Acyl chlorides reaction with alcohols

Esterification with acyl chlorides (Section 15 8) Acyl chlorides react with alcohols to give esters The reaction is usually carried out in the presence of pyridine... 

Reaction of the acyl chloride 1 with alcohol 4 thus formed leads to formation of an ester 6 ... 

When acyl chlorides react with alcohols and phenol, we get esters (and HCl) formed. The reactions happen more quickly than the reactions of alcohols or phenol with carboxylic acids. The acyl chloride reactions also go to completion and do not form an equilibrium mixture. Therefore they are useful in the synthesis of esters in the chemical industry. 

The intermediate products, which are represented within brackets, are exceptionally labile since they contain OH and the negative acetoxyl group attached to the same carbon atom (cf. p. 103) they therefore decompose into two molecules of acid or, in the case of ammonia, into acetic acid and acetamide. The reaction with alcohols is to be formulated in the same way. It will be observed that, when an acyl group is introduced (into an alcohol, amine, etc.) by means of an anhydride, one of the two acid radicles in the molecule is always converted into the acid and is consequently not used in the acylation. The great reactivity of the acid chlorides has the same cause as that discussed in connexion with the anhydrides. 

Preparation of esters Acid chlorides react with alcohols to give esters through a nucleophilic acyl substitution. Because acid chloride is reactive towards weak nucleophile, e.g. alcohol, no catalyst is required for this substitution reaction. The reaction is carried out in base, most commonly in pyridine or triethylamine (EtaN). 

Synthesis of trifluoromethylated compounds 152 has been achieved via ester-enolate [2,3]-Wittig and [3,3]-lreland-Claisen rearrangements. Perfluorocyclo-butane phosphonium ylides, e.g. 153, have been used as a masked fluoride anion source in their reactions with alcohols and carboxylic acids which lead to alkyl-and acyl-fluorides. Ylides 153 are also reported to cleave Si-C and Si-O bonds, cause dimerisation of fluoro-olefins, and also react with acid chlorides or other activated aromatic compounds under halogen exchange. ... 

The synthesis of 2-acylamino-2-deoxy-/3-D-glucopyranosides can be effected from the acetylated glycosyl acetates by reaction with alcohols in the presence of iron(lll) chloride. The procedure is satisfactory with primary, secondary, or tertiary alcohols, and with a range of A-acyl substituents. It is believed that the... 

Acid anhydrides are not as reactive as acid chlorides, but they are still activated toward nucleophilic acyl substitution. Reaction with an alcohol gives an ester. Notice that one of the two acid units from the anhydride is expelled as the leaving group. 

Anions obtained from acetoacetic esters undergo acylation when they are treated with acyl chlorides or acid anhydrides. Because both of these acylating agents react with alcohols, acylation reactions cannot be carried out in ethanol and must be carried out in aptotic solvents such as DMF or DMSO (Section 6.13C). (If the reaction were to be carried out in ethanol, using sodium ethoxide, for example, then the acyl chloride would be rapidly converted to an ethyl ester and the ethoxide ion would be neutralized.) Sodium hydride can be used to generate the enolate ion in an aptotic solvent ... 

The acylation of arenes with alcohols has been shown to be possible using a palladium chloride catalyst in the presence of f-butylhydroperoxide. In 2-arylpyridines, substitution is directed to the ortho-position and, after initial paUadation, the formation of intermediate (59) is likely before reductive elimination yields the acylated product. The regioselective acetoxylation of indoles, at the 3-position, has been achieved using the palladium-catalysed reaction with phenyliodonium acetate. 3-Acyl indoles may also be prepared using acetyl chlorides with zirconium tetrachloride as a Lewis acid catalyst. 

Among other reactions, the bis-metallated species (151) derived from nitroalkanes condense with dialkyl carbonates to give comp>ounds (152), in 60—80% yield, which can serve as precursors of both a-amino-acids and a-hydroxyamino-esters as well as a-keto-esters. Oxazolin-5-ones (153) can be alkylated at the 4-position by alkyl halides in hot DMF containing HMPA and ethyldi-isopropylamine. Yields are good (60—90%) for allylic, benzylic, and propargylic halides but otherwise poor (e.g. 32% with EtI) under these conditions acid hydrolysis of the products affords substituted a-amino-acids. Mesoionic l,3-oxazol-5-ones (154), obtained from imidoyl chlorides and acyl-tetracarbonylferrates, react with alcohols to give N-acyl-a-amino-acid esters. ... 

Functionalized terpyridines can be created to contain a variety of binding and catalytic functional groups (15). Bromomethyl derivatives can be reacted with the sodium salts of alcohols to form ethers, or reacted with the sodium salts of amines to form substituted amines. Each sodium salt was formed by reaction with sodium hydride. Gabriel synthesis leads to the creation of an aminomethyl derivative, which can be converted into amide with acyl chlorides, ureas with isocyanates, or thioureas with isothiocyanates. Terpyridine-5-carboxylic acid is converted to the acyl chloride with thionyl chloride and can be coupled with a variety of amines to form amide derivatives. 

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