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All solvents and reagents were used as obtained from commercial source. Standard 1H NMR and 13C NMR were recorded at 300 and 75.4 MHz from CDCl3 solutions. All runs were conducted at least in duplicate.
General Preparation of 4-Formylpyrazoles. The procedure for 1,3-diphenyl-4-formylpyrazole (Table
[1]
, run 1) is representative for all cases. 2,4,6-Trichloro-[1,3,5]-triazine (1.83 g,
10.0 mmol) was added to DMF (2 mL), maintained at 25 °C. After the formation of a
white solid, the reaction was monitored (TLC) until complete disappearance of TCT,
then the phenylhydrazone of acetophenone (1.00 g, 5.0 mmol) in DMF (15 mL) was added.
After the addition, the mixture was stirred at r.t., monitored (TLC) until completion
(16 h). A 15% solution of Na2CO3 (20 mL) was added then the organic phase extracted twice with 15 mL of Et2O. The organic layer was dried (Na2SO4) and the solvent evaporated to yield 1,3-diphenyl-4-formylpyrazole that was recovered
without other purifications (1.12 g, 90%): mp 145 °C. 1H NMR: δ = 10.12 (s, 1 H), 8.55 (s, 1 H), 7.86-7.74 (m, 5 H), 7.54-7.44 (m, 5 H) ppm.
13C NMR: δ = 185.5, 158.1, 139.7, 136.5, 129.7, 129.1, 128.5, 127.3, 127.0, 126.5, 118.8,
106.3 ppm.
All new compounds were identified through their elemental analyses and spectroscopic
data.
Preparation of 4-(Dimethoxymethyl)-1,3-diphenyl-1
H
-pyrazole. To a solution of 1,3-diphenyl-4-formylpyrazole (0.50 g, 2.01 mmol) in dry MeOH (20
mL) was added of NH4Cl (0.01 g) and of 0.50 g of molecular sieves (4 Å). The mixture was refluxed under
argon atmosphere for 10 h, and then concentrated in vacuo. The organic residue washed
with H2O (20 mL), aq Na2CO3 (20 mL), dried on Na2SO4, and filtered on Celite. After evaporation of the solvent 4-(di-methoxymethyl)-1,3-diphenyl-1H-pyrazole was recovered (0.59 g, 100%): 1H NMR: δ = 8.15 (s, 1 H), 7.90 (d, 2 H), 7.80 (d, 2 H), 7.47 (t, 4 H), 7.39 (t, 1
H), 7.25 (t, 1 H), 5.61 (s, 1 H), 3.38 (s, 6 H) ppm. 13C NMR: δ = 150.7, 139.8, 132.9, 129.3, 129.1, 128.7, 128.4, 128.0, 127.9, 127.6, 127.3,
126.3, 120.2, 118.8, 112.3, 98.3, 52.1 ppm. Anal. Calcd for C18H18N2O2 (294.35): C, 73.45; H, 6.16; N, 9.52. Found: C, 73.45; H, 6.12; N, 9.50.
Preparation of 1,3-Diphenyl-1
H
-pyrazole-4-carboxylic acid. The reported procedure is representative for all experiments. An aq 15% solution
of NaHCO3 (15 mL) was added to a solution of 1-phenyl-3-p-tolyl-1H-pyrazole-4-carbaldehyde (0.34 g, 1.3 mmol) in acetone (20 mL), stirred and maintained
at 0 °C, followed by solid NaBr (0.05 g, 0.5 mmol) and TEMPO (0.015 g, 0.1 mmol).
Trichloroisocyanuric acid (0.58 g, 2.5 mmol) was then slowly added within 10 min, at 0 °C. After
the addition, the mixture was warmed to r.t., stirred for the required time until
completion, then i-PrOH (1 mL) was added. The mixture was filtered on Celite, concentrated under vacuum
and treated with 15 mL of a sat. solution of Na2CO3. The aqueous phase was washed with portions of EtOAc, treated with 1 N HCl and extracted
twice with EtOAc. The organic layer were dried (Na2SO4), and the solvent evaporated to yield 1-phenyl-3-p-tolyl-1H-pyrazole-4-carboxylic acid that was recovered without other purifications (0.35 g,
97%): 1H NMR: δ = 10.95 (s, 1 H), 8.00 (s, 1 H), 7.62 (d, 2 H) 7.42 (m, 5 H), 7.25 (d, 2
H), 2.40 (s, 3 H) ppm. 13C NMR: δ = 172.0, 147.4, 140.3, 129.8, 129.6, 129.2, 114.1, 21.4 ppm. Anal. Calcd
for C17H14N2O2 (278.31): C, 73.37; H, 5.07; N, 10.07. Found: C, 73.35; H, 5.12; N, 10.04.
1-Phenyl-3-(4-chlorophenyl)-1
H
-pyrazole-4-carboxylic acid: 1H NMR: δ = 11.00 (s, 1 H), 8.10 (s, 1 H), 7.52 (d, 2 H) 7.43 (d, 2 H), 7.30-7.22 (m,
5 H) ppm. 13C NMR: δ = 170.0, 149.4, 139.7, 134.4, 131.2, 129.6, 129.2, 126.3, 120.2, 114.3 ppm.
Anal. Calcd for C16H11ClN2O2 (298.72): C, 64.33; H, 3.71; Cl, 11.87; N, 9.38. Found: C, 64.35; Cl, 11.82; N, 9.34.
Preparation of [3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methanol. To a solution of 3-(4-chloro-phenyl)-1-phenyl-1H-pyrazole-4-carbazole (0.23 g, 0.8 mmol) in dry THF (30 mL) was added LiAlH4 (0.03 g, 0.8 mmol), and refluxed for 45 min. The mixture was then left at r.t. for
1 h, hydrolyzed with HCl 1 N (10 mL), added with H2O (50 mL), extracted with portions (15 mL) of Et2O. The extracts were washed with 15 mL of a sat. solution of Na2CO3 (20 mL), dried on Na2SO4, filtered on Celite and concentrated under vacuum to give [3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]methanol (0.23 g, 100%): 1H NMR: δ = 9.95 (s, 1 H), 8.65 (s, 1 H), 7.62 (d, 2 H) 7.42 (d, 2 H), 7.28 (m, 5 H),
2.37 (s, 3 H) ppm. 13C NMR: δ = 152.2, 140.4, 134.3, 130.8, 129.6, 129.2, 126.3, 123.1, 117.1, 54.4 ppm.
Anal. Calcd for C16H13ClN2O (284.74): C, 67.49; H, 4.60; N, 9.84. Found: C, 67.49; H, 4.62; N, 9.93.
