VILSMEIER FORMYLATION OF HYDRAZONES AND SEMICARBAZONES
415
1
-Phenyl-3-butylpyrazole-4-carbaldehyde IVc: C H ), 7.30 t (1H, CH), 7.43 t (2H, 2CH), 7.68 d
1
0
15
2
0
bp 160 162 C (3 mm Hg), n 1.5790. Mass spec-
trum, m/z: 228 [M] . H NMR spectrum, , ppm:
(2H, 2CH), 8.40 s (1H, CHN), 10.18 s (1H, CHO).
Found, %: C 78.35; H 7.28. C H N O. Calculated,
D
+
1
2
0
22
2
0
1
7
.94 t (3H, CH ), 1.25 1.40 m (2H, CH ), 1.60
%: C 78.40; H 7.24.
3
2
.80 m (2H, CH ), 2.83 t (2H, CH ), 7.36 t (1H, CH),
2
2
Reactions of semicarbazones VIIa, VIIb, Xa,
and Xb with I. A 153.5-g portion of freshly distilled
.49 t (2H, 2CH), 7.87 d (2H, 2CH), 9.15 s (1H,
CHN), 9.94 s (1H, CHO). Found, %: C 73.51; H 7.14.
C H N O. Calculated, %: C 73.66; H 7.06.
POCl was added dropwise at 0 C to 220 g of anhy-
3
1
4
16
2
drous DMF; the mixture was left for 20 min. Under
external cooling, 0.5 mol of freshly distilled VIIa,
VIIb, Xa, or Xb was slowly added dropwise in por-
tions, avoiding warming-up of the mixture above
50 C. After adding the whole amount of semicarba-
zones, the mixture was stirred for 1 h at 80 C and
poured while hot onto 0.5 kg of ice. The resulting
mixture was alkalized with 30% NaOH to pH 8 9, left
for 20 min, and neutralized with 20% HCl to pH 7.
In the case of VIIa and VIIb, the mixture was ex-
tracted with chloroform (3 250 ml). After removing
Reactions of phenylhydrazones Va Vc with I.
A 153.5-g portion of freshly distilled POCl was
3
added dropwise at 0 C to 220 g of anhydrous DMF;
the mixture was left for 20 min. Under external cool-
ing, 0.5 mol of freshly distilled phenylhydrazone was
slowly added dropwise (for Va, Vb) or in portions
for Vc), avoiding warming-up of the mixture above
5 C. After adding the whole amount of Va Vc, the
(
5
mixture was stirred for 2 h at 80 C and poured while
hot onto 0.5 kg of ice. The resulting mixture was alka-
lized with 30% NaOH to pH 8 9, left for 20 min, and
neutralized with 20% HCl to pH 7. The mixture was
extracted with chloroform (3 180 ml). After remov-
1
the solvent, the residue was analyzed by H NMR
spectroscopy and recrystallized from hexane (for VIIa)
or immediately subjected to oxidation (for VIIb). In
formylation of Xa and Xb, the precipitates formed
upon neutralization were filtered off and recrystallized
from water. Yields: VIIIa 59.7 g (70%), VIIIb 45 g
(62%), XIa 26.55 g (35%), and XIb 38.8 g (40%).
1
ing the solvent, the mixture was analyzed by H NMR
spectroscopy and distilled in a vacuum with a Vigreux
column (for VIa, VIb). Compound VIb slowly crystal-
lized, after which it was recrystallized from hexane.
Pyrazole VIa was purified by additional vacuum dis-
tillation. Crude pyrazole VIc was dissolved in pure
chloroform and treated with a solution of sodium
bisulfite at 50 C. The resulting precipitate of the
bisulfite derivative was filtered off, washed with hot
chloroform, dried, treated with 20% H SO , and ex-
3
-Cyclohexylpyrazole-4-carbaldehyde VIIIa:
+
1
mp 111 112 C. Mass spectrum, m/z: 178 [M] . H
NMR spectrum, , ppm: 1.15 1.40 m (3H, C H ),
6
11
1
1
.45 1.58 q (2H, C H ), 1.66 1.74 d (1H, C H ),
6 11 6 11
.74 1.86 t (4H, C H ), 3.12 t (1H, C H ), 8.05 br
6
11
6
11
2
4
(
1H, CHN), 9.86 s (1H, CHO), 13.15 br (1H, NH).
tracted with chloroform (2 150 ml). After removing
the solvent, pyrazole VIc was recrystallized from
isopropyl alcohol. Yields: VIa 82.1 g (72%), VIb
Found, %: C 67.30; H 7.96. C H N O. Calculated,
1
0
14
2
%
: C 67.39; H 7.92.
1
6
4.2 g (60%), and VIc 88.7 g (58%).
3-Isobutylpyrazole-4-carbaldehyde VIIIb. H
NMR spectrum, , ppm: 0.85 d (6H, 2CH ), 1.95 m
3
1
-Phenyl-3-isobutylpyrazole-4-carbaldehyde
2
0
(1H, CH), 2.73 d (2H, CH ), 7.95 s (1H, CHN),
2
VIa: bp 173 174 C (4 mm Hg, n 1.5815. Mass spec-
trum, m/z: 228 [M] . H NMR spectrum, , ppm:
.92 d (6H, 2CH ), 1.97 2.09 m (1H, CH), 2.77 d
2H, CH ), 7.39 t (1H, CH), 7.53 t (2H, 2CH), 7.90 d
2H, 2CH), 9.16 s (1H, CHN), 9.95 s (1H, CHO).
D
+
1
9.83 s (1H, CHO), 13.25 br (1H, NH).
0
(
(
3-Methyl-4-phenylpyrazole XIa: mp 144 145 C.
3
+
1
Mass spectrum, m/z: 158 [M] . H NMR spectrum,
2
, ppm: 2.32 and 2.38 d (3H, CH ), 7.22 t (1H, CH),
3
Found, %: C 73.63; H 7.05. C H N O. Calculated,
7.38 t (2H, 2CH), 7.43 d (2H, 2CH), 7.67 and 7.91 d
(1H, CHN), 12.65 d (1H, NH). Found, %: C 75.90; H
1
4
16
2
%
: C 73.66; H 7.06.
-Phenyl-3-isopropylpyrazole-4-carbaldehyde
VIb: bp 140 150 C (2 mm Hg), mp 58 59 C. Mass
6
.36. C H N . Calculated, %: C 75.92; H 6.37.
10 10 2
1
3-Methyl-4-(3 ,4 -methylenedioxyphenyl)pyrazole
+
1
+
spectrum, m/z: 214 [M] . H NMR spectrum, , ppm:
.28 d (6H, 2CH ), 3.37 3.49 m (1H, CH), 7.37 t
XIb: mp 97 99 C. Mass spectrum, m/z: 202 [M] .
1
1
H NMR spectrum, , ppm: 2.31 s (3H, CH ), 6.00 s
3
3
(
(
1H, CH), 7.52 t (2H, 2CH), 7.84 d (2H, 2CH), 9.14 s
1H, CHN), 9.95 s (1H, CHO). Found, %: C 72.83;
(2H, OCH O), 6.90 q (2H, 2CH), 7.00 s (1H, CH),
2
7.67 s (1H, CHN). Found, %: C 65.24; H 4.92.
C H N O . Calculated, %: C 65.34; H 4.98.
H 6.57. C H N O. Calculated, %: C 72.87; H 6.59.
1
3
14
2
11 10
2
2
1
-Phenyl-3-(1 -adamantyl)pyrazole-4-carbalde-
Oxidation of aldehydes VIIIa and VIIIb. Al-
dehyde VIIIa (23.32 g) or a reaction mixture from
synthesis of VIIIb (70% main substance, 26.55 g,
hyde VIc: mp 116 118 C. Mass spectrum, m/z: 306
+
1
[
M] . H NMR spectrum, , ppm: 1.75 2.20 m (15H,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005