Amides acylating reagents

From amide-acylating reagent adducts and amines or amine derivatives... 

Ruonnated carboxylic anhydrides and acyl halides as common acylating reagents to convert amines to amides and to acy late suitable heterocyclic nitiogen atoms have already been described in the first edition [10] Like in the acylation at oxygen, much synthetic activity was concentrated m the past few years on the denvatization of biomolecules by fluoroacylation reactions, that is, tnfluoroacetylation of amino sugars,... 

Scheme 7.109 Amide synthesis utilizing a reusable polymer-supported acylation reagent.

Two factors are responsible for the high reactivity of the imidazolides as acylating reagents. One is the relative weakness of the amide bond. Because of the aromatic character of imidazole, there is little of the N —> C=0 delocalization that stabilizes normal amides. The reactivity of the imidazolides is also enhanced by protonation of the other imidazole nitrogen, which makes the imidazole ring a better leaving group. 

The imide (86) (see (16a) in Section 4.06.5.2) is a reactive acylating reagent under mild conditions. Reaction with aniline or phenol yields diphenylurea (PhNH)2CO or diphenyl carbonate (PhO)2CO respectively. With benzoic acid, 2-phenyl-4-benzoyl-l,3,4-oxadiazoline-5-thione is formed, hence reaction of (86) with benzoic acid and nucleophiles NuH (Nu = NHPh, OPh, SPh) yields amide PhCONHPh, ester PhC02Ph, and thioester PhCOSPh respectively. With diamines R(NH2)2, (86) forms polyureas [-CONHRNH-] <89BCJ539>. 

Ion pair extraction has also been used to extract polar analytes in bioanalytical procedures. Figure 15.2 exemplifies the determination of the amino acid taurine by gas chromatography-mass spectrometry (GC-MS) this figure also illustrates a useful property of amines (and phenols), which is that they will react more rapidly than water with an acylating reagent in an aqueous environment thus improving their organosolubility. After acylation and ion pair extraction with tetrabutyl ammonium sulphate the taurine is converted to an amide prior to analysis by GC-MS. 

Amide hydrolysis is carried out in water and requires some solubility of the substrate, while amide synthesis is carried out in a suitable solvent with an acylating reagent. The substrates are most commonly primary amines, with few reports of secondary amines [5]. The acylating reagent is selected to be unreactive toward the amine in the absence of the enzyme, but must be compatible with the enzyme providing acceptable rates. Enzymes that selectively hydrolyze or acylate the (R) amide or primary amine are most common, for example. Pseudomonas fiuorescens... 

Despite the huge structural diversity of known carboxylic acids, most of these are readily converted into esters or amides. Even sterically hindered acids, for example pivalic, triphenylacetic [1], or 2,6-disubstituted benzoic acids [1, 2], can be converted into suitable acylating reagents for alcohols or amines (Scheme 7.1). Esters of sterically demanding carboxylic acids can, alternatively, also be prepared by O-alkylation of the corresponding carboxylates [3, 4]. 

Fig. 11.2 (A) Acylating reagents PEG binding yields stable amide bonds but with loss of positive amino charge. The reagents may be on an activated carboxylate or a carbonate.

The second group of hydroxy compound derivatization reactions includes acylation of OH groups with the formation of esters. The most important are listed below (for the table of physicochemical and gas chromatographic constants of acylation reagents refer to the entry Derivatization of Amines, Amino Acids, Amides, and Imides for GC Analysis). 

Adducts from Amides (Thioamides) and Acylating Reagents... 

From carboxylic acid amides and acylating reagents... 

X halogen) Adducts from amides and acylating reagents 1-7... 

Weinreb s amide) as acylating reagent Nahm, S Weinreb, S. M. Tetrahedron Lett., 1981,22, 3815-3818. 

Formation of the oxazolone occurs more readily because the carbonyl group of amides is more nucleophilic than that of urethanes [22]. Both symmetrical anhydrides and 5(4H)-oxazolone are also acylating reagents. The O-acylisourea can be trapped by a nucleophile present in the medium, predominantly hydroxylamine derivatives (R"R NOH), to give a less reactive but more stable species (8). 

Scheme 16.80. Amide synthesis by use of a re-usable polymer-supported acylation reagent.

At about the same time we were struggling with our acylatiOTi problem, Helm-chen and coworkers reported difficulties during the attempted acylation of a similar bicyclic structure using an unsaturated acyl reagent. In particular, they noted that enolate formation with lithium amide bases gave poor and... 

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