Synthesis of 5-Hydroxy- and 5-Amino-1-tosyl-5-phenyl-3-(2-arylvinyl)-4,5-­dihydropyrazoles

Abstract

The reaction of β-arylacryloyloxiranes with tosylhydrazine leads to unexpected 5-hydroxysubstituted Δ²-pyrazolines. A series of 3-styryl substituted pyrazoles and 5-amino-Δ²-pyrazolines were synthesized from the 5-hydroxy-Δ²-pyrazolines. The mechanism of this process has been proposed based on current and previous results.

epoxy enones - hydrazones - rearrangements

References

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2 Zvonok AM. Kuz’menok NM. Stanishevsky LS. Khim. Geterotsikl. Soedin.  1990,  5:  633 

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Typical Procedure:
Tosylhydrazine (1.02 g, 5.5 mmol) and catalytic amount of the concentrated HCl were added to a solution of 3-aryl-1-(3-phenyloxiran-2-yl)prop-2-en-1-one (1, 5 mmol) in 20 mL THF. The reaction was carried out at r.t. for 12-18 h (control by TLC). After evaporation of the solvent in vacuo the residue was diluted with a mixture of Et₂O-benzene (1:3). Further solid pyrazoline 2 was filtered off and purified by recrystallization using EtOH or benzene. The residue mixture was divided on a column and pyrazole 3 and additional pyrazolines 2 were taken.

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Selected physical and spectroscopic data.
Compound 2a: yield 77%, mp 169-172 °C (EtOH). IR (KBr): ν_max = 3504 (OH), 1600 (C=N), 1364, 1168 (S=O), 960 (HC=) cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.39 (3 H, s, CH₃), 3.23 (1 H, d, J = 17.6 Hz, CH ₂), 3.51 (1 H, d, J = 17.6 Hz, CH ₂), 6.63 (1 ,H d, J = 16.4 Hz, CH=), 7.02 (1 H, d, J = 16.4 Hz, CH =), 7.23 (2 H, d, J = 8.3 Hz, C₆H₄), 7.29-7.50 (10 H, m, arom.), 7.69 (2 H, d, J = 8.3 Hz, C₆H₄). MS: m/z (%) = 418 (5.4) [M⁺], 91 (100).
Compound 2c: yield 83%, mp 98-100 °C (C₆H₆). ¹H NMR (400 MHz, CDCl₃): δ = 2.39 (3 H, s, CH₃), 3.21 (1 H, d, J = 17.6 Hz, CH ₂), 3.49 (1 H, d, J = 17.6 Hz, CH ₂), 6.55 (1 H, d, J = 16.4 Hz, CH =), 7.00 (1 H, d, J = 16.4 Hz, CH=), 7.22 (2 H, d, J = 8.3 Hz, C₆H₄), 7.25 (5 H, m, C₆H₅), 7.32-7.50 (4 H, m, C₆H₄), 7.68 (2 H, d, J = 8.3 Hz, C₆H₄). ¹³C NMR (125.77 MHz, CDCl₃): δ = 21.61 (CH₃), 50.50 (CH₂), 97.82 (C-OH), 121.91 (CH=), 125.02 (CH=), 125.05, 126.90, 127.96, 128.33, 128.59, 128.94, 129.38, 130.08, 135.15, 137.6, 142.8 (arom.),153.02 (C-3).
Compound 3a: yield 12%, mp 122-124 °C (EtOH). IR (KBr): ν_max = 1383, 1176 (S=O), 970 (HC=) cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.37 (3 H, s, CH ₃), 6.53 (1 H, s, 4-H), 7.08 (1 H, d, J = 16.6 Hz, CH=), 7.16 (1 H, d, J = 16.6 Hz, CH =), 7.20 (2 H, d, J = 8.2 Hz, arom.), 7.27-7.52 (10 H, m, arom.), 7.56 (2 H, d, J = 8.2 Hz, C₆H₄).
Compound 4i: yield 79%, mp 190-192 °C (MeOH). IR (KBr): ν_max = 3385 (NH), 2928, 2856 (CH), 1344, 1160 (S=O) cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.20-2.25 (10 H, m, C₆H₁₁), 2.38 (3 H, s, CH₃), 2.81 (1 H, m, C₆H₁₁), 3.17 (1 H, d, J = 18.0 Hz, CH₂), 3.56 (1 H, d, J = 18.0 Hz, CH₂), 6.60 (1 H, d, J = 16.4 Hz, CH=), 7.10 (1 H, d, J = 16.4 Hz, CH=), 7.12-7.45 (14 H, m, arom.).

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Amine (propyl-, cyclohexyl- or benzylamines) (1 mmol) was added to the colorless solution of the pyrazoline 2 (1 mmol) in 10 mL THF or MeOH (the color of the solution becomes brightly orange). Reaction mixture was left at r.t. for 12 h. After evaporation of the solvent in vacuo, the residue was diluted with a mixture of CHCl₃-MeOH. Further solid 5-aminopyrazoline 4 was filtered off or taken as an oil.

12 Igidov NM. Koz’minykh EN. Kolotova NV. Koz’minykh VO. Russ. Chem. Bull.  1999,  7:  1383 

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Pyrazoline 2 (1 mmol) was dissolved in 10 mL THF with catalytic amount of the concentrated HCl and left at 50 °C for 6 h. After solvent evaporation in vacuo, the oil was diluted with Et₂O from which pyrazole 3 was crystallized.