The Reactions of Acyl Chlorides

What will be the product of a nucleophilic addition-elimination reaction—a new carboxylic acid derivative, a mixture of two carboxylic acid derivatives, or no reaction—if the new group in the tetrahedral intermediate is the following  

Acyl chlorides react with alcohols to form esters, with water to form carboxylic acids, and with amines to form amides because, in each case, the incoming nucleophile is a stronger base than the departing halide ion (Table 16.1). 

All the reactions follow the general mechanism described on page 736. 

MECHANISM FOR THE REACTION OF AN ACYL CHLORIDE WITH AN ALCOHOL 

The weaker base is eliminated from the tetrahedral intermediate. 

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The acylstannanes 874 and 875 are prepared by the reaction of acyl chlorides with (MciSnl - The symmetrical 1,2-diketones 877 can be prepared by the reaction of an excess of benzoyl chloride with (EtjSn) . Half of the benzoyl chloride is converted into the benzoyltin reagent 876, which is then coupled with the remaining benzoyl chloride under a CO atmosphere to afford the a-diketone 877[748], Triethyl phosphite is used as a ligand. 

The customary method for the laboratory synthesis of acid anhydrides is the reaction of acyl chlorides with carboxylic acids (Table 20.1). 

The reaction of acyl chlorides 150 led to the corresponding ketenes 108 while the allylamines 103 were deactivated as ammonium salts 103-HCl (Schotten-Baumann conditions). 

The alkynyl ketones 840 can be prepared by the reaction of acyl chlorides with terminal alkynes. Cul in the presence of Et3N is the cocatalyst[719]. (1-Alkynyl)tributylstannanes are also used for the alkynyl ketone synthesis[720]. The a, 9-alkynic dithio and thiono esters 842 can be prepared by the reaction of the corresponding acid chloride 841 with terminal alkynes[721,722],... 

Carbon atom 2 of the oxazole ring is also supplied by aldehydes in their reaction with a- (hydroxylamino) ketones, which proceeds in the presence of sulfuric acid and acetic anhydride (equation 109). Three further oxazole syntheses involving incorporation of a C(2) fragment are the condensation of triethyl orthoformate with the hydrochlorides of a-aminoacetophenones (equation 110), the reaction of acyl chlorides with a-azido ketones or a-azido esters in the presence of triphenylphosphine (equation 111), and the preparation of 2-aminobenzoxazole and benzoxazoleimines from o-aminophenols and cyanogen bromide (equation 112). 

Olefinic ketones have been obtained from the reaction of acyl chlorides or anhydrides with olefins using the conditions of the Friedel-Crafts reaction. The intermediate chloro ketones are oftentimes stable and must be treated with sodium bicarbonate or dimethylaniline to complete the de-hydrohalogenation. In this manner, 1-acetyl-1-cyclohexene (62%) ° and 1-butyryl-1-cyclohexene (60%) are prepared. 

The reaction of acyl chlorides with hydroxy compounds and amines has already been met in previous experiments. Generally, hydroxy compounds, ROH, primary amines, RNHj, and secondary amines, R2NH, react Avith acyl chlorides, the reactive hydrogen being replaced by the acyl group ... 

A useful variant of die Curtius reaction comprises the reaction of acyl chlorides in dichloromethane with sodium azide under phase transfer conditions, followed by treatment of the dried dichloromethane solution, which contains acyl azides, with a slight excess of trifluoroacetic acid. The resulting trifluo-roacetamides can easily be cleaved with potassium carbonate in aqueous methanol at room temperature, giving the amines (equation 30). ... 

The full paper concerning the reaction of acyl chlorides (benzoyl and toluene-p-sulphonyl chlorides) with the steroidal nitrone derivative (23) of conanine has been published. Additional information concerning the mechanism of these reactions is given. Thus, it was shown that the formation of the a -benzyloxyimine (24) needs acidic conditions which favour the heterolysis of the N—O bond (Scheme 2). At room temperature, under Schotten-Baumann conditions, the epimeric compounds (25) were obtained from (23) with benzoyl chloride. Compound (25) gave (24) on refluxing in neutral solvent or by treatment with acid, whereas (24) was obtained directly from (23) when treated with a benzene solution of benzoyl chloride in the presence of aqueous sulphuric acid. 

Dialkyl acylphosphonates were obtained for the first time by Kabachnik and Rossiiskaya in 1945 by the reaction of acyl chlorides with trialkyl phosphites. The reaction proceeds readily at room temperature and even on cooling by slowly adding trialkyl phosphite to acyl chlorides. Improvements have been made, especially by controlling the temperature of the reaction. The different versions of this reaction, which are distinguished by the nature of the acylating agent and the structure of the phosphite, have been covered by the reviews of Zhdanov et al. in 1980, Breuer in 1996," and McKenna and Kashemirov in 2002. ... 

Some hexahydrotriazinium salts, derived from the reaction of acyl chlorides, aliphatic carbo-dimides and antimony(V) chloride, lose alkyl substituents in the 1- and 3-positions to afford the corresponding 1,3,5-triazinium hexachloroantimonates, e.g. 2 from l.15... 

Acylsilanes. The reaction of acyl chlorides with McjSiSnBu is Pd-catalyzed. P-Aryl allylsilanes. The Pd(0)-catalyzed reaction of allenes with Me,SiSnBui in the presence of Arl proceeds by addition and Stille coupling. 

Identification of Acyl Chlorides.—The reactions of acyl chlorides which are most helpful in their identification, are those which take place when they are treated with water, with alcohol, and with ammonia. Reaction takes place readily with these substances. When an acyl chloride is mixed with a small quantity of water or alcohol, hydrogen chloride is evolved. In the case of certain chlorides gentle heat is necessary to bring about reaction. The physical properties of the chloride together with those of the acid, ester, or amide prepared from it serve to complete its identification. 

For a review of the reaction of acyl chlorides with organometallic reagents, see Dieter, R.K. Tetrahedron, 1999, 55, 4177. 

The reaction of acyl chloride with potassium thiocyanate under PTC conditions (with PEG 400 as catalyst) is a good method for preparation of acyl isothiocyanate (Eq. 58). It has been conducted efficiently under solvent-free conditions and MW activation [81, 82]. 

This reaction might proceed by the reaction of acyl chlorides with bis(phenyl-seleno)iodoindium(lll), lnl(SePh)2, formed from Inl and PhSeSePh [75]. 

This reaction was first reported by Arndt and Eistert in 1935. It is the extension of carboxylic acid by one CH2 unit via the reaction of acyl chloride with diazomethane and is generally known as the Arndt-Eistert synthesis. In addition, this reaction is also occasionally referred to as the Arndt-Eistert acid synthesis, Arndt-Eistert homologation," and Arndt-Eistert reaction. This reaction has been extensively reviewed. Other reagents instead of diazomethane have been similarly applied to extend the length of the carboxylic acids7... 

The reaction of acyl chlorides with alcohols is one of the best ways to synthesize an ester. 

The reaction of acyl chlorides with diazomethane is fast and selective in the presence of a C=C bond, but not in the presence of other carbene acceptors. Knowledge of the chemoselective reactivity of carbenes is of prime importance for planning the retro-Amdt-Eistert disconnection of the target molecule. 

Amination Reactions. Hexamethyldisilazane is a useful syn-thon for ammonia in amination reactions. Preparation of primary amides by the reaction of acyl chlorides and gaseous Ammonia, for example, is not an efficient process. Treatment of a variety of acyl halides with HMDS in dichloromethane gives, after hydrolysis, the corresponding primary amide (eq 10). Omitting the hydrolysis step allows isolation of the corresponding monosilyl amide. 

The heteroaromatic strategy is extended to the synthesis of fu-rans when acylium ions are employed as the heteroallenophile (eq 16). Acylium ions are generated in situ via the reaction of acyl chlorides and aluminum chloride. Typically, the allenylsilane is added to a solution of 1.0 equiv each of AICI3 and the acyl chloride in methylene chloride at — 20 °C. The reaction is complete in 1 hat-20°C. 

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