Trialkyl phosphites trimethyl phosphite

The interaction of an ethenyl ether and a trialkyl phosphite (trimethyl phosphite was actually used) under dry acid conditions (HCl gas in MeOH) leads to a phosphonic diester according to Scheme 2. Little dealkylation of the phosphite triester appears to occur, and the reaction appears therefore not to involve addition of dialkyl hydrogenphosphonate (the product of phosphite dealkylation), all the more so since triphenylphosphine also reacts under the same conditions to give related triphenylphosphonium salts. Ethenyl ethyl ether, 2,3-dihydrofuran and 2,3-dihydropyran were used as substratesThe ease of reaction under mild conditions, coupled with high yields, testifies to the importance of a cationic intermediate species. 

Trimethyl phosphite P(OMe)3 spontaneously iso-merizes to methyl dimethylphosphonate MePO-(OMe)2, whereas other trialkyl phosphites undergo the Michaelis-Arbusov reaction with alkyl halides via a phosphonium intermediate ... 

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

Alkoxy (R0 ) radicals react at near diffusion controlled rates with trialkyl phosphites to give phosphoranyl radicals [ROP(OR )3] that typically undergo very fast -scission to generate alkyl radicals (R ) and phosphates [OP(OR )3]. In a mechanistic study, trimethyl phosphite, P(OMe)3, has been used as an efficient and selective trap in oxiranylcarbinyl radical systems formed from haloepoxides under thermal AIBN/n-Bu3SnH conditions at about 80 °C (Scheme 27) [64]. The formation of alkenes resulting from the capture of allyloxy radicals by P(OMe)3 fulfils a prior prediction that, under conditions close to kinetic control, products of C-0 cleavage (path a. Scheme 27), not just those of C-C cleavage (path b. Scheme 27) may result. 

B. l,3>2>Dioxaphospholens.—The kinetics of the addition of trialkyl phosphites to benzil have been investigated spectrophotometrically. The second-order reaction of trimethyl phosphite in dioxan has activation parameters of A// = 8.4 kcal mol and AS = — 47.5 e.u. In benzene the rate constant increases linearly with low concentrations of added organic acid and decreases linearly with low concentrations of added base. The Diels-Alder mechanism is considered unlikely on the basis of these data, and the slow step is considered to be nucleophilic addition of the phosphite to the carbon of the carbonyl group (see Scheme). 

These results establish the conditions for the formation of trialkyl phosphites in high yields. However attempts to distil the ester from the reaction mixture were unsuccessful as codistillation and some decomposition always occurred. Other workers who carried out similar experiments independently, report a 50% yield of isolated trimethyl phosphite. 

The allyl complex [Rh(i/3-C3H5)(cod)] reacts with trialkyl phosphites to form [RhHL2] complexes. The dimeric triisopropyl phosphite complex has already been mentioned. Trimethyl and triethyl phosphite, however, form trimeric products.64,100 The structure of the trimethyl phosphite complex (14) has been determined by X-ray crystallography.100-102... 

Although the coordinating character of trifluorophosphine and trialkyl phosphite can be assumed to be very similar, the observed coupling constants J( Co- P) differ substantially from one another. The smaller value found in the octahedral complex has therefore been accounted for by the larger fractional s-character of the Co-P bond in the trimethyl phosphite complex. (238)... 

Dialkyl 1-alkynylphosphonates (22) were formed in good to high yields by treatment of 1-alkynyliodonium tosylates (23) with trialkyl phosphites the reaction is exothermic with trimethyl phosphite but requires heating with triethyl or triisopropyl phosphite. The addition of trimethyl or triethyl phosphite to 3-alkylene-2-oxindoles (24) has led to new product types for a, -unsaturated carbonyl compounds, i.e. a stable tri-alkoxyphosphonium zwitterion (25), and a C-alkylated phosphonate (26). ... 

Treatment of trialkyl phosphites with dimethyl acetylenedicarboxylate in toluene at 80 °C in the presence of the fullerene, Ceo, results in the formation of the stabilised phosphite-ylides (81), involving a cyclopropane ring on the fullerene unit. These ylides readily undergo hydrolysis with hydrobromic acid to give the phosphonates (82) in good yield. Protonation of the initial adducts of trimethyl phosphite and dialkyl acetylenedicarboxylates by indane-1,3-dione leads to the formation of vinyltrimethoxyphosphonium cations. 

Because of the commercial importance of fosfomycin, it is not surprising that several important and attractive synthetic methods are reported in patents. They include, for example, precursors such as dimethyl hydroxymethylphosphonate, dimethyl, dibenzyl, and diallyl formylphosphonate, trimethyl phosphite and 2-cyano-1-hydroxypropene, 9 trialkyl phosphite and 2-chloro-propionaldehyde or 2-acetoxypropionaldehydc, diethyl chloromethylphosphonate, dibenzyl phosphite, and 1-chloro-1,2-propylene oxide,2 propynylphosphonic acid, propenylphos-phonic acid,2 2-chloro-(czT-l,2-epoxypropyl)phosphonic acid, and extrusion reactions on thermolysis. The resolution of racemic acids has also been reported. In search of new effective antibiotics, a large variety of substituted epoxyethylphosphonic acids have been pre-pared.249... 

The previous reactions suggest that trialkyl phosphites are able to react with acylphosphonates. Effectively, it has been shown that the reaction of trimethyl phosphite with dimethyl aroylphos-phonates under appropriate conditions leads to the formation of anionic adducts that decompose to give phosphonyl carbenes and trimethyl phosphate. These carbene intermediates can react with further trimethyl phosphite to give ylidic phosphonates, or, when suitable < rt/z<9-substituents are present on the aromatic ring, intramolecular carbene insertion reactions can occur to give cychc systems (Scheme 7.4).38.4o,56,58-65... 

The reactive 1 1 intermediate formed in the initial reaction between trialkyl phosphite and dialkyl acetylenedicarboxylates can be trapped. Thns, reaction of dialkyl acetylenedicarboxylates with trimethyl phosphite in the presence of indane-1,3-dione leads to dimethyl 2-(3-methoxy-l-oxoindenyl)-l,2-fczXalkoxycarbonyl)ethylphosphonate in high yields. Treatment of trialkyl phosphites with Cgo and dimethyl acetylenedicarboxylate at 80°C give fullerenecyclopropyl phosphite ylides, which, on hydrolysis at ambient temperature, give the corresponding phosphonates. ... 

Another attractive route to co-amino-(o-(hydroxycarbonyl)alkylphosphonic adds involves the use of the classical Michaelis-Arbuzov and Michaelis-Becker reactions. For example, the suitably protected 2-amino-(o-bromoalkanoates are readily converted into 3-amino-3-carboxypropylphosphonates (Scheme 8,82) ° or substituted 6-amiuo-6-c trboxyhcxylphosphonatcs by the Michaelis-Arbuzov rearrangement with trialkyl phosphites. However, it appears that, when enantiomerically pure bromide is used, the Michaelis-Arbuzov reaction is responsible for some racemization. It has been found that the extent of racemization is greater when the reaction is run at 150°C using triethyl phosphite than with trimethyl phosphite at 110°C for only the required amount of time. ... 

Olefin synthesis. This reagent has an advantage over trialkyl phosphites (see Trimethyl phosphite, 1, 1233, and this volume) for stereospecific generation of olefins from trithio- and thionocarbonates in that the conditions are mild (30°)-s Thus optically active /rans-cyclooctene (6) has been prepared from cis-cyclooctene in the following way.3 Addition of thiocyanogen to cis-cyclooctene (3) affords trans-, 2-dithiocyanocyclooctane (4), which when refluxed with 47% hydrobromic acid affords the iminodithiocarbonate (5). This was resolved via the salt with (—)-l-phenyl-ethanesulfonic acid by thirteen recrystallizations from 2-butanone. The (+)-(5) was... 

Between 1948 and 1952 Morris and Van Winkle (1952), Arbuzov and Alimov (1951), and Perkow et al. (1952) investigated independently the reaction of polyhalogen aldehydes, primarily of chloral, with trialkyl phosphites. The conversion was assumed by some workers to be a true Michaelis-Arbuzov reaction and, accordingly, it was thought erroneously that the product formed in the reaction of chloral and trimethyl phosphite is the phosphonate of formula 66. Perkow et al. (1952) established that a-halogen carbonyl compounds give with trialkyl phosphites an anomalous Michaelis-Arbuzov reaction, so that the actual reaction product is 2,2-dichlorovinyl phosphate, 67. This reaction is known in the literature as Perkow s reaction. 

General procedure for the preparation of dialkyl aroylphosphonates 279 The aroyl chloride (0.03 mole) is treated under nitrogen dropwise with the trialkyl phosphite (0.04 mole) at such a rate that the internal temperature does not exceed 35°. The resulting mixture is fractionated in a vacuum. As example, dimethyl benzoylphosphonate, b.p. 146°/2.5 mm, is obtained in 81 % yield from benzoyl chloride and trimethyl phosphite. 

Normally, trialkyl phosphite esters are stable in alcoholic or phenolic solutions except for transesterification (134). However, at 210-215°, trimethyl phosphite is isomerized to dimethyl methylphosphonate, and triethyl phosphite is converted to diethyl methylphosphonate by methanol (79). The formation of these substances has been rationalized as proceeding via the intermediate [AIeOP(i Ie)(OR)2]+ OH. 

The failure to obtain an ester of (2-bromoethyl)phosphonic acid from trimethyl phosphite and 1,2-dibromoethane is due partly to competitive reaction between the evolved methyl bromide and the phosphite and partly to debromination. On the other hand, the use of higher trialkyl phosphites is more successful, although it still becomes necessary... 

Attack on Saturated Carbon. - Ethylene dicarboxylic diphosphonic acid (EDCP, 2) has been prepared in 70% yield from 2,3-dichlorosuccinic anhydride (3) and trimethyl phosphite, followed by hydrolysis of the Arbuzov product. Tris(trimethylsilyl) phosphite, in contrast to trialkyl phosphites, attacks an oxirane carbon of epibalohydrins (4) to give the phosphonates (5). Bis(trimethylsilyl) phosphonite (6) has previously been prepared in situ and used to obtain y-ketophosphinic acids similar reactions with simple alkyl halides to give alkylphosphinic and dialkylphosphinic acids acids in high yields have now been described. ... 

Triethyl phosphite can be obtained from Virginia Carolina Chemical Corp., Eastman Kodak Co., Aldrich Chemical Co., K and K Laboratories, and Matheson, Coleman and Bell. The presence of dialkyl hydrogen phosphite or trialkyl phosphate is not deleterious, but a correction for assay is required. Fractionation readily separates triethyl phosphite (b.p. 48-49°/ll mm.) from diethyl hydrogen phosphite (b.p. 72°/ll mm.) and triethyl phosphate (b.p. 90°/10 mm.). The presence of amines and amine hydrochlorides may seriously interfere with the alkylation, especially in the case of trimethyl phosphite (see Table I). The checkers redistilled triethyl phosphite obtained from Matheson, Coleman and Bell. 

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