Metal-Free Synthesis of C-3-Alkoxycarbonylated 2H-Indazoles Using Alkyl Carbazates

This paper is dedicated to Professor Brindaban C. Ranu on the occasion of his 75^th birthday.

Abstract

A simple, efficient, and environmentally benign method for the direct C-3-alkoxycarbonylation of 2H-indazoles using alkyl carbazates has been developed under metal-free conditions at room temperature. This current protocol represents a facile access to C-3-carboxylic ester derived 2H-indazoles with wide functional group tolerance in good to excellent yields. The mechanistic studies suggest that the reaction proceeds through a radical pathway.

Key words

metal-free - C-3-alkoxycarbonylation - 2H-indazole - synthetic transformations - alkyl carbazate

Publication History

Received: 23 March 2024

Accepted after revision: 29 April 2024

Accepted Manuscript online:
29 April 2024

Article published online:
16 May 2024

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• 15 General Experimental Procedure for the Synthesis of C-3-Alkoxycarbonylated 2H-Indazoles 3 and 5 A mixture of 2-arylindazoles 1/4 (0.2 mmol), alkyl hydrazinecarboxylate 2 (2.0 equiv), and TBHP (4.0 equiv, 0.14 mL) was taken in an oven-dried reaction tube under N₂ atmosphere. Then 1,2-DCE (2 mL) was added to it using a syringe, and the reaction mixture was further stirred at room temperature for 8 h under N₂ atmosphere. After completion of the reaction (TLC), the reaction mixture was extracted with DCM (10 mL). The organic phase was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to get the crude residue which was purified by column chromatography on silica gel (100–200 mesh) using a mixture of petroleum ether and ethyl acetate as an eluent to afford the corresponding products 3/5. Analytical Data for Compound 3ha White solid (67%, 42.9 mg); R_f = 0.50 (PE:EtOAc = 96:4); mp 155–156 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.10 (d, J = 8.4 Hz, 1 H), 7.85 (d, J = 8.4 Hz, 1 H), 7.80 (d, J = 8.4 Hz, 2 H), 7.68 (d, J = 8.0 Hz, 2 H), 7.46–7.42 (m, 1 H), 7.39–7.35 (m, 1 H), 3.94 (s, 3 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 160.0, 148.9, 143.6, 131.6, 131.3, 127.7, 127.0, 126.2, 125.9 (q, J _C–F = 4.0 Hz), 124.2, 123.8 (q, J _C–F = 271.0 Hz), 121.6, 118.8, 52.3. FTIR: ν = 3055, 1708, 1616, 1462, 1296, 1103 cm^–1. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for [C₁₆H₁₂F₃N₂O₂]⁺: 321.0845; found: 321.0841. Analytical Data for Compound 5aa White solid (77%, 45.6 mg); R_f = 0.5 (PE:EtOAc = 94 : 6); mp 134–135 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.72 (d, J = 9.2 Hz, 1 H), 7.39–7.37 (m, 2 H), 7.31–7.29 (m, 3 H), 7.10–7.07 (m, 1 H), 3.92 (s, 3 H), 3.89 (s, 3 H), 2.45 (s, 3 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 160.3, 158.1, 145.2, 139.3, 138.7, 129.3, 126.0, 125.0, 123.9, 122.0, 120.1, 97.9, 55.6, 51.9, 21.4. FTIR: ν = 3032, 1712, 1631, 1442, 1211, 1126 cm^–1. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for [C₁₇H₁₇N₂O₃]⁺: 297.1234; found: 297.1225.