Esters, ammonolysis preparation

The strategy described here explains the different possibilities of enzymatic ammonolysis and aminolysis reaction for resolution of esters or preparation of enantiomerically pure amides, which are important synthons in organic chemistry. This methodology has been also applied for the synthesis of pyrrolidinol derivatives that can be prepared via enzymatic ammonolysis of a polyfunctional ester, such as ethyl ( )-4-chloro-3-hydroxybutanoate [30]. In addition, it is possible in the resolution of chiral axe instead of a stereogenic carbon atom. An interesting enzymatic aminolysis of this class of reaction has been recently reported by Aoyagi et al. [31[. The side chain of binaphthyl moiety plays an important role in the enantiodis-crimination of the process (Scheme 7.14). 

The amide can be prepared classically from the acid chloride or by ammonolysis of the ester, prepared directly by cyclization (15, 75, 78-80). 

In general, the reactions of the perfluoro acids are similar to those of the hydrocarbon acids. Salts are formed with the ease expected of strong acids. The metal salts are all water soluble and much more soluble in organic solvents than the salts of the corresponding hydrocarbon acids. Esterification takes place readily with primary and secondary alcohols. Acid anhydrides can be prepared by distillation of the acids from phosphoms pentoxide. The amides are readily prepared by the ammonolysis of the acid haUdes, anhydrides, or esters and can be dehydrated to the corresponding nitriles (31). 

Here, we have selected a few representative examples of the enzymatic resolution of esters by aminolysis or ammonolysis reactions. On the other hand, the enzymatic acylation of racemic amines is also of great utility for the preparation of optically pure... 

The first peptide amides prepared by solid-phase synthesis were obtained by ammonolysis of resin-bound benzyl esters of peptides in solvents containing methanol (Figure 5.16, A). The method was occasionally employed but was not popular because it was inefficient, producing some ester in addition to the amide. A new variant employing gaseous ammonia will likely rekindle this approach (see Section 8.3). During the early developments of solid-phase synthesis, it was known that the... 

Mandelamide has been prepared by treating the ethyl ester with concentrated aqueous ammonia,12 and a saturated alcoholic solution of ammonia has been used to effect ammonolysis of the methyl ester.1 3 Esters of mandelic acid were treated with liquid... 

The bicyclic tropane ring of cocaine of course presented serious synthetic difficulties. In one attempt to find an appropriate substitute for this structural unit, a piperidine was prepared that contained methyl groups at the point of attachment of the deleted ring. Condensation of acetone with ammonia affords the piperidone, 17. Isophorone (15) may well be an intermediate in this process conjugate addition of ammonia would then give the aminoketone, 16. Further aldol reaction followed by ammonolysis would afford the observed product. Hydrogenation of the piperidone (18) followed then by reaction with benzoyl chloride gives the ester, 19. Ethanolysis of the nitrile (20) affords alpha-eucaine (21), an effective, albeit somewhat toxic, local anesthetic. 

Preparation of tertiary alkyl esters of carbamic acid by the ammonolysis of mixed phenyl alkyl carbonates to yield alkyl carbamate and phenol [24, 40, 41]. 

Amides are very easily prepared by the interaction of carboxylic esters with concentrated aqueous ammonia (ammonolysis). 

A further example of the preparation of amides by the ammonolysis of esters (cf. succinamide, Expt 5.155) is provided by the preparation of nicotinamide described in Expt 6.169 as a stage in the synthesis of 3-cyanopyridine. 

Practically all methods which have been proposed for the preparation of guanidine salts involve either ammonation or ammonolysis of some derivative of carbonic acid. Phosgene,1 chloropicrin,2 and esters of orthocarbonic acid2 react with aqueous ammonia to give small yields of guanidine. The hydrochloride is obtained when carbon tetrachloride3 is acted upon by liquid ammonia under pressure. Urea4 is partially ammonolyzed in the presence of ammonium chloride. 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

The acylation of simple /3-keto esters with acyl chlorides to form di-acylacetic esters proceeds readily however, the subsequent cleavage for removing the smaller acyl group is complicated in that the original keto ester may be regenerated. The optimum conditions for the conversion of benzoylacetoacetic ester to benzoylacetic ester with ammonium chloride and ammonium hydroxide have been studied. The over-all synthesis of this ester has been described (57%). An improved procedure for the ammonolysis of ethyl a-acetyl-/3-oxocaproate using gaseous ammonia has been described. By a similar process, a series of alicyclic /3-keto esters has been prepared in over-all yields of 20-40%. ... 

Introduction. The general methods for the preparation of amides are (1) ammonolysis of esters, acyl halides, and anhydrides (2) the dehydration of the ammonium salts of carboxylic acids ... 

Sulphamoyl chloride when reacted with hydroperoxides in the presence of pyridine below — 30 °C leads to the formation of the novel alkyl sulphamoyl peroxides H2NS0200CH2R (R = CH2CH3, CH2CH2CH3) 303 (equation 98)305. Hydrolysis or ammonolysis of these compounds leads to formation of sulphamic acid or sulphamide respectively. 2-Nitrophenylsulphamoyl chloride (304), prepared from the corresponding sulphamic acid by reaction with PC15, has been used to prepare iV-(2-nitrophenyl)-iV -substituted sulphamides (305) and aryl esters (306) (equation 99)306. 

Gill I, Patel RN. Biocatalytic ammonolysis of (5S)-4,5-dihydro-lH-pyrrole-l,5-dicarboxylic acid, l-(l,l-dimethylethyl)-5-ethyl ester preparation of an intermediate to the dipeptidyl peptidase IV inhibitor saxagliptin. Bioorganic and Medicinal Chemistry Letters 16(3), 705, 2006. 

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