Acid halides reactions with esters

An acid halide can be converted to an ester by an acid catalyzed reaction with an alcohol. 

Most acid halide reactions occur by a nucleophilic acyl substitution mechanism. As shown in Figure 21.6, the halogen can be replaced by -OH to yield an acid, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discus-sing in this section are jl lustra ted only for acid chlorides, they also occur with other acid halides. 

Other reactions forming sulphonyl halides from sulphonic acid derivatives include sulphonyl chlorides from esters with PC13647, sulphonyl fluorides from anhydrides with fluoride salts627 and sulphonyl chlorides from trimethylsilyl derivatives of sulphonic acids by reaction with dichloromethyl methyl ether648. 

Hydroxyethyl esters can be prepared from the free acid by reaction with ethylene carbonate. During an attempt to protect the ketone group of a keto-acid by 1,3-dioxolane formation, it has been found that mixed carboxylate sulphonate esters [e.g. (121) from ethylene glycol and tosic acid] can easily be formed extensions of this reaction show it to have a general applicability. In the presence of fluoride ions, carboxylic acids become sufficiently nucleophilic to attack alkyl halides. Thus, reaction between an acid and 1,3-dibromopropane leads to diesters (122). Molecular sieves have been recommended as suitable absorbants... 

In a series of experiments it was found that the formation of (I) was independent of the concentration of aluminum halide as long as at least two moles was used. Hydrolysis of (I) with hydriodic acid in glacial acetic acid afforded optically pure (/ )-cystine, while the acid catalyzed reaction with ethanol gave an almost quantitative yield of 7V-phthaloyl-cysteine ethyl ester. 

Group VI metal carbonyls catalyze the thermal or photochemical reaction of acyclic and cyclic ethers with acid halides to give esters (e.g., 4-chloropentylacetate, XLVIII) in good yields (Alper and Huang, 1973). The order of effectiveness for M(CO)g is Mo > W > Cr. Group V substituted... 

Strictly speaking the alkyl halides are esters of the halogen acids, but since they enter into many reactions (t.g., formation of Grignard reagents, reaction with potassium cyanide to yield nitriles, etc.) which cannot be brought about by the other eaters, the alkyl halides are usually distinguished from the esters of the other inorganic acids. The preparation of a number of these is described below. 

Thiazolecarboxylic acid hydrazides are prepared by the same general methods used to prepare amides, that is, by treating acids, esters, amides, anhydrides, or acid halides with hydrazine or substitued hydrazines. For example, see Scheme 21 (92). The dihydrazides are obtained in the same way (88). With diethyl 2-chloro-4,5-thiazoledicarboxylate this reaction gives the mono hydr azide monoester of 2-hydrazine-4,5-... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

Substituted Amides. Monosubstituted and disubstituted amides can be synthesized with or without solvents from fatty acids and aLkylamines. Fatty acids, their esters, and acid halides can be converted to substituted amides by reaction with primary or secondary aLkylamines, arylamines, polyamines, or hydroxyaLkylamines (30). Di- -butylamine reacts with oleic acid (2 1 mole ratio) at 200—230°C and 1380 kPa (200 psi) to produce di-A/-butyloleamide. Entrained water with excess -butylamine is separated for recycling later (31). 

Reaction with Alkyl Halide. The active methylene group of an Al-acylamino-malonic acid ester or Ai-acylamino cyanoacetic acid ester condenses readily with primary alkyl hahdes. 

Esterification. Esters are formed by the reaction of ethanol with inorganic and organic acids, acid anhydrides, and acid halides. If the inorganic acid is oxygenated, eg, sulfuric acid, nitric acid, the ester has a carbon—oxygen linkage that is easily hydrolyzed (24—26). 

Michael addition reactions, 4, 302 reactions with ally halides, 4, 301 Pyrrole-2-carboxylic acid, 1-methyl-conformation, 4, 194 esters... 

Closely related to the carboxylic acids and nitriles discussed in the previous chapter are the carboxylic acid derivatives, compounds in which an acyl group is bonded to an electronegative atom or substituent that can net as a leaving group in a substitution reaction. Many kinds of acid derivatives are known, but we ll be concerned primarily with four of the more common ones acid halides, acid anhydrides, esters, and amides. Esters and amides are common in both laboratory and biological chemistry, while acid halides and acid anhydrides are used only in the laboratory. Thioesters and acyl phosphates are encountered primarily in biological chemistry. Note the structural similarity between acid anhydrides and acy) phosphates. 

Conversion of Acid Halides into Esters Alcoholysis Acid chlorides react with alcohols to yield esters in a process analogous to their reaction with water to yield acids. In fact, this reaction is probably the most common method for preparing esters in the laboratory. As with hydrolysis, alcoholysis reactions are usually carried out in the presence of pyridine or NaOH to react with the HC1 formed. 

Conversion of Acid Halides into Amides Aminolysis Acid chlorides react rapidly with ammonia and amines to give amides. As with the acid chloride plus alcohol method for preparing esters, this reaction of acid chlorides with amines is the most commonly used laboratory method for preparing amides. Both monosubstituted and disubstituted amines can be used, but not trisubstituted amines (R3N). 

---