Dialkyl acylphosphonates

Takamizawa et al. developed a general ring-expansion reaction of heterocycles that, applied to thiazolium salts, yields 1,4-thiazines (496, 497) thiamine (220) reacts with dialkyl acylphosphonates (221) to give the tricyclic 1,4-thiazine (222) (498), which is easily hydrolyzed to dihydro-1,4-thiazinone (223) (499) (Scheme 106). In the case of thiazolium slats containing no functional groups (224), 1,4-thiazine derivatives (226) were directly obtained in fairly good yields (Scheme 107). 

Sekine, M., Kume, A., Nakajima, M., and Hata, T., A new method for acylation of enolates by means of dialkyl acylphosphonates as acylating agents, Chem. Lett., 1087, 1981. 

Reaction of Azolium Ylides with Dialkyl Acylphosphonate New Synthesis of Heterocyclic Compounds A. Takamizawa et al., Heterocycles, 1974, 2, 521-554. 

The oxazoliumcarboxylic acid (147) is easily decarboxylated via the ylide (148) the neutral compound (149) is much more stable due to the low equilibrium concentration of the zwitterionic tautomer (150 Scheme 7). Oxazolium salts lacking substituents at the 2-position react with dialkyl acylphosphonates in the presence of triethylamine to give mixtures of l,4-oxazin-3-ones and 2-azetidinones the reaction (see Scheme 8) proceeds by electrophilic attack of the phosphonate on an oxazolium ylide, e.g. (151), followed by insertion of oxygen into the carbon-phosphorus bond, ring-opening, and formation of the enolate anion (152) which can cyclize in two alternative ways with expulsion of the phosphonate group. 

Dialkyl acylphosphonates were obtained for the first time by Kabachnik and Rossiiskaya in 1945 by the reaction of acyl chlorides with trialkyl phosphites. The reaction proceeds readily at room temperature and even on cooling by slowly adding trialkyl phosphite to acyl chlorides. Improvements have been made, especially by controlling the temperature of the reaction. The different versions of this reaction, which are distinguished by the nature of the acylating agent and the structure of the phosphite, have been covered by the reviews of Zhdanov et al. in 1980, Breuer in 1996," and McKenna and Kashemirov in 2002. ... 

Reaction between equimolar amounts of dialkyl chlorophosphites and acyclic acid anhydrides at 50°C has been reported to produce the corresponding dialkyl acylphosphonates in satisfactory yields (70-75%), but the general utility of this procedure remains to be demonstrated. On pyrolysis, diethyl 1-oxoethyIphosphonate produces ketene and diethyl phosphite. ... 

Hydroxylamine reacts with acylphosphonates to give the corresponding oximes. The reactions are usually carried out by reacting hydroxylamine hydrochloride with dialkyl acylphosphonates in the presence of Py in absolute EtOH (Scheme Yields are generally near quantitative, and... 

Dialkyl acylphosphonates have been reduced to 1-hydroxyphosphonates using... 

When submitted to LiAlH4 in excess (3 eq) in boiling EtjO, dialkyl acylphosphonates are converted into primary phosphines in good yields (62-84%). ... 

Breuer, E., Karaman, R., Goldblum, A., and Leader, H., Sulfonic acid-induced fragmentation of dialkyl acylphosphonates. Formation of alkyl carboxylates and alkyl sulfonates, 7. Chem. Soc.. Perkin Trans. 2, 2029, 1988. 

Sekine. M.. Satoh, M., Yamagata, H., and Hata. T. Acylphosphonates. Phosphorus-carbon bond cleavage of dialkyl acylphosphonates by means of amines. Substituent and solvent effects for acylation of amines../. Org. Chem., 45, 4162, 1980. 

Maeda. H., Takahashi. K.. and Ohmori. H., Reactions of acyl tribulylphosphonium chlorides and dialkyl acylphosphonates with Grignard and organohthium reagents. Tetrahedron, 54, 12233, 1998. 

An example of process 92 is provided by the reaction of thiazolium salts with dialkyl acylphosphonates it provides a valuable synthetic entry to... 

Certain 1,2,4-thiadiazoles undergo ring expansion on treatment with dialkyl acylphosphonates. Thus, the action of diethyl acetyl(or benzoyl)-phosphonates (383, R = Me, Ph) on 4-benzyl-3-methyl-l,2,4-thiadiazolium bromide (382) produces substituted 1,2,4-thiadiazines (384), albeit in low yield. The pyrimidyl analog (385, formally comparable with thiamin) behaves similarly, but a cyclization (to 387) competes with the ring expansion (to 386). The structure of these and other complex products, and the mechanism of their formation, were discussed in detail.286... 

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. 

NMR spectroscopy has shown that many compounds, previously described as (1-hydroxyalkylidene)bisphosphonic esters, are actually either totally rearranged compounds or mixtures of initial and rearranged compounds. Such was the case with the products from dialkyl hydrogenphosphonates and dialkyl acylphosphonates, for which, when R R the potential for confusion is obvious (Scheme 18). Provided that the compounds 104 are not heated above 80 °C, they may sometimes be isolated by crystallization, but others, e.g. 104 (R = Ph or aryl), rearrange very easily and cannot be isolated. (1-Hydroxyethylidene)bisphosphonic acid is stable in solution at pH 1.6 up to 125 °C, and in alkaline solutions at pH 8.5-11.5 up to 195 °C the compound then undergoes thermolysis with fission of the carbon-phosphorus bond to give, initially, acetylphosphonic and (1-hy dr oxyethy l)phosphonic acids ... 

Synthesis of mixed dialkyl acylphosphonates by the Arbuzov reaction is of practical value only with mixed phosphites in which there is clear preference of the different alkyl groups to be cleaved. For example reaction of diethyl phenyl phosphite with benzoyl chloride give phenyl ethyl benzoylphosphonate (equation 6) . 

In contrast, dialkyl chlorophosphites behave differently. They react with acyclic acid anhydrides with the formation of dialkyl acylphosphonates and acyl halides (equation 8)". ... 

Alkyl hydrogen acylphosphonates have been converted into alkyl acylphosphonochlo-ridates by thionyl chloride (equation 36). The latter are versatile intermediates that have been used for the synthesis of mixed dialkyl acylphosphonates or alkyl acylphospho-namidates (equation 36) . ... 

Because of the strong electron-withdrawing effect of dialkyl phosphoryl groups, the carbonyl in dialkyl acylphosphonates is highly electrophilic and therefore reacts rapidly with all types of nucleophiles. 

Dialkyl acylphosphonates are sensitive to water in neutral and alkaline conditions and hydrolyse rapidly to the corresponding carboxylic acids and to dialkyl hydrogen-phosphonate (equation 47) This occurs following the rapid addition of water to the carbonyl group with the formation of stable hydrates. The involvement of stable carbonyl hydrates in the hydrolysis of dimethyl acetylphosphonate and aroylphosphonates was established by H NMR and UV spectroscopy, respectively. In the latter case, the rates of formation and decomposition of the tetrahedral carbonyl hydrates were also determined. 

In contrast to dialkyl acylphosphonates, the reaction of methyl sodium benzoylphos-phonate or disodium benzoylphosphonate with methylamine gave the imine without severing the C—P bond, demonstrating that the high reactivity of the carbonyl group is preserved even in the anion (equation 58) ... 

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