Phosphonic alkyl-, dialkyl esters

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. 

Alkyl ethers of dialkyl (hydroxymethyl)phosphonic acid have been obtained by a modified Arbuzov procedure in the presence of BF3 Et20, triethyl phosphite reacts with the formals ROCH20Ar according to Scheme 16 the reactions are best carried out in the presence of TiCl4 at -78 °C, but the Lewis acid catalyst and the experimental conditions have to be chosen carefully, otherwise mixed alkyl aryl esters are produced. Boron trifluoride etherate also catalyses the interaction of acetals of 4-substituted benzaldehydes with triethyl phosphite to give diethyl (a-alkoxybenzyl)phosphonates. Both aliphatic and aromatic aldehydes are reported to react with trialkyl phosphites at 100 °C to give the ethers 204 ... 

In the Michaelis reaction (which usually gives lower yields than the corresponding Arbusov reaction), a metal dialkylphosphite (dialkylphosphonate - see below) is reacted with an alkyl halide to give a dialkyl ester of an alkyl phosphonate (6.272). Alkyl p-toluene sulphonates or dialkyl sulphates may be used in place of alkyl halides. Esters of unsaturated phosphonic acids, containing OH and CO groups can be obtained from an unsaturated aldehyde and a dialkyl phosphite (6.273). 

Many representatives of the trialkyl orthophosphate ester, dialkyl alkyl (or aryl) phosphonate ester, alkyl dialkyl (or diaryl)-phosphinate, and trialkyl (or triaryl) phosphine oxide class have been investigated. Judging from the reviews available, none of the more exotic types appears to offer any particular advantage over tributyl orthophosphate as a selective extractant for resolving lanthanide mixtures. Most are either viscous liquids or solids that require a diluent, and for the most part the individual separation factors to be had are unspectacular. 

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. 

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... 

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 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. 

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... 

JO Sulfur and Selenium Containing Compounds. - The interaction of 0,0-dialkyl methylphosphonothioates acid with POCI3 to give the chloridates (286) and alkyl phosphorodichloridates parallels reactions of thiophosphoric esters already encountered. The use of Lawesson s reagent to replace the phosphoryl bond in (l,l-difluoroalkyl)phosphonic esters by thiophosphoryl, has been noted (see also reference 258). - ... 

Alkyl esters of phosphonous and phosphinous acid also react readily y with carbon tetrachloride, while analogous aryl esters, e.g., EtP(OPh)2, are resistant even at 160° (152,173). The reaction of bromotrichloro-methane with triethyl phosphite, which occurs smoothly at 80° to furnish dialkyl trichloromethylphosphonate in excellent yield (99%), is light catalyzed. Chloroform is unchanged in the presence of triethyl phosphite (98,156) even under drastic conditions, and diethyl dichloro-methylphosphonate is not produced unless a free radical initiator is present (118). 

There are other reactions which lead from prop-2-ynyl compounds to allenic phospho-nic acid derivatives. The alkylation of diethyl hydrogenphosphonate with 3-bromopropy-ne under phase transfer conditions yields a mixture of diethylpropadienyl- and (prop-l-ynyl)-phosphonates in 85 15 ratio " The action of heat on a mixture of prop-2-ynol and a phosphoramidous ester, (RO)2PNR 2, results in elimination of R 2NH followed by its re-addition to the rearranged residue to afford a dialkyl (2-amino-prop-1-enyl)-phosphonate. ... 

The well established alkylation of phosphorylated benzyl carbanions has been complemented by the arylation of purely alkyl species. Thus, diethyl (chloromethyl)phosphonate reacts with aryllithium reagents to give the diethyl esters of benzylic phosphonic acids The alternative procedure has been adopted in a synthetic route to isoprenyl (phos-phinylmethyl)phosphonates. Here, a lithiated dialkyl alkylphosphonate is acylated using an ester of the phosphonochloridic acid, R P(0)(0H)C1, where R is an isoprenoid residue. The acylation process has also been carried to with (R0)2P(0)C1 or (Me2N)2P(0)Cl ... 

R = O-alkyl, n= 1) in the same way, diethyl phenylphosphonite affords 11 (R = Ph, R = Et, = 1, X = I). Bromoform and iodoform, although reactive to trialkyl phosphites, tend to yield alkyl halide, dialkyl hydrogenphosphonate and dialkyl phosphorohalidate, but (halomethyl)phosphonate esters are not obtained. With tetrahalomethanes, particularly those based on two or more different halogens, a more interesting picture is presented. Triethyl phosphite and tetrabromomethane are reported to yield EtBr quantitatively but... 

The use of trichloroacetaldehyde is also to be particularly noted. Although reactions between this aldehyde and various dialkyl hydrogenphosphonates have been report- 269,274,294,295 it is the dimethyl ester of (l-hydroxy-2,2,2-trichloroethyl)phosphonic acid which has received particular attention, and which has been studied widely from the structural point of view in the light of its commercial importance as the powerful insecticide dipterex (also known as trichlorphon and chlorophos). Polyfluoroalkyl esters of the related alkyl(l-hydroxy-2,2,2-trichloroethyl)phosphinic acids have been prepared by the unusual combination of chloral hydrate and the bis(polyfluoroalkyl) alkylphosphonite ester ... 

The mode of addition of hydrogenphosphonates to fluorinated ketones can also be complex. The addition of dialkyl, diphenyl or bis(trimethylsilyl) hydrogenphosphonates to methyl trifluoromethyl ketones occurs in the expected manner, but this contrasts with the behaviour of aryl perfluoralkyl ketones in the presence of triethylamine at room temperature, when the products, obtained even under such mild conditions, are phosphate esters (reaction 6), a situation which represents lack of stability of the hydroxyphospho-nate rather than novelty of the reaction under identical conditions, the corresponding alkyl aryl ketones fail to react. The same reaction with mixed-halogen ketones is still more involved, and the nature of the products depends on the reaction conditions if these are of a mild nature, and with catalysis by triethylamine or pyridine (depending on the particular ketone), the product is the expected (hydroxyalkyl)phosphonate 177, whereas with... 

The Michaelis-Arbuzov procedure, illustrated in general terms in reaction 16, has been used extensively to prepare dialkyl [alkyl(or aryl)thiomethyl]phosphonic diesters " (2-Alkylthioethynyl)phosphonic diesters (375) were prepared from RSC CCl ", whilst the esters 376 and 377 were obtained in an analogous fashion, the latter being a useful... 

The direct alkylation of hydrogenphosphonic diesters with a diazoketone has been recorded alongside that with diazoalkanoic esters, and explored particularly with methyl 2-diazo-3-oxobutanoate but also for several chloroacetones. Reactions involving 1-chloro-3-diazo-2-propanone are effectively catalysed by [Cu(acac)2], but more heavily chlorinated substrates suffer stepwise dechlorination. Thus l,l,l-trichloro-3-diazo-propan-2-one initially yields the expected dialkyl (3,3,3-trichloro-2-oxopropyl)phospho-nate, but under the experimental conditions, dechlorination then proceeds to give the dialkyl (3,3-dichloro-2-oxopropyl)phosphonate only the monochloroketone undergoes a reaction in which the original halogen content is retained in the final product ... 

The acylation of phosphonic carbanions with carboxylic esters is a procedure which has received widespread attention and employed to prepare the protected dimethyl (3,4-dihydroxy-2-oxobutyl)phosphonate 608 and dimethyl [(35)-3-methyl-2-oxo-5-octynyljphosphonate (609), intermediates required in natural product synthesis d An example of intramolecular acylation is the formation of 610 by the action of potassium tert-butoxide on ethyl 2-[(ethoxy)methylphosphinoyl]benzoate d. Acylations of lithiated phosphonoyl carbanions provide dialkyl [(l-formyl)alkyl]phosphonates d ... 

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