Preparation of Phosphites

The interaction of phosphorns trihalides with alcohols involves a series of consecntive and concnr-rent reactions. In the case of phosphorus trichloride, these can be represented by Eqnations 6.306 through 6.309 in which triesters are first formed, followed by stepwise dealkylation to phosphorous acid. 

With alcohols of normal reactivity, the product is often mainly dialkyl hydrogen phosphite (6.310). This can be made np to 85% yield, by adding PCI3 to a mixture of methanol and a higher alcohol at -5°C. The methyl and hydrogen chlorides are then removed by heating under reduced pressure on a steambath. 

PCI3 + 2ROH + MeOH (RO)2POH + MeCl + 2HC1 

By carrying out reactions (6.306-6.308) in the presence of hydrogen chloride acceptors such as pyridine, the isolation of mono, di and trialkyl phosphites is possible. Triphenyl phosphite is more stable than the trialkyl derivatives, and can be made by reaction (6.306), an HCl acceptor not being 

Some phosphites can be prepared by tran -esterification (6.311). Such exchanges are catalysed by sodium alkoxides which can alternatively be used in stoichiometric amounts (6.312). 

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A common synthetic strategy involves reaction of an appropriate chlorophosphine and the amine (primary, secondary, aliphatic, aromatic) in the presence of base (usually triethylamine, pyridine, or DBU (l,8-diazabicyclo[5.4.0]undec-7-ene). Care is often required during these syntheses to exclude water, thereby preventing the formation of Ph2PP(0)Ph2. Work-up procedures are similar to those for the preparation of phosphites, phosphonites, etc. and yields are often high. In some cases this strategy may yield mixtures of (phosphino)amines in which both full and partial aminolysis has resulted. 

Scheme 2.102 Generai method for the preparation of phosphite-modified Rh precatalysts.

Preparation of Phosphites. Alcohols, diols, and phenols are readily converted to phosphites. Analogous reactions are seen with thiols and amines. Diaryl phenols react to form medium-sized heterocyclic ring systems (eq 1 ). ... 

The following preparation of triethyl phosphite illustrates the interaction of phosphorus trichloride and ethanol in the presence of dimethylaniline the preparation of di-isopropyl hydrogen phosphite illustrates that of phosphorus trichloride and isopropanol in the absence of a tertiary amine. 

Triethyl phosphite is a colourless mobile liquid, insoluble in water. Trialkyl phosphites are valuable intermediates in the preparation of many organophosphorus compounds they readily form dialkyl esters of alkylphosphonic acids by the Arbusov reaction (p. 311). 

Meanwhile set up the ether distillation apparatus as used in the preparation of triethyl phosphite (p. 308). Distil off the ether and then fractionally distil the residue at water-pump pressure. The di-isopropyl hydrogen phosphite distils at 79Vi4 mm. other b.ps. are 8o°/i5 mm., 82-5°/i7 mm. Yield, 25 g., 89%. 

B) The following simpler preparation of di-isopropyl hydrogen phosphite using the same quantities of reactants requires no solvent or ammonia, but gives a lower yield. 

Organophosphorus Derivatives. Neopentyl glycol treated with pyridine and phosphorus trichloride in anhydrous dioxane yields the cycHc hydrogen phosphite, 5,5-dimethyl-l,3-dioxaphosphorinane 2-oxide (2) (32,33). Compounds of this type maybe useful as flameproofing plasticizers, stabilizers, synthetic lubricants, oil additives, pesticides, or intermediates for the preparation of other organophosphoms compounds (see Flame retardants Phosphorus compounds). 

Preparation of (Me0)2P-0-R ROH, (MeO)3P, CBr4, Pyr, 70-98% yield. The alkyl dimethyl phosphite may then be oxidized to the corresponding phosphate by aq. iodine, t-butyl hydroperoxide, or peracid. 

First synthesis of aji organo-P comp iund by J. L. Lassaigne who made alkyl phosphites from H P04 + ROH. T. Graham (who later became the Hrst President of the Chemical Society) classiHed phosphates as ortho, pyro or meta, following J. J. Berzelius s preparation of pyrophosphoric acid by heat. 

Most common is the preparation of alkyl phosphonic acid esters (phospho-nates) 4 (Z,Z = OR) from phosphorous acid esters (phosphites) 1 (Z,Z = OR). The preparation of phosphinic acid esters (Z = R, Z = OR) from phosphonous acid esters, as well as phosphine oxides (Z,Z = R) from phosphinous acid esters is also possible. 

In a similar way, the preparation of alkylenediphosphonic acids occurs by using dialkyl phosphite with a,co-dichloralkanes in the presence of sodium see Eq. (48). 

Another method for the preparation of hydroxyalkanephosphonic acids is the conversion of aldehydes with dialkyl phosphites in the presence of triethylamine or sodium methylate leading directly to the corresponding a-hydroxyalkane-phosphonates. This reaction is reversible, leading to the starting materials aldehyde and diethyl phosphite again [143,146]. 

The photo-Arbuzov rearrangement of allyl-, benzyl- and naphtylmethyl-phosphites (Scheme 13), first developed by Bentrude et al. [20], found applications in the preparation of phosphonates (70-90%) [38]. Arylphosphonates have been shown to act as protein tyrosine kinase inhibitors [39] or non-hy-drolyzable analogs of phosphorylated tyrosine residues [40]. 

Properly substituted phosphonates, which serve as key intermediates for the synthesis of biologically active compounds [39,54], have been prepared via the photo-induced 1,4-addition of phosphites onto Michael ketones (Scheme 19). 

During the last decade, Bentrude et al. [65] has shown that the triplet-sensitized photorearrangement of allylphosphites and analogs (Scheme 28) is a powerful method for preparation of alkylphosphonates from phosphites. Moderate to high yields were observed when triphenylene was used as photosensitizer [66,67]. 

A simple, high-yield procedure for the conversion of ArTlXj into ArjTlX compounds has recently been described 90). This symmetrization reaction, the mechanism of which is not known, can be effected by treatment of the ArTlX2 compound either with triethyl phosphite or with hot aqueous acetone. As a wide variety of ArTlXj compounds can now be easily prepared by electrophilic thallation of aromatic substrates with thallium(III) trifluoroacetate (q. v.), symmetrization represents the method of choice for the preparation of the majority of ArjTlX compounds. Only about twenty mixed compounds, RR TIX, have been prepared so far, and the only general synthetic procedure available consists of a disproportionation reaction between an RTIX2 species and another organometallic reagent [e.g., Eqs. (5)-(7)]. 

B. Electrophilic Reactions.—Transesterification followed by rearrangement is a common route from simple phosphites to more complex phos-phonates. This has now been applied to the preparation of cyclic phos-phonates (85). Both phosphites (86) and phosphoranes (87) containing phosphorus-hydrogen bonds are obtained from the cyclic biphosphite (88) and butanol. ... 

The preparation of the bicyclic phosphite (89) from tri(hydroxymethyl)-phosphine and trimethyl phosphite has been reinvestigated following reports that it could not be repeated. The reasons for the difficulties... 

Japanese workers have prepared diethyl phosphite in 43% yield from the reaction of white phosphorus with ethanol and oxygen. 

The vinylphosphonic esters (77) are obtainable by distillation of the phosphite esters (76)(Scheme 13). No reaction takes place at the vinyl halogen during the preparation of the esters (78), but the interaction of phosphonites and... 

Cobalt(III) complexes of formula cis- and trans-[Co(dtc)L4]2+ and [Co(dtc)2L2]+ where dtc = dimethyl-, diethyl- or piperidino-dithiocarbamate were prepared with phosphites P(OMe)3, P(OEt)3 and 4-ethyl-2,6,7-trioxa-l-phophabicyclo[2.2.2]octane as ligands L.1048 Whereas Co—P bonding is found, as defined in the crystal structures of each of the two forms of complexes isolated, a linkage isomer in which the phosphite is O bound was detected for the bis(dithio-carbamate) compounds. 

Not only phosphines or phosphites but also phosphoric acid trisdialkyl-amides (40), sulfoxides (41), etc. have been used as electron donors in the preparation of the catalyst. In addition, the catalytic activity of tetra-methylcyclobutadienenickel dichloride and alkylaluminum halides has been studied in detail (42, 43). 

Preparation of trisodium phosphonoformate — Reaction of a chloroformate with a trialkyl phosphite and cleavage of the ester linkages... 

Preparation of tris(trimethylsilyl) phosphite — Preparation of a silyl ester of a trivalent phosphorus acid for Michaelis-Arbuzov reaction... 

Preparation of 2,3-dioleoyloxypropylphosphonic acid — Reaction of an alkyl halide with a silyl phosphite ester... 

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