Microwave in Organophosphorus Syntheses

The spread of professional microwave (MW) reactors in the last 25 years brought about a revolutionary change in synthetic organic chemistry. This methodology has also had a positive inpact on organophosphorus chemistry enhancing reluctant reactions, or just making the reactions more efficient in respect of rate, selectivity and yield. In special cases, MW irradiation may substitute catalyst, or may simplify catalytic systems. Introduction The use of the microwave (MW) technique spread fast in synthetic laboratories, and these days it knocks at the door of industry. At the beginning, only domestic MW ovens were available, but later, different variations of professional MW equipment were developed and utilized in many kind of syntheses, such as substitutions, additions, eliminations, condensations, acylations, esterifications, alkylations, C–C coupling reactions, cycloadditions, rearrangements and the formation of heterocycles [1]. The main problem with industrial application is the scale-up [2,3]. On the one hand, there is a problem with the structural material, as the batch reactors may be made of only teflon or glass. On the other hand, the limited penetration depth of MWs into the reaction mixtures prevents the construction of bigger size batch reactors. Presently, the only possibility for a certain degree of scale-up is the use of continuous-flow reactors [2,4]. A batch MW reactor may be supplied with a flow cell, where the mixture is moved by pumps. In another variation, a continuous tube reactor with a diameter of up to 6–9 mm was elaborated that makes possible the processment of ca 300 l/day [5]. A capillary microreactor consisting of four parallel capillary tubes was also described. The above equipment may be used well in industrial research and development laboratories. The only criterion of such application is that the reaction mixtures must not to viscous and heterogeneous. The author of this paper believes that “bundle of tubes” reactors incorporating a number of glass tubes with a diameter of several mm-s may bring a breakthrough in the industry. Another good accomplishment is to apply assembly linetype equipment that transports the solid reaction components placed in suitable vessels into a tunnel, where the irradiation takes place [6]. The most common benefits from MW irradiation is the considerable shortening of reaction times and the increase in the selectivities. However, the most valuable benefit is when a reaction can be performed that is otherwise rather reluctant under traditional thermal conditions. This may be the consequence of a so-called special MW effect [7]. There are, of course, other advantages as well that will be shown below within the pool of organophosphorus chemistry that is a dynamically developing field. Organophosphorus compounds including P-hetereocycles find applications in synthetic organic chemistry as reactants, solvents (ionic liquids), catalysts and P-ligands and, due to their biological activity, also as components of drugs and plant protecting agents [8-9]. The utilization of MW irradiation in organophosphorus chemistry is a relatively new field [10-13]. In this article, the attractive features of the application of the MW technique in organophosphorus syntheses are summarized in four groups. Reactions those are Reluctant under Thermal Conditions The most common way to prepare esters is the acid catalyzed direct esterification of carboxylic acids with alcohols (Figure 1). The reaction is reversible, hence the alcohol should be applied in excess and/or the water formed should be removed by distillation, in most cases, in the form of binary or ternary azeotropes. Phosphinic acids, however, do not undergo esterification with alcohols to afford phosphinates, or the reaction is rather reluctant (Figure 2/A). For this, the esters of phosphinic acids are synthesized by the reaction of phosphinic chlorides with alcohols in the presence of a base (Figure 2/B) [8]. An alternative possibility is preparation by the Arbuzov reaction (Figure 2/C) [8].