Amides base-catalysed

Kinetic studies of base-catalysed hydrogen exchange have been carried out by Roberts, by Shatenshtein, and by Streitweiser and their coworkers. In earlier work, potassium amide was used as base in liquid ammonia as solvent, whereas later workers used lithium and caesium cyclohexylamides in cyclohexylamine. The reaction can be represented by equilibria (239) and (240)... 

The initial product is an amide (197), but this also undergoes ready acid- or base-catalysed hydrolysis (see above), and the actual reaction product is often the carboxylic acid, RC02H, or its anion. 

Interaction of the two compounds led to the evolution of a toxic gas thought to be chlorine [1], It is the far more poisonous phosgene, arising from the known base-catalysed disproportionation of the carbonate to oxalyl chloride and phosgene, which occurs even at ambient temperature [2], (The editor knows that amides, too, catalyse this rearrangement and suspects that Lewis acids will also)... 

Neighbouring-group participation in the hydrolysis of esters and amides has been reviewed. The effects of urea, Na+ and Li+ on the intramolecular general-base-catalysed glycolysis of phenyl salicylate (217) in glycol-acetonitrile solvent at constant water concentration have been reported. ... 

It then remains to remove protecting groups and release the product from the support. All of these tasks, except for the removal of the dimethoxytrityl group, are achieved by use of a single deprotection reagent, aqueous base (ammonia). The cyanoethyl groups are lost from the phosphates by base-catalysed elimination, and amide protection of the bases is removed by base-catalysed hydrolysis. The latter process also achieves hydrolysis of the succinate ester link to the support. 

Activated A-alkyl-O-acylhydroxamic acid derivatives 75 undergo base catalysed rearrangement to give 2-acyloxyamides 76 in good to excellent yields (50-100%) (equation 26). These precursors of 2-hydroxy amides (77) are good intermediates to prepare ethanol-amines, oxindoles and oxazolidinediones. 

Enyne ethers HC=CCH=CHOR are useful synthetic intermediates. They can be prepared by base-catalysed addition of alcohols to diacetylene. The required conditions are rather forcing and not very attractive for laboratory scale preparations. A much more convenient way to prepare the enyne ethers (in these cases more than 80 rel.% of the -isomer is obtained) consists in treatment of the easily accessible 1,4-dialkoxy-2-alkynes with two equivalents of alkali amide in liquid ammonia. The first step in this elimination is the (transient) formation of an "anion RO-fiH-C CCH OR, which eliminates ROH (143). The resulting cumulenic ether ROCH=C=C=CH2 is immediately converted into the metallaied enyne ether. 

Base-catalysed hydrolysis. The hydroxide ion attacks the nitrile carhon, followed hy protonation on the unstable nitrogen anion to generate an imidic acid. The imidic acid tautomerizes to the more stable amide via deprotonation on oxygen and protonation on nitrogen. The base-catalysed amide is converted to carboxylic acid in several steps as discussed earlier for the hydrolysis of amides. 

The synthesis of sodium amide, NaNH2 (or sodamide ), by passing ammonia over heated sodium metal, was first reported almost two centuries ago. A number of studies have since been made of its properties, but no crystal structure has been reported. Sodamide is used as a strong base in organic chemistry (often in liquid ammonia solution). In contrast, sodium bis(trimethylsilyl)amide NaN(SiMe3)2 (or sodium hex-amethyldisilazide , NaHMDS), whose crystal structure is discussed later, is widely used for deprotonation reactions or base catalysed reactions due to its solubility in a wide range of non-polar solvents. An overview of some of the types of chemical reactions in which NaHMDS is used is presented in Scheme 2.3. 

The kinetic order of base-catalysed amide hydrolyses may vary considerably with the structure of the amide. Orders in hydroxide ion both smaller and larger than unity have been observed for a number of hydrolyses28 29,33. An order less than unity is observed when the amide itself is sufficiently acidic to be partially ionised, as in the hydrolysis of trifluoroacetanilide27,28 and higher orders are observed in anilide hydrolyses in which it appears that the tetrahedral intermediate can be further ionised. 

At elevated temperatures, the base catalysed dissociation of structure (XIX) at the keto amide unit (XIII) yields two linear molecules... 

An ingenious application was in the asymmetric synthesis of coniine15 114, the alkaloid in hemlock by which Socrates met his death. The sultam amide 111 incorporates a protected ketone so that acidic hydrolysis forms the cyclic nitrone 112 by capture of that ketone. Reduction and base-catalysed cleavage of the amide gives coniine 114. 

Palladium-catalysed amidation of halo-arenes allows simple assembly of precursors (above) to 4-quino-lones, in which the 2,3-bond is formed by base-catalysed condensation. ... 

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