Acid chlorides acylation

This homoenolate anion also acylates acid chlorides readily to give y-keto esters (equation I), but does not react with aldehydes or epoxides. 

The liquid phosphorus oxychloride, b.p. 107°, is a by-product and is removed by fractional distillation under normal pressure. Unless the b.p. of the acid chloride differs very considerably (say, <] 100°) from that of the phosphorus oxychloride, the acyl halide is liable to contain traces of the latter. In such circumstances it is preferable to use thionyl chloride for the preparation of the acid chloride. 

Keto acids are obtained by acylation of cyclopentanone enamines (see p. I3f.) with acid chlorides and subsequent base-catalyzed mro-aldol cleavage (S. Hdnig, 1960). 

Acyl halides are intermediates of the carbonylations of alkenes and organic-halides. Decarbonylation of acyl halides as a reversible process of the carbo-nylation is possible with Pd catalyst. The decarbonylation of aliphatic acid chlorides proceeds with Pd(0) catalyst, such as Pd on carbon or PdC, at around 200 °C[109,753]. The product is a mixture of isomeric internal alkenes. For example, when decanoyl chloride is heated with PdCF at 200 C in a distillation flask, rapid evolution of CO and HCl stops after I h, during which time a mixture of nonene isomers was distilled off in a high yield. The decarbonylation of phenylpropionyl chloride (883) affords styrene (53%). In addition, l,5-diphenyl-l-penten-3-one (884) is obtained as a byproduct (10%). formed by the insertion of styrene into the acyl chloride. Formation of the latter supports the formation of acylpalladium species as an intermediate of the decarbonylation. Decarbonylation of the benzoyl chloride 885 can be carried out in good yields at 360 with Pd on carbon as a catalyst, yielding the aryl chloride 886[754]. 

The reduction of acyl halides with hydrogen to form aldehydes using Pd catalyst is well known as the Rosenmund reduction[756]. Some acyl chlorides give decarbonyiation products rather than aldehydes under Rosenmund conditions. The diene 890 was obtained by decarbonyiation in an attempted Rosenmund reduction of acetyloleanolic acid chloride (889)[757], Rosenmund reduction of sterically hindered acyl chlorides such as diphenyl- and tnpheny-lacetyl chloride (891) gives the decarbonylated products 892[758],... 

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],... 

These acylating agents are the most commonly used (246). Acid chlorides react with 5-nitro-2-aminothiazoIe (88) despite the deactivating effect of the nitro group (Scheme 61) (247), but more vigorous conditions are required (248). 

Benzoyl chloride and derivatives acylate 2-amino-4-aryithiazoles in dioxane in yields of 80 to 90% (249, 250). The location of the acyl group on the exocyclic N has been demonstrated by the fact that the benzoyla-tion product is identical to the benzamidothiazole synthesized from benzamide and 2-bromothiazole (251). 3-Indolyl acetic acid chloride (89) acylates 2-aminothiazole in pyridine (Scheme 62) (81). 

Acylation takes place similarly with a,/3-unsaturated acid chlorides such as 92 (260) and with ethylmalonyl chloride (93) (130) (Scheme 65). 

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

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). 

Acylation. Acylation is the most rehable means of introducing a 3-substituent on the indole ring. Because 3-acyl substituents can be easily reduced to 3-aLkyl groups, a two-step acylation—reduction sequence is often an attractive alternative to direct 3-aLkylation. Several kinds of conditions have been employed for acylation. Very reactive acyl haUdes, such as oxalyl chloride, can effect substitution directiy without any catalyst. Normal acid chlorides are usually allowed to react with the magnesium (15) or 2inc (16) salts. The Vilsmeier-Haack conditions involving an amide and phosphoms oxychloride, in which a chloroiminium ion is the active electrophile, frequentiy give excellent yields of 3-acylindoles. 

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). 

Acylation. Aromatic amines react with acids, acid chlorides, anhydrides, and esters to form amides. In general, acid chlorides give the best yield of the pure product. The reaction with acetic, propionic, butanoic, or benzoic acid can be catalyzed with phosphoms oxychloride or trichloride. 

N-Acylation is readily carried out by reaction of the alkaU metal salts with the appropriate acid chloride. C-Acylation of pyrroles carrying negative substituents occurs in the presence of Friedel-Crafts catalysts. Pyrrole and alkylpyrroles can be acylated noncatalyticaHy with an acid chloride or an acid anhydride. The formation of trichloromethyl 2-pyrryl ketone [35302-72-8] (20, R = CCI3) is a particularly useful procedure because the ketonic product can be readily converted to the corresponding pyrrolecarboxyUc acid or ester by treatment with aqueous base or alcohoHc base, respectively (31). 

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

Sahcyhc acid can be converted to sahcyloyl chloride [1441 -87-8] hy reaction with thionyl chloride in boiling ben2ene. The formation of acyl haUde may also extend to reaction with the phenoHc hydroxyl. The reaction with phosphoms tri- and pentachlorides is not restricted to the formation of the acid chloride. Further interaction of the phosphoms haUde and the phenoHc hydroxyl results in the formation of the phosphoric or phosphorous esters. 

Esters of the phenohc hydroxyl are obtained easily by the Schotten-Baumaim reaction. The reaction ia many cases iavolves an acid chloride as the acylating agent. However, acylation is achieved more commonly by reaction with an acid anhydride. The single most important commercial reaction of this type is the acetylation of sahcyhc acid with acetic anhydride to produce acetylsahcyhc acid [50-78-2] (aspirin). 

Acylated Protein Hydrolysates. These surfactants are prepared by acylation of proteia hydrolysates with fatty acids or acid chlorides. The hydrolysates are variable ia composition, depending on the degree of hydrolysis. CoUagen from leather (qv) processiag is a common proteia source. Acylated proteia hydrolysates (Maypoa, by laotex Chemical Company) are mild surfactants recommended for personal-care products (see Cosmetics). 

Acylation. To achieve acylation of thiophenes, acid anhydrides with phosphoric acid, iodine, or other catalysts have been widely used. Acid chlorides with AlCl, SnCl, ZnCl2, and BF also give 2-thienylketones. AH reactions give between 0.5 and 2.0% of the 3-isomer. There has been much striving to find catalyst systems that minimize the 3-isomer content attempting to meet to customer specifications. The standard procedure for formylation is via the Vil smeier-H a ack reaction, using phosphoms o xycbl o ri de / /V, / V- dim e tb yl fo rm a m i de (POCl /DMF) or /V-m ethyl form an i1 i de. 

Acid chlorides are used for the quantitative deterrnination of hydroxyl groups and for acylation of sugars. Industrial appHcations include the formation of the alkyl or aryl carbonates from phosgene (see Carbonic and chloroformic esters) and phosphate esters such as triethyl, triphenyl, tricresyl, and tritolyl phosphates from phosphoms oxychloride. 

Acylation of pyridazinones and related compounds in the presence of weakly basic catalysts such as pyridine or sodium acetate produces IV-acylated products, while O-acylated products are obtained under strongly basic conditions. However, the reaction between 6-chloropyridazin-3(2//)-one with chlorocarbonates and that of maleic hydrazide with unsaturated acid chlorides or chloromethylsulfonyl chloride gives preferentially N-substituted products. 

Acid moieties include formic acid itself, formates and orthoesters, formamide, DMF dimethyl acetal and ethyl diethoxyacetate, acids, acid chlorides and anhydrides, the last including a rare [3,4-oxalate esters, 2-acyl or 2-ethoxycar-bonyl derivatives e.g. 180) are formed. 

Substituted imidazoles can be acylated at the 2-position by acid chlorides in the presence of triethylamine. This reaction proceeds by proton loss on the (V-acylated intermediate (241). An analogous reaction with phenyl isocyanate gives (242), probably via a similar mechanism. Benzimidazoles react similarly, but pyrazoles do not (80AHC(27)24l) cf. Section 4.02.1.4.6). 

Pyrazoles, isoxazoles and isothiazoles with a hydroxyl group in the 3-position (491 Z = NR, O, S) could isomerize to 3-azolinones (492). However, these compounds behave as true hydroxy derivatives and show phenolic properties. They give an intense violet color with iron(III) chloride and form a salt (493) with sodium hydroxide which can be O-alkylated by alkyl halides (to give 494 R = alkyl) and acylated by acid chlorides (to give 494 R = acyl). 

When pyrazolecarboxylic acids (Section 4.04.2.3.3(iii)) are treated with thionyl chloride instead of the acid chloride, compound (254) is isolated. This corresponds to a double iV-acylation (67HC(22)1). 

V-Acylation of oxaziridine (54) is of more importance, yielding 2-acyloxaziridines which were unaccessible otherwise until recently. Oxaziridines (54) derived from cyclohexanone, butanone or benzaldehyde are acylated readily by acetic anhydride, acid chlorides or isocyanates. Oxaziridines from aliphatic aldehydes, too unstable to be isolated, may be trapped in situ by benzoylation (67CB2593). 

Claisen ester condensation, 6, 279 Thiazolecarboxylic acid chlorides reactions, 6, 279-280 Thiazolecarboxylic acid hydrazides synthesis, 6, 280 Thiazolecarboxylic acids acidity, 6, 279 decarboxylation, 6, 279 reactions, S, 92 6, 274 Thiazole-2-carboxylic acids decarboxylation, S, 92 Thiazole-4-carboxylic acids stability, S, 92 Thiazole-5-carboxylic acids decarboxylation, S, 92 Thiazole-4,5-dicarboxylic acid, 2-amino-diethyl ester reduction, 6, 279 Thiazole-4,5-dicarboxylic acids diethyl ester saponification, 6, 279 Thiazolediones diazo coupling, 5, 59 Thiazoles, 6, 235-331 ab initio calculations, 6, 236 acidity, S, 49 acylation, 6, 256 alkylation, S, 58, 73 6, 253, 256 analytical uses, 6, 328 antifogging agents... 

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