Dialkyl H-phosphonates

Silver carbonate catalyzes the carbon phosphonation of aryl propiolates with dialkyl H-phosphonates in order to prepare 3-phosphonated conma-rins (140L3356). Other propiolates undergo copper(II)-mediated direct trifluoromethylation with Togni s reagent 19 providing 3-trifluoromethyl-coumarins (Scheme 54) (14OL4240). 

Dialkyl H-phosphonates are produced in the USA, Japan, Germany and other countries on an industrial scale primarily from phosphorus trichloride and alcohols. (The general procedure for the preparation of dialkyl H- phosphonates is given in the Appendix). 

The synthesis of higher dialkyl H-phosphonate homologues usually includes the initial treatment of phosphoms trichloride with methyl alcohol, and then the transesterification of so-formed dimethyl H-phosphonate with higher alcohols [16,17],... 

Saks et al. [27] used for the first time H-phosphonic add for the preparation of dialkyl H-phosphonates. There are a few patents devoted to the preparation of dialkyl H-phosphonates via direct esterification of H-phosphonic add with alcohols [28-31]. The process involves heating under reflux a mixture of H-phosphonic acid, an alcohol in excess of that reqnired... 

This method for preparation of dialkyl H-phosphonates involves oxidation of white phosphorus followed by treatment of the intermediate with alcohols [39],... 

Asymmetric dialkyl H-phosphonates are formed by heating equimolar mixtures of two types symmetric dialkyl H-phosphonates [40,41]. 

It has been shown [42] that mixed (asymmetric) dialkyl H-phosphonates can also be... 

The mixed dialkyl H-phosphonates are of particular interest in organophosphorus chemistry because of the presence of a chiral center at the phosphorus atom. 

Other methods for synthesis of dialkyl H-phosphonates have also been reported [43], but the above mentioned are the most frequently used and are of major practical importance. 

Dialkyl H-phosphonates are liquids under normal conditions, soluble in alcohols, diethyl ether, acetone, chloroform, tetrahydrofurane, benzene, and other common... 

Higher dialkyl H-phosphonate homologues such as butyl and amyl usually decompose at higher temperatures. 

General procedure for the preparation of dialkyl H-phosphonates from phosphorus trichloride (ref U.S. Pat. 2,582,817 (1952). 

In dialkyl H-phosphonates, the phosphorus atom is in the sp hybrid state. To obtain this state, the phosphorus atom has to render a 3s electron to the oxygen atom of the phospho-ryl group and as a result, the phosphorus becomes positively charged and the oxygen, negatively charged. 

In this hybrid state, the phosphorus atom forms four a bonds and it is positively charged. This is its first special feature. The sp hybrid state defines the fourth valence of the phosphorus atom, but in dialkyl H-phosphonates it is of fifth valence. In the nontransition elements including phosphorus, s and p atomic orbitals do not form hybridized orbitals with hole exponents, that is, valence states such as sp, sp, and sp are formal and arbitrary to a great extent. This is the second special feature of the phosphorus atom in dialkyl H-phosphonates, which can be explained by the type of bonds in the phosphoryl group (P=0). 

The chemical bonds in the phosphoryl group of the dialkyl H-phosphonates are one a bond and one n bond, formed at the expense of the phosphorus free d orbitals and one of the free 2p electron pairs of the oxygen. 

Although there is no direct experimental evidence for the existence of the three-coordinated phosphite form, the tautomerization of dialkyl H-phosphonates to dialkyl phosphites has often been invoked to explain the mechanism of other reactions of dialkyl H-phosphonates, which result in a P-H bond cleavage. Dimethyl phosphite, although never experimentally observed, has been studied recently by ab-initio computations. Conformational analysis for this compound [6] results in four stable conformers (Figure 2.2). Conformer... 

These computational results provide indirect support to the early considerations that the tautomerization of dialkyl H-phosphonates is a catalytic process that is accelerated in... 

There is currently no proof for the existence of dialkyl H-phosphonates in phosphite form in basic medium. Studies of the dialkyl H-phosphonate structure in a basic medium (e.g., amines) by H and NMR and IR spectroscopy have shown that dialkyl H-phosphonates exist entirely in their four-coordinate phosphonate form [19-22], An alkylation of the amine and not a deprotonation of dialkyl H-phosphonates occurs ... 

The IR spectra of diesters of H-phosphonic acid contain characteristic bands attributed to the P=0, P-H, and P-O-C vibrations that are used in the structural characterization of this type of compound. The positions of the P-H and P=0 absorption bands depend largely on the type of the substituents R. More detailed studies of the vibrational spectra and force constants for some dialkyl H-phosphonate representatives have been reported recently [24]. 

NMR spectroscopy is one of the most powerful tools for structural characterization of dialkyl H-phosphonates, since the latter are not suitable for X-ray analysis. The most... 

The following ranges for the coupling constants have been observed for H-phosphonate diesters V(PH) from 670 to 740 Hz V(PH) from 6.5 to 12.0 Hz. The H NMR data for some representative dialkyl H-phosphonates are given in Table A2. 

A characteristic feature of the carbon NMR spectra of dialkyl H-phosphonates is the /(PC) coupling through the oxygen heteroatom. These coupling constants have values in the range 5-8 Hz and can be observed through up to three bonds V(PC) and V(PC) (see A4). 

Dialkyl H-phosphonates are reduced by organomagnesium compounds to dialkyl phos-phinous acids [10-13],... 

Dialkyl H-phosphonates are hydrolytically unstable compounds. The hydrolysis of H-phos-phonate diesters and phosphate esters is believed to proceed via pentacoordinated intermediates and transition structures that are formed by nucleophilic attack of the tetracoordinated phosphorus atom [14-16]. These intermediates undergo further pseudorotation [17] and elimination of alcohol to form the final products of the nucleophilic substitution. 

It has been established that the hydrolysis of dialkyl H-phosphonates is general-base and general-acid catalyzed [18]. The hydrolysis of phosphonic acid diesters is facilitated significantly under basic conditions. The mechanism of the base-catalyzed hydrolysis of dimethyl H-phosphonate has been proposed to take place according to the following scheme [19] ... 

The second methoxy group hydrolyzes in the same way to yield H-phosphonic acid as a final product. The rate of the alkaline hydrolysis of dialkyl H-phosphonate depends on the substituent type at the phosphorus atom [18] (Table 3.2). 

Taft constants a, aP, and of the substituent R for the alkaline hydrolysis of dialkyl H-phosphonates with general formula (R0)2P(0)H [20]... 

It is suggested that when the transesterification reaction is carried out in the presence of a basic catalyst, dialkyl H-phosphonates react via their tricoordinated phosphite tautomeric form [32,35], The first step of the reaction is tautomerization of phosphonate form into phosphite. 

More recent studies of the interaction between dialkyl H-phosphonates and amines indicate that the amine catalysis has a more complex character than initially assumed. 

The transesterification of dialkyl H-phosphonates with hydroxyl-containing compounds is accompanied by side reactions, resulting in the formation of ether compounds and H-phos-phonic acid monoalkyl esters [28,36,37]. The formation of these side products is due to the nucleophilic attack of the oxygen atom of the alcohol on the ot-carbon atom of the alkoxy group, the second electrophilic center in the molecule of dialkyl H-phosphonates. 

The oxidation of dialkyl H-phosphonates with chlorine leads to the formation of the corresponding chlorophosphates [69]. 

Reaction of dialkyl H-phosphonates and sulfuric dichloride yields fcw-(dialkoxyphos-phonyl) disulfides [72],... 

Dialkylchlorophosphites can be obtained reacting dialkyl H-phosphonates with phosphorus pentachloride or thionylchloride [79]. 

The Atherton-Todd reaction is an interaction of dialkyl phosphonates with chlorocarbons in the presence of a base (see Appendix) [80]. This is a route for the oxidation of dialkyl H-phosphonates to the highly reactive dialkyl chlorophosphates, which are usually not isolated, but rather used in situ under mild conditions [81]. 

Reaction mechanism. The commonly proposed mechanism of the reaction [81-85] is based primarily on the early kinetic investigations by Steinberg [81], The initial step of this mechanism involves deprotonation of dialkyl H-phosphonate (RO)2P(0)H by a base B to give the dialkyl phosphite anion, (ROljPO". This anion then reacts as a nucleophile toward carbon tetrachloride, resulting in the sequence of reactions shown on the next scheme. In this scheme, step 1 leads to the formation of the active species (RO)2PO , while steps 2 and 3 in the scheme represent the cycle of reactions that lead to the formation of the products. 

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