Esters, reaction with ammonia

Reaction with water to yield a carboxylic acid Reaction with an alcohol to yield an ester Reaction with ammonia or an amine to yield an amide Reaction with a hydride reducing agent to yield an aldehyde or an alcohol... 

The resistance of the furoxan ring to chemical attack allows derivatives to be prepared via the reactions of the substituents (Section 4.22.3.4). Carboxylic acids are available by permanganate oxidation of methyl derivatives or by hydrolysis of the corresponding esters reaction with ammonia affords carboxamides. Acylfuroxans provide a source of hydroxyalkyl compounds by reduction, and oximes, for example, via nucleophilic addition. Acylation and oxidation of aminofuroxans allows the amide and nitro derivatives to be prepared. Nucleophilic displacements of nitro substituents can take place, but can be somewhat hazardous on account of the explosive nature of these compounds. Alkoxy derivatives are formed with sodium alkoxide, while reaction with thiolate anions yields sulfides, from which sulfones can be synthesized by peracid oxidation. Nitrofuroxans have also been reduced to... 

Reaction with ammonia and amines (Sec tion 20 12) Esters react with ammonia and amines to form amides Methyl and ethyl esters are the most reactive... 

Amides can be produced from fatty acid methyl esters by reaction with ammonia at 220 °C at 12.4 MPa (1800 psi) pressure. Reaction times are reduced to 1 h by this route however, the fatty acid feedstocks must fkst be converted to methyl esters (21). 

In the second major method of peptide synthesis the carboxyl group is activated by converting it to an active ester, usually a p-nitrophenyl ester. Recall from Section 20.12 that esters react with ammonia and amines to give fflnides. p-Nitrophenyl esters are much more reactive than methyl and ethyl esters in these reactions because p-nitrophenoxide is a better (less basic) leaving group than methoxide and ethoxide. Simply allowing the active ester and a C-protected amino acid to stand in a suitable solvent is sufficient to bring about peptide bond formation by nucleophilic acyl substitution. 

The carboxyl groups of amino acids undergo all the simple reactions common to this functional group. Reaction with ammonia and primary amines yields unsubstituted and substituted amides, respectively (Figure 4.9a,b). Esters... 

If an alcohol R OH is used as solvent instead of water, the corresponding ester 7 can be obtained directly. In analogous reactions with ammonia or amines (R NHa) the amides 8 and 9 respectively are accessible. 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

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). 

When the -OH of a carboxylic acid is replaced by an -NH2, the compound produced is an amide. Amides are neutral to mildly basic compounds. They can be made from acids, acid chlorides, acid anhydrides, and esters by reaction with ammonia or primary and secondary amines. The amide linkage is found in polyamide resins such as nylon. 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

Nitrile 241 was reduced to the amine 242 with Red-Al in morpholine at —40 °C. However aluminium hydrides are mostly unsuitable if there is an A-acetyl group that is required to be conserved and this is discussed further in Section 8.06.8. Also, 240 could be prepared from the ester 243 by reaction with ammonia <1982AP538>. 

Reaction of the imidazole (7-4) with the benzofuran derivative (6-7) leads to the displacement of the benzylic halogen and the formation of the alkylation product (8-1). Treatment of that intermediate with trifluoroacetic acid breaks open the urethane to afford the corresponding free amine. This is allowed to react with ttiflic anhydride to afford the trifluoromethyl sulfonamide (8-2). The ester group on the imdidazole is then saponified, and the newly formed acid is reacted with carbonyl diimidazole. Reaction with ammonia converts the activated carboxyl group to the amide. There is thus obtained the angiotensin antagonist saprisartan (8-3) [6]. 

On the other hand, the acyl esters of 2-ketoses follow a completely different pathway, as heterocyclic, nitrogenated compounds and melanoidins are the principal products of their reaction with ammonia. The free 2-ketoses show similar behavior, but they present a significant difference in the extent of formation of these compounds, the presence of the esterifying acyl groups in the molecule being decisive in increasing their yields. 

El-Sayed and Ohta140 applied the reaction to the formation of 1-sub-stituted pyrazolo[4,3-c]pyridones. Dicyanopyrazole 145 was cyclized under acid or basic conditions to furnish the ester or acid 146 (R — Et or H, respectively). An N-unsubstituted product was obtained by heating the ester 147 with ammonia in a steel bomb.141... 

A malonic ester synthesis is used to form 4-methylpentanoic acid. Hell-Volhard-Zelinskii bromination of the acid, followed by reaction with ammonia, yields leucine. The last reaction is an Sn2 displacement of bromide by ammonia. 

Polysaccharides, Sugars, acyl esters of, reaction with ammonia, 31,81-134... 

It will be noted that in all of the reactions of the anhydrides the tendency is to reform the acid by removing one hydrogen from the other compound present. The remaining acyl group then unites with the residue of the reagent and a new compound is formed. The character of the new compound depends upon the residue of the reagent. With water H—OH we obtain the hydroxyl compound of the acyl radical, that is, the acid itself, while with alcohols we obtain the alkyl-oxy compound of the radical, i.e.y an ester, and with ammonia the amino, (—NH2), compound of the acyl radical, i.e., an amide. 

In the laboratory, amides and esters are usually prepared from the acid chloride rather than from the acid itself. Both the preparation of the acid chloride and its reactions with ammonia or an alcohol are rapid, essentially irreversible reactions. It is more convenient to carry out these two steps than the single slow, reversible reaction with the acid. For example n... 

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