Halogenation acyl chlorides

The reaction between tris(trimethylsilyl) phosphite and a perfluoroacyl chloride proceeds without any apparent difficulty to give the predicted phosphonate diester 489 [R = Me3Si, R = CF3 or (CF3)2CH] but the use of longer chain polyfluorinated acyl halides or other heavily halogenated acyl chlorides leads to complications with such substrates, the initially formed acylphosphonate reacts with more phosphorus(III) ester to give the (Z)-enol phosphate 490 (Scheme 47). The halides, XCH2COX (X = Cl or Br) afford only the esters 491 (X = H). ... 

M acid or acyl halides these are organic compounds containing die group —CO.X, where X is a halogen. Acyl chlorides, have the general formula R.CO.Cl. In systemi-caily naming acyl halides the names end with the suffix -oyl, e.g. ethanoyi chloride CH3COCI. 

Hydrogen fluoride, HP, when used alone is a comparatively ineffective exchange agent and replaces only active halogens (13), eg, acyl fluorides from acyl chlorides and ben2otrifluoride [98-08-8] from hen2otrich1 oride (eq. 12). 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives. Acyl halides can be a brominated or chlorinated by use of NBS or NCS and HBr or HCl. The latter is an ionic, not a free-radical halogenation (see 14-2). Direct iodination of carboxylic acids has been achieved with I2—Cu acetate in HOAc. " ° Acyl chlorides can be a iodinated with I2 and a trace of HI. Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium A-isopropylcyclohexylamide in THF and treatment of this solution at -78°C with... 

Aldehydes can be directly converted to acyl chlorides by treatment with chlorine however, the reaction operates only when the aldehyde does not contain an a hydrogen and even then it is not very useful. When there is an a hydrogen, a halogenation (12-4) occurs instead. Other sources of chlorine have also been used, among them S02Cl2 and r-BuOCl. The mechanisms are probably of the free-radical type. V-Bromosuccinimide, with AIBN (p. 912) as a catalyst, has been used to convert aldehydes to acyl bromides. 

Carboxylic acids can be converted to acyl chlorides and bromides by a combination of triphenylphosphine and a halogen source. Triphenylphosphine and carbon tetrachloride convert acids to the corresponding acyl chloride.100 Similarly, carboxylic acids react with the triphenyl phosphine-bromine adduct to give acyl bromides.101 Triphenviphosphine-iV-hromosuccinimide also generates acyl bromide in situ.102 All these reactions involve acyloxyphosphonium ions and are mechanistically analogous to the alcohol-to-halide conversions that are discussed in Section 3.1.2. 

The best yields are obtained when the ketene has an electronegative substituent, such as halogen. Simple ketenes are not very stable and must usually be generated in situ. The most common method for generating ketenes for synthesis is by dehydrohalo-genation of acyl chlorides. This is usually done with an amine such as triethylamine.167 Other activated carboxylic acid derivatives, such as acyloxypyridinium ions, have also been used as ketene precursors.168 Ketene itself and certain alkyl derivatives can be generated by pyrolysis of carboxylic anhydrides.169... 

Catalytic hydrogenation is hardly ever used for this purpose since the reaction by-product - hydrogen chloride - poses some inconveniences in the experimental procedures. Most transformations of acyl chlorides to alcohols are effected by hydrides or complex hydrides. Addition of acyl chlorides to ethereal solutions of lithium aluminum hydride under gentle refluxing produced alcohols from aliphatic, aromatic and unsaturated acyl chlorides in 72-99% yields [5i]. The reaction is suitable even for the preparation of halogenated alcohols. Dichloroacetyl chloride was converted to dichloro-... 

The scope of the Negishi-coupling is not limited to aryl and vinyl halides and sometimes acyl chlorides might also be converted to ketones by this protocol. The 2,3-dihalopyrrole derivative shown in 6.22. was converted into its 2-lithio derivative by selective lithium-halogen exchange at -78 °C. Addition of zinc chloride effected the formation of the appropriate pyrrolylzinc chloride, which was coupled with a functionalised butyroyl chloride in the presence of tetrakis(triphenylphosphino)palladium and furnished the expected 2-acylpyrrole in 61% yield.27... 

The carbon-halogen bond distances in acyl halides increase in the direction F < Cl < Br < I, and are similar, but slightly larger than, those of the alkyl halides (Table 7). Nuclear quadrupole resonance frequencies of halogen compounds suggest that the charge density on the chlorine atom of an acyl chloride is greater than that on an alkyl chloride (Table 8). 

Reaction XLVm. (a) Action of Alkali Cyanides on Alkyl and Acyl Halides. (Bl., [2], 50, 214.)—This reaction is capable of very wide application, all the simple alkyl halogen compounds, the acyl halides, and the halogen fatty acids come within its scope. The nitriles so formed yield acids by hydrolysis, so it is frequently the first step in the synthesis of an acid—the preparation and hydrolysis of the nitrile are often combined. The preparations of malonic, succinic, tricarballylic and other acids (Preparations 60, 61, 62) illustrate this. The extension of this reaction to acyl halides is important, and should be referred to, as should the interaction of silver cyanide, and alkyl iodides, to give isonitriles. Mercuric and silver cyanides, it may be noted, give with acyl chlorides and bromides better yields of normal acyl nitriles than do the alkali cyanides. 

Aminopropyl)silatranes (105 and 105a) react with halogen-containing compounds including acyl chlorides (equations 140 and 141)96 99 365 366 and with aldehydes (equation 142)366 367 to give the corresponding derivatives (106-108). 

There is no ambiguity in the halogenation of acids as they can of course enolise on one side only. Reliable methods are bromination with PCI3 and bromine or red phosphorus and bromine. The acid is converted into the acyl chloride with PCI3 or the acid bromide by PBr3, formed in the reaction mixture from red phosphorus and bromine. Bromohexanoic acid 34 can be made in good yield if the reaction mixture is worked up with water.7... 

The classical Hunsdiecker reaction (equation 18), involving the reaction of silver caiboxylates widi halogens, and the various associated side reactions, has been reviewed several tunes. Optimum yields are obtain widi bromine, followed by chlorine. Iodine gives acceptable yields provid diat the correct stoichiometry of 1 1 is used. The reaction is most frequently carried out in tetrachloromediane at reflux. From a practical pmnt of view, one drawback is the difficulty encountered in the preparation of dry silver caiboxylates the reaction of silver oxide on the acyl chloride in tetrachloromediane at reflux has been employed to circumvent diis problem. Evidendy the use of molecular bromine limits die range of functional groups compatible widi die reaction the different reaction pathways followed by the silver salts of electron poor (equation 19) and electron rich (equation 20) aryl carboxyl s illustrate this point well. 

Studies on the conditions of the reaction have been made using simple compounds as model substances, A comparison of thirty-nine metallic chlorides shows aluminum chloride to be the most effective in the preparation of p-methylacetophenone. Optimum yields result when the molar ratios of aluminum chloride to anhydride, acyl chloride, and acid are 3.3, 1,0, and 2.5, respectively. Halogen and oxyhalogen carriers are not helpful. Inconsistent yields in the Friedel-Crafts reaction have been attributed to the presence of ferric chloride or moisture in the aluminum chloride Catalyst. Prolonged heating causes condensation of the ketone product. 

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