Esters amine conversion into amides

Similarly 8-hydroxy rather than 11-hydroxy structures have been demonstrated for alangicine and alangimarckine (417) by synthesis from the ester prepared as an intermediate in the synthesis of ankorine, by conversion into amides of 3-benzyl-oxy-4-methoxypheny1ethyl amine and tryptamine respectively, followed by Bischer-Napieralski ring closures (T. Fujii et al.. Tetrahedron Letters, 1976, 2553 1977, 3477 1978, 3111). 

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). 

Conversion of Esters into Amides Aminolysis Esters react with ammonia and amines to yield amides. The reaction is not often used, however, because it s usually easier to start with an acid chloride (Section 21.4). 

Conversion of Amides into Carboxylic Acids Hydrolysis Amides undergo hydrolysis to yield carboxylic acids plus ammonia or an amine on heating in either aqueous acid or aqueous base. The conditions required for amide hydrolysis are more severe than those required for the hydrolysis of add chlorides or esters but the mechanisms are similar. Acidic hydrolysis reaction occurs by nucleophilic addition of water to the protonated amide, followed by transfer of a proton from oxygen to nitrogen to make the nitrogen a better leaving group and subsequent elimination. The steps are reversible, with the equilibrium shifted toward product by protonation of NH3 in the final step. 

A useful method for conversion of esters into amides involves treatment with primary or secondary amines in the presence MgCl2 or MgBr2 <2001TL1843>. Dimethylpyridine-2,3-dicarboxylate and the 2,5-isomer react selectively at the 2-ester. 

In addition to those described, there are many other methods for purifying organic compounds. Examples which might be irientioned are sublimation, chromatography, and conversion into more crystal-lizable derivatives, such as amines into their acetyl, benzoyl, or other acyl derivatives, or acids into their chlorides, amides, esters, etc. These are the methods which are generally used in research laboratories. Although they are used also in industrial laboratories, and the technical chemist should be familiar with them, it is beyond the scope of this book to treat them in detail. 

What is needed for the alkylation is rapid conversion of the ester into a reasonably stable enolate, so rapid in fact that there is no unenolised ester left. In other words the rate of proton removal must be faster than the rate of combination of enolate and ester. These conditions are met when lithium enolates are made from esters with lithium amide bases at low temperature, often 78 °C. Hindered bases must be used as otherwise nucleophilic displacement will occur at the ester carbonyl group to give an amide. Popular bases are LDA (Lithium Di-isopropyl Amide, 66), lithium hexamethyldisilazide 67, and lithium tetramethylpiperidide 68, the most hindered of all. These bases are conveniently prepared from the amine, e.g. 65 for LDA, and BuLi in dry THF solution. 

Conversion of acid derivatives into amines with the loss of the carbonyl group can be done in various ways. In chapter 36 we recommended the Curtius and the Hofmann. The Hofmann degradation is the easier if we start with an ester, converting into the amide with ammonia and then treating with bromine in basic solution. The N-bromo amide undergoes a-elimination to a nitrene that rearranges to an isocyanate. 

Lithium aluminium hydride as a reagent for the alkylation of amines by esters and the conversion of amides into amines is well known. The synthetic utility of these procedures has now been combined into a one-step conversion of amides, lactams, or urethanes into unsymmetrical tertiary amines (Scheme 13). ... 

Carboxylic acids also react with alcohols to give esters. This process is heavily used in the production of polyesters. Similarly carboxylic acids are converted into amides, but this conversion typically does not occur by direct reaction of the carboxylic acid and the amine. Instead esters are typical precursors to amides. The conversion of amino acids into peptides is a major biochemical process that requires ATP. 

Amines may also be prepared by conversion of esters into amides followed by reduction. See section 83 (Amides from Esters) and section 95 (Amines from Amides)... 

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