Copper(I) Iodide Catalyzed Formation of Aryl Hydrazides from a Mitsunobo Reagent and Aryl Halides

Abstract

The Mitsonubo reagent (triphenylphosphine and dialkyl azodicarboxylates) was employed as a potential anionic nucleophile in a reaction involving aryl halides to produce aryl hydrazides. Aryl iodides and bromides, with electron-withdrawing as well as electron-releasing groups on the aromatic ring, undergo coupling reactions in good yields. The optimized conditions are developed for aryl iodides at room temperature and for aryl bromides at 60-75 ˚C.

aryl iodide - aryl bromide - Mitsonubo reagent - aryl ­hydrazide - copper(I) iodide

References and Notes

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11 Typical Procedure for the Preparation of Aryl Hydrazides 3a-i To a stirred solution of aryl iodide (1 mmol) and Ph₃P (0.263 g, 1 mmol) in THF (2 mL), was added CuI (9 mg, 0.05 mmol) in one portion. The mixture was stirred at r.t. for 30 min under N₂. Then, the DAAD (1.2 mmol) was added to the reaction mixture, which was stirred at r.t. for 18 h under nitrogen. After removal of the solvent, the residue was purified by chromatography (silica gel, hexane-EtOAc = 5:1) to give hydrazides 3a-i. Representative Analytical DataDiethyl 1-Phenyl-hydrazine-1,2-dicarboxylate (3a) Colorless solid, mp 81-83 ˚C; yield 0.23 g (91%). IR (KBr): ν_max = 3280, 1599, 1518, 1340, 1100 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 1.27 (3 H, t, ^³ J = 7.0 Hz, Me), 1.28 (3 H, t, ^³ J = 7.0 Hz, Me), 4.22 (4 H, m, 2 CH₂O), 7.09 and 7.19 (1 H, br s, NH), 7.20 (1 H, t, ^³ J = 7.1 Hz), 7.33 (2 H, t, ^³ J = 7.6 Hz), 7.42 (2 H, d, ^³ J = 7.4 Hz). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 14.4 (Me), 14.5 (Me), 62.3 (CH₂O), 63.0 (CH₂O), 124.3 (2 CH, br), 126.3 (2 CH), 128.6 (CH), 141.7 (C), 155.0 (C=O), 156.4 (C=O). MS: m/z (%) = 252 (1) [M⁺], 180 (10), 152 (100), 134 (16), 108 (22), 107 (69), 106 (14), 91 (17), 77 (32). Anal. Calcd (%) for C₁₂H₁₆N₂O₄ (252.27): C, 57.13; H, 6.39; N, 11.10. Found: C, 57.59; H, 6.44; N, 11.23. Diisopropyl 1-Phenyl-hydrazine-1,2-dicarboxylate (3b) Colorless solid, mp 90-92 ˚C; yield 0.25 g (92%). IR (KBr); ν_max = 3241, 1569, 1500, 1325, 1110 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 1.26 (6 H, t, ^³ J = 6.6 Hz, 2 Me), 1.29 (6 H, t, ^³ J = 6.8 Hz, 2 Me), 5.08-5.10 (2 H, m, CHO), 6.96 and 7.12 (1 H, br s, NH), 7.20 (1 H, t, ^³ J = 7.1 Hz), 7.36 (2 H, t, ^³ J = 7.1 Hz), 7.46 (2 H, d, ^³ J = 7.4 Hz). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 21.0 (2 Me), 21.7 (2 Me), 70.0 (CHO), 70.7 (CHO), 121.2 (2 CH, br), 125.9 (2 CH), 128.9 (CH), 139.3 (C), 154.7 (C=O), 156.0 (C=O). MS: m/z (%) = 280 (1) [M⁺], 194 (16), 152 (100), 134 (11), 108 (19), 107 (65), 106 (12), 91 (14), 77 (25). Anal. Calcd (%) for C₁₄H₂₀N₂O₄ (280.32): C, 59.99; H, 7.19; N, 9.99. Found: C, 59.69; H, 7.24; N, 9.93.

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Typical Procedure for the Preparation of Aryl Hydrazides 3j-s
To a stirred solution of aryl bromide (1 mmol), Ph₃P (0.263 g, 1 mmol), and Phen (0.036 g, 20 mol%) in MeCN (2 mL) was added CuI (9 mg, 0.05 mmol) in one portion. The mixture was stirred at r.t. for 30 min under N₂. Then, the DAAD (1 mmol) was added to the reaction mixture, which was stirred at 60-75 ˚C for 16 h under N₂. After removal of the solvent, the residue was purified by chromatography (silica gel, hexane-EtOAc = 5:1) to give hydrazides 3j-s.
Representative Analytical DataDiethyl 1-(3-Methylphenyl)-hydrazine-1,2-dicarboxylate (3j) Yellow oil; yield 0.22 g (83%). IR (KBr): ν_max = 3310, 1539, 1510, 1321, 1132 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 1.27 (3 H, t, ^³ J = 7.2 Hz, Me), 1.30 (3 H, t, ^³ J = 7.1 Hz, Me), 2.32 (3 H, s, Me), 4.20 (4 H, m, 2 CH₂O), 6.96 and 7.07 (1 H, br s, NH), 7.12 (1 H, d, ^³ J = 7.2 Hz, CH), 7.20 (1 H, d, ^³ J = 7.3 Hz, CH), 7.26 (1 H, s, CH), 7.45 (1 H, t, ^³ J = 7.2 Hz, CH). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 19.6 (Me), 19.9 (Me), 26.6 (Me), 67.6 (CH₂O), 68.2 (CH₂O), 125.4 (CH, br), 130.3 (CH, br), 133.6 (CH), 136.3 (CH), 141.2 (C), 143.8 (C), 156.5 (C=O), 161.5 (C=O). MS: m/z (%) = 266 (1) [M⁺], 194 (13), 166 (100), 148 (16), 122 (14), 120 (68), 105 (17), 91 (8). Anal. Calcd (%) for C₁₃H₁₈N₂O₄ (266.29): C, 58.63; H, 6.81; N, 10.52. Found: C, 58.83; H, 6.88; N, 10.69.
Diisopropyl 1-(3-Methylphenyl)-hydrazine-1,2-dicarboxylate (3k) Yellow oil; yield 0.24 g (81%). IR (KBr): ν_max = 3291, 1527, 1524, 1314, 1112 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 1.17 (6 H, d, ^³ J = 7.2 Hz, Me), 1.28 (6 H, t, ^³ J = 7.1 Hz, Me), 2.32 (3 H, s, Me), 4.97-4.99 (2 H, m, 2 CHO), 6.67 and 6.71 (1 H, br s, NH), 6.90 (1 H, d, ^³ J = 7.2 Hz, CH), 6.97
(1 H, d, ^³ J = 7.3 Hz, CH), 7.20 (1 H, s, CH), 7.28 (1 H, t, ^³ J = 7.2 Hz, CH). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 21.6 (2 Me), 21.9 (2 Me), 29.6 (Me), 70.6 (CHO), 70.8 (CHO), 121.4 (CH, br), 124.3 (CH, br), 126.6 (CH), 128.3 (CH), 138.2 (C), 141.8 (C), 154.5 (C=O), 156.5 (C=O). MS: m/z (%) = 294 (1) [M⁺], 208 (13), 166 (100), 148 (16), 122 (14), 120 (68), 105 (17). Anal. Calcd (%) for C₁₅H₂₂N₂O₄ (294.35): C, 61.21; H, 7.53; N, 9.52. Found: C, 61.42; H, 7.62; N, 9.60.

13

The reaction of aryl bromides was improved in the presence of Phen.