.45 (s); MS (m/e) 357 (M + 1), 266 (M -benzyl).
(
1
+
+
+
Anal. Calcd. for C H O S : C, 67.38; H, 5.84; S, 17.98.
2
0
20
2
2
159.83 (s), 163.07 (s), 183.76 (s); MS (m/e) 267 (M + 1);
Found: C, 67.35; H, 5.31; S, 16.98%.
Anal. Calcd. for C H O S : C, 58.61; H, 5.29; S, 24.07.
1
3 14 2 2
Found: C, 58.08; H, 4.70; S, 24.05%.
5.5. 5-[(4-Tetrahydropyran-2-yloxy)-phenyl]-1,1-bis(methyl-
thio)-penta-1,4-dien-3-one (9a)
5
.7. 5-(3-Methoxy-4-hydroxyphenyl)-1,1-bis(methylthio)-
penta-1,4-dien-3-one (10b)
To a solution of p-hydroxybenzaldehyde (5.49 gm,
4
5 mmol) in dry dichloromethane (80 ml) was added ppts
To a solution of vanillin (1.52 gm, 10 mmol) in dry dichlo-
romethane (40 ml) was added dihydropyran (1.36 gm,
16 mmol) and ppts (0.08 gm, 1 mmol) and stirred it for 5 h at
room temperature. The reaction mixture was taken up in sepa-
rating funnel and washed with aqueous sodium carbonate
solution (5 × 50 ml). It was dried (Na SO ). Solvent was
(0.36 gm) and dihydropyran (6.12 gm, 72 mmol) and stirred
at room temperature for 5 h. The reaction mixture was taken
up in separating funnel and washed with aqueous sodium car-
bonate solution (5 × 100 ml). Solvent was removed in vacuo
to get 8a in 90% yield. It was used for the next step without
further purification.
2
4
removed in vacuo to get 8b as a thick liquid (1.89 gm).