Sodium dialkyl phosphites

Cyclohexene oxide and its 3-hydroxy derivatives have been opened regio- and stereospecifically with phosphodiesters. The mechanism of the reaction of oxiranes with sodium dialkyl phosphite and diphenylphosphines has been studied. Cyclopropanecarboxylic acid derivatives have been obtained from substituted oxiranes with triethylphosphonoacetate anion.The mechanism of formation of isomeric alkoxyalkylacetates from oxiranes with alkyl halides and mercuric acetate has been discussed. ... 

Two methods have been presented for the phosphonation of poly(bro-moaryloxyphosphazenes), viz. via sodium dialkyl phosphite as reagent or via a treatment with Bu Li in combination with dialkyl chlorophosphate. The reactions are visualized by the product formation of (206) and (208) from (205) and (207), respectively. Polyphosphazenes with diphenyl phosphonate groups (209) have been synthesized by the reaction of the bromophenoxy substituted polymer (207) with Bu Li followed by a rapid addition of diphenyl chlorophosphate in thf. Only 50% of the available bromophenoxy groups are converted to diphenyl phosphonate esters groups. ... 

Reactions of Sodium Dialkyl Phosphite with a-Haloketones... 

Sturtz, G., Chartier, C., and Normant, H., Effect of 1-bromoacetylene derivatives on sodium dialkyl phosphites. Preparation of long-chain P-oxo phosphonates. Bull. Soc. Chim. Fr., 1707, 1966. 

The first synthesis of dialkyl fluoromethylphosphonates by a Michaelis-Becker reaction was described in 1967. The halogenofiuoromethane, which is no longer commercially available because of its mutagenic properties, is added to a refluxing toluene solution of sodium dialkyl phosphite. The corresponding fluoromethylphosphonate is obtained in modest yields (36 0%, Scheme 3.4). ... 

Sodium dialkyl phosphites readily react with 1,1-difluoroalkenes at low temperature to provide the corresponding dialkyl a-fluorovinylphosphonates in excellent yields (88-93%, Scheme 3.8). Some of them (R = OBn) can be converted into P-fluoro-a-keto esters, which are useful precursors of P-fluoro-cx-amino acids. ... 

The reaction of sodium dialkyl phosphites with difluorochloromethane in petroleum ether at 30-35°C affords the desired dialkyl difluoromethylphosphonates in 48-67% yield.-- Improved yields (54-77%) are obtained when the reaction is conducted in THF (Scheme 3.35).226-23o This procedure allows the synthesis of difluoromethylphosphonates bearing functionalized substituents (allyl, P-silylethyl) on the phosphorus. The reaction presumably proceeds via the generation and subsequent trapping of difluorocarbene. ... 

Te aalkyl difluoromethylenediphosphonates can be also obtained in modest yields (34-47%) by the reaction of dialkyl 1-bromo-1,1-difluoromethylphosphonates with sodium dialkyl phosphites at 0°C in a formal Michaelis-Becker reaction. 126,282,303,525 mechanism probably involves an... 

Soborovskii, L.Z., and Baina. N.F., Difluorochloromethane as a difluoromethylating agent. Part 2. Reaction of difluorochloromethane with sodium dialkyl phosphites, Zh, Obshch. Khim., 29, 1144, 1959 J. Gen. Chem. USSR (Engl. Transl.), 29, 1115, 1959,... 

The reaction between a-halo ketones and sodium dialkyl phosphites has been extended to phosphonate carbanions. For example, diisopropyl 1 -lithio-1-fluoromethylphosphonate, generated from diisopropyl fluoromethylphosphonate and LDA, reacts with 3-chloro-2-butanone at low temperature in THF to give diisopropyl l-fluoro-2-nicthyl-2,3-cpoxybutylphosphonate in 46% yield. 33.134... 

A report of the synthesis of thermodynamically stable ( )-vinylphosphonates from diethyl 1-formyl-l-phenylalkylphosphonates by a Homer-Wadswoilh-Ermnons-type reaction has appeared. Sodium P-hydroxyphosphonates, generated by the reaction of sodium dialkyl phosphites with... 

The reaction of sodium dialkyl phosphite with a-halogenokctoncs leads to a mixture of products consisting of P-ketophosphonates, 1,2-epoxyphosphonates, and vinyl phosphates (Scheme The subject has been covered in the Section 4.1.1.2. 

Ring opening of diethyl 1,2-epoxyalkylphosphonates by refluxing ethanolic solutions of sodium dialkyl phosphites proceeds by attack at the P-carbon atom of the epoxide via the sodium phos-phite-alcoholate equilibrium. For example, diethyl 1-methyl-1,2-epoxypropylphosphonate undergoes ring opening by sodium dialkyl phosphites with concomitant elimination of dietliyl phosphite to afford dialkyl l-methyl-2-oxopropylphosphonates in reasonable yields (Scheme 7.47). ... 

A convenient synthesis of cyclic P-ketophosphonates has been reported from sodium dialkyl phosphites and oc-nitroepoxides. The phosphite anions attack regiospecifically the carbon P to nitro group with epoxide ring opening and elimination of sodium nitrite. All the cyclic dialkyl P-ketophosphonates are isolated in good yields (56-96%, Scheme 7.50). 

At room temperature, diethyl l-phenyl-2-oxoalkyIphosphonates undergo attack at the carbonyl by sodium dialkyl phosphites in THF to give transient hydroxyphosphonates, which eliminate sodium diethyl phosphate according to a Homer-Wadsworth-Emmons-type reaction to provide stable dialkyl ( )-l-phenylalkeny Iphosphonates in moderate to good yields (20-94%) (Scheme 7.112). The elimination is favored by the presence of the phenyl group. ... 

Evidence has been presented which appears to support an earlier hypothesis regarding the reaction between sodium dialkyl phosphites and polyhalogeno - methanes according to this, the phosphite salt and bromotrifluoromethane yield (difluoromethylene)bisphosphonic tetraesters through the abstraction of the bromonium cation by the phosphite anion, and this is followed by phosphorylation of the subsequent carbanion. The present evidence is based on the treatment of diethyl (dichlorofluoromethyl)phosphonate with sodium diethyl... 

The addition of dialkyl phosphites to isocyanates has been studied more often.118-122 The uncatalysed reaction gives poor yields119 (addition of dimethyl thiophosphite to phenyl isocyanate does not require a catalyst120), and weak bases such as sodium carbonate, sodium cyanide, and tributylamine are poor catalysts, and the reaction proceeds best on addition of sodium, sodium dialkyl phosphites, or triethylamine.122 A typical example is the preparation of diisopropyl [A-(p-clilorophenyl)carbamoyl]phosphonate 122... 

The alkyl halides used in the Michaelis-Becker reaction (cf. page 728) may be replaced by other alkylating agents such as dialkyl sulfates326 or alkyl sulfonates 295,327 even the use of carboxylic esters for alkylation of sodium dialkyl phosphites is the subject of a patent.328 It is noteworthy that p-toluene-sulfonates often have advantages over alkyl halides in that alcohols are readily converted into these esters and, further, that the p-toluenesulfonate ion liberated, being a weak nucleophile, causes fewer side reactions. Alkyl p-toluene-sulfonates rank between alkyl chlorides and bromides in their reactivity towards sodium dialkyl phosphites.286 p-Toluenesulfonates of secondary alcohols give poor yields of phosphonate. 

Alkylation of dialkylphosphorous salts by dialkyl phosphites and by phos-phonic diesters has been mentioned above (page 729). The latter reaction can be used for nearly quantitative preparation of salts of alkylphosphonic monoesters, by converting the dialkyl phosphite into its sodium salt and heating this in a sealed tube with a catalytic amount of a phosphonic diester containing the same alkyl group.329 Further, when heated alone, sodium dialkyl phosphites afford, according to the conditions, sodium alkylphosphonates or disodium phosphonates and dialkyl phosphonates.330... 

Like tertiary phosphines, trialkyl phosphites can be alkylated by quaternary salts or hydrohalides of Mannich bases, this reaction widening the applicability of the Michaelis-Arbuzov reaction (cf. page 725) analogous alkylation of sodium dialkyl phosphites (cf. page 728) gives poorer yields of phosphonic esters.354,355... 

The classical procedure, and the one still extensively employed, consists in the alkylation of compounds containing the P(0)H moiety, as an appropriate metal salt, with an alkyl halide or similar type of compound such a procedure can sometimes be a successful alternative when the classical Michaelis-Arbuzov reaction fails, one such example being illustrated in equation 19. No reaction takes place between triethyl phosphite and 3-chloro-cyclopentadiene at below 120 °C, above which the main reaction is then dehydrochlorination the use of sodium dialkyl phosphites leads, however, to the desired dialkyl cyclopent-2-enylphosphonates. ... 

Although it might be expected that reactions which employed triarylmethyl halides would occur very readily, such reactions are rendered potentially more complex by the known nature of the halides and their propensity for involvement in free radical reactions. Whereas normal alkylation proceeds between sodium diethyl phosphite and diphenyl-methyl halides, success, or otherwise, in the use of the triphenylmethyl halides depends to some extent on the individual halide and on the metal in the phosphite salt. Thus, in an early study (in 1939), Arbuzov found that in reactions between silver dialkyl phosphites and triphenylmethyl bromide, dialkyl triphenylmethylphosphonates were indeed formed, but the use of the corresponding alkyl chloride provided the phosphite triester instead (metal dialkyl phosphites possess ambident anions ). A later study confirmed the behaviour of the silver salts towards the chloride, but also showed that, whereas dialkyl phophites with primary alkyl groups yielded phosphonic diesters (as had already been found), those with secondary alkyl groups afforded phosphite triesters moreover, the presence and nature of aromatic substituents were also able to control the course of the reaction. Reactions which involve triarylmethyl halides and sodium dialkyl phosphites may well be of a free radical nature since repeated studies have demonstrated the forma-... 

Those Michaelis-Becker reactions between even relatively simple primary or benzylic-type halides and sodium dialkyl phosphites are not without their unwanted side-reactions. Halomethylfurylcarboxylic esters, for example, undergo concomitant dehalogenation or Michaelis-Becker phosphonation (the two processes may also occur side by side) depending on the relative positions in the furan nucleus of both carboxylic ester and halomethyl groups and on the halogen. Chlorides react normally, bromides do not . 

Michaelis-Becker reactions between sodium dialkyl phosphites and halogenated alkenes, seem to occur only with polyhalogenated alkenes, but the course of the reaction is then complicated by elimination and addition steps. Thus sodium dialkyl phosphites and 1,1,2-trichlorophenylethene react to give, ultimately, esters of (1-phenyl-1,2,2-ethane)trisphosphonic acid. Such reactions have been reviewed. ... 

Much more successful is the use of sodium dialkyl phosphites in conjunction with diaryliodonium salts to give dialkyl aryphosphonates in yields of 81-93%". ... 

As a novel example of the use of sodium dialkyl phosphites. Scheme 39 indicates the preparation the phosphonoyl orthoesters 410, also obtainable from tetraalkyl diphos-phites ". ... 

Rare examples of normal Michaelis-Becker reactions which involve co-chloroalkanal diethyl acetals are to be found, and although the formation of dialkyl acylphosphonates from sodium dialkyl phosphites and, for example, benzoyl chloride, is to be observed at -85 °C, the system is further complicated, even at -10 °C, by further addition steps followed by rearrangements which would seem to render the process of little value for the synthesis of oxoalkyl phosphonic esters On the other hand, in a more detailed and systematic study of reactions between sodium dialkyl phosphites, (RO)2PONa(R = Et or Bu), and the ketones R CO(CH2) Cl, Sturtz and others have observed the formation of epoxides when n = 1 and (1-hydroxy alk-2-enyl)phosphonic diesters when n = 2(R = Me or Pr ), according to the displacement in 532, and of derivatives of tetrahydrofuran or tetrahy-dropyran, according to 533 n = 3 or 4) when R = Et, the formation of the cyclic ethers was accompanied by low yields of the expected (oxoalkyl)phosphonic diester, but otherwise the latter were isolated as a single product only for R = Me, n = 5, and R = Et or Pr when n = 2. 

The reactions between Y-(co-haloalkyl)phthalimides and sodium dialkyl phosphite were reported as early as 1949 by Chavane in the successful sytheses of several (co-aminoalkyl)phosphonic diesters. The advantage over the Michaelis-Arbuzov reaction in the preparation of (2-aminoethyl)phosphonic diesters with Y-alkyl or Y-silvl substituents is worth recalling, and several reports of its successful use may be noted, including the preparation of nitrogen-functionalized polyphosphonic esters (Scheme 17). Other substrates for the reaction have included l,3-bis(bromomethyl)benzene and 4-(co-bromoalkyl)arenes ... 

Sodium dialkyl phosphites add to the 4-arylidene-4,5-dihydro-1,3-oxazoles 273 to give the enolate anions 274 on the other hand, the adducts 275—the potential products of the silylation of 274—are more conveniently obtained by additions of dialkyl trimethylsilyl phosphite. The adducts 275 undergo alcoholysis with alcohols, R OH, to give the 2-amino-3-phosphinoylpropanoic acid esters 276, whilst the action of water yields the acids 276... 

Slightly unconventional modifications have been applied, occasionally with advantage, to otherwise conventional preparative reactions. Thus, the Michael-Becker reaction between dibromomethane and sodium dialkyl phosphites in solvents containing liquid ammonia is aided by exposure of the reaction mixtures to ultraviolet radiation. Dialkyl arylphosphonates are obtained in very high yield from the reaction between trialkyl phosphites and aromatic hydrocarbons when carried out in the presence of trisodium phosphate in an electrochemical system (see Organophosphorus Chemistry , Vol. 12, p. 105). The bond between phosphorus and aromatic carbon is also formed when aryl halides react with the P(0)H function in the presence of a combination of tetrakis-... 

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