Alloxans

Supplement 1936 3458-3793 Picrolonic acid, 51. Hydantoin, 242. Uracil, 312. Indigo, 416. Barbituric j acid, 467. Alloxan, 500. ... 

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). 

Alloxan (1003) has been observed in the mucus associated with dysentery and it was the very first pyrimidine made synthetically when Brugnatelli oxidized uric acid in 1818. Alloxan has an interesting diabetogenic action which appears to be associated with removal of essential zinc from insulin by chelation. Such permanent diabetes may be induced in fish, dogs, cats, sheep, some birds, monkeys and other creatures, but not in man, owls or guinea-pigs certain pyrimidines related to alloxan show some such activity. 

There are many synthetic routes to alloxan. Probably the best is direct oxidation of barbituric acid (1004 R = H) with chromium trioxide (5208(32)6) but it may be made from barbituric acid via its benzylidene derivative by direct or indirect oxidation of uric acid from 5-chlorobarbituric acid (1004 R = C1) by nitration or from 5-nitrobarbituric acid (1004 R = N02) by chlorination, both via the intermediate (1005) (64M1057) or by permanganate oxidation of uracil (1006) under carefully controlled conditions (73BSF1167). 

Alloxan forms an oxime (1007) which is the same compound, violuric acid, as that formed by nitrosation of barbituric acid likewise, a hydrazone and semicarbazone. Reduction of alloxan gives first alloxantin, usually formulated as (1008), and then dialuric acid (1004 R = OH) the steps are reversible on oxidation. Vigorous oxidation with nitric acid and alkaline hydrolysis both give imidazole derivatives (parabanic acid and alloxanic acid, respectively) and thence aliphatic products. Alloxan and o-phenylenediamine give the benzopteridine, alloxazine (1009) (61MI21300). 

The use of 2-substituted amino-3-aminopyridines (or corresponding 3-substituted amino-2-amino, 3-substituted amino-4-amino and 4-substituted amino-3-amino derivatives) gives the corresponding TV-substituted pyridopyrazinones with esters or alloxan, or with diketones gives quaternary salts such as (403) or their anhydro bases (404) e.g. 56CB2684, 78HCA2452). 

Allomaltol, methyl — see Pyran-4-one, 5-methoxy-2-methyl-Allopurinol applications, 5, 343 metabolism, 1, 237 synthesis, 5, 316, 340 tautomerism, 5, 308 xanthine oxidase inhibition by, 1, 173 Allopurinol, oxy-applications, 5, 343 synthesis, 5, 316 Alloxan... 

Alloxan [2,4,5,6(l//,3//]pyrimidine, tetrone] [50-71-5] M 142.0, m 170 (dec), pK 6.64. Crystn from water gives the tetrahydrate. Anhydrous crystals are obtained by crystn from acetone, glacial acetic acid or by sublimation in vacuo. 

AVm//(Ws-. —Evaporate a little of the acid with a few c.c of dilute nitiic acid to dryness on the watei-bath. An oiange 01 led residue remains. On cooling, add ammonia. A fine purple colour is pioduccd (murc-xide test) see also Reaction for alloxan (p 130). 

Reactions.—i. A small cpiantity of the alloxan solution is evaporated to dryness on the water-bath in a porcelain iDasin. A reddish residue is left, which turns purple on the addition of ammonia (murexide). See Appendix., p. 26S. 

A renewed interest attaches to alloxan since E. Fischer s discovery of the new synthesis of mic acid. The steps in the synthesis are briefly the following. Alloxan and amnioniuin sulphite foim thionuiic acid, which is decomposed by hydio-chloric or sulphuric acid into tiramil. 

Condensation of o-phenylenediamine or xV-methyl-o-phenylcne-diamine with alloxan (8) in neutral solution gives the ureides (9) and (10), respectively However, reaction of o-phenylenediamine with 1,3-dimethylalloxan (13) yields quinoxalin-3-one-2-carboxymethyl-amide (14), rather than the dimethyl ureide. Methylation of (9) in acetone in the presence of potassium carbonate gives the spiro-hydantoin (11). 

The structure of this compound is confirmed by the preparation of the 1-acetyl derivative, acid degradation to 4-methylquinoxalin-3-one-2-carboxylic acid (12), and alternative synthesis from the acid chloride of (12) and AW -dimethyluread A most unusual cyclization occurs when AW-dimethyl-o-phenylenediamine (15) is treated with alloxan in ethanolic solution this apparently involves an A-methyl group and leads to the formation of the spirobarbituric acid (16). The struc-... 

Condensation of 594 with alloxan followed by methylation of the presumably formed purino[7,8-g]-6-azapteridine gave 597. Treatment of the latter with alkylamines afforded (87CPB4031) [1,2,4]triazino[2,3-/]purines 598. Compound 597 was active against P388 leukemia. Vascular relaxing effects of 598 were determined, but none showed potent activity (87CPB4031) (Scheme 123). 

Alloxan und Alloxantin wcrden in einer Acetatpuffer-Losung (get. Zelle) zu Dialur-sdure reduziert. Aus dem Elcktrolysegemisch fallt das Natriumsalz der Dialursaure (Hg-Kathode, C-Anode Hydrazin im Anolyten)1 aus ... 

The ureides hydantoin, parabanic acid, alloxan, barbituric acid, and 4-methyluracil show resonance energies of between 2.3 v.e. and 3.1... 

The unlikely transformation of a pyrimidine into a quinoxaline has, indeed, been reported. Thus 4,5-dimethyl-1,2-benzenediamine (402) and alloxan (403, R = H) under acidic conditions gave 6,7-dimethyl-3-ureidocarbonyl-2(17/)-quinoxalinone (404, R = H) ( 30% see original for details) A(-methylalloxan (403, R = Me) likewise gave 6,7-dimethyl-3-(A(-methylureido)carbonyl-2(17/)-quinoxalinone (404, R = Me) in 50% yield.Such condensations gave improved yields under solid-state conditions. 

The extent of diastereoselectivity observed in the reaction of l-(l-phenylalkoxy)buta-1,3-dienes with indantrione and alloxane is associated with the steric requirements of the alkoxy function in the chiral auxiliary <96SYN105>. 

---