C5H4N4

PURIN  , in chemistry, the name given by Emil Fischer to the parent substance of a large group of compounds, the more important of which are sarcine, xanthine, uric acid, adenine, paraxanthine, guanine, theophylline, theobromine and caffeine . Its formula is shown in the inset, the positions taken by substituent atoms or groups being numbered as shown . E . Fischer (Ber., 31, p . 2564) obtained it in 1898 by reducing 2.6-di-iodo purin, obtained from 2.6.8 trichlor purin (see below sub Uric acid), hydriodic acid and phosphonium iodide at o°, with zinc dust and water, the zinc double salt so obtained being decomposed by sulphuretted hydrogen, the precipitated zinc sulphide filtered off and the solution concentrated . It has also been synthesized by O . Isay (Ber., 1906, 39, p . 250) from 5-nitro-uracil . This substance with phosphorus oxychloride gives 2.4-dichlor-5-nitro pyrimidine, which with ammonia gives 4-amino-2-chlor-5-nitro pyrimidine; by reducing this compound with hydriodic acid and phosphonium iodide, 4.5-diamino-pyrimidine is obtained, which with formic acid furnishes purin; thus: NH•CH N:CH N:CH N:CH N:CH O•NO2-CICC•NO2--> C1CC•NO2->HCC•NH2- HC .NH i i NH-CO N u•iCl ii•NH2 ii• —N~ Ni >CH . N•C•NH2 g-.8 Purin crystallizes in microscopic needles, which melt at 216° C . It possesses the properties of both an acid and a base . It is characterized by its ready solubility in water and by its stability towards oxidizing agents .

Oxypurins.—Sarcine or hypoxanthine, C5H4N40, is 6-oxypurin . It is found in many

animal liquids and organs and in the seeds of many plants, and was discovered by J . Scherer in milk (Ann . 185o, 73, p . 328) and by A . Strecker in muscle . It crystallizes in needles which decompose at 15o° C . It was synthesized by E . Fischer (Ber., 1897, 30, p . 2228) by heating 2.6.8-trichlorpurin with aqueous caustic potash, and reducing the dichlorhypoxanthine so obtained by hydriodic acid . Its aqueous solution shows acid properties, decomposing carbonates . It also forms a hydrochloride, C5H4N40•HC1.H20 .

When oxidized by hydrochloric acid and

potassium chlorate it yields alloxan and urea, whilst with potassium permanganate it gives oxalic acid . 3-Methylhypoxanthine was synthesized by W . Traube and F . Winter (Arch . Pharm., 1906, 244, p . 11), whilst 8-oxypurin was obtained by E . Fischer and L . Ach in 1897 (Ber., 30, p . 2213), and by 0 . Isay (Ber., 1906, 39, p . 251) . Xanthine, C5H4N402, or 2.6-dioxypurin, was discovered in 1817 by Marcet in a urinary calculus; it also occurs in various animal organs (the liver, pancreas and muscular tissue), in urine, and in beetroot juice .

It may be prepared by boiling nuclein with water (A . Kossel, Zeit. physiol . Chem., 188o, 4, p . 290) ; by the decomposition of guanine with nitrous acid (A . Strecker, Ann., 1858, 1o8, p.141) ; and by heating the formyl derivative of 4.5-diamino-2.6-dioxypyrimidine to 120° C . (W . Traube, Ber., 1900, 33, p . 3035) . This pyrimidine is prepared from cyanacetyl urea, which on treatment with a concentrated solution of

sodium hydroxide is converted into 4-amino-2.6-dioxypyrimidine . The isonitroso derivative of this compound is then reduced by ammonium sulphide to 4.5-diamino-2.6-dioxypyrimidine, the formyl derivative of which, on heating passes into xanthine . CO.CH2 CO• ICH2 CO.C:NOH CO•C•NH2 CO-IC•NH NHCN~NHC NH-~NHC:NH—3NHC•NH2~NH C—Na' CO•NH2 CO•NH CO•NH CO•NH CO—NH It decomposes when heated, giving ammonia, carbon dioxide and hydrocyanic acid . It possesses both acid and basic properties .

When heated with concentrated hydrochloric acid to 220° C, it decomposes into carbon dioxide, ammonia, glycine and formic acid . Potassium chlorate and hydrochloric acid oxidize it to alloxan and urea . Methylation of its

lead salt gives theobromine . The isomeric 6.8-dioxypurin was prepared by E . Fischer and L . Ach (loc. cif) . 1-Methylxanthine was found in urine by M . Kruger and G . Salomon (Zeit. physiol . Chem., 1897, 24, p . 364) ; 3-methylxanthine was obtained by E . Fischer and F .

Ach.(Ber., 1898, 30, 1980) from 3-methyl uric (1)N=CH(6) (2)HC(5)C.NH(7) (3) N—C—• N>CH (8) (4) (9) Purin . it to amalic acid or tetramethyl

alloxantin (Fr . Rochleder, Ann . 1849, 71, p . 1), and that hydrolysis with baryta gave caffeidine (A . Strecker, Ann., 1862, 123, p . 360), which could be further hydrolysed to sarcosine, methylamine, formic acid and carbon dioxide (O . Schultzen, Zeil. f . Chemie, 1867, p . 614) . Fischer confirmed these results and showed further that oxidation with chlorine water gave monomethyl urea and dimethyl alloxan, pointing to the presence of three methyl groups in the molecule . Further, on bromination, a brom-derivative is obtained which on treatment with alcoholic potash yields ethoxy-caffeine, which readily hydrolyses to hydroxy-caffeine .

This substance behaves as an unsaturated compound and combines with a molecule of

bromine to form a derivative which on treatment with alcoholic potash yields diethoxy-hydroxycaffeine . Diethoxy-hydroxycaffeine on hydrolysis with concentrated hydrochloric acid yields apocaffeine, C7H7N30s, and hypo- acid; and 7-methylxanthine or heteroxanthine, which is found in human urine, may be obtained from theobromine (E . Fischer, Ber., 1897, 30, p . 2400; see also ibid., 1898, 31, p . 117) . Theophylline, C5(CH3)2H202N4, or I.3-dimethyl-2.6-dioxypurin, was isolated by A . Kossel from tea-leaves (Ber., 1888, 21, p . 2164) . It was synthesized by E . Fischer and L . Ach (Ber., 1895, 28, p . 3135) from I.3-dimethyl uric acid, which on treatment with phosphorus pentachloride yields chlortheophylline, from which theophylline is obtained by reduction with hydriodic acid .

W . Traube (Ber., 1900, 33, p . 3035) formed the nitroso derivative of iminodimethyl barbituric acid (obtained by the

action of phosphorus oxychloride on cyanacetic acid and dimethyl urea), and reduced it by ammonium sulphide to 1.3-dimethyl-4.5-diamino-2.6-dioxypyrimidine, the formyl derivative of which, when heated to 250° C., loses the elements of water and yields theophylline (cf . Xanthine) . It behaves as a weak base . When oxidized by potassium chlorate and 'hydrochloric acid it yields dimethylalloxan . Its silver salt on methylation yields caffeine . The isomeric Paraxanthine, or I.7-dimethyl-2.6-dioxypurin, occurs in urine . It has been obtained from theobromine (E . Fischer, Ber., 1897, 30, p . 2400); from I.7-dimethyl uric acid (E . Fischer and H .

Clemm, Her., 1898, 31, p . 2622); and from 8-chlorcaffeine (E . Fischer, Ber., 1906, 39, p . 423) . On methylation it yields caffeine . A third isomer Theobromine, or 3.7-dimethyl-2.6-dioxy urin, is found in the

cocoa-bean (from Theobroma cacao) and in the kola-nut . It is obtained by methylating xanthine, or from 3.7-dimethyl uric acid (E . Fischer, Ber., 1897, 30, p . 1839) . This acid, by the action of phosphorus oxychloride and pentachloride, is converted into 3.7-dimethyl-6-chlor-2.8-dioxypurin, which with ammonia gives the corresponding amino compound . This substance with phosphorus oxychloride yields 3.7-dimethyl-6-amino-2-oxy-8-chlorpurin, which on reduction with hydriodic acid leads to 3.7-dimethyl-6-amino-2-oxypurin, from which theobromine is obtained by the action of nitrous acid . It is also obtained by W .

Traube's method (

Bee., 1900, 33, p . 3047) from cyanacetyl methyl urea, which gives 3-methyl-4.5-diamino-2.6-dioxypyrimidine, whose formyl derivative yields 3-methylxanthine, from which theobromine is obtained by methylation . It crystallizes in anhydrous needles which sublime at 290-295° C . It behaves as a weak base . Potassium chlorate and hydrochloric acid oxidize it to methyl alloxan and methyl urea, chromic acid mixture oxidizes it to carbon dioxide, methylamine and methylparabanic acid . When boiled with baryta it yields carbon dioxide, ammonia, methylamine, formic acid and sarcosine . Methylation of its silver salt yields caffeine . Caffeine, C5H(CH3)3N402, is I.3.7-trimethyl-2.6-dioxypurin . For its general properties and method of extraction see CAFFEINE . It may be synthesized by methylating chlortheophylline and reducing the resulting product (E . Fischer and L . Ach, Ber., 1895, 28, p .

3135) ; by the action of phosphorus oxychloride on tetramethyl uric acid, the resulting chlorcaffeine being reduced (

Bet., 1897, 30, p . 3010); from dimethylalloxan (Ber., 1897, 30, p . 564); from 3-methyl uric acid (Ber., 1898, 31, p . 1980), and from I.3-dimethyl-4.5-diamino-2.6-dioxypyrimidine (W . Traube, Ber., 1900, 33, p . 3042) . The three latter methods may be outlined as follows .