Thionyl chloride, reaction with acids

The equivalence of sulfur and oxygen in this ring system carries over to NSAIDs as well. Preparation of the sulfur analogue of isoxepac (6-4) starts with the alkylation of thiophenol (27-1) with benzyl chloride (26-1). Cyclization of the intermediate thioether (27-2) then affords the homothioxanthone (27-3). The carboxyl side chain is then extended by means of the Amdt-Eistert homologation reaction. The acid is thus hrst converted to its acid chloride by means of thionyl chloride. Reaction with excess diazomethane leads to the diazoketone (27-4). Treatment of that intermediate with silver benzoate and triethylamine leads the ketone to rearrange to an acetic acid. There is thus obtained tiopinac (27-5) [28]. 

Fig. Mechanism for the thionyl chloride reaction with a carboxylic acid to form an acid chloride.

Now let s draw the forward scheme. The primary alcohol is oxidized to the carboxyhc acid, and subsequently converted to the acid chloride upon treatment with thionyl chloride. Reaction with lithium diethyl cuprate then produces the desired ketone. 

Alkanesulfinyl chlorides have been prepared by the action of thionyl chloride on alkanesulfinic acids and by the solvolysis of alkylsulfur trichlorides with water, alcohols, and organic acids. The present procedure, which appears to be general for the preparation of sulfinyl chlorides in either the aliphatic or the aromatic series, is based on an improvement in the solvolysis method whereby the use of inert solvent is eliminated and the reaction is carried out in a one-phase system. ... 

The a -halosulfone, required for the Ramberg-Backlund reaction, can for example be prepared from a sulfide by reaction with thionyl chloride (or with N-chlorosuccinimide) to give an a-chlorosulfide, followed by oxidation to the sulfone—e.g. using m-chloroperbenzoic acid. As base for the Ramberg-Backlund reaction have been used alkoxides—e.g. potassium t-butoxide in an etheral solvent, as well as aqueous alkali hydroxide. In the latter case the use of a phase-transfer catalyst may be of advantage. ... 

Once again, one reaction and only one must be an inversion, but which7" It may also be noticed [illustrated by the use of thionyl chloride on (+)-malic acid and treatment of the product with KOH] that it is possible to convert an optically active compound into its enantiomer." ... 

Quinoxaline-2-carboxylic acid with thionyl chloride gives the acid chloride (79%), which undergoes the expected reactions.166 The gas-phase pyrolysis of quinoxaline-2,3-dicarboxylic anhydride (157) over a Nichrome coil gives o-phthalonitrile (158) (72%), probably via 2,3-quinoxalyne (159) which ring-cleaves, and the diisocyanide subsequently rearranges thermally to the dinitrile.167... 

Pure sulphuric acid gradually yields chlorosulphonic acid and pyro-sulphuryl chloride by concurrent independent reactions on treatment with thionyl chloride.8 Nitric acid vigorously oxidises thionyl chloride to sulphuric acid, probably with intermediate formation of iii tryl chloride,... 

Indeed, if methanol is heated with fuming sulfuric acid, dimethyl sulfate, CH30(S02)0CH3, is obtained but other alcohols are better converted to dialkyl sulfates by oxidation of the corresponding dialkyl sulfites formed by the reaction of 1 mole of thionyl chloride (SOCl2) with 2 moles of the alcohol ... 

Halogenoalkylquinuclidines were prepared by the reaction of the corresponding alcohols with thionyl chloride or halogen acids.24,49,121>... 

The traditional methods utilize sulfur or phosphorous halides to convert the acid to die acid chloride. Of these methods, thionyl chloride [often with a catalytic amount of dimethyl formamide (DMF)] is the most useful since the by-products of die reaction are gases (SO2, HC1) which can be easily purged from the reaction mixture with a stream of nitrogen. The acid chloride product can then be purified on a small scale by bulb-to-bulb distillation or crystallization. Because an excess of thionyl chloride is usually used, there must be a purification step to remove the excess reagent. 

An example of the separation of the anilides of the eight lowest straight-chain carboxylic acids on sodium dodecylbenzene sulphonate is shown in Fig. 5.14. The problem of the procedure described above consists in that formanilide cannot be prepared as CO, SO2 and HC1 are produced by the action of thionyl chloride on formic acid. Formanilide must, therefore, be prepared in an aqueous medium, the other acids must be extracted into a non-aqueous medium. The yield of the extraction varies considerably depending on the type of the acid, and the presence of water in the reaction medium may affect the reaction yield significantly, which makes quantitative analysis difficult. Condensates with toluidine, which were used for the determination of formic acid by GC, are prepared by an analogous procedure. As other toluidine isomers may serve as the reagents, formyl derivatives have been suggested for the separation of these substances [181]. 

Propose a mechanism for the reaction of benzoic acid with oxalyl chloride. This mechanism begins like the thionyl chloride reaction, to give a reactive mixed anhydride. Nucleophilic acyl substitution by chloride ion gives a tetrahedral intermediate that eliminates a leaving group, which then fragments into carbon dioxide, carbon monoxide, and chloride ion. 

Incidental reactions that have been reported include the preparation of derivatives of 5-(hydroxymethyl)-2-furaldehyde by reaction of D-fructose in acetic or propionic acid in the presence of the respective anhydride.158 The condensation of D-glucose with phenol has been effected in acetic acid in the presence of dry hydrogen chloride, prior to resinification,157 and the reaction of sucrose with thionyl chloride in acetic acid-acetic anhydride produced partially acetylated chlorodeoxysucroses.158 Sucrose has been condensed with maleic anhydride in acetic anhydride mixed with acetic acid or formic acid, to give solid products having an undetermined structure.159... 

Thus thionyl chloride reacted with either ethylenimine or 2-methyl-aziridine in the presence of triethylamine, which neutralized the hydrochloric acid produced by the reaction. The resulting 1,T-sulfinyldiaziridine and its 2-methyl analog were readily purified by distillation at reduced pressure. Similarly l,T-dithiodiaziridine and l,T-dithiobis(2-methylaziridine) were obtained by reaction of sulfur monochloride with the appropriate aziridine. 

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