Koch–Haaf reaction of adamantanols in an acid-tolerant hastelloy-made microreactor

Takahide Fukuyama,Ilhyong Ryu,Yu Mukai

doi:10.3762/bjoc.7.149

Abstract

The Koch–Haaf reaction of adamantanols was successfully carried out in a microflow system at room temperature. By combining an acid-tolerant hastelloy-made micromixer, a PTFE tube, and a hastelloy-made microextraction unit, a packaged reaction-to-workup system was developed. By means of the present system, the multigram scale synthesis of 1-adamantanecarboxylic acid was achieved in ca. one hour operation.

Highlights

The recent evolution of microreactor technology has allowed synthetic chemists to use this precisely sophisticated reaction apparatus in place of the well-established glassware batch flask [1-10]
The Koch–Haaf reaction [25], that is the carbonylation of alcohols or olefins with formic acid in the presence of a strong acid, is an important reaction for the preparation of carboxylic acids, which are widely used in organic synthesis [26-31]
When the reaction of 1a (45 mmol) was performed for 55 min, 7.1 g of 2a was obtained in 88% yield, demonstrating that the present microflow system can be used for multigram scale synthesis without any problems (Scheme 3)

Summary

Introduction

The recent evolution of microreactor technology has allowed synthetic chemists to use this precisely sophisticated reaction apparatus in place of the well-established glassware batch flask [1-10]. We report that the Koch–Haaf reaction in a microflow reactor can be carried out at room temperature without any cooling equipment. 1-Adamantanol (1a) dissolved in HCOOH (flow rate: 0.30 mL/min) and 98% H2SO4 (flow rate: 0.88 mL/min) were mixed in the micromixer at room temperature, and the resulting reaction mixture was fed into the PTFE tube and into the extraction unit, in which Et2O (flow rate: 2.5 mL/min) and water (2 mL/min) were introduced to extract the carbonylation product and remove excess acids (Scheme 1).

Results

Conclusion