Acid chlorides, acylation reactions

In an attempt to resolve this question of stereochemistry and also to determine whether or not the decarbonylation of an acid chloride containing a f3 hydrogen takes place stereospecifically, erythro- (XI) and fhreo-2,3-diphenylbutanoyl chlorides (XII), obtained by the reaction of the known acids (13, 14) with oxalyl chloride, were synthesized. The reaction of these acid chlorides (see Reaction 8) with chlorotris( triphenyl-phosphine) rhodium gave the corresponding acyl complexes of type lib [R = C6H5CH(CH3)CH(C6H5)]. Decarbonylation of the erythro- cy complex in benzene at 30 °C gave a 90% yield of frans-a-methylstilbene while decarbonylation of the threo-acyl complex under similar reaction... 

Reaction XXH. (c) Action of Zinc Alkyl on Acyl Chlorides in certain proportions.—The preparation of alcohols by this method has already been discussed (Reaction XV.). By using only 1 mol. of zinc alkyl to 2 mols. of acid chloride, the reaction can be stopped at the intermediate ketone stage. In the Grignard reaction with acid chlorides, it has not been found possible to do this owing to the greater reactivity of the Grignard compounds. 

The Fries rearrangement of acyloxybenzene or naphthalene derivatives proceeds smoothly in the presence of a catalytic amount of Sc(OTf)3 (Eq. 6) [19]. It has also been found that the triflate was an efficient catalyst in 2-acylation (direct acylation) reactions of phenol or naphthol derivatives with acid chlorides. Both reactions were successfully conducted by use of a small amount of Sc(OTf)3. 

Acylation of copper derivatives with acid chlorides works well, but they do not react with free carboxylic acids, unlike the more basic alkyl-lithiums. A dramatic illustration of chemoselectivity comes in the interaction of Bu2CuLi with the free acid 59 and its acid chloride 61. Reaction occurs24 at the alkyl iodide with the one to give 60 and at the acid chloride with the other to give the ketone 62. Acylation can also be achieved by many other metal complexes, from A1 to Zr, but to make those we need hydrometallation, the subject of the next section. 

Methylenedioxyphenol in ethereal solution by conversion with ethyl magnesium bromide to the ethoxymagnesio derivative at ambient temperature and removal of solvent and its replacement with toluene, was acylated with cinnamoyl chloride by dropwise introduction of a toluene solution of the acid chloride and reaction at ambient temperature for 5 hours following which work-up by quenching with ammonium chloride solution, gave 2-hydroxy-4,5-methylenedioxychalcone in 70% yield (ref.32). 

Activation of Carboxylic Acids Synthesis of Acyl Imidazoles. iV,AA-Carbonyldiimidazole (1) converts carboxylic acids into the corresponding acylimidazoles (2) (eq 1). The method can be applied to a wide range of aliphatic, aromatic, and heterocyclic carboxylic acids, including some examples (such as formic acid and vitamin A acid) where acid chloride formation is difficult. The reactivity of (2) is similar to that of acid chlorides, but the former have the advantage that they are generally crystalline and easily handled. Isolation of (2) is sirr5>le, but often unnecessary further reaction with nucleophiles is usually performed in the same reaction vessel. Conversion of (2) into acid chlorides (via reaction with HCl), hydrazides, hydroxamic acids, and peroxy esters have all been described. Preparation of the more irr5)ortant carboxylic acid derivatives is described below. 

The route chosen was to react the lithium enolate of 4-t-butyl cyclohexanone with the correct acid chloride. This reaction worked well, as did the rest of the synthesis of pallescensin A, which was first made by this route. The key step, the acylation of the lithium enolate, is interesting because alkylation could have occurred instead. The acid chloride is more electrophilic than the alkyl chloride in this reaction, although alkylation does occur in the next step. Notice how the lithium atom holds the molecules together during the reaction. 

The preparation of diethyl benzoylmalonate (entry 12) represents the use of an acid anhydride, a function in which it is much more reactive than an ester, as the acylating agent. The reaction must be carried out in nonnucleophilic solvents to prevent solvolysis of the anhydride from competing with the desired reaction. Other limitations on the use of highly reactive acylating agents, such as acid anhydrides and acid chlorides, in reactions with enolates derive from the fact that O-acylation may be the dominant reaction. The magnesium salt of diethyl malonate (entries 12 and... 

Most often, the esterquats are prepared by reaction of a tertiary alkanolamine with a fatty acid, followed by reaction with an alkylating agent to the corresponding quaternary [6]. Other sources of the acyl chain include triglycerides, methyl esters, and acid chlorides. The reaction scheme for the preparation of the diester of bis-2-hydroxyethyldimethylammonium chloride from methyldiethanolamine and fatty acid is given in Fig. 3. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Friedel-Crafts acylation of aromatic compounds (Section 12 7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi num chloride The reaction is electrophil ic aromatic substitution in which acylium ions are generated and attack the ring... 

A/-Ttifluoroacetylamino acid chlorides also undergo iatermolecular Ftiedel-Crafts acylation reaction with complete preservation of chiraUty to provide similar natural products (102,103). 

The synthesis of 2,4-dihydroxyacetophenone [89-84-9] (21) by acylation reactions of resorcinol has been extensively studied. The reaction is performed using acetic anhydride (104), acetyl chloride (105), or acetic acid (106). The esterification of resorcinol by acetic anhydride followed by the isomerization of the diacetate intermediate has also been described in the presence of zinc chloride (107). Alkylation of resorcinol can be carried out using ethers (108), olefins (109), or alcohols (110). The catalysts which are generally used include sulfuric acid, phosphoric and polyphosphoric acids, acidic resins, or aluminum and iron derivatives. 2-Chlororesorcinol [6201-65-1] (22) is obtained by a sulfonation—chloration—desulfonation technique (111). 1,2,4-Trihydroxybenzene [533-73-3] (23) is obtained by hydroxylation of resorcinol using hydrogen peroxide (112) or peracids (113). 

Substitution at the Alcohol Group. Acylation of the OH group by acylating agents such as acid chlorides or anhydrides is one of the important high yielding substitution reactions at the OH group of lactic acid and its functional derivatives. AUphatic, aromatic, and other substituted derivatives can be produced. 

As a dibasic acid, malic acid forms the usual salts, esters, amides, and acyl chlorides. Monoesters can be prepared easily by refluxing malic acid, an alcohol, and boron trifluoride as a catalyst (9). With polyhydric alcohols and polycarboxyUc aromatic acids, malic acid yields alkyd polyester resins (10) (see Alcohols, polyhydric Alkyd resins). Complete esterification results from the reaction of the diester of maUc acid with an acid chloride, eg, acetyl or stearoyl chloride (11). 

Other unsymmetrical peroxides can be prepared by this reaction by employing other acylating agents, eg, alkyl chloroformates, organosulfonyl chlorides, and carbamoyl chlorides (210). Unsymmetrical and symmetrical di(diacyl peroxides) also are obtained by the reaction of dibasic acid chlorides directiy with peroxycarboxyhc acids or monoacid chlorides directiy with diperoxycarboxyhc acids in the presence of a base (44,187,203). 

PoIysuIfonyIa.tlon, The polysulfonylation route to aromatic sulfone polymers was developed independendy by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerisation step, sulfone links are formed by reaction of an aromatic sulfonyl chloride with a second aromatic ring. The reaction is similar to the Friedel-Crafts acylation reaction. The key to development of sulfonylation as a polymerisation process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accompHshed with only catalytic amounts of certain haUdes, eg, FeCl, SbCl, and InCl. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

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