Phosphonic acid chlorides synthesis

A general synthesis of phosphonyl thiadiazoles has been recently disclosed starting from the hydrazone 55. The hydrazones were prepared from acyl phosphonates, which in turn were made from acid chlorides 54. Thus treatment of the hydrazone 55 with thionyl chloride in the presence of DMF and sodium chloride provided the thiadiazoles in... 

Several methods for the preparation of the parent compound in this system, tris(trimethylsilyl)phosphite, have been reported.114 118 The application of this and related reagents in reaction with alkyl halides has been reported and used for the preparation of a variety of phosphonic acid analogues of phospholipids.114119-124 Interestingly, alkyl chlorides appear to be more reactive with the silyl reagents than do alkyl iodides, a reversal of the normally observed trend with alkyl esters of the phosphorus acids. (The particular use of silyl phosphorus reagents for the synthesis of biologically significant compounds has... 

The reactions of dimethyl phenylphosphonite with acid chlorides, a-halogeno-ketones, and iV-(bromomethyl)phthalimide have been used to prepare acyl phos-phinates, /3-keto-alkylphosphinates, and phthalimidomethylphosphinates as intermediates in the synthesis of a-diazophosphinic esters.39 a-Amino-phosphonates have also been prepared by the addition of secondary phosphites to nitriles40 and to isocyanides.41... 

As outlined in Scheme 28, the synthesis of the P-ketophosphonate 131 began with a one-pot anh -aldol/reduction step between ethyl ketone 101 and aldehyde 133, giving the 1,3-syn diol 134 (>30 ldr) [130, 132-136, 145, 146], The diol 134 was then converted into the carboxylic acid 135 in six steps. Completion of the subunit 131 required conversion into the acid chloride and reaction with the lithium anion of methyl-(di-l,l,l-trifluoroethyl)-phosphonate. The C9-C24 aldehyde 132 was prepared in two steps from 136, an intermediate from previous routes [55-58], The Still-Gennari-type coupling of 131 and 132 was readily achieved via treatment with... 

The discovery of the statin mevalonic acid synthesis inhibitors focused new attention on control of blood lipid levels as a measure to stave off heart disease. A number of compounds have been found that treat elevated lipid levels by other diverse mechanisms. The phosphonic acid derivative ibrolipim (9) is believed to lower those levels by accelerating fatty acid oxidation. The phosphoms-containing starting material 7 can in principle be obtained by the Arbuzov reaction of a protected from of p-bromomethylbenzoic acid (6) with triethyl phosphate. Removal of the protecting group and conversion of the acid to an acyl chloride then affords 7. Condensation of this intermediate with substituted aniline 8 leads to the hypolipidemic agent (9). ... 

Preparation of Derivatives. A -Acyl- and A-enoylsul-tam derivatives are routinely prepared in good yields using either sodium hydride-acid chloride or trimethyl-aluminum-methyl ester single-step protocols. A variant of the former method employing in situ stabilization of labile enoyl chlorides with CuCl/Cu has also been reported. A two-step procedure via the A-TMS derivative (1) is useful when a nonaqueous work-up is desirable and for synthesis of the A-acryloyl derivative. A-Enoyl derivatives may also be prepared via the phosphonate derivative (2) by means of an Homer-Wadsworth-Emmons reaction (eq... 

Coutrot, P., and Ghribi, A., A facile and general, one-pot synthesis of 2-oxoalkane phosphonates from diethylphosphonocarhoxylic acid chlorides and organometallic reagents, Synthesis, 661, 1986. 

Partial reaction of phosphoryl chloride with amines can be used for synthesis of phosphonic acids 392,393 if applied to phosphonic dichlorides it affords unsymmetrical phosphinic acids.396... 

The synthesis of the natural (9Z)-methylbixin (270) was accomplished by application of the C7 + C10 + C7 = C24 strategy [108,109]. Condensation of the lactone 271 with the phosphonate 272 led to the ( /Z) mono ester 273 which was converted, with thionyl chloride, into the acid chloride subsequent reduction with lithium tributoxyaluminium hydride resulted in the C7-aldehyde 274 in an overall yield of 22% referred to 271 Scheme 56). 

Given a sufficiently strong base, the activation produced by the phosphoryl group next to an adjacent C—H bond will allow deprotonation and the generation of a highly reactive carbanion. Butyllithium has been commonly used for this purpose, but a preference has been shown in recent work for Ida. Treatment of the anion from methyl methyl(4-morpholinyl)phosphinate (284) with farnesyl chloride yields 285, which, on acidolysis, affords the phosphonic acid 286, employed in the synthesis of a pyrophosphonate analogue of farnesyl pyrophosphate ". Alkylation of the carbanion from the chiral phosphonic diamide 287 (X = Me or higher alkyl) leads to the diastereoisomeric phosphonic... 

Insertions into Aldehyde C-H Bonds. The a-diazo ketones (and esters) derived from diazomethane and an acid chloride (or chloroformate) will also insert into the C-H bond of aldehydes to give 1,3-dicarbonyl derivatives. The reaction is catalyzed by SnCL, but some simple Lewis acids, such as BF3 etherate, also work. The reaction works well for ahphatic aldehydes, but gives variable results with aromatic aldehydes, at times giving none of the desired diketone (eq 32). StericaUy hindered aldehydes will also participate in this reaction, as illustratedin eq 33 with the reaction of ethyl a-diazoacetate and pivaldehyde. In a related reaction, a-diazo phosphonates and sulfonates will react with aldehydes in the presence of SnCL to give the corresponding -keto phosphonates and sulfonates. This reaction is a practical alternative to the Arbuzov reaction for the synthesis of these species. 

PCI3 r.d. 1.57 m.p. -112°C b.p. 75.5°C. it is soluble in ether and in carbon tetrachloride but reacts with water and with ethanol, it may be prepared by passing chlorine over excess phosphorus (excess chlorine contaminates e product with phosphorus(V) chloride). The molecule is pyramidal in the gas phase and possesses weak electron-pair donor properties, it is hydrolysed violently by water to phosphonic acid and hydrogen chloride. Phosphorus(lll) chloride is an important starting point for the synthesis of a variety of inorganic and organic derivatives of phosphorus. 

The synthesis of DAAmEP was conducted in three steps. The first step was a Michaelis-Arhuzov reaction between N-(2-bromoethyl)phthalimide and an excess of triethyl phosphite under reflux at 160 °C for 12 h. In the second step, the reaction between the resulting phthalimide and hydrazine led to the formation of (2-aminoethyl)phosphonic acid diethyl ester. The final step consisted of the reaction between the actyloyl chloride and the diethyl ester, which was achieved in the presence of poly(4-vinylpyridine), 2% crosslinked, to trap the hydrochloric acid produced during the acryloylation. The final DAAmEP monomer was obtained after purification by chromatography on silica gel. All intermediate products were characterized by H and P NMR. The H NMR spectrum of the DAAmEP monomer allowed validation of the expected chemical structure and as a consequence the synthetic pathway. RAFT homopolymerization of DAAmEP was carried out with two different trithiocarbonate chain transfer agents (see Scheme 2.6). 

Carraher recently reviewed these s3mtheses, emphasizing polymerizations employing the interfacial condensation technique. For the synthesis of poly-phosphonate and polyphosphate esters and amides Carraher, Millich and others have reported that hydrolysis of the acid chloride typically limits the product yield and molecular weight.The synthesis of polyesters ... 

---