Solvent-Free Michaelis–Arbuzov Rearrangement under Flow Conditions

Abstract

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.

Optically Active Selenoxides: Structural and Synthetic Aspects

“…It is reasonable to expect that further research will allow the preparation of model compounds containing sterically demanding substituents, which in turn enable the preparation of optically active selenoxides with optical stability comparable to sulfoxides. Experimental works currently carried in our laboratories, focused on methodological and stereochemical aspects of flow processes [72] and mechanochemical procedures, allow us to have legitimate hope for reaching this goal.…”

Continuous Flow Organophosphorus Chemistry

“…[63] A continuous flow system was recently developed by Jasiak and co-workers to host a Michaelis-Arbuzov reaction (including rearrangements). [65] The procedure led to a significantly reduced reaction time down to a 8.33-50 min range with conversions up to ≥99 % under neat conditions ( Figure 16). However, the effectiveness of the system was strongly dependent on substrate and temperature.…”

“…Continuous flow system used for the preparation of various phosphonate derivatives by a Michaelis-Arbuzov reaction. [65] substituents. Typically, excellent selectivities towards the desired product could be achieved with 1-1.5 equiv.…”

Electrochemical Phosphorylation of Organic Molecules

“…[1][2][3][4][5][6][7][8] Considering this, the development of new strategies for obtaining new PÀ C and PÀ heteroatom bonds is of great interest, expanding the application possibilities. Generally, the most common paths for the construction of PÀ C and PÀ X (X=N, O, S and Se) bonds proceed by the nucleophilic substitution of toxic halides with ROH/RSX, [9] Friedel-Crafts reaction, [10] Michaelis-Arbuzov reaction [11] and also with the use of organometallic and a phosphine. [12] Likewise, phosphorus reagents can be applied as nucleophilic species for the formation of new bonds, starting for example from dialkyl-or diaryl-phosphine oxides, phosphonates esters, hypophosphite, phosphines, phosphine-borane, among others.…”