Amides formation from methyl esters

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

Methylation of X with silver oxide and methyl iodide gave the lactone of methyl 2,5-dimethyl-j8-D-glucofururonoside (XIII) which was characterized by its conversion to the crystalline amide (XIV). Further methylation of XIII, form, with methyl sulfate and sodium hydroxide gave methyl 2,3,5-trimethyl-/3-D-glucofururonoside (XVI) from which by hydrolysis of the glycosidic methyl group and subsequent oxidation with bromine, there was obtained 2,3,5-trimethyl-D-glucosaccharolactone (XVII) characterized by the formation of its crystalline methyl ester. 

All attempts to obtain free 1-esters from 77 by alkaline hydrolysis failed,246 because the splitting of the 1-ester linkage always occurred before deacetylation of the molecule was complete. Thus, the use of methanolic ammonia, or various molar ratios (1 1 to 5 1) of methan-olic sodium methoxide, led invariably to formation of the corresponding aglycon amide and methyl ester, respectively with catalytic amounts (ratio 100 3) of sodium methoxide, most of the starting material remained unchanged. 

A two-electron oxidation of N-acetyltyrosine ethyl ester with mushroom tyrosinase, or with periodate, afforded the N-acetyIdopa ester 142, together with the (Z)-enamide 145 and the 6-acetoxydopa amide 146 (Fig. 40) (284). It is assumed that 145 originates from dopaquinone 143 via 144 by tautomerization. Michael addition of acetate to quinone 143 is believed to be the origin of 146. The formation of quinone methide 144 from dopa ester 142 by tyrosinase is reminiscent of the formation of iminochromes and quinone methides catalyzed by this enzyme in their formation from a-methyl dopa ester (285), and such reactions may well occur in mammalian systems. 

Acid Amides can be produced by acylating ammonia with esters, acid anhydrides, or the acids themselves (above 100 °C) an important product is formamide from methyl formate. Alternatively acid amides can be synthesized by reacting acid halides with ammonia. Catalytic hydrogenation converts the acid amides to primary amines. Ammonia and aldehydes or ketones are the basis for different stable products. With formaldehyde hexamethylenetetramine (urotropine) is obtained with acetaldehyde, ammono acetaldehyde with benzaldehyde, hydrobenzamide with ethylene and propylene oxides, aqueous ammonia reacts to form ethanol- or propanolamine. 

AUcyl esters (e.g., methyl, ethyl, benzyl esters) are usually stable toward amines and, thus, are used as protecting groups. Some anecdotic examples of amide bond formation with aUcyl esters, however, are reported in the literature. High reaction temperature, addition of a Lewis acid (52), or use of organoaluminium species generated from DIBAL-H-H2NR (53) can enable these reactions. Saturated ammonia in methanol can also react with... 

In the formate esters, the free energy difference decreases from esters to thioesters and amides for the methyl and tert-butyl groups, and E-methyl formate is only observed in very small amounts (<0.3%) at low temperature (190 K), as shown by 13C NMR spectroscopy [3], The energy is significantly lower for the bulky tert-butyl moiety relative to the methyl group and this seems to be a function of steric hindrance since ethyl formate and iso-propyl formate have intermediary values [4,5]. In the tert-butyl formate, a strong electronic repulsion accounts for the relatively high proportion of E isomer (10%). 

Ketones from amides. A methylenating agent is generated from CH2CI2 in the presence of TiCU and magnesium metal and it reacts with amides to give methyl ketones, after hydrol)dic workup. Since enamine formation is imphcated it can be exploited for the synthesis of 8-keto esters and congeners. ... 

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