Nóra Zsuzsa Kiss

Insights into a surprising reaction: The microwave-assisted direct esterification of phosphinic acids

It is well-known that phosphinic acids do not undergo direct esterifications with alcohols under thermal conditions. However, the esterifications take place under microwave (MW) irradiation due to the beneficial effect of MW. As a comparison, maximum 12-15% conversions were observed on traditional heating. It was proved experimentally that the MW-assisted esterifications are not reversible under the conditions applied that may be the consequence of the hydrophobic medium established by the long chain alcohol/phosphinic ester. Neither the thermodynamic, nor the kinetic data obtained by high level quantum chemical calculations justify the direct esterification of phosphinic acids under thermal conditions. The thermodynamic data show that there is no driving force for the reactions under discussion. As a consequence of the relatively high values of activation enthalpy (102-161 kJ mol(-1)), these esterifications are controlled kinetically. Comparing the energetics of the esterification of phosphinic acids and the preparative results obtained under MW conditions, one can see the potential of the MW technique in the synthesis of phosphinates. During our study, a series of new cyclic phosphinates with lipophilic alkyl groups was synthesized.

Novel Synthesis of Phosphinates by the Microwave-Assisted Esterification of Phosphinic Acids

Abstract 1-Hydroxy-3-phospholene oxides (1 and 3) and phenyl-H-phosphinic acid (6) are converted to the corresponding phosphinic esters (2, 4, and 7, respectively) by reaction with simple alcohols on microwave irradiation. Under traditional heating conditions, the esterification does not take place, as in the cases of 1 and 3, or is highly incomplete, as in the case of 6. Steric hindrance in diphenylphosphinic acid prevents efficient microwave-assisted esterification.

Microwave-Assisted Organophosphorus Synthesis

The spread of microwave (MW) equipment has brought about a tremendous development in synthetic organic chemistry. This environmentally friendly methodology, associated often with solventless conditions, has also had a positive impact on organophosphorus chemistry, allowing new reactions to be carried out, or increasing the rate, selectivity and yield. In special cases, MW irradiation may replace phase transfer or other kinds of catalysts. Reactions, such as the derivatization of phosphinic acids, the inverse Wittig protocol, Diels– Alder cycloadditions, fragmentation-related phosphorylations, phospha-Michael additions, Kabachnik–Fields condensations, the addition of >P(O)H species to carbonyl compounds, substitution of

A quantum chemical study on the mechanism and energetics of the direct esterification, thioesterification and amidation of 1-hydroxy-3-methyl-3-phospholene 1-oxide

The direct esterification of 1-hydroxy-3-methyl-3-phospholene 1-oxide (1) with 1-butanol is an interesting model, as it fails to occur upon conventional heating, but does, however, take place upon microwave (MW) irradiation. To be able to explain this phenomenon, high level quantum chemical calculations were carried out, considering all relevant intermolecular interactions and applying the explicit and implicit solvent model. The precise energetics (thermodynamic and kinetic data) were in accordance with our experimental observations, and on this basis, we could explain the beneficial effect of MW irradiation. The direct thioesterification and amidation of hydroxy-phospholene oxide 1, occurring only with incomplete conversions under MW irradiation, were also evaluated.

The Potential of Microwave in Organophosphorus Syntheses

GRAPHICAL ABSTRACT Abstract In this paper, our recent results in microwave (MW)-assisted organophosphorus chemistry have been summarized. First, the esterification and amidation of cyclic phosphinic acids are discussed to represent reactions that are practically impossible on conventional thermal heating. Then, our results on the alcoholysis of dialkyl phosphites are demonstrated to show reactions which are reluctant on simple heating, but proceed better on MW irradiation. This is followed by the alkylation of CH acidic compounds, where MW may substitute the phase transfer catalyst. It is also possible that MW and a phase transfer catalyst synergize each other. Finally, our recent findings on the P-ligand-free Hirao reaction under MW conditions are presented.

The synthesis of phosphinates : traditional versus green chemical approaches

Abstract Three alternatives are discussed in comparison with the classical esterification of phosphinic chlorides by reaction with alcohols. All novel methods, such as microwave (MW)-assisted direct esterification, MW-assisted phase transfer catalyzed alkylating esterification and the propylphosphonic anhydride-promoted esterification, start from phosphinic acids and offer different advantages and disadvantages. The methods are analyzed from green chemical point of view.

Direct Estirification and Amidation of Phosphinic Acids Under Microwave Conditions

Abstract Phosphinic acids may be efficiently esterified in microwave-assisted reactions with alcohols. Especially alcohols with longer alkyl chain are suitable reagents for direct esterifications. At the same time, the direct amidation cannot be complete under such conditions. Hence, the tradional amidations via the phosphinic chloride intermediates have to be applied. The values of activation enthalpies and reaction enthalpies obtained by quantum chemical calculations justified the experimental observations. Microwave has a potential in overcoming relatively high activation enthalpies. GRAPHICAL ABSTRACT

Green chemical syntheses and applications within organophosphorus chemistry

Application of the microwave (MW) technique offers many advantages in organophosphorus syntheses. Reluctant reactions may take place on MW irradiation. In most cases, MWs make the reactions more efficient in respect of rate, selectivity and yield. The benefits are shown via representative examples. MW irradiation may replace a catalyst, or simplify catalytic systems. The synthesis of catalysts incorporating heterocyclic P-ligands is also discussed. Where it was relevant, structural chemical details were also provided.

Synthesis of n-butyl ester and n-butylamide of methyl-phenylphosphinic acid: Two case studies

ABSTRACT n-Butyl methyl-phenylphosphinate and methyl-phenylphosphinic n-butylamide were synthesized by different methods: the reaction of methyl-phenylphosphinic chloride with nBuOH or nBuNH2, respectively, the T3P®-promoted derivatization of methyl-phenylphosphinic acid with nBuOH or nBuNH2, the microwave-assisted direct esterification of the model phosphinic acid, and finally the alkylating esterification with n-butyl bromide under phase-transfer-catalytic and microwave-assisted conditions. The different methods, mostly elaborated by us, were compared from practical and environmentally friendly points of view. GRAPHICAL ABSTRACT

To date the greenest method for the preparation of α-hydroxyphosphonates from substituted benzaldehydes and dialkyl phosphites

Abstract Recent synthetic methods for α-hydroxyphosphonates comprise a green, solvent-free accomplishment of the Pudovik reaction that was typically followed by extractions and recrystallization, or even by chromatography, or other operations. We now developed a general procedure applying 10% of triethylamine as the catalyst and a minimum quantity of acetone as the solvent, giving the products in a pure form after a reflux of 5–120 min following the addition of some n-pentane and crystallization on cooling.