# 1H-Indoles from Deoxybenzoin Schiff Bases by Deprotonation—SNAr Cyclization

## TL;DR

A new method for making 1H-indoles without using transition metals is described, using a sequence of deprotonation and SNAr cyclization from deoxybenzoin Schiff bases.

## Contribution

The paper introduces a transition metal-free synthesis of 1,2,5-trisubstituted 1H-indoles via deprotonation–SNAr cyclization of deoxybenzoin Schiff bases.

## Key findings

- The synthesis uses Friedel-Crafts acylation to prepare deoxybenzoins from activated aromatic compounds.
- Schiff bases were formed by slow distillation of toluene from heated solutions of deoxybenzoin and amines.
- Benzyl and phenethyl amines gave excellent yields, while volatile amines resulted in low yields.

## Abstract

A transition metal-free synthesis of 1,2,5-trisubstituted 1H-indoles by a deprotonation–SNAr cyclization sequence from 1-aryl-2-(2-fluoro-5-nitrophenyl)ethan-1-one (deoxy-benzoin) Schiff bases is reported. The starting deoxybenzoins were prepared by Friedel-Crafts acylation of activated aromatic compounds by 2-(2-fluoro-5-nitrophenyl)acetyl chloride with AlCl3 or the corresponding acid with (CH3SO2)2O. The Schiff bases were generated by slow distillation of toluene (18–24 h) from a heated solution of each deoxybenzoin (1 equiv) with a benzyl- or phenethylamine, a high-boiling aliphatic amine, or an aniline derivative (5 equiv). Subsequent addition of N,N-dimethylformamide, 2 equiv of anhydrous K2CO3, and heating at 90–95 °C for 18–24 h completed the synthesis. Benzyl-, phenethyl-, and high-boiling amines gave excellent yields while the heating requirements for the initial condensation made volatile aliphatic amines difficult to use and gave low yields. Aniline reactivities correlated with substituent-derived base strength, although modified conditions allowed some yields to be improved. Several anticipated competing processes had minimal impact on the outcome of the cyclizations.