A Resourceful Access to α-Functionalized Arylhydrazones

Abstract

Several compounds containing active methylene groups flanked by carbonyl, cyano or nitro groups were reacted with N-nonaflylbenzotriazole (BtNf, 1) at room temperature. An instantaneous reaction took place, which was complete within 10-30 minutes. All active methylene compounds gave hydrazono derivatives by the attack of the carbon nucleophile at the nitrogen in position 2 of the BtNf followed by ring-opening, thus providing a new access to α-functionalized arylhydrozones.

arylhydrazones - ring-opening - nonaflone - benzo­triazole

References and Notes

1

Crystal structure.

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Typical Procedure:
NaH (24 mg, 60% suspension in oil) was added to a stirred solution of diethyl malonate (160 mg, 1 mmol) and 1 (401 mg, 1 mmol) in anhyd toluene (50 mL) at r.t. under argon. The mixture was allowed to stir for 30 min while controlling the progress of reaction by TLC. At the end of this period, EtOAc (100 mL) and H₂O (25 mL) were added, and the suspension was treated with concd HCl. The organic phase was separated, dried (Na₂SO₄), filtered, and solvent was evaporated. The crude product was purified by recrystallization from PE (bp 60-90 °C) to give pure 3.

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Compound 3: yield 460 mg (82%); mp 89-90 °C (PE). UV/Vis (MeCN): λ_max (ε = mol^-1 dm³ cm^-1) = 233 (8929), 343.50 nm(15521). ¹H NMR (400 MHz, CDCl₃): δ = 12.99 (s, 1 H, NH), 10.75 (s, 1 H, NH), 7.77 (d, J = 8.08 Hz, 1 H_arom), 7.22-7.27 (m, 1 H_arom), 7.14-7.18 (m, 1 H_arom), 7.07-7.10 (m, 1 H_arom) 4.34-4.44 (m, 4 H, CH₂), 1.42 (t, J = 8.00 Hz, 3 H, CH₃), 1.34 (t, J = 8.00 Hz, 3 H, CH₃). ¹³C NMR (400 MHz, CDCl₃): δ = 14.00, 62.10, 118.60, 124.00, 125.60, 125.13, 127.00, 131.00, 161.37, 163.40. MS (FAB): m/z = 562.00 [M⁺ + 1]. Anal. Calcd for C₁₇H₁₆F₉N₃O₆S: C, 36.37; H, 2.87; N, 7.49; S, 5.71. Found: C, 35.85; H, 2.81; N, 7.27; S, 5.25.

20 Parmerter SM. Org. React.  1959,  10:  1 

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As an example, compound 5: yield 421 mg (84%); mp 118-119 °C (PE). UV/Vis (MeCN): λ_max (ε = mol^-1 dm³ cm^-1) = 243.50 (12455), 357 nm(15331). ¹H NMR (400 MHz, CDCl₃): δ = 15.11 (s, 1 H, NH), 7.59-7.61 (m, 1 H_arom), 7.40-7.44 (m, 1 H_arom), 7.22-7.26 (m, 1 H_arom), 7.53 (d, J = 8.08 Hz, 1 H_arom) 2.53 (s, 3 H, CH₃), 2.47 (s, 3 H, CH₃). ¹³C NMR (400 MHz, CDCl₃): δ = 26.69, 31.65, 118.00, 123.25, 126.22, 127.35, 129.45, 133.89, 136.21, 196.83, 198.54. MS (FAB): m/z = 502 [M⁺ + 1]. Anal. Calcd for C₁₅H₁₂F₉N₃O₄S: C, 35.94; H, 2.41; N, 8.38; S, 6.40. Found: C, 36.10; H, 2.39; N, 8.47; S, 6.39.

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As an example, compound 6: yield 421 mg (82%); mp 169-170 °C (PE-EtOAc). UV/Vis (MeCN): λ_max (ε = mol^-1 dm³ cm^-1) = 246 (9883), 387.50 nm (11819). ¹H NMR (400 MHz, acetone-d ₆): δ = 15.35 (s, 1 H, NH), 7.92 (d, J = 8.32 Hz, 1 H_arom), 7.54-7.60 (m, 2 H_arom), 7.33-7.40 (m, 1 H_arom), 5.62 (s, 1 H, =CH) 2.78 (t, J = 6.32 Hz, 2 H, COCH₂), 2.68 (t, J = 6.44 Hz, 2 H, HCOCH₂), 2.11 (m, 2 H, COCH₂CH ₂). ¹³C NMR (400 MHz, acetone-d ₆): δ = 19.00, 55.00, 39.60, 118.40, 123.64, 127.14, 130.20, 131.20, 140.00, 199.00, 193.40. MS (FAB): m/z = 514 [M⁺ + 1]. Anal. Calcd for C₁₆H₁₂F₉N₃O₄S: C, 37.44; H, 2.36; N, 8.19; S, 6.25. Found: C, 37.63; H, 2.39; N, 8.04; S, 6.18.

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CCDC No. 294289 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; or [e-mail]].

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We thank one of the referees for pointing out this interesting possibility.