The first solvent-
and catalyst-free procedure for the Michaelis–Arbuzov
reaction under flow conditions was developed. A variety of alkylphosphonic
esters could be obtained using this protocol starting from the corresponding
trialkyl phosphites and even catalytic amounts of alkyl halides with
very short reaction times (8.33–50 min) and excellent conversions.
In general, this protocol works effectively when the alkyl halide
is used in catalytic amounts as low as 5–10% only if it concerns
the synthesis of homo alkylphosphonates. One equivalent and an excess
of alkyl halides should be used in the reaction with alkyl phosphite
if the alkyl group of the selected substrates differ. Thus, it provides
a sustainable, fast alternative to the existing methods for the preparation
of alkylphosphonates. The isolation of the reaction products is straightforward
due to the lack of solvents and a high purity of the obtained products
(conv ≥ 99%), and notably, in the catalytic procedures there
are only traces of alkyl halides formed after the reaction is complete.
The reactions conducted using a glass microreactor chip with an internal
volume of 250 μL allow the production of 1.6–1.95 g of
organophosphorus esters per hour.
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