One-Pot Synthesis of Novel 2,3-Dihydro-1H-indazoles

Abstract

A copper(I)-mediated one-pot synthesis of 2,3-dihydro-1H-indazole heterocycles has been developed. This synthetic route provides the desired indazoles in moderate to good yields (55%–72%) which are substantially better than those achievable with an alternative two-step reaction sequence. The reaction is tolerant of functionality on the aromatic ring.

Convenient Synthesis of Monobenzylated Hydrazides via Aqueous Zinc-Mediated Addition Reactions

“…. According to Method A, from 0.250 g (1 mmol) of 1-bromo-2-(bromomethyl)benzene was obtained 0.335 g (86% yield) of 5e as a white solid: 97.2-98.1 °C; 1 H NMR (CDCl 3 , 60 °C)  7.52 (d, J = 7.8 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.26 (t, J = 7.8 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 6.40 (br s, 1H), 4.76 (s, 2H), 1.47 (s, 9H), 1.44 (s, 9H); 13 C NMR (CDCl 3 , 60 °C)  155. 3, 155.0, 136.4, 132.9, 130.5(br), 129.0, 127.4, 124.0(br), 81.5, 81.2, 53.8(br) 6.28;N,6.98.…”

“…. 1 According to Method A, from 0.297 g (1 mmol) of 1-iodo-2-(bromomethyl)benzene was obtained 0.351 g (79% yield) of 5f as a white solid: mp 122.5-124.5 °C; 1 H NMR (CDCl 3 , 60 °C)  7.80 (d, J = 7.9 Hz, 1H), 7.32-7.26 (m, 2H), 6.93 (dt, J = 7.9, 2.5 Hz, 1H), 6.40 (br s, 1H), 4.71 (s, 2H), 1.47 (s, 9H), 1.44 (s, 9H). 13 C NMR (CDCl 3 , 60 °C)  155.…”

“…The combined organic layers were dried over Na 2 SO 4 , filtered, and concentrated. Column chromatography on SiO 2 using a 4:1 mixture of hexanes: ethyl acetate as eluent afforded 0.286 g (97% yield) of 7 as a white solid: mp 90.0-90.5 °C; 1…”

“…Method A, from 0.185 g (1 mmol) of(1bromoethyl)benzene was obtained 0.257 g (77% yield) of 5k as a white solid: mp 86.5-88.0 °C (lit. 3 87-88 °C);1 H NMR (CDCl 3 , 60 °C)  7.30-7.20 (m, 5H), 6.01 (br s, 1H), 5.41 (br m, 1H [this signal is a quartet, J = 7 Hz, at 60 MHz]), 1.52 (d, J = 6.8 Hz, 3H), 1.45 (s, 9H), 1.43 (br s, 9H); 13 C NMR (CDCl 3 , 60 °C)  155.8, 154.8, 141.5, 128.4, 127.4(2C), 81.2, 80.9, 55.9(br), 28.3, 28.2(br), 17.0.…”

Recent Synthetic Developments and Applications of the Ullmann Reaction. A Review

“…177,178 On the basis of this work, Breton and Lepore 179 designed a copper-catalyzed protocol for the one-pot synthesis of 2,3-dihydro-1 H -indazoles using L10 as the ligand in 2011 (Scheme 43). Copper-catalyzed reaction of o -halophenyl aldehydes or ketones with monosubstituted hydrazines was reported in the synthesis of 1-aryl-1 H -indazoles by Ding’s team.…”