Barbituric acid Riboflavin

Xylidine is used as a raw material in the production of riboflavin (vitamin B2), the synthesis of which is based on the condensation of 3,4-dimethylaniline with D-ribose to give the Schiff s base. By hydrogenation with Raney nickel and coupling the amine with benzenediazonium chloride followed by condensation with barbituric acid, riboflavin is obtained. 

More conveniently, compound (13) was directly condensed with barbituric acid (14) in acetic acid (28) or in the presence of an acid catalyst in an organic solvent (29). The same a2o dye intermediate (13) and alloxantin give riboflavin in the presence of palladium on charcoal in alcohoHc hydrochloric acid under nitrogen. This reaction may involve the reduction of the a2o group to the (9-phenylenediamine by the alloxantin, which is dehydrogenated to alloxan (see Urea) (30). 

Figure 2 Chemical synthesis routes to riboflavin. In the upper part of the figure the laboratory route via W-(2-amino-4,5-dimethylphenyl)-D-1 -ribitylamine followed by Kuhn and Karrer is depicted. The lower part shows the technical route devised by Tishler using 3,4-dimethylaniline, o-ribose, benezenediazonium chloride, and barbituric acid. During the reaction of the azo compound with barbituric acid aniline is produced in molar stoichiometry.

Riboflavin or vitamin B, is obtained entirely by synthesis and its usage and role is predominantly as a vitamin rather than as a permitted colourant. The synthesis by Karrer was later improved by Tischler and proceeds from 3,4-xylidine (available through the nitration of o-xylene and reduction of the product), the Schiff s base of which with D-ribose is catalytically reduced. Benzenediazonium chloride is coupled with the hydrogenation product and the resultant azo compound is then condensed with barbituric acid in acetic acid (with loss of aniline) to give the final product. The process is illustrated in Scheme 28. 

Lactoflavin 20 (riboflavin, vitamin B2) was established by Kuhn and Karrer (1935). It is synthesized by condensation of 3,4-dimethylaniline with D-ribose giving the imine 21, followed by reduction to 22 and coupling with benzenediazonium chloride producing the azo compound 23 reaction of 23 with barbituric acid, after loss of aniline and cyclocondensation of the intermediate 24, yields lactoflavin 20. 

Barbituric acid had no effect on riboflavin synthesis when used as a rat dietary supplement. On the other hand, uric acid markedly decreased, whereas urea increased, riboflavin excretion [133]. 

Use Pharmacologically important P. compounds include the derivatives of barbituric acid, vitamins (thiamine, riboflavin), some diuretics, nucleoside antibiotics, and antimetabolites (antipyrimidines) that are used in cancer therapy (e.g 5-fluorouracil and thio-uracil). 

Tsao (1940). Pollen from Antirrhinum majus. Asparagine, urea nitrate, urea,. sodium ureate, choline, adenine, guanine, uracil, barbituric acid, sodium nucleate, Ihiamine, riboflavin, pyridoxine, niacin, niacinamide, inositol, and p-amino-benzoic acid. 

An important advance in the synthesis of riboflavin was made by Tishler and associates, by the discovery that iV-(i -D-ribityl)-2-arylazo-4,5-dimeth-ylaniline (but not the -6-arylazo isomer) would react directly with barbituric acid in a weak acid medium. Large amounts of unusually pure riboflavin can be synthesized by this procedure. 

The availability of the exceptionally successful method for the purification of flavins developed by Pasternack and Brown makes this method the one of choice for the synthesis of several flavins. In addition to riboflavin, [2- C]riboflavin 2 6,7-dimethyl-9-(i -L-lyxityl)isoalloxazine , b-ethyl-y-methyl-9-, 6-methyl-7-ethyl-9-, 6,7-diethyl-9-, and 3,6,7-trimethyl-9-(i -D-ribityl)isoalloxazine ° (using 2-methylbarbituric acid) have been prepared by this method. AT-(i -D-Ribityl)-2-/)-tolylazo-4-ethylaniline , -2-/)-nitrophenylazo-4-chloro-5-methylaniline2 and -2-/>-nitrophenylazo-4-methyl-5-chloroaniline react poorly or not at all with barbituric acid under a variety of conditions. 

The synthesis of riboflavin begins (Scheme 12.115) with the formation of barbituric acid by the condensation of diethyl malonate [(CH3CH202C)2CH2] with urea [(NH2)2C=0] in ethanolic sodium ethoxide. Then, the barbituric acid can either (a) be oxidized directly to the hydrate of alloxan or (b) first be converted to the ben-zylidine adduct and then oxidized to the same compound. Both oxidations are... 

Haley and Lambooy 120) exposed riboflavin-2-C to L. casei for 40 days and found that 16% of the flavin was destroyed only 0.17% of the radioactivity appeared as carbon dioxide. An unidentified radioactive nonfluorescent material was found in the cells which was not urea, oxaluric acid, lactic acid, uracil, alloxan, barbituric acid, lumichrome, lumiflavin, 1,2-dihydro-2-keto -1 - (d -1 - ribityl) -6,7- diraethylquinoxaline - 3 - carboxy-ureide 118, 119), or 1,2-dihydro-2-keto-1-methyl-6,7-dimethyl-quinoxa-line-3-carboxyureide. 

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