Acyl halides conversion

The conversion of an aliphatic carboxylic acid into the a-bromo- (or a-chloro ) acid by treatment with bromine (or chlorine) in the presence of a catal3rtic amount of phosphorus tribromide (or trichloride) or of red phosphorus is known as the Hell-Volhard-Zelinsky reaction. The procedure probably involves the intermediate formation of the acyl halide, since it is known that halogens react more rapidly with acyl haUdes than with the acids themselves ... 

Note The conversion of a quinoxahnecarboxyhc acid into a quinoxalinecarbox-amide is usually done indirectly via the corresponding acyl halide or ester. However, the direct conversion of an acid or anhydride into an amide is possible. 

The Conversion of Acyl Halides to Ketones With Organometallic Compounds ... 

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

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... 

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. 

Alkynylzinc chlorides are useful imermedtates in Pd°-catalysed couplings with vinyl, heteroaryl [56) and acyl halides [89] tsee Chaps. V and X). The conversion of lithium alkyn-vlides into alkynylzinc halides with anhydrous zinc chloride in THF proceeds smoothly and quantitatively under mild conditions. 

We have previously seen (0-96) that dianions of carboxylic acids can be alkylated in the a position. These ions can also be acylated on treatment with a carboxylic ester1705 to give salts of p-keto acids. As in 0-96, the carboxylic acid can be of the form RCH2COOH or RR"CHCOOH. Since p-keto acids are so easily converted to ketones (2-40), this is also a method for the preparation of ketones R COCHiR and R COCHRR", where R can be primary, secondary, or tertiary alkyl, or aryl. If the ester is ethyl formate, an a-formyl carboxylate salt (R = H) is formed, which on acidification spontaneously de-carboxylates into an aldehyde.1706 This is a method, therefore, for achieving the conversion RCH2COOH — RCH2CHO, and as such is an alternative to the reduction methods discussed in 0-83. When the carboxylic acid is of the form RR CHCOOH. better yields are obtained by acylating with acyl halides rather than esters.1707... 

From carboxylic acids 0-75 Conversion of acid derivatives to acyl halides... 

Acyl halides may be identified by —hydrolysis to the corresponding acids (the latter may be further characterised as in Section IV,175) conversion into amides (Section IV,191), anilides or p-toluidides (Section IV,100) and conversion into solid esters (Section IV,183). 

A considerable difference between Friedel-Crafts alkylation and acylation is the amount of the Lewis acid necessary to induce the reaction. Friedel-Crafts alkylation requires the use of only catalytic amounts of the catalyst. Lewis acids, however, form complexes with the aromatic ketones, the products in Friedel-Crafts acylations, and the catalyst is thus continuously removed from the system as the reaction proceeds. To achieve complete conversion, therefore, it is necessary to use an equimolar amount of Lewis acid catalyst when the acylating agent is an acyl halide. Optimum yields can be obtained using a 1.1 molar excess of the catalyst. With... 

The facts that the phenylacetyl complex Villa also undergoes a reaction with phenylacetyl chloride under identical experimental conditions to yield dibenzyl ketone, XVIII (218% with respect to Villa), and that XVII was also obtained from the reaction of phenylacetyl chloride with dichlorobis(triphenylphosphine)palladium(0), XIX, implicate XIX in the catalytic cycle. The palladium (II) complex XIX does indeed catalyze the conversion of an acyl halide to the corresponding symmetrical ketone (123% with respect to XIX). The palladium (IV) structures are only... 

Treatment of A and B with hydrogen over a nickel catalyst results in quantitative conversion of each compound to ferf-butyl alcohol. A reacts with acyl halides and anhydrides, whereas B is unaffected by these reagents. Treatment of 1 mole of A with excess methylmagnesium iodide in diethyl ether solution produces 1 mole of methane and 1 moie each of ferf-butyl alcohol and methanol. One mole of B with excess methylmagnesium iodide produces 1 mole of 2-methoxy-2-methylpropene and 1 mole of ferf-butyl alcohol. 

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