Phosphorus pentachloride, reaction amino acid

Conversion of the phenoxypropanoic acid into the acid chloride enhances the ease of cyclization and the use of phosphorus pentachloride and aluminum chloride provides an example of this technique (51JA4205). The formation of 3-aminochroman-4-one has been achieved in this way starting from 2-amino-3-phenoxypropanoic acid (76TL271). Cyclization of the phenoxyethanoic acid shown in Scheme 234 occurs on reaction with sodium methoxide to give the chroman-3-one (63JCS5322). 

The 8-oxo-7-phenylacetylamino-5-thia-l-aza-bicyclo[4.2.0]oct-l-ene-2-carboxylic acid benzhydryl ester is reacted with phosphorus pentachloride/pyridine reagent in methylene dichloride, and the reaction mixture is thereafter cooled to -35°C and treated with methanol to produce hydrochloride of 7-amino-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester. This hydrochloride is reacted with 4-(3-aminothiophen-2-yl)-5-oxohex-3-enoic acid 3-methylbut-2-enyl ester. Then 7-[2-(2-benzoylamino-thiazol-5-yl)(3-tert-butyl-4,4-dimethylpent-2-enoxycarbonyl)-pent-2-enoylamino]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid synthesized is reacted with aluminum chloride in anisole and diluted hydrochloric acid and then with dimethylmalonate to give 5-thia-l-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2Z)-2-(2-amino-4-thiazolyl)-4-carboxy-l-oxo-2-butenyl)amino)-8-oxo-, (6R,7R)- (Ceftibuten). 

Diketopiperazines (the bimolecular self-condensation products of a-amino acids) also react with phosphoryl and phosphorus halides to give halopyrazines. Treatment of 2,5-diketo-3,6-dimethylpiperazine with phosphoryl chloride yields a mixture of 2-chloro- and 2,5-dichloro-3,6-dimethylpyrazines the monochloro compound is the predominant product [Eq. (14a)].134,135 Trichloropyrazine has been isolated from the reaction of triketopiperazine with phosphoryl chloride or phosphorus pentachloride [Eq. (15)].273... 

When primary amines react with a-acylaminoketones the resulting Schiff bases can be cyclized in the presence of phosphoryl chloride, phosphorus pentachloride, or triphenylphosphine and triethylamine in hexachloroethane to give 1-substituted imidazoles (11) (Scheme 2.1.4). The starting a-acyl-aminocarbonyls are readily prepared from a-amino acids by reduction with sodium amalgam [31, 32] or by the Dakin-West reaction [33, 34], which is most conveniently conducted in the presence of 4-(AUV-dimethylamino)pyridine (DMAP) as an acylation catalyst [35 37]. 

The synthesis of 5-alkoxyoxazoles (10) from acylated a-amino acid esters is analogous to the cyclization of a-acylamino carbonyl compounds (1). The reactions are usually carried out in the presence of phosphorus pentachloride or pentoxide in chloroform solution. 

According to data in [190], the reaction of the anhydride 1 with 1-amino-2-mercapto-5-methyl-1,3,4-triazole takes place in an unusual manner it leads to the formation not of the corresponding anthranilamide but to the N-substituted anthranilic acid 306 (yield 62%), which is transformed into compound 307 with a yield of 57% when treated with phosphorus pentachloride or phosphorus oxychloride. 

Thus, as shown in Scheme 14.7, the reaction of ethyl formate with ethyl acetate in ether in the presence of sodium metal yielded ethyl sodium formyl acetate. Then, the addition product of ethyl bromide with thiourea was treated with aqueous base and the ethyl sodium formyl acetate was added so that, after standing for a number of hours, acidification with acetic acid yielded 2-ethylmercapto-6-oxypyrimidine. Treatment of the latter with phosphorus pentachloride yielded the corresponding 2-ethylmercapto-6-chloropyrimidine subsequent alcoholic ammonolysis generated 2-ethylmercapto-6-aminopyrimidine and boiling aqueous hydrobromic acid resulted in the production of 6-amino-2-oxypyrimidine (cytosine). 

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