H3C·C·OH H2N·CO H3C·C·NH·CO·NH2 H3C·C·NH—CO
CH·CO2C2.+ H2N CH-CO2C2H5 -9 CH»CO-NH
(I.) (II.)↓ (III.)
HC·NH·CO HC-NH·CO Hozc-C-NH·CO
H2N·C-co-Nut-02N-c-co-NH* O2N-C-CO-NH
L <v1.) <v.) <1v.)
Hc-NH-co Ho-C-NH-co /NH-C-NH-CO
+ n is II →CO n I
HO·C·CO-lH Ho-c-co-NH NH-c-co-NH
(VII.) (VIII.) (IX.)
E. Fischer dehydrated pseudo-uric acid (formed from potassium cyanate and uramil) by heating it with anhydrous oxalic acid to 185° C, or with a large excess of 20 % hydrochloric acid (Ber., 1897, 30, p. 560), and so obtained uric acid. This method is quite general. W. Traube condenses the sulphate of 4 · 5-diamino-2 · 6-dioxypyrimidine (I.) (see Xanthine, above) with chlorcarbonic ester. The resulting urethane (II.) when heated to 180–190° C loses a molecule of alcohol, giving uric acid (III.).
HN·CO·C·NH2 HN-CO·C-NHCO2C2H5 HN-CO-C·NH
||| →|||→ |||
OC·NH·C·NH2 OC·NH·C·NH; O·NH·C·NH
(I.) (II.) (III.)
Uric acid is a white, micro crystalline powder. It is odourless and tasteless, and is insoluble in most reagents. Its solubility in water is increased by the presence of various inorganic salts, such as sodium phosphate, sodium acetate, borax, and particularly by lithium carbonate. It dissolves completely in concentrated sulphuric acid, but is reprecipitated on the addition of water. It behaves as a weak dibasic acid. It is decomposed by heat into ammonia, urea, cyanuric acid and carbon dioxide. On fusion with caustic alkalis it yields alkaline cyanide, cyanate, oxalate and carbonate. It may be recognized by means of the “murexide” reaction, which consists in evaporating the acid to dryness with nitric acid, when a yellowish residue is obtained which becomes purple-red if moistened with ammonia. On the quantitative estimation of uric acid see F. W. Tunnicliffe (Chem. Centralb., 1897, 11, p. 987; E. H. Bartley, ibid., p. 644 and F. G. Hopkins, Chem. News, 1892, 66, p. 106).
Methyl Uric Acids.—1-Methyl uric acid was prepared by F.. Fischer and H. Clemm (Ber., 1897, 30, p. 3091) from mono methyl alloxan and ammonium sulphite, which condense together to form 1-methyluramil. This, with potassium cyanate, gives 1-methyl-4ψ-uric acid, which on dehydration gives 1-methyl uric acid. 3- or a.-Methyl uric acid was prepared by Hill (Ber., 1876, 9, p. 370) by heating acid lead urate with methyl iodide. It is best obtained by heating 3-methyl chlorxanthine with hydrochloric acid to 125° C. (E. Fischer, Ber., 1898, 31, p. 1984). 7- or γ-Methyl uric acid is prepared by heating 7-methyl-2 - 6- 8-trichlorpurin (which results from phosphorus pentachloride and theobromine) with hydrochloric acid to 130° C., or by the condensation of alloxan with methyl amine in the presence of sulphur dioxide (E. Fischer, Ber., 1897, 30, p. 563; cf. 1-methyl uric acid). It is the most soluble in water of the methyl uric acids. 9- or β-Methyl uric acid was obtained by E. Fischer (Ber, 1884, 17, pp. 332, 1777) by heating normal lead urate with methyl iodide to 100° C. The product so obtained was converted by the action of phosphorus oxychloride and pentachloride into 9-methyl-8-oxy-2 -6-dichlorpurin, and this when heated with hydrochloric acid to 140° C. gave the required methyl uric acid. It is distinguished from 3-methyl uric acid by its much smaller solubility in water and by the greater stability of its ammonium salt. A fifth isomer, 6-methyl uric acid, has been described by W. v. Loeben (Ann., 1897, 298, p. 181) who obtained it by condensing acetoacetic ester and mono methyl urea according to Behrend's method. The constitution of this acid is not definitely known.
1·3 or γ-Dimethyl uric acid is obtained by converting dimethyl alloxan into dimethyluramil, which with potassium cyanate gives dimethyl-ψ-uric acid; this acid is then dehydrated (E. Fischer, Ber., 1895, 28, p. 2475;-1897, 30, p. 560). 1-7-Dimethyl uric acid is similarly obtained by starting with mono methyl alloxan and methyl amine (E. Fischer and H. Clemm, Ber., 1897, 30, p. 3095).
1·9-Dimethyl uric acid is obtained from 9-methy1-8-oxy-2·6-dichlorpurin (see 9-Mellzyl uric acid above). By successive treatment with ammonia and nitrous acid this is converted 'into 9-methyl-6 - 8-dioxy-2-chlorpurin, which on condensation with formaldehyde in alkaline solution yields 9-methyl-7-oxymethyl-6 - 8-dioxy-2-chlorpurin. Methylation of this latter compound introduces a methyl group into position I, and the dimethyl compound so formed on dilution with water and the simultaneous action of superheated steam yields 1·9-dimethyl-6 - 8-dioxy-2-chlorpurin, from which 1-9-dimethyl uric acid is obtained by hydrolysis with concentrated hydrochloric acid at IO0° C. (E. Fischer, and F. Ach Ber., 1899, 32, p. 257). 3·7 or δ-Dimethyl uric acid is prepared by methylating 7-methyl uric acid (E. Fischer, Ber., 1897, 30, p. 564) or by heating bromtheobromine with alkalis (Ber., 1895, 28, p. 2482). 3·9-Dimethyl uric acid is prepared by heating neutral lead urate with methyl iodide (H. B. Hill and C. F. Mabery, Amer. Chem. Journ., 1880–1881, 2, p. 308) and by methylating 3-methyl uric acid (E. Fischer, Ber., 1899, 32, p. -269). 7-9 or 13-Dimethyl uric acid is prepared by heating O78-dimethyl-8-oxy-2·6-dichlorpurin with hydrochloric acid to 130 .
1·3·7-Trimethyl uric acid or hydroxycaffeine, may be prepared from caffeine, or by direct methylation of uric acid at 0° C. (E. Fischer). 1·3·9-Trimethyl uric acid is prepared by methylating 1-3-dimethyl uric acid (E. Fischer and L. Ach, Ber., 1895, 28, p. 2478). 1·7·9-Trimethyl uric acid is prepared by methylating 9-methyl-6·8-dioxy-2-chlorpurin (see 1·9-dimethyl uric acid, above) and heating the resulting trim ethyl dioxychlorpurin with concentrated hydrochloric acid to 110—115° C. (E. Fischer and F. Ach, Ber., 1899, 32, p. 256).
Tetramethyl uric acid was first prepared (Ber., 1884, 17, p. 1784) by methylating 3·7·9-trim ethyl uric acid. It may also be obtained by methylating uric acid and the other methyl uric acids. It has a neutral reaction.
Aminopurins.—Adenine is 6-aminopurin. It has been found in ox pancreas and also in tea. It is prepared by heating 2·6·8-trichlorpurin with ammonia, and reducing the resulting 6-amino-2·8-dichlorpurin with hydriodic acid; or by heating 8-oxy-2·6-dichlorpurin (from uric acid and phosphorus oxychloride) with alcoholic ammonia to obtain 8-oxy-2-chlor-6-aminopurin, .which with phosphorus oxychloride at 140° C., gives 6-amino-2·8-dichlorpurin. Reduction of this compound with hydriodic acid yields adenine (E. Fischer, Ber., 1897, 30, p. 2238; 1898, 31, p. 104). It crystallizes from water in leaflets which contain three molecules of water of crystallization. The anhydrous base melts at 360–365° C. Nitrous acid converts it into hypoxanthine; whilst hydrochloric acid at 180-200° C. decomposes it completely into ammonia, carbon dioxide, formic acid and glycocoll (A. Kossel, Ber., 1890, 23, p. 225; 1893, 26, p. 1914).
Isoadenine or 2-aminopurin, is obtained from 2·4-dichlor-5-nitropyrimidine (see Purin, above) by heating it with ammonia, when 2·4-diamino-5-nitropyrimidine is formed. Reduction of this compound by means of stannous chloride and hydrochloric acid gives 2·4·5-triaminopyrimidine which readily condenses with formic acid to isoadenine (O. Isay, Ber., 1906, 39, p. 250). It has also been obtained by J. Tafel and B. Ach (Ber, 1901, 34, p. 1177) by the electrolytic reduction of guanine to desoxyguanine, the acetate of which is warmed with bromine and subsequently oxidized.
9-Methyl adenine was first obtained by I. Krüger (Zeit. f. physiol. Chem., 1894, 18, p. 434) by methylating adenine, and has been synthesized by E. Fischer (Ber, 1898, 31, p. 104) from 9-methyl-2·6-dichlor-8-oxypurin. For 7-methyl adenine see E. Fischer, Ber., 1898, 31, p. 104.
Guanine, or 2-amino-6-oxypurin, is found in the pancreas of various animals and also very abundantly in guano, from which it was first extracted by B. Unger (/inn., 1844, 51, p. 395; 1846, 58, p. 18). It has been obtained synthetically from 6-oxy-2-8-dichlorpurin (E. Fischer, Ber., 1897, 30, p. 2252) by heating it with alcoholic ammonia to 150° C. and reducing the resulting 6-oxy-2-amino-8chlorpurin with hydriodic acid. W. Traube (Bern, 1900, 33, p. 1371) condensed cyan acetic ester with guanidine and the resulting compound (I.) with caustic soda gives 2·4-diamino-6-oxypyrimidine (lI.). This substance yields an isonitroso-derivative which on reduction with ammonium sulphide gives 2·4·5-triamino-6-oxypyrimidine (III.), from which guanine (IV.) is obtained by heating with concentrated formic acid:—
HN·CO N:C·ON N:Q-OH HN-co
HN:C CH2→H2N-c CH -9H2N·C C·NH, +H.N-C C-NH
| n n n n ll n 'CH
H2N CN N·C·NH2 N-C-NH2 N·C–N/
(I.) (II.) (III.) (IV.)
It may also be obtained as follows [E. Merck, German Patents 158591 (1903); 162336 (1904)]. Dicyandiamide (I.) condenses with cyan acetic ester to form 2-cyan amino-4-amino-6-oxypyrimidine (lI.). This yields an isonitroso-derivative which on reduction gives 2-cyan amino-4·5-diamino-6-oxypyrimidine (III.). This compound when boiled with a 90% solution of formic acid gives guanine formate:—
NH N-C-NH2 N-C·NH2
CN-NH-C → CN-NH-C CH e CN-NH-C C-NH,
NH; N:C·OH, N:C·OH
(I.)(II.) (III.)
It is an amorphous powder, insoluble in water, alcohol and ether, and has both acid and basic properties. Nitrous acid converts it into xanthine. When oxidized by hydrochloric acid and potassium chlorate it yields guanidine, parabanic acid and carbon dioxide.
6-Amino-2-oxypurin, an isomer of guanine, is prepared by heating dichloradenine or 6-amino-2·6·8-trichlorpurin, obtained from 2-6-8 trichlorpurin and ammonia (Fischer, Ber., 1897, 30, p. 2239) with sodium ethylate to 130° C. and reducing the resulting 6-amino-2-ethoxy-8-chlorpurin with hydriodic acid (E. Fischer, Ber., 1897, 30, p. 2245). 6-Amino-S-oxypurin, another isomer of guanine, is prepared by heating 8-oxy-2-6-dichlorpurin with alcoholic ammonia and reducing the resulting amino-oxy-chlor compound with hydriodic acid (E. Fischer, loc. cit.).
