Dialkyl phosphonates alkylation

Me(Ph)SiCl2 reacts with dimethyl phosphonate in a 1 1-mixture at 100°C to the O.O-disilylated phosphonate. In contrast to this observation the O-alkyl O-silyl phosphonate is formed solely by reaction of both compounds in acetonitrile at 80°C (line 7,8). An excess of the corresponding phosphonate as polar solvent leads to the mixed ester 2 only. The excess of the dialkyl phosphonate is removed from the mixture by vacuum distillation (line 9). 

The enhanced reactivity of the chlorine atom in the dichloro diorgano silanes can also be observed in Me2(MeO)SiCl 4 or Me(EtO)2SiCl 5. In both cases the O-alkyl O-silylphosphonates (6, 7) are formed in high yields after reaction of 4 or 5 with dialkyl phosphonates. 

Dialkoxydichloro silanes exhibit a higher nucleophilicity compared to the chlorosilanes described before. Diethoxysilyl-bis(0-alkyl)phosphonates of type 8 are formed in 90% yield besides 10% of disilylated phosphonates in the reaction of dialkyl phosphonates with dichlorodiethoxy silanes at 50-80°C. 

De-alkylation by alkoxide ion increases the acidity of the medium and this accounts for the formation of dialkyl phosphonate in the later stages of the reaction. 

The palladium-catalysed cross-coupling of aryl halides or vinyl halides with dialkyl phosphonates (31) to yield dialkyl arylphosphonates and dialkyl vinylphosphonates, respectively, was first reported by Hirao and co-workers 69 the halides used most frequently are bromides and the reaction is stereospecific with haloalkenes. Subsequently, analogous reactions of alkyl alkylphosphinates (32), alkyl arylphosphinates (32), alkyl phosphinates (33), and secondary phosphine oxides (34), replacing [P—H] bonds with [P—C] bonds to yield various phosphinates and tertiary phosphine oxides, have been developed (Figure 7.1). Alkyl phosphinates (33) may be mono- or diarylated as desired by the selection of appropriate conditions. Aiyl and vinyl triflates have also found limited... 

The hydrophosphonylation (addition of dialkyl phosphonates), hydrophos-phinylation (addition of alkyl alkylphosphinates or alkyl phosphinates) and addition of secondary phosphine oxides to unfunctionalized alkenes and alkynes occur under free radical conditions or with transition metal catalysis.10,39 63 90... 

Alkylation chemistry has also been reported for alkylphosphine oxides and dialkyl phosphonates. The phosphonate carbanions are often preferred as they offer many advantages over the phosphonium ylides. In particular, the phosphonate group is highly acidifying and the resulting organolithium can be smoothly alkylated. 

Meisters, A., and Swan, J. M., Organophosphorus compounds. Part 5. Dialkyl alkylphosphonates from alkyl haUdes and sodium dialkyl phosphonates in liquid ammonia, Aust. J. Chem., 18, 163. 1965. 

Dialkyl-phosphonates and alkyl-diesters Same trend as for alkyl-phosphonates. 

Trialkyl phosphites undergo the Michaelis-Arbusov reaction with alkyl halides to give dialkyl phosphonates the initial phosphonium ion is attacked at one the alkyl groups by the newly liberated halide. The reaction is useful in producing non-fissile but isosteric analogues of activated sugars for mechanistic studies (Figure 6.51). ... 

In the reaction of phosphorus trichloride with three moles of alcohol, dialkyl phosphonate ( dialkyl phosphite ) is formed, together with hydrochloric acid and alkyl chloride. 

With alkylating agents, the salts of dialkyl phosphorothionates form 0,0,S-trialkyl phosphorothioates. Dialkyl phosphonate can also be used as an alkylating agent (Melnikov et al., 1965). 

They also undergo the Michaelis-Arbusov reaction with alkyl halides, forming dialkyl phosphonates Q... 

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... 

Sulphamides containing the dialkyl ester of the phosphoric acid functional group are prepared by reacting the sodium salt of the phosphoric acid with A-sulphonylaziridines (399) at room temperature (equation 130). Acidification gives the N,iV-dialkyl-iV -alkyl phosphonate) sulphamides (400) in good yields376. 

Hydrocarbons, dialkyl alkyl-phosphonates, alkyl alkyl-phosphonic acids... 

The phosphonomethylation of dialkyl [(alkylamino)alkyl]phosphonates (238) in the customary way yields products with mixed phosphoryl functions, e.g. the acids 239 or their esters 240 and 241 are obtained by the phosphonomethylation of alkyl[(alkylamino)-methyljphosphinic acids ... 

Dialkyl [(diethylamino)alkyl] phosphonates have been prepared by the 198... 

However, it has been established that, in the initial step, amines as a base are actually alkylated and not protonated at the nitrogen by dialkyl phosphonates. Therefore, an alternative mechanism is proposed in agreement with both experimental and computational results. ... 

Unequivocal evidence for the formation of o -adducts has been obtained by X-ray diffraction analysis of those adducts which are stable enough to obtain their single crystals [11]. Indeed, the X-ray crystallography data are available for the anionic trinitrobenzene-methoxide and the Janovsky trinitrobenzene-acetone complexes [11, 201, 202] and for the o -adducts of isoquinoline [203], phthalazine [160], and 4,7-phenanthroline [161, 162] with dialkyl phosphonates. Also the X-ray data have been obtained for the neutral o -adducts resulting from the reactions of iV-methylacridinium ion with N-nucleophiles [204, 205] and for the o -adducts of iV-alkyl-substituted 2,3-dicyanopyrazinium and quinoxalinium salts with 0-, C-and P-nucleophiles [163, 194]. 

Within this reaction cycle, dialkyl H-phosphonate and carbon tetrachloride react to form dialkyl chlorophosphate and chloroform as the final products of the Atherton-Todd reaction. A simple equilibrium shift (without salt formation) toward the dialkyl phosphite tautomer in step 1 [82] or formation of pentacoordinated phosphorane intermediates in step 2 [84,85] has also been discussed. It has been shown that the rate of this reaction depends on the strength of the applied base [86]. Amines are the most commonly used bases under Atherton-Todd conditions [80-85]. The validity of the deprotonation step in the above mechanism in the case of the base being an amine is, however, questionable, since it has been established that amines are alkylated and not protonated at the nitrogen by dialkyl phosphonates. It has been shown, however, [87] that in the case of basic activation with amines, which are the most commonly used bases, the phosphite intermediates are formed according to a different and more complex pathway (see Section 3.8.1). This pathway includes alkylation of the amine and formation of a monoalkyl H-phosphonate salt. 

However, when amines are employed for base catalysis, one has to take into consideration the fact that in this case, the actual base is produced after alkylation of the amine as it was previously shown (see Section 3.8.1). When the reaction of dialkyl phosphonates with isocyanates is carried out in the absence of a catalyst, it is accompanied by carbon dioxide evaluation and results in the formation of three types of reaction products I, n, and HI [262]. 

Phosphonyl radicals can be generated by photolysis or radical abstraction from secondary phosphine oxides, alkyl phosphinates or dialkyl phosphonates. They can be obtained from tertiary butoxy radicals and dialkyl phosphites or tetra alkyl diphosphites (13.175) and (13.176). Phosphonyl radicals react with alkyl halides according to (13.177). 

Feringa and coworkers reported a copper-catalyzed O-arylation of dialkyl phosphonates and phosphoramidates with diaryliodonium triflates and 2,6-di-ferf-butylpyridine (DTBP), giving easy access to mixed alkyl aryl phosphonates via elimination of one of the alkyl groups as the alkyl triflate prior to arylation (Scheme 10a) [133]. Aryl(mesityl)iodonium salts reacted in a chemoselective way. Copper-catalyzed arylations of hydroxamic acids [134] and carboxylic acids [135] have also been reported, the latter utilizing thiophosphoramides as cooperative catalysts to allow arylation at room temperature. Onomura s group discovered a Cu-catalyzed monoarylation of vicinal diols in toluene at 100 °C. Only traces of product were obtained with alcohols lacking the vicinal hydroxyl group [136]. 

Hexafluoroacetone was one of the ketones used in a study of the reactions of thiols with reactive carbonyl compounds (to yield a-hydroxy-sulphides) as part of an investigation of radioprotective aminoalkanethiols. Insertion of hexafluoroacetone into the P—H bond of dialkyl phosphonates has been shown to give both possible products, the ratio of these being dependent on the nature of the alkyl group present... 

Alkali metal salts of 0-alkyl 1-(substituted phenoxyacetoxy)alkylphosphonic acids IIA-IIE could be easily synthesized by the reaction of (9,(9-dialkyl 1-(substituted phenoxyacetoxy)alkylphosphonates lA or IC with corresponding lithium bromide, sodium iodide, or potassium iodide in refluxing acetone. The synthetic route of IIA-IIE is shown in Scheme 3.5. For the synthesis of IIA-IIE, 1-hydrox-yalkylphosphonates M2, substituted phenoxyacetyl chloride MS, and 0,(9-dialkyl 1-(substituted phenoxyacetoxy)alkylphosphonates lA or IC could be prepared according to the known methods as stated in Chap. 2. 0,0-Dialkyl phosphonate Ml was used directly as obtained commercially or prepared by the reaction of phosphorus trichloride and methanol. Ml reacted with different aldehydes to give 0,0-diaUtyl 1-hydroxyalkylphosphonates M2. The substituted phenoxyacetic acids M4 were prepared in satisfactory yields by the reaction of corresponding substituted phenols with 2-chloroacetic acid or ethyl 2-bromoacetate followed by hydrolysis. The substituted phenoxyacetyl chlorides M5 could be easily obtained by the treatment of M4 with excess thionyl chloride. M2 reacted with MS to provide lA or IC (Scheme 3.5). 

F-Methylation. Phosphonium salts are prepared by the quat-ernization of phosphines with methyl iodide. The displacement reaction is usually conducted in polar solvents such as acetonitrile or DMF. Dialkyl phosphonates are prepared from the reaction of trialkyl phosphites with alkyl halides, commonly known as the Arbuzov reaction. For example, diisopropyl methylphosphonate is prepared by heating a mixture of methyl iodide and Triisopropyl Phosphite (eq 34). ... 

Formation of alkyl phosphonic acid degradation products in the environment follows a highly specific hydrolysis pathway from the parent dialkyl phosphonate ester CWA s. Nerve agent hydrolysis products are unique compared with... 

Trialkyl esters of phosphonic acid exist ia two structurally isomeric forms. The trialkylphosphites, P(OR)2, are isomers of the more stable phosphonates, 0=PR(0R)2, and the former may be rearranged to resemble the latter with catalytic quantities of alkylating agent. The dialkyl alkylphosphonates are used as flame retardants, plasticizers, and iatermediates. The MichaeUs-Arbusov reaction may be used for a variety of compound types, including mono- and diphosphites having aryl as weU as alkyl substituents (22). Triaryl phosphites do not readily undergo the MichaeUs-Arbusov reaction, although there are a few special cases. 

Diesters of phosphorous acid are in general neutral because the phosphorous acid exists mostly in the phosphonate form with one hydrogen directly attached to the phosphorus. But with alkali metals the H can be changed against the alkali and reactive intermediates formed. Such alkali metal derivatives of dialkyl phosphites react with alkyl halides to give dialkyl alkanephosphonates, according to Eqs. (45) and (46). 

It has been reported that the geometry of olefins obtained from the reaction of dialkyl l-(ethoxycarbonyl)ethylphosphonates and a-phenylpropionaldehyde can be controlled by choice of the phosphonate ester alkyl groups diisopropyl ester gives (E), while dimethyl ester gives (Z). This has now been confirmed for the... 

The addition of any one of several dialkyl chlorophosphates to an arylalkyne-derived vinyl zirconocene in the presence of catalytic amounts of CuBr in THF leads to the corresponding vinyl phosphonate in high yields (78—92% see, for example, Scheme 4.38) [25]. Here, alkyl-substituted acetylenic starting materials do not react beyond the initial hydrozirconation stage. Vinyl phosphonates may be readily converted to acyloins by oxidation to the diol followed by base-induced cleavage. 

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