Tetraalkyl Hydroxymethylene-bisphosphonate and Dialkyl 1-Diphenylphosphinoyl-1-hydroxy-ethylphosphonate Derivatives by the Pudovik Reaction and Their Rearranged Products.

Zsuzsanna Szalai,György Keglevich

doi:10.3390/molecules26247575

Zsuzsanna Szalai, György Keglevich

Open Access

https://doi.org/10.3390/molecules26247575

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Abstract

The reaction of diethyl α-oxoethylphosphonate and diethyl oxobenzylphosphonate with diethyl phosphite, dimethyl phosphite, and diphenylphosphine oxide affords, depending on the substrates and conditions (nature and quantity of the amine catalyst, temperature, and solvent), the Pudovik adduct and/or the corresponding >P(O)–CH–O–P(O)< product formed by rearrangement. The nature of the substituent on the central carbon atom (a methyl or phenyl group) influences the inclination for the rearrangement. The asymmetric products (either adducts or rearranged species) with different P(O)Y functions (Y = RO or Ph) exhibit interesting NMR features.

Highlights

Hydroxymethylene bisphosphonic acid derivatives are of importance due to their beneficial effect in the treatment of bone diseases [1,2,3,4]
Their synthesis, starting from the corresponding substituted acetic acid and phosphorus trichloride/phosphorous acid, was thoroughly investigated [1,5,6]. Another approach is the Pudovik reaction, the original version of which involves the addition of dialkyl phosphites onto the carbonyl carbon of oxo compounds, such as aldehydes and ketones [7,8]
Diethyl α-oxoethylphosphonate obtained by the Arbuzov reaction of the firstand case,triethyl diethylphosphite, α-oxoethylphosphonate obtained by thereaction

Summary

Introduction

Hydroxymethylene bisphosphonic (dronic) acid derivatives are of importance due to their beneficial effect in the treatment of bone diseases [1,2,3,4] Their synthesis, starting from the corresponding substituted acetic acid and phosphorus trichloride/phosphorous acid, was thoroughly investigated [1,5,6]. Later on, on, both both the the diethyl diethyl α-oxoethylphosphonate–diethyl α-oxoethylphosphonate–diethyl phosphite phosphiteadduct adduct and and the the related rearranged product could be selectively prepared in a solvent-free microwave-assisted related rearranged product could be selectively prepared in a solvent-free microwavemanner, applying temperature of 120 ◦ C forof20120 min withtogether.

Results and Discussion

31 P-NMR spectra comprising doublet patterns for Products

C15 H26 as

General

Synthesis of the Target Compounds

Conclusions