Acylation esters

The formation of amides can be accompHshed by dehydration of the ammonium salts of sahcyhc acid. The more common method for amines is the reaction of the ester, acyl hahde, or anhydride with an amine or ammonia. Each step is fast and essentially irreversible. 

Indole-2-carboxylic acid, 5-hydroxy-ethyl ester acylation, 4, 219... 

Acylation (Sections 16.3,21.4) The introduction of an acyl group, —COR, onto a molecule. For example, acylation of an alcohol yields an ester, acylation of an amine yields an amide, and acylation of an aromatic ring yields an alkyl aryl ketone. 

This chapter covers not only nuclear and extranuclear quinoxahnecarboxylic acids (and anhydrides) but also the carboxylic esters, acyl halides, carboxamides, carbohydrazides, carbonitriles, carbaldehydes, and (ketonic) acyl derivatives of quinoxaline a few related speceis are also included. To avoid repetition, the interconversions of these quinoxaline derivatives are discussed only at the first opportunity thus the esterification of quinoxalinecarboxylic acids in covered as a reaction of carboxylic acids rather than as a preparative route to carboxylic esters, simply because the section on carboxylic acids precedes that on carboxylic esters. To minimize any confusion, appropriate cross-references have been inserted. 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

If k2 > kj, the glycosyl-enzyme intermediate will accumulate, and may be trapped by the rapid denaturation of the enzyme in the presence of (saturating) amounts of substrate. With -glucoside Aj from Asp. wentii and 4-nitrophenyl [ C]-2-deoxy-) -D-irra />jo-hexopyranoside, it was possible to identify the intermediate as a glycosyl ester (acylal) of 2-deoxy-D-arabino-hexose bound to the same aspartate residue that had previously been labeled with the active-site-directed inhibitor conduritol B epoxide and with D-glucal." This constituted an important proof that the carboxylate reacting with the epoxide is directly involved in catalysis. 

In summary, reactions of nitronates with acid anhydrides or acyl chlorides give the O-acylated products, and reactions with acyl imidazoles, phenyl esters, acyl nitriles, and enol-lactones gives the C-acylated products, (see Eq. 5.13).25 The C/O selectivity of nitronate acylation by RCOX is qualitatively correlated with strength (pKJ of the acid HX conjugated to the leaving group X .25... 

R1 = H, alkyl, aryl R4 = aryl, alkyl, heterocycle E = ester, acyl, amide nitro... 

Reagent control This involves the addition of a chiral enolate or allyl metal reagent to an achiral aldehyde. Chiral enolates are most commonly formed through the incorporation of chiral auxiliaries in the form of esters, acyl amides (oxazolines), imides (oxazolidinones) or boron enolates. Chiral allyl metal reagents are also typically joined with chiral ligands. 

Peptide bond formation involves activation of the carboxyl group of an amino acid residue, followed by aminolysis of the activated residue by the amino group of a second amino acid residue. Two types of activated molecules are recognized those that are not detectable but are postulated and those that are detectable and can be isolated. Postulated intermediates are necessary to account for the formation of the detectable intermediates. The postulated intermediates are consumed as fast as they are formed, either by aminolysis by an amino group or by nucleophilic attack by an oxygen nucleophile, which produces activated molecules that are also immediate precursors of the peptide. More than one activated compound may be generated by a postulated intermediate. Activated esters, acyl halides and azides, and mixed and symmetrical anhydrides are isolatable activated compounds that are generated from postulated intermediates. Peptides are produced by one of three ways ... 

Method 2 addition of the amine nucleophile to one of the activated forms of the acid (activated ester, acyl azide, anhydrides, etc.) to which it is to be combined. 

Amino-substituted naphthoquinones and heterocyclic variants have been disclosed in the patent literature as 5-LO inhibitors. Compounds represented by (80) (X = C, N) from Lilly inhibited SRS-A release from sensitized guinea-pig lung tissue [218]. Similar compounds such as (81) (R = carboxylic ester, acyl, or aryl) and related naphthalene derivatives, from American Cyanamid, gave good inhibition in guinea-pig ISN (at 10 //g/ml) and in passive cutaneous anaphylaxis in mice (25-60 /zM i.p.) [219,220]. 

Ammonolysis. Reactions involving ammonia. Ammonolysis of esters, acyl chlorides, and anhydrides give amides aniline is produced by ammonolysis of chlorobenzene. The reaction is analogous to hydrolysis, with ammonia substituted for water. 

Overview of the Databank. A profile of the Phase I databank of compounds is presented in Tables II-IV 202 of the 2652 permutations possible from 12 dione moieties, 13 aryl substitution patterns, and 17 different enol ester acyl groups constituted the Phase I dataset. The structures and data given below exemplify how activity varied with structure throughout the dataset. 

In Chapter 9 you see the basic structure of each of the carboxylic acids and Ccirboxylic acid derivatives. In this chapter we focus on the carboxylic acids and related compounds, such as esters, acyl chlorides, and acid anhydrides, and we also include some information on amides (see Chapter 13 for an additional examination of cimides). Before you can get into synthesis and reactions, though, you need to understand the structure and nomenclature of these compounds. 

Hydrolase-catalyzed enantioselective N-acylation is an important tool for the preparation of enantiopure a- and P-aminoacids. It has been observed that the reactions of many amino acid esters with ester acyl donors catalyzed by CALB is sometimes complicated by interesterification reactions. CALA has, however, emerged as a very chemoselective catalyst in favor of N-acylation of P-aminoesters. Some reviews on CALA and other hydrolases as catalysts for N-acylations of aminoesters are available [109, 126, 127]. 

It also occurs at a measurable rate at low temperatures for the protonated esters of secondary alcohols, but is not important for primary alkyl esters. Acyl-oxygen cleavage, on the other hand, becomes significant only in very... 

The use of protecting groups is common in penicillin chemistry the amino function is normally protected by a triryl, benzyloxycarbonyl. p-nitrobenzyloxycarbonyl. tridlloroethyloxycarbonyl. or trimethylsilyl group and the carboxylic acid is usually protected as a benzyl, p-nitrobenzyl. p-methoxybenzyl. or trichloroethyl ester. Acylations may thus be carried out... 

Reaction XIV. (b) Action of Magnesium Alkyl or Aryl Halide on Esters, Acyl Chlorides, and Acid Anhydrides. (C., 1901,1., 725 II., 622 1902, I., 1411.)—In all the above cases tertiary alcohols are obtained, except, of course, in the case of- formic esters when secondary alcohols are formed. Using esters, the reaction has a wide application, as the examples given below show the use of the acyl chlorides and anhydrides is only of theoretical interest. The reactions in all cases take the usual Grignard course. 

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