CAN-Mediated Oxidation of Electron-Deficient Aryl and Heteroaryl Hydrazines and Hydrazides

Bogdan Štefane; Slovenko Polanc

doi:10.1055/s-2007-1072749

LETTER

CAN-Mediated Oxidation of Electron-Deficient Aryl and Heteroaryl Hydrazines and Hydrazides

Bogdan Štefane*, Slovenko Polanc
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia
Fax: +386(1)2419220; e-Mail: bogdan.stefane@fkkt.uni-lj.si;

Abstract

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Abstract

Aryl and heteroaryl hydrazines and hydrazides were successfully oxidised using CAN, deriving dehydrazinated products. The reaction pathway strongly depends on the nature of the substrate, resulting in the formation of hydrocarbons or alkoxy derivatives. When deuterated solvents such as methanol-d ₄ or acetonitrile-d ₃ were used, a regiospecific incorporation of deuterium was achieved.

Key words

deuteration - CAN - oxidation - hydrazines - hydrazides

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References

References and Notes

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The products were analysed using MS spectrometry.

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Typical Procedure: To a solution of CAN (2.193 g, 4 mmol) and 1,2-dibromotetrachloroethane (1.302 g, 4 mmol) in MeOH (5 mL) was added 2,4-dinitrophenylhydrazine (198 mg, 1 mmol) in one portion. The reaction mixture was stirred at r.t. for an additional 5 min, evaporated to dryness below 40 °C, treated with H₂O (10 mL) and extracted with CH₂Cl₂ (5 × 10 mL). The organic phase was dried over anhyd Na₂SO₄ and concentrated under reduced pressure to give a mixture of products (2a:3Br:3Cl = 50:7.5:1). The mixture was purified by column chromatography (SiO₂, EtOAc-light petroleum, 1:10). 2a: orange solid (134 mg, 80%); R _f (light petroleum-EtOAc, 3:1) 0.34. ¹H NMR (300 MHz, CDCl₃): δ = 7.87 (t, J = 8.0 Hz, 1 H), 8.60 (dd, J = 2.0, 8.0 Hz, 2 H), 9.08 (t, J = 2.0 Hz, 1 H). 3Br: yellow oil (24 mg, 10%); R _f (light petroleum-EtOAc, 3:1) 0.44. ¹H NMR (300 MHz, CDCl₃): δ = 8.04 (d, J = 9.0 Hz, 1 H), 8.32 (dd,
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General Procedure for the Oxidation of Hydrazines and Hydrazides: The hydrazine or hydrazide (1 mmol) was added at r.t. within a period of 10-15 min to a solution of CAN (4 mmol) in MeOH (5 mL). The reaction mixture was stirred at r.t. for an additional 10-40 min, evaporated to dryness below 40 °C, treated with H₂O (10 mL) and neutralised with NaHCO₃ (pH ca. 7). After extraction with CH₂Cl₂ (5 × 10 mL), the organic phase was dried over anhyd Na₂SO₄ and concentrated under reduced pressure to give dehydrazinated products 2. If necessary the products were purified by column chromatography on SiO₂. Products 2a-f, 8a and 8b were compared with the authentic samples. 2g: yellow solid; R _f (light petroleum-EtOAc, 5:3) 0.43; mp 69-72 °C (MeCN). IR (KBr): 3119, 1543, 1517, 1471, 1442, 1371, 1341, 1167, 1066, 1004, 849, 836, 762, 606, 566
cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.53 (s, 3 H), 3.87 (s, 3 H), 8.08 (s, 1 H). 2h: white solid; R _f (CH₂Cl₂-MeOH, 10:1) 0.39; mp 47-50 °C (light petroleum-EtOAc). IR (KBr): 3121, 3105, 1619, 1531, 1475, 1345, 1298, 1271, 1144, 1024, 928, 872, 797, 756, 635, 571 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.02 (dd, J = 4.0, 9.0 Hz, 1 H), 7.78 (d,
J = 1.0 Hz, 1 H), 7.96 (dd, J = 1.0, 9.0 Hz, 1 H), 7.98-7.99 (m, 1 H), 8.30 (dd, J = 1.0, 9.0 Hz, 1 H). 2i: white solid; R _f (CH₂Cl₂-MeOH, 10:1) 0.40; mp 98-102 °C (light petroleum-EtOAc). IR (KBr): 3096, 1614, 1541, 1419, 1370, 1348, 1327, 1255, 1130, 1087, 1011, 810, 764 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.57 (dd, J = 4.0, 9.5 Hz, 1 H), 8.46 (dd, J = 1.5, 9.5 Hz, 1 H), 8.72 (dd, 1 H). 7a: yellow oil; R _f (light petroleum-EtOAc, 5:3) 0.25. IR (KBr): 2949, 1618, 1574, 1500, 1447, 1371, 1098, 976, 875, 771 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 4.17 (s, 3 H), 7.54 (ddd, J = 1.0, 7.0, 8.0 Hz, 1 H), 7.81 (ddd, J = 1.5, 7.0, 8.5 Hz, 1 H), 7.92 (ddd, J = 1.0, 1.0, 8.5 Hz, 1 H), 8.14 (ddd, J = 1.0, 1.5, 8.0 Hz, 1 H), 8.80 (s, 1 H). MS (CI): m/z (%) = 160 (100) [M⁺], 131 (40), 103 (95). 7b: yellow oil; R _f (CH₂Cl₂-MeOH, 10:1) 0.40. IR (KBr): 2946, 1561, 1493, 1462, 1367, 1122, 832 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 4.29 (s, 3 H), 7.78 (dd, J = 4.0, 8.5 Hz, 1 H), 8.28 (dd, J = 1.5, 8.5 Hz, 1 H), 8.87 (s, 1 H), 8.99 (dd, J = 1.5, 4.0 Hz, 1 H). MS (EI, 70 eV): m/z (%) = 161 (100) [M⁺], 104 (98), 77 (40). HRMS (EI): m/z calcd for C₈H₇N₃O: 161.0589; found: 161.0590.

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Representative Procedure for the Oxidation of Aryl Hydrazinecarboxylates 4a-c: An aryl hydrazine-
carboxylate (1 mmol) was added at r.t. in one portion to a solution of CAN (2.1 mmol) in MeOH (5 mL). The reaction mixture was stirred at r.t. for an additional 5 min, evaporated to dryness below 40 °C, treated with H₂O (10 mL) and extracted with CH₂Cl₂ (5 × 10 mL). The organic phase was dried over anhyd Na₂SO₄ and concentrated under reduced pressure to give the pure products 5a-c. 5a: ref. 19. 5b: orange oil (213 mg, 94%); R _f (light petroleum-EtOAc, 3:1) 0.59. IR (NaCl): 2985, 1758, 1572, 1503, 1389, 1368, 1296, 1245, 1211, 1165, 1029, 977, 889, 863, 826, 748 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.48 (t, J = 7.0 Hz, 3 H), 2.48 (s, 3 H), 4.53 (q, J = 7.0 Hz, 2 H), 7.41 (d, J = 8.0 Hz, 1 H), 7.79 (dd, J = 2.0, 8.0 Hz, 1 H), 7.93 (d, J = 2.0 Hz, 1 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 14.0, 20.2, 64.3, 122.90, 122.95, 131.3, 135.3, 142.3, 150.4, 161.8. MS (CI): m/z (%) = 225 (85) [M + 2]⁺, 178 (50), 150 (55), 122 (100). HRMS (EI): m/z calcd for C₉H₁₁N₃O₄: 225.0750; found: 225.0759. 5c: orange oil (176 mg, 73%); R _f (light petroleum-EtOAc, 5:1) 0.14. IR (NaCl): 2938, 1762, 1544, 1514, 1446, 1359, 1235 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.49 (t, J = 7.0 Hz, 3 H), 2.54 (s, 3 H), 4.05 (s, 3 H), 4.55 (q, J = 7.0 Hz, 2 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 13.2, 14.1, 38.8, 65.3, 144.1, 146.2, 160.7, 171.1. MS (CI): m/z (%) = 243 (8) [M + 2]⁺, 125 (14), 67 (100). HRMS (EI): m/z calcd for C₈H₁₃N₅O₄: 243.0968; found: 243.00968.

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