# Synthesis of Fused sp3‐Enriched Imidazoles

## TL;DR

A new method was developed to synthesize fused imidazoles with specific chemical groups using two known reactions.

## Contribution

A scalable synthesis of fused sp3-enriched imidazoles using Neber and Marckwald reactions was developed.

## Key findings

- Previously unknown α-amino ketones were prepared in bulk using the Neber rearrangement.
- High-purity imidazol-2-thiones and imidazol-2-ones were synthesized using potassium thiocyanate and cyanate.
- Desulfurization with Raney nickel produced new 2-unsubstituted fused imidazoles in high yields.

## Abstract

A synthetic approach to imidazoles annulated to saturated six‐membered cycles featuring S, SO2, NH, NCbz was developed. It was achieved by combining the Neber rearrangement and the Marckwald reaction. The Neber rearrangement applied to cyclic ketones allowed us to prepare in hundred gram quantities previously unknown α‐amino ketones. Unstable tosyl ketoximes were used without purification immediately after their preparation. α‐Amino ketones react with potassium thiocyanate and cyanate in almost a quantitative yield affording highly pure imidazol‐2‐thiones or imidazol‐2‐ones. Desulfurization of imidazole‐2‐thiones using Raney nickel led to the formation of previously unknown 2‐unsubstituted fused imidazoles in high yields.

Imidazoles annulated to saturated six‐membered cycles featuring S, SO2, NH, NCbz have been prepared in bulk quantities. The starting previously unknown cyclic α‐amino ketones were obtained via the Neber rearrangement. Unstable tosyl ketoximes were used without purification immediately after their preparation. Marckwald reaction with desulfurization using Raney nickel led to the formation of the annulated imidazoles.