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

Abstract

SummaryThe 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.

The Use of Gases in Flow Synthesis

“…The same group published a similar protocol for the carbonylation of alcohols through the Koch–Haaf reaction . Again, concentrated sulfuric acid and formic acid were directly mixed with the substrate in a Hastelloy-made micromixer.…”

Controlled generation and use of CO in flow

“…2,4,6-Trichlorophenyl formate has been reported as a CO surrogate in the Pd catalyzed synthesis of (hetero)aromatic 2,4,6-trichlorophenol esters, 14 and the dehydration of formic acid by concentrated H 2 SO 4 has been employed as an in situ CO source for the Koch-Haaf reaction in a specialist hastelloy microreactor. 15 The main limitation of these kinds of surrogates is that the chemistry must be compatible with both the surrogate itself and the conditions needed for CO release. Pd catalyzed carbonylation of aryl halides using 2,4,6-trichlorophenyl formate as CO source leads to the corresponding trichlorophenol esters, requiring an additional step to obtain other derivatives, and dehydration of formic acid with H 2 SO 4 limits the reaction to substrates that are very acid resistant.…”

Carbonylation in microflow: close encounters of CO and reactive species

“…We recently reported a microfluidic approach for the Koch-Haaf reaction, 5 where the carbonylation of alcohols with formic acid occurs in the presence of a strong acid, such as sulfuric acid. 32 While the reaction in a batch flask is typically carried out at controlled temperature using a cooling bath, such as an ice bath, 33 the reaction could be carried out at room temperature without the use of any cooling equipment when a microflow system was employed. For example, the flow carbonylation of 1-adamantanol can be performed successfully at room Scheme 10 Pd-catalyzed carbonylative Sonogashira reaction in an ionic liquid, [bmim]PF 6 , using a stainless-steel made tubular reactor (a photo is taken using a PTFE tube).…”