Amino acid reaction with ammonia

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... 

When forced, reactions with ammonia commonly lead to derivatives of pyrrole or pyridine, e.g., 2-furoic acid at 210r,C gives 2-amino-3-hydroxyri-dine.189 Hydrazine is a better nucleophile and attacks 3-acylfurans in hot ethanol if there is no group to be displaced the ring opens and a pyrazole is formed.190... 

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. 

Iodopyrimidine 7 was prepared by iodination of 2,4-diaminopyrimidine 6, which was derived from commercially available 2-amino-4-chloro-6-methylpyrimidine (5) via an SNAr reaction with ammonia [8]. Similarly, iodination of 6-chloro-2,4-dimethoxypyrimidine (8) with N-iodosuccinimide in trifluoroacetic acid led to dihalopyrimidine 9 [9],... 

Bartlett etal. [14] described the synthesis of a series of fluoroolefin tripeptide isosteres Cbz-Glyi/r[(Z)-CF=CH]LeuXaa (Xaa = Gly, Ala, Leu, Phe, and NH2) (10) (Scheme 3) as the ground-state analog inhibitors of thermolysin. Treatment of acid (15) with ammonia gave 10e. The inhibitors 10a-d are formed by conventional amide acid coupling reactions of suitably protected amino acids followed by saponification with lithium hydroxide. 

Reaction with ammonia and primary and secondary amines can also give two types of products, 0-hydroxyamides or amino acids (equation 49). The amide is obtained from the reaction of 0-propiolactone with ammonia in water, while the amino acid is obtained from the reaction in acetonitrile, both in good yield. 0-Lactones react very generally with both aliphatic and aromatic amines, but the type of product does not correlate with polarity of solvent or basicity of amine. Fortunately, conditions can usually be found for the formation of the desired product. 

DL-Norleucine (2-aminohexanoic acid). Use 65 g (0.33 mol) of 2-bromo-hexanoic acid (Expt 5.164) and 400 ml of concentrated ammonia. Ensure that the bung is securely wired to the reaction bottle and allow the latter to stand in a warm place (50-55 °C) for 30 hours. Filter the amino acid at the pump and keep the filtrate (A) separately. Wash the amino acid well with methanol to remove the ammonium bromide present. Concentrate the filtrate (A) almost to dryness and add 150 ml of methanol. A second crop of amino acid contaminated with ammonium bromide is thus obtained wash it with methanol and recrystallise from hot water, thus affording a further 6 g of pure dl-norleucine. The total yield is 28 g -(65%) the decomposition point is about 325 °C. 

Fig. 1.8 Asaccharolytic fermentation produces ammonia and short-chain fatty acids. This group of fermentations by oral bacteria utilizes proteins, which are converted to peptides and amino acids. The free amino acids are then deaminated to ammonia in a reaction that converts nicotinamide adenine dinucleotide (NAD) to NADH. For example, alanine is converted to pyruvate and ammonia. The pyruvate is reduced to lactate, and ammonium lactate is excreted into the environment. Unlike lactate from glucose, ammonium lactate is a neutral salt. The common end products in from plaque are ammonium acetate, ammonium propionate, and ammonium butyrate, ammonium salts of short chain fatty acids. For example, glycine is reduced to acetate and ammonia. Cysteine is reduced to propionate, hydrogen sulfide, and ammonia alanine to propionate, water, and ammonia and aspartate to propionate, carbon dioxide, and ammonia. Threonine is reduced to butyrate, water, and ammonia and glutamate is reduced to butyrate, carbon dioxide, and ammonia. Other amino acids are involved in more complicated metabolic reactions that give rise to these short-chain amino acids, sometimes with succinate, another common end product in plaque.

Amino acids react with cyclic a-methylene carbonates (195) to give 4-hydroxyoxazolidinones <93SL423>. Sodium salts of the carboxylic acids are obtained in 93-97% yield, but protonation with HCl afforded the products in only about half that yield (Scheme 100). Reaction of the carbonates with ammonia gives A-unsubstituted 4-hydroxyoxazolidinones. 

Irradiation of the diazepine N-oxide 8 gives a mixture of the 1,2-dihydroquinoxaline (10) and the oxadiazocine 11 through an intermediate oxaziridine (9). The dihydroquinoxaline undergoes acid hydrolysis to the quinoxalinone 12. It was subsequently shown that quinoxalinones of type 12 undergo ready reaction with ammonia or primary or secondary amines, in the presence of titanium tetrachloride, to give 3-amino- or... 

Condensation of the pyrrolidine enamine of V-[4-(/-butyloxycarbonylphe-nyl)]piperidone and (chloromethylene)malononitrile followed by reaction with ammonia in methanol at room temperature afforded the amino nitrile (IV.234) in 72% overall yield [148]. Cleavage of the t-butyl ester was accomplished readily with HCl in nitromethane, and the resulting acid ((IV.235), 77% yield) was coupled to di-t-butyl L-glutamate with the aid of diphenyl... 

Chemists do not have to rely on nature to produce amino acids they can synthesize them in the laboratory, using a variety of methods. One of the oldest methods replaces an a-hydrogen of a carboxylic acid with a bromine in a Hell-Volhard-Zelinski reaction (Section 19.5). The resulting a-bromocarboxylic acid then undergoes an Sn2 reaction with ammonia to form the amino acid (Section 10.4). 

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