Acids Phosphorus halides

In all cases, dithio-phosphorus acids can be liberated from their alkali-metal salts by reacting them with acids such as HC1. Thio-ester derivatives of the dithio-phosphorus acids can be synthesised via reaction of the acids themselves with an alcohol or phenol (Equation 26) or from reaction of their alkali-metal salt with an alkyl halide (Equation 27). 

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 classical Friedel-Crafts approach toward attaching a phosphorus site directly to an aromatic ring would seem a promising route. Phosphorus-centered acid halides would be anticipated to participate in electrophilic aromatic substitution much in the manner of ordinary acyl halides. Early efforts confirmed this concept.48-52 However, difficulties have been encountered in the use of the classical conditions,53 and modifications to the approach have been necessary. 

From Amines and Phosphorus(v) Halides.—Given a suitable primary amine, the Kirsanov reaction remains one of the most convenient routes to these compounds, e.g. (I)7 and (2).8 In both investigations the trichlorophosphazenes were characterized by their now familiar reaction with formic acid ... 

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... 

In contrast to the inertness of carbon halides, the halides of silicon and phosphorus are extremely reactive with water, to the extent that they must be protected from atmospheric moisture. A clue to the reactivity of these halides is provided hy the somewhat Similar reactivity of acid halides which readily react with water... 

Other halides that are useful in converting alcohols to alkyl halides are PC15, PC13, PBr3, and Pl3, which are acid halides of phosphorus oxyacids. As with thionyl chloride, a weak base often is used to facilitate the reaction. The base acts to neutralize the acid formed, and also to generate bromide ion for SN reactions ... 

General methods for the preparation of acid halides from aliphatic carboxylic acids are described in Section 5.12.1, p. 692. Phosphorus pentachloride is the preferred chlorinating agent for aromatic acids which contain electron-withdrawing substituents, and which do not react readily with thionyl chloride. The preparation of both p-nitrobenzoyl chloride and 3,5-dinitrobenzoyl chloride is described in Expt 6.161. These particular acid chlorides are valuable reagents for the characterisation of aliphatic alcohols and simple phenols, with which they form crystalline esters (see Section 9.6.4, p. 1241 and Section 9.6.6, p. 1248). 

To get a broader concept of the nucleophilic reactivity of phosphorus acid derivatives towards organosilanes we studied mechanism of reactions of triorganosilyl halides with esters of tricoordinate and tetracoordinate phosphorus having the general formulae ... 

Amide chlorides are readily available from amides via phosgenation but other reactive acid halides are equally used (thionyl chloride, oxalyl chloride, phosphorus pentachloride and oxychloride, pyrocatechol phosphorus trichloride) (37) 69). 

These and other methods of introducing halogen into heterocycles, such as the transformation of a- and y-hydroxypyridinoid bases with inorganic acid halides, the treatment of pyridinoid A-oxides with sulfur or phosphorus halides, and the decomposition of diazonium compounds, are treated adequately in existing references. 

Chlorobenz[d]isothiazole-l, 1-dioxide ( pseudosaccharin chloride ) (6)3,24.25, lee, 25i, 26i, 262 displays the reactivity of a cyclic imidoyl chloride263 resembling very much carboxylic acid halides. In previous sections preparation of 3, 4, 5, 13, 68, 86, 89 from 6 has been mentioned. Derivatives of 6 substituted in the phenyl ring have been described.250 Interestingly, Meadow observed231 that crude 6 and material that contained phosphorus pentachloride reacted with thiols more readily than the pure compound. In the reaction of 6 with aromatic sulfonamides, aluminum chloride had been added for activation.252... 

A different approach toward preparation of phosphinous and phosphonous iodides uses the reaction of iodoalkanes with either PI3 or PI5. This reaction is specific for iodoalkanes and phosphorus iodides and is not applicable to other halides. From the resultant highly reactive phosphinous and phosphonous iodides, the full range of the parent acid derivatives may be prepared (esters, other acid halides, anhydrides, amides). We will not be concerned here with these preparations of derivatives of the parent acids, topics that are considered in other reports. ... 

The conversion of a carboxylic acid to its halide is usually accomplished by thionyl chloride or phosphorus halides. Phosphorus trichloride and glacial acetic acid give acetyl chloride (67%). The other product is phosphorus acid. Phosphorus pentachloride is converted to phosphorus oxychloride (b.p. 103°), from which the acyl halide is sometimes separated with difficulty. This reagent, however, finds use in the preparation of certain higher-molecular-weight halides. .. Most acyl bromides are made from phosphorus tribromide. ... 

Several dibasic acid halides are best prepared by this method from the readily available anhydrides. Thionyl chloride in the presence of a small amount of zinc chloride converts succinic and phthalic anhydrides to succinyl chloride (74%) and phthalyl chloride (86%), respectively. Phosphorus halides are used in similar preparations of phthalyl bromide (83%) and diphenic acid chloride (71%). ... 

Cleavage of tetrahydrofuran and its derivatives with other reagents has been carried out—acid halides lead to 4-halobutyl esters and phosphorus oxychloride to chloro ethers. - ... 

Sulfonic acids are converted to the corresponding acid halides in much the same way as carboxylic acids. Thionyl chloride is the best reagent for the preparation of methanesulfonyl chloride (83%). By heating with a large excess of thionyl chloride, however, p-toluenesulfonic acid is converted into its anhydride (87%). Benzenesulfonyl chloride is made in 80% yield by the action of either phosphorus pentachloride or phosphorus oxychloride at 180° on sodium benzenesulfonate. Chlorosulfonic and fluorosulfonic acids are used in the conversion of sodium p-chloro-benzenesulfonate to the corresponding sulfonyl halides (85 8S>%). ... 

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