1802 Current Organic Chemistry, 2011, 15, 1802-1810 1385-2728/11 $58.00+.00 © 2011 Bentham Science Publishers Ltd. Microwave-Assisted Esterification of Phosphinic Acids György Keglevich, 1 * Erika Bálint, 1 Nóra Zs. Kiss, 1 Erzsébet Jablonkai, 1 László Hegeds, 2 Alajos Grün 1,2 and István Greiner 3 1 Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary 2 Research Group of the Hungarian Academy of Sciences at the Department of Organic Chemistry and Technology, Budapest Univer- sity of Technology and Economics, 1521 Budapest, Hungary 3 Gedeon Richter Plc., 1475 Budapest 10, PO Box 27, Hungary Abstract: The usual synthesis of phosphinates involving the reaction of phosphinic chlorides with alcohols or phenols in the presence of a tertiary amine in an apolar solvent cannot be regarded as “green” and requires expensive P-reagents. We have found that in certain cases phosphinic acids can be esterified by simple alcohols under microwave (MW) conditions. Hence, cyclic phosphinic acids, such as 1-hydroxy-3- and 2-phospholene 1-oxide derivatives (A), 1-hydroxyphospholane 1-oxides (B) and 1-hydroxy-1,2,3,4,5,6- hexahydrophosphinine 1-oxide (C) could be converted to the corresponding esters by reaction with alcohols. Using a 15-fold excess of the alcohol at around 200 °C, the preparative yields of the phosphinates amounted to 45-60%. The novel reaction is the consequence of the beneficial specific MW effect that was proved by comparative thermal experiments. Phosphinates may also be prepared by the alkylating esterification of phosphinic acids with alkyl halides. Under solventless and MW conditions in the presence of a phase transfer (PT) catalyst and K2CO3, cyclic phosphinic acids A, B and C mentioned above were con- verted to the corresponding phosphinates in 85-95% yields. It was found that the simultaneous use of the MW and PT catalytic tech- niques is beneficial when alkyl halides of normal or decreased reactivity are applied. Both methods described can be regarded as environmentally friendly and offer advantages over the traditional esterifications of phosphinic acids. Key Words: Microwave, green chemistry, esterification, phosphinic acids, phosphinates. 1. INTRODUCTION As phosphinic acids cannot undergo direct esterification with alcohols, phosphinates are usually prepared by the reaction of phosphinic chlorides with alcohols and phenols (Scheme 1) [1,2]. R 1 R 2 P(O)Cl + NEt 3 ArH - HCl 1 2 R 3 OH R 1 R 2 P(O)OR 3 Scheme 1. A general route for the preparation of phosphinates. Although this method has drawbacks from the point of view of “green” chemistry and costs, it is widely applied in industry. The hydrochloric acid liberated is removed by a tertiary amine or alkali hydroxide. The phosphinic chlorides are mostly obtained from phosphoryl chloride, P(O)Cl 3 , by two sequential substitutions. It is also possible to make available the starting phosphinic chlorides from phosphinic acids by reaction with (inorganic) acid chlorides, such as thionyl chloride, phosphorus pentachloride or phosgene. In a one-pot accomplishment, the phosphinic chloride is prepared “in situ” from the corresponding acid by thionyl chloride and the P- chloride so-formed reacts immediately with the alcohol present in the mixture [3]. It is also possible to synthesize phosphinates by the alkylation of phosphinic acids. In this case, either alkyl halides, or unsaturated *Address correspondence to this author at the Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521 Budapest, Hungary; Tel: +36 1 4631111/5883; Fax: +36 1 4633648; E-mail: gkeglevich@mail.bme.hu agents, such as olefins or acetylenes may be the reactants. Using alkyl halide, the phosphinic acid should first be converted to an alkali salt [4,5], or the alkylation should be carried out under phase transfer catalytic conditions [6]. The addition of acids to unsatu- rated systems may be accomplished in the presence of catalysts [7]. The esterification of phosphinic acids is also possible by special methods applying orthoacetates [8], chloroformates [9], orthosili- cates [10-12] and trialkyl phosphites [13,14]. Direct esterification was only described for the dithio derivative of phenylphosphinic acid. In reaction with primary alcohols, phenylphosphinothioates, PhP(S)(OR)H, were obtained [15]. The phosphinic chloride  phosphinate conversion is also ap- plicable for the synthesis of cyclic phosphinates. For example, 1- alkoxy-3-phospholene oxides (6) were synthesized from the 1- hydroxy-3-phospholene oxides 4, obtained by the hydrolysis of the so-called McCormack cycloadducts 3, via 1-chloro-3-phospholene oxides 5 (Scheme 2) [16]. The 1-alkoxy-3-phospholene oxides (6) may also be obtained directly from the tribromophospholium salts (3) by alcoholysis [17-19]. It was a challenge for us to try to make use of the microwave (MW) technique in the synthesis of phosphinates either in direct esterification, or in phase transfer catalyzed alkylating esterifica- tion. We have found that MW irradiation made possible transforma- tions that were otherwise impossible under thermal conditions [20]; in other instances, MW irradiation was highly beneficial regarding the rate [20,21] and selectivity [22,23], or as a substitute for catalyst [24,25].