1- Acylimidazoles carboxylic acids

Carboxylic acid hydrazides from carboxylic acids—Hydroxamic acids from 1-acylimidazoles—Carboxylic acid amides s. 18, 441... 

The diimidazolide is very hygroscopic.[24] In analogy to CDI it is also called phenoxyphosphoryldiimidazole. Just like CDI, it reacts with carboxylic acids to give the corresponding JV-acylimidazoles. 

Table 3-1. Monoesters prepared from carboxylic acids and alcohols or phenols using AyV -carbonyldiimid-azole (CDI), N-acylimidazole (RCOIm), or AyV -sulfinyldiimidazole (ImSOIm).

Y/ .v-(3-Lactains have also been obtained by the Staudinger reaction carried out between divinylimine and /V-acylimidazoles possessing an electron-withdrawing group (EWG) in a position [111]. This latter were prepared by treatment of a-EWG substituted carboxylic acids with 1,1-carbonyldiimidazole. 

Methyl esters may be prepared by reaction of the aromatic carboxylic acid with diazomethane (cf. Section 4.2.25, p. 433) or, more conveniently, by reaction with a boron trifluoride-methanol reagent. The latter procedure is illustrated by the preparation of methyl m-chlorobenzoate and dimethyl terephthalate (Expt 6.164). t-Butyl esters may be prepared by conversion of the acid into an N-acylimidazole by reaction with N,N -carbonyldiimidazole, followed by reaction with t-butyl alcohol in the presence of DBU62 (Expt 6.165). 

Among the most useful of these azolides is l,l -carbonyldiimidazole (253). This compound is extremely reactive towards nucleophilic reagents because the carbonyl group is subject to electron withdrawal from both sides. Also, although it is very rapidly hydrolyzed by water at room temperature with vigorous carbon dioxide evolution, tihe compound is crystalline, and much more easily handled than phosgene which has similar reactivity. In the formation of 1-acylimidazoles compound (253) reacts in equimolar proportions with a carboxylic acid in an inert solvent to give practically quantitative yields. This reaction comprises a two-step mechanism (Scheme 145) in which the carboxylic acid reacts initially... 

Tris- and tetrakis(imidazol-l-yl)silanes are effective dehydrating reagents for the formation of carboxylic acid derivatives via 1-acylimidazole intermediates <2005CL734>. 

The requisite W-methoxy-W-methylamides may be pre >ared from acid chlorides by employing a slight excess of the commercially available W,G-dimetiiylhydroxylamine hydrochloride in the presence of pyridine. They have also been pre >ared from acylimidazoles and from mixed anhydrides of carboxylic acids. Once prepared, these systems X)ssess stability equivalent to that of most tertiary amides and, in... 

The major classes of carbonyl compounds include aldehydes, ketones, carboxamides, esters, carboxylic acids and anhydrides, and carbonyl halides (acyl halides). These groups differ in the identity of the substituent X on the carbonyl group. At this point we concentrate on these examples, but a number of other carbonyl derivatives have important roles in synthetic and/or biological reactions. These other compounds include acyl cyanides, acyl azides, A-acylimidazoles, 0-aryl esters, and thioesters. The carbonyl compounds are arranged below in the order of the increasing reactivity toward nucleophilic addition. 

Acylimidazoles also give carboxylic anhydrides on reaction with carboxylic acids.972... 

Acylation of amines by carboxylic acids occurs in excellent yield at room temperature if carried out in the presence of the calculated amount of 1,1 -carbonyldiimidazole in an inert solvent such as tetrahydrofuran.701 It involves formation of the acylimidazole as intermediate which is transamidated by the amine.702,703 It is necessary to use dry reagents and to exclude moisture. 

The synthesis of carbohydrazides from the corresponding 1-acylimidazoles by Staab s method703,1166 proceeds under very mild conditions an equimolar mixture of carboxylic acid and l,Tcarbonyldiimidazole is heated in anhydrous tetrahydrofuran until evolution of carbon dioxide ceases and is then treated with the requisite hydrazine derivative. Hydrazine hydrate can be used to provide unsubstituted hydrazides since hydrazinolysis of the acylimidazole is faster than its hydrolysis.703,1166... 

The bisacylation of methylene-active compounds mentioned above can be avoided by using acylimidazoles in place of acyl halides (acylimidazoles are obtained from the carboxylic acid and sulfinyldiimidazole) for example, reaction of the magnesium enolate of ethyl hydrogen malonate and an acylimid-azole, with concomitant decarboxylation, gives the corresponding / -oxo ester 430... 

The most frequently used approaches for derivatizing carboxylic acids are esterification with a variety of single-enantiomer alcohols, or formation of amides with single-enantiomer amines [234,252]. The formation of amide derivatives requires activation of the carboxylic acid by formation of the acid chloride with thionyl chloride, mixed anhydrides with chloroformates, N-acylimidazoles with 1,1 -carbonyldiimidazole or N-acylureas with dicyclohexylcarbodiimide. Esterification reactions generally re-... 

RCOOH RCH2OH. On conversion into the A-acylimidazole, a carboxylic acid becomes reducible to the primary alcohol by NaBH in the presence of water. ... 

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. 

Esters from Carboxylic Acids. Reaction of equimolar amounts of carboxylic acid, alcohol, and (1) in an inert solvent (e.g. THF, benzene, or chloroform) results in ester formation (eq 2). Since alcoholysis of the intermediate acylimidazole is relatively slow, the reaction mixture must be heated at 60-70 °C for some time. However, addition of a catalytic amount of a base such as Sodium Amide to convert the alcohol to the alkoxide, or a... 

Aldehydes and Ketones from Carboxylic Acids. Reduction of the derived acylimidazole (2) with Lithium Aluminum Hydride achieves conversion of an aliphatic or aromatic carboxylic acid to an aldehyde (eq 6). DiisobutyUduminum Hydride has also been used, allowing preparation of a-acylamino aldehydes fromiV-protected amino acids. Similarly, reaction of... 

C-Acylation of Active Methylene Compounds. Treatment of an acylimidazole, derived from a carboxylic acid and (1), with the magnesium salt of a malonic or methyhnalonic half thiol ester results in C-acylation under neutral conditions (eq 7)7 The presence of secondary hydroxyl functionality in the carboxylic acid is tolerated, but primary alcohols require protection. Magnesium salts of malonic esters may be used equally effectively. Intramolecular C-acylation of ketones has also been reported. ... 

C-Acylation. C-Acylation can be realized by treatment of acylimidazoles, derived from carboxylic acids and 1, with the magnesium salts of malonic esters prepared by using Bu2Mg. Acyl imidazoles can also undergo Claisen-type condensation with the dianion of -keto esters (eq 38). ... 

Catalytic Effect of Carbon Dioxide in Amidation Reactions using CDL 1 is widely used in the formation of amides from carboxylic acids and amines. It was found that when the CO2 released in the acylimidazole formation step was thoroughly removed from the reaction vessel, by means of better agitation and ventilation, the amidation became substantially slower. Further investigation confirmed the catalytic effect of CO2 in amidation... 

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