Month 2018
Synthesis and Biological Study of 4-formylpyrazoles
3315 (NH str), 1616 (C¼N str). 1H NMR (400 MHz,
CDCl3): δ 7.67–7.75 (m, 2H, ArH), 7.57 (d, J = 8.0 Hz,
1H, ArH), 7.35 (t, J = 8.0 Hz, 1H, ArH), 7.18 (t,
J = 8.0 Hz, 1H, ArH), 6.95 (dt, J = 8.6, 2.6 Hz, 1H,
ArH), 6.86 (ddd, J = 11.5, 8.8, 2.6 Hz, 1H, ArH), 4.46
NMR (400 MHz, DMSO-d6): δ 10.06 (s, 1H, CHO), 9.36
(s, 1H, pyrazole-H), 7.93 (d, J = 8.6 Hz, 2H, ArH), 7.82–
7.86 (m, 2H, ArH), 7.36 (d, J = 8.3 Hz, 1H, ArH), 7.05
(d, J = 8.6 Hz, 2H, ArH), 3.86 (s, 3H, OCH3), 2.48 (s,
3H, CH3). 13C NMR (100 MHz, CDCl3): δ 184.6, 158.4,
153.3, 143.8, 136.6, 135.8, 135.3, 130.0, 128.4, 122.9,
121.9, 113.8, 55.1, 21.1. ESI-MS (m/z): 350.0 [M + H]+
(100%). Anal. Calcd for C19H15N3O2S: C, 65.31; H,
(bs, 1H, NH), 2.33 (s, 3H, CH3).
2-(2-(1-(4-Bromophenyl)ethylidene)hydrazinyl)-6-
chlorobenzo[d]thiazole 3j. Obtained as a gray solid in 75%
yield; mp 147–149°C (lit. [31] 148–150°C). IR (υ cmꢀ1
,
4.33%. Found: C, 65.43; H, 4.24%.
1-(6-Methylbenzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazole-4-
KBr): 3256 (NH str), 1592 (C¼N str). 1H NMR
(400 MHz, DMSO-d6): δ 7.84–7.92 (m, 3H, ArH), 7.32–
7.40 (m, 4H, ArH), 4.42 (s, 1H, NH), 2.30 (s, 3H, CH3).
6-Chloro-2-(-2-[1-(4-fluorophenyl)ethylidene]hydrazinyl)
carbaldehyde 4c.
Obtained as a light yellow solid
(380 mg) in 65% yield; mp 149–151°C. IR (υ cmꢀ1
,
1
KBr): 1688 (C¼O str), 2260, 2849 (C–H str). H NMR
(400 MHz, DMSO-d6): δ 10.08 (s, 1H, CHO), 9.25 (s,
1H, pyrazole-H), 7.91–7.96 (m, 2H, ArH), 7.82 (d,
J = 8.3 Hz, 1H, ArH), 7.77 (s, 1H, ArH), 7.50–7.52 (m,
3H, ArH), 7.34 (d, J = 8.3 Hz, 1H, ArH), 2.50 (s, 3H,
CH3). 13C NMR (100 MHz, CDCl3): δ 184.3, 157.8, 153.6,
148.1, 135.2, 133.1, 129.5, 128.6, 128.5, 128.3, 128.0,
125.6, 123.1, 121.9, 21.1. DEPT-135: δ 184.3, 129.5, 128.6,
128.5, 128.3, 128.0, 125.6, 121.9, 21.1. ESI-MS (m/z):
320.0 [M + H]+ (100%). Anal. Calcd for C18H13N3OS:
benzo[d]thiazole 3k.
Obtained as an off-white solid in
65% yield; mp 211–213°C (lit. [31] 210–212°C). IR (υ
1
cmꢀ1, KBr): 3320 (NH str), 1618 (C¼N str). H NMR
(400 MHz, DMSO-d6): δ 7.79–8.22 (m, 3H, ArH), 7.30–
7.38 (m, 4H, ArH), 4.28 (s, 1H, NH), 2.26 (s, 3H, CH3).
Method for preparing the OPC-VH reagent. A mixture
of DMF (32.0 g, 0.44 mol) and OPC (45.0 g, 0.22 mol) in
2-chlorotoluene (105 mL, 0.88 mol) was stirred for 3 h at
50°C to afford the OPC-VH reagent as white crystals
(23 g, 82% yield), which were subsequently filtered
under nitrogen and dried under reduced pressure. The
dried OPC-VH reagent was characterized by its melting
point {mp 128–130°C (decomp.) (lit. [34] 132°C)}.
C, 67.69; H, 4.10%. Found: C, 67.78; H, 4.21%.
1-(6-Bromobenzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazole-4-
carbaldehyde 4d.
Obtained as a light yellow solid
(465 mg) in 81% yield; mp 166–168°C. IR (υ cmꢀ1
,
1
KBr): 1682 (C¼O str), 2763, 2856 (C–H str). H NMR
(400 MHz, DMSO-d6): δ 10.07 (s, 1H, CHO), 9.42 (s,
1H, pyrazole-H), 8.36 (d, J = 2.0 Hz, 1H, ArH), 7.93–
7.95 (m, 2H, ArH), 7.88 (d, J = 8.7 Hz, 1H, ArH), 7.68
(dd, J = 8.7, 2.0 Hz, 1H, ArH), 7.51–7.54 (m, 3H, ArH).
13C NMR (100 MHz, CDCl3): δ 184.5, 159.7, 149.3,
135.9, 135.0, 130.1, 129.7, 128.7, 128.4, 125.1, 123.8,
123.4, 117.9. ESI-MS (m/z): 386.0 [M + H, 81Br], 384.0
[M + H, 79Br]. Anal. Calcd for C17H10BrN3OS: C, 53.14;
General preparation of 4-formylpyrazoles (4a–k). The
procedure for 1-(benzo[d]thiazol-2-yl)-3-phenyl-1H-
pyrazole-4-carbaldehyde 4a is representative for all cases.
A
mixture of 2-(2-(1-phenylethylidene)hydrazinyl)
benzo[d]thiazole (0.93 g, 3.47 mmol) and OPC-VH
reagent (1.33 g, 10.41 mmol) in dioxane (25 mL) was
stirred at 60°C for 4 h. After complete consumption of
the starting material, the reaction mixture was cooled at
room temperature and poured into ice water. The solid
then separated on neutralization with NaHCO3 was
filtered, washed with water, and crystallized from ethanol
to afford 1-(benzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazole-
4-carbaldehyde 4a as a light yellow solid (850 mg) in
80% yield. mp 132–134°C, IR (υ cmꢀ1, KBr): 1685
H, 2.62%. Found: C, 52.91; H, 2.53%.
1-(Benzo[d]thiazol-2-yl)-3-(4-chlorophenyl)-1H-pyrazole-4-
carbaldehyde 4e. Obtained as a light yellow solid (430 mg)
in 65% yield; mp 154–156°C. IR (υ cmꢀ1, KBr): 1694
1
(C¼O str), 2727, 2822 (C–H str). H NMR (400 MHz,
DMSO-d6): δ 10.06 (s, 1H, CHO), 9.54 (s, 1H, pyrazole-
H), 8.15 (d, J = 7.4 Hz, 1H, ArH), 7.99–8.02 (m, 3H,
ArH), 7.58–7.63 (m, 3H, ArH), 7.51 (t, J = 8.1 Hz, 1H,
ArH). ESI-MS (m/z): 342.0 [M + H, 37Cl], 340.0 [M + H,
1
(C¼O str), 2755, 2866 (C–H str). H NMR (400 MHz,
DMSO-d6): δ 10.08 (s, 1H, CHO), 9.39 (s, 1H, pyrazole-
H), 8.07 (d, J = 8.0 Hz, 1H, ArH), 7.93–7.97 (m, 3H,
ArH), 7.50–7.58 (m, 4H, ArH), 7.46 (dt, J = 8.2, 1.2 Hz,
1H, ArH). 13C NMR (100 MHz, CDCl3): δ 184.5, 155.5,
133.6, 132.6, 130.3, 129.9, 129.0, 128.8, 126.9, 125.5,
123.4, 122.9, 121.8. DEPT-135: δ 184.5, 132.6, 129.9,
129.0, 128.8, 126.9, 125.5, 122.9, 121.8. ESI-MS (m/z):
306.0 [M + H]+ (90%), Anal. Calcd for C17H11N3OS: C,
66.87; H, 3.63%. Found: C, 66.71; H, 3.53%.
35Cl]. Anal. Calcd for C17H10ClN3OS: C, 60.09; H,
2.97%. Found: C, 60.21; H, 3.13%.
3-(4-Chlorophenyl)-1-(6-methylbenzo[d]thiazol-2-yl)-1H-
pyrazole-4-carbaldehyde 4f.
Obtained as a light yellow
solid (455 mg) in 66% yield; mp 159–161°C. IR (υ
1
cmꢀ1, KBr): 1692 (C¼O str), 2742, 2844 (C–H str). H
NMR (400 MHz, DMSO-d6): δ 10.08 (s, 1H, CHO), 9.25
(s, 1H, pyrazole-H), 7.96 (d, J = 8.4 Hz, 2H, ArH), 7.81
(d, J = 8.3 Hz, 1H, ArH), 7.75 (s, 1H, ArH), 7.49 (d,
J = 8.4 Hz, 2H, ArH), 7.34 (d, J = 8.3 Hz, 1H, ArH),
2.50 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3): δ
3-(4-Methoxyphenyl)-1-(6-methylbenzo[d]thiazol-2-yl)-1H-
pyrazole-4-carbaldehyde 4b.
Obtained as a light yellow
solid (485 mg) in 71.5% yield; mp 160–162°C. IR (υ
1
cmꢀ1, KBr): 1690 (C¼O str), 2756, 2860 (C–H str). H
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet