Phosphorus halides acid halide synthesis

B. By Hydrolysis Reactions.—Details have appeared of the synthesis of dibenzophosphorin oxides (15) from 5-alkyldibenzophospholes, by reaction with methyl propiolate in the presence of water, and of confirmatory syntheses from phosphinic acid chlorides, as shown below. Evidence for the suggested mechanism of the ring-expansion reaction is presented. The hydrolysis of enamine phosphine oxides is an efficient, although somewhat indirect, method for the preparation of j8-ketoalkylphosphine oxides (16) [see Section 3(iii), for the preparation of enamine oxides]. Reasonable yields (48—66%) of trialkylphosphine oxides (17) have been obtained by the alkaline hydrolysis of the products from the pyrolysis at 220 °C of red phosphorus with alkyl halides, in the presence of iodine. 

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 most convenient synthesis of halogenopyrazines and -quinoxalines is by halogenation of pyrazinones and quinoxalinones with phosphoryl or other acid halides for example, 5-hydroxy-2-pyrazinecarboxylic acid, rather than 5(477)-pyrazinone-2-carboxylic acid, is chlorinated with phosphorus pentachloride/phosphoryl chloride to afford a 63% yield of 5-chloro-2-pyrazinecarbonyl chloride <1994SL814>. Sato and Narita provided an improved synthesis of various halogenopyrazines in which 2(l//)-pyrazinones were activated with chlorotrimethylsilane to give silyl ethers (Section 8.03.7.3). This procedure is most effective for synthesis of bromopyrazines whose overall yields are 62-81% <1999JHC783>. Bromopyrazine is directly prepared by treatment of 2-(l//)-pyrazinone with phosphoryl... 

Most of the conventional reagents for the synthesis of acid chlorides from carboxylic acids are unsatisfactory for the preparation of a-keto acid chlorides. For example, the reaction of pyruvic acid with phosphorus halides does not give pyruvoyl chloride7 whereas the use of phosgene8 or oxalyl chloride9,10 affords ether solutions of the acid chloride in low yield. Recently a useful preparation of pyruvoyl chloride from trimeth-ylsilyl pyruvate and oxalyl chloride has been described.11... 

Conant, J.B.. and Coyne, B.B., Addition reactions of the phosphorus halides. Part 5. The foimation of an unsaturated phosphonic acid, J. Am. Chem. Soc., 44, 2530, 1922 Chem. Abstr., 17, 273a. 1923. Gajda. T.. A convenient synthesis of diethyl 1-chloroalkylphosphonates, Synthesis, 111, 1990. Pudovik, A.N.. Zimin, M.G., and Sobanov, A.A., Reactions of dialkyl phosphites withketones activated by electronegative groups, Zh. Obshch. Khim., 42, 2174. 1972 Chem. Abstr., 78, 58543, 1973. Johnson. R.A.. Aryhnethylphosphonates and phosphonic acids useful as anti-inflammatory agents, their preparation, and their activity, Upjohn, U.S. Patent Appl. US 5500417, 1996 Chem. Abstr. 124. 307587. 1996. 

Tetravalent phosphorus halides are known to react with lithium reagents, but data is scarce. Aryllithium reagents easily displace chloride ion from phosphoryl chloride in the synthesis of tertiary phosphine oxides (143,144,174). A small quantity of the corresponding phosphinic acid (42) was isolated in the preparation of tris(p-dimethylamino-phenyl)phosphine oxide (43) (174). Choice of conditions and concentrations of reactants may well favor either the single or the double dis-... 

A rapid survey of the contents of the previous four chapters, which dealt primarily with the synthesis of various types of phosphonic and phosphinic acids, is all that is necessary to realize that both classes of acids are synthesized by the direct formation of a limited selection of types of derivatives. Most often these are either esters as, for example, in the Michaelis-Arbuzov reaction, or acid halides, almost invariably the chloride as in the phosphorylation of alkenes with PCI5. In any multi-step synthesis, the interconversions of acids, acid halides and esters are consequently amongst the most important of translocations of ligands attached to phosphorus, and their success may even become of critical importance. 

By analogy with the general synthesis of imidoyl chlorides it can be expected that carbamates and thiocarbamates undergo reaction with a variety of acid halides to afford 1-haloformimidates and 1-halothio-formimidates, respectively. For example, carbamates have been reacted with carbonyl chloride ( ), pyrocatecholphosphorus trichloride ( ), and phosphorus pentachloride ( ), and isocyanates were obtained. In view of the catalytic effect of N,N-dimethylformamide in the phosgenation of carbamates to isocyanates, the intermediacy of 1-chloroformimidates X is anticipated ( ). 

Reactive impurities are substances that can react with the monomers, the growing chain-ends, or the acid acceptor to terminate the polymerization prematurely. They can be introduced with the solvent or with the intermediates. The acid chloride may contain impurities originating in its synthesis or storage such as hydrogen chloride, thionyl chloride, phosphorus halides, or monoacid halides. The diamine may contain monoamines, water, or carbonates. It may degrade oxidatively in air or absorb moisture and carbon dioxide. The degree of interference caused by these impurities depends on both the quantity of the impurities as well the relative reaction rates of the desired polymerization vs. those of the impurities. 

Acyl phenols are sufficiently stable to permit their occasional use in the UUmann synthesis [131] and they are normally unreactive towards thionyl chloride and the phosphorus halides. This property permits the preparation of acid chlorides of protected phenolic acids which are employed widely in the synthesis of esters and depsides [122, 124, 125, 126, 127]. Fully acylated phenols are, in contrast to certain alkylated phenols, stable to a range of oxidants such as permanganate and chromic acid and using this property the dihydroxyphenanthra-quinone (76) was prepared from (75) [132]. 

Halides are often prepared in a single step from alcohols through use of the Appel reaction. The reagents in this synthesis are tri-phenylphasphine and a halogen species such as tetrachloromethane, hexachloroacetone, or iodine. In place of the Appel reaction it is often possible to use inorganic acid chlorides, including phosphorus tribromide or thionyl chloride (see Chapter 16). 

Thieno[2,3-c]isothiazole-3-carboxylic acid was the compound obtained by the reaction of ethyl 3-cyano-5,5-diethoxy-2-oxopentanoate with phosphorus pentachloride in refluxing toluene, previously assumed (55JA4069) to yield thieno[3,4-c ]isothiazole-4-carboxylic acid. The proposed mechanism involves the cyclization of the intermediate 3-cyano-2,5-dithioxopentanoate as shown in Scheme 20. The parent heterocycle, which is a weak base and fails to give quaternary salts with alkyl halides, was obtained by decarboxylation of the acid and also by independent synthesis (82AJC385). 

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