Purin
PURIN, C 6 H 4 N4, 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, theophyUine, theobromine and caffeine. Its formula is shown in the , \N_pjj/ 6 ', inset, the positions taken by sub- (2)HC(5)C-NH(7) stituent atoms or groups being numbered as shown. E. Fischer (Ber., 31, (3)N C N/ c p. 2564) obtained it in 1898 by reduc- & /9)
ing 2-6-di-iodo purin, obtained from 2 6-8 trichlor purin (see below sub Uricacid), 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 0. Isay (Ber., 1906, 39, p. 250) from s-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- s-diamino-pyriinidine is obtained, which with formic acid furnishes purin; thus:
NH-CH N:CH NiCH N:CH N:CH COC-NOz-^ClCC-NOj-^ClCC-NOs-^HCCNHz-^HCCNH inlet) MCI N-C-NH, N-C-NH, 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, CjI^N/), 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. 1850, 73. P- 3 2 8) and by A. Strecker in muscle. It crystallizes in needles which decompose at 150 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, C^-UNiO-HCl-HzO. When oxidized by hydrochloric acid and potassium chlorate it yields alloxan and urea, whilst with potassium permanganate it gives oxalic acid.
3-Methyihypoxanthine was synthesized by W. Traube and F. Winter (Arch. Pharm., 1906, 244, p. n), whilst 8-oxypurin was obtained by E. Fischer and L. Ach in 1897 (Ber., 30, p. 2213), and by O. Isay (Ber., 1906, 39, p. 251).
Xanthine, CsHiNiO?, 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. Ghent., 1880, 4, p. 290); by the decomposition of guanine with nitrous acid (A. Strecker, Ann., 1858, 108, 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-S- diamino2 -6-dioxy pyrimidine, the formyl derivative of which, on heating passes into xanthine.
CO-CH 2 CO-CH 2 CO-C:NOH CO-C-NHj CO-C-NH X NH CN^NHC :NH->NHC -.NH-^NHC-NHj-^NH C N^ CO-NHj CO-NH CO-NH CO-ftH 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).
i-Methylxanthine was found in urine by M. Kriiger and G. Salomon (Zeit. physiol. Ghent., 1897, 24, p. 364) ; 3-methylxanthine was obtained by E. Fischer and F. Ach (Ber., 1898, 30, 1980) from 3-methyl uric acid; and j-methylxanthint 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, C,(CH,),H,O.N., 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 l-3-dimethyl uric acid, which on treatment with phosphorus pentachloride yields chlortheophylline, from which theopnylline .lined 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 i-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 1 ^ caffeine.
The isomeric Paraxanthine, or l'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, Ber., 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-dioxypurin, 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 v7-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 (Ber., 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 rnethylparabanic acid. When boiled with baryta it yields carbon dioxide, ammonia, methylamine, formic acid and sarcosine. Methylation of its silver salt yields caffeine.
Caffeine, CsH(CHj)aN4Os, 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 (Ber., 1897, 30, 3042). The three latter methods may be outlined as follows. Dimethylalloxan (I.) condenses with methylamine in the presence of sulphurous acid to form an addition product (II.), which on hydrolysis yields i*3*7-trimethyl uramil; this substance gives with potassium cyanate, i -3-7-trimethyl pseudo-uric acid (III.), which on dehydration yields l-3-7-trimethyl uric acid (hydroxycaffeine) ; this substance with phosphorus pentachloride gives chlcrcaffeine, which yields caffeine (IV.) on reduction:
H.C-N-CO C C-N< H.C-N-CO H.C-N-CO H.C-N-CO OC CO- OC CH-NHCH,-*OC CH-N/ ' -O( \CO-NH, >CH H.C-N-CO H.C-N-CO H.C-N-CO H.C-N-C-N^ (I.) (II.) (III.) (IV.)
3-Methyl uric acid (I.) (H. Hill, Ber., 1876, 9, p. 370) by the action of phosphorus oxychloride is converted into 3-methyl-2-6-dioxy-8- chlorpurin (3-methyl-chlorxanthine) (II.), which, on treatment with methyl iodide in alkaline solution, gives chlortheobromine (III.), from which chlorcaffeine (IV.) can be obtained by further methylation:
HN-CO <!> HN-CO (II.)
HN-CO CH^J-CO (III.)
(IV).
Dimethyl-diamino-dioxypyrimidine (see Theophyllin above) yields a formyl derivative which on treatment with sodium ethylate furnishes a sodium salt. This salt heated for some hours with methyl iodide yields caffeine.
The constitution of caffeine was settled by E. Fischer (Ann., 882, 215, p. 253). Earlier investigations had shown that oxidation M c nit . nc aci " Sa ve dimethylparabanic acid or cholesterophane U- stennouse, Ann., 1843, 45, p. 366) ; that chlorine water oxidized it to amalic acid or tetramethyl alloxan tin (Fr. Rochleder, Ann. 1849, 71, p. i), 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, Zeit. 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 unsatu rated 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, C7H;NiO, and hypocaffeine, C e H 7 N,O,:
C,H,(OC,H,),(OH)N40,- C,H,N,O,+CH,NH,+2C,H 4 OH C,H,N,0,+CO,+CH,NH,+2C 2 H,OH.
Apocaffeine when boiled with water loses carbon dioxide and yields caff uric acid, C 6 HN>O, which on hydrolysis with basic lead acetate is converted into mesoxalic acid, methylamine and monomethyl urea. Reduction of caffuric acid yields hydrocaffuric acid, CiHfN'iOi, which readily hydrolyses to methyl hydantoin. Consequently hydrocaffuric and caffuric acids, apocaffeine and caffeine must contain the grouping (I.). Hypocaffeine on hydrolysis loses carbon dioxide and gives caffolin, CjHjNjC^, which on oxidation with alkaline potassium ferricyanide yields monomethyl urea and methyl pxamic acid, whilst if oxidized by alkaline potassium permanganate it yields dimethyl oxamide. Hence caffolin contains the grouping (II.), and in consequence of its close relationship to hydrocaffuric acid is to be written as (III.). It follows that the caffeine molecule must be written as (IV.), a result confirmed by the later synthesis of caffeine itself from dimethyl alloxan (see above).
CH, xN-C <1>C<~-V^ \ N-CH,, (I.)
CH, N-C N-C-NCH (II.)
CH, CHOH NH-CH,, (III.)
H.C CO-N-CH, /N-C CO CH<( jl I ^N-C-N-( (IV.)
The above decomposition products of caffeine probably possess the following constitutions:
CH3-N-C(CO 2 H)-O-CO OC I N:C - N-C ApocaSeine.
CH 3 N-CH-OCO 06 ] I 3 N:C- - fc-C Hypocaffonc.
H3C-N-C(OH)(CO 2 H) HaC-N-CHOH Co] C0| j N.C-NHCH 3 N:C-NHCH, Caffuric acid. Caflolin.
Uric acid, CiHiNiO,, or 2-6-8-trioxypurin, was discovered in 1776 in urinary calculi by Scheele. It is found in the juice of the muscles, in blood, in urine, in the excrement of serpents and birds, and in guano. The determination of the constitution and of the relation of uric acid to the other members of the group has been a process of gradual growth. G. Brugnatelli ((Zornaie di fisica, chemica, etc., di Brugnatelli, 1818, u, pp. 38, 117) obtained alloxan, and W. Prout (Phtt. Trans., 1818, p. 420) obtained ammonium purpurate from uric acid, but the first elaborate investigation on the acid was by J. v. Liebig and F. Wohler (Ann., 1838, 26, p. 241), who obtained from it allantoin, alloxantin, dialuric acid, parabanic acid, oxaluric acid, mesoxalic acid, etc. Further examination of the group was undertaken by A. Schlieper (Ann., 1845, 55, p. 256; 56, p. i), who obtained hydurilic acid and dilituric acid, and by A. v. Baeyer (Ann., 1863, 127, pp. i, 199; 1864, 130, p. 129; 131, p. 291), who showed that uric acid and many of its derivatives may be looked on as derivatives of barbituric acid. In 1875 L. Medicus (Ann., 1875, 175, p. 230) proposed the formula (I.) for the acid, whilst R. Fittig in 1877 (Traite de Mm. org., p. 324 [1878]) suggested the formula (II.); subsequent investigations of R. Behrend and HN-CO HN-C - NH (I.) OC C ' NH \^ OC ^COCO HN-C-NH/ HN-C - NH of E. Fischer showed the first formula to be correct. The first synthases of uric acid are due to J. Horbaczewski (Monals., 1882, p. 796; 1885, p. 356), who obtained very poor yields. These were followed by the more satisfactory methods of R. Behrend and O. Roosen (Ann., 1888. 251, p. 235) of E. Fischer and L. Ach (Ber., 1895, 28. p. 2473) and of W. Traube (Ber., 1900, 33, p. 3035). Horbaczewski obtained the acid by heating urea with ammo-acetic acid (glycine) to 200-230 C, and by fusing urea with trichlorlactamide. In Behrend's method acetoacetic ester and urea (I.) are condensed and the resulting /J-uramidocrotonic ester (II.) on hydrolysis gives methyl uracil (III.), which on treatment with concentrated nitric acid yields nitro-uracil carboxylic acid (IV.). This acid when boiled with water loses carbon dioxide, forming nitro-uracil (V.), which on reduction gives amido-uracil (VI.) and oxy-uracil (VII). Oxidation of oxy-uracil with bromine water leads to dioxyuracil (VIII.), which when heated with urea and concentrated sulphuric acid yields uric acid (IX.):
66 A.
HuC-C-OH H 2 N-CO H,C-C-NH-CONH 2 H S C-C-NH CO CH-C0 2 C 2 H 5 + H 2 N~ CH-C0 2 C 2 H S ~> CH-CO-NH (i.) (ii.) 4, (in.)
HC-NH-CO HC-NH-CO HO 2 C-C-NH-CO H 2 N-C-CO-NH^~O 2 N-C-CO-NH^- O 2 N-C-CO-NH 4, (vi.) (v.) (iv.)
HC-NH-CO HO-C-NH-CO .NH-C-NH-CO -C-CO-NH HO-C-CO-NH SiH-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-NH 2 HN-CO-C-NHCO 2 C 2 H 6 HN-CO-C-NH.
I II -> I II -> 1 H / OC-NH-C-NH 2 OC-NH-C-NH 2 OC-NH-C-NH/ (I.) (II.) (III.)
Uric acid is a white, microcrystalline 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, II, p. 987; E. H. Hartley, ibid., p. 644 and F. G. Hopkins, Chem. News, 1892, 66, p. 106).
Methyl Uric Acids. i-Methyl uric acid was prepared by E. Fischer and H. Clemm (Ber., 1897, 30, p. 3091) from monomethyl alloxan and ammonium sulphite, which condense together to form l-methyluramil. This, with potassium cyanate, gives i- methyl4^-uric acid, which on dehydration gives i-methyl uric acid. 3- or a-Methyl uric acid was prepared by Hill (Ber., 1876, 9. P- 37) 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 7-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 methylamine in the presence of sulphur dioxide (E. Fischer, Ber., 1897, 30, p. 563; cf. i-methyl uric acid). It is the most soluble in water of the methyl uric acids. 9- or /3-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, S-methyl uric acid, has been described by W. v. Loeben (Ann., 1897, 298, p. 181) who obtained it by condensing acetoacetic ester and monomethyl urea according to Behrend's method. The constitution of this acid is not definitely known.
1-3 or 7- Dimethyl uric acid is obtained by converting dimethyl alloxan into dimethyluramil, which with potassium cyanate gives dimethyl-^-uric acid; this acid is then dehydrated (E. Fischer, Ber., 1895, 28, p. 2475; 1897, 30, p. 560). l-7-Dimethyl uric acid is similarly obtained by starting with monomethyl alloxan and methylamine (E. Fischer and H. Clemm, Ber., 1897, 30, p. 3095).
l-9-Dimethyl uric acid is obtained from 9-methyl-8-oxy-2 6- dichlorpurin (see Q-Melhyl uric acid above). By successive treatment with ammonia and nitrous acid this is converted into 9-methyI- 6 8-dioxy-2-chlprpurin, 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 l-9-dimethyl-6 8-dioxy-2-chlorpurin, from which l-9-dimethyl uric acid is obtained by hydrolysis with concentrated hydrochloric acid at too" C. (E. Fischer, and F. Ach Ber., 1899, 32, P- 2 57). 3'7 or 8-Dimethyl uric acid is prepared by methylating 7-methyl uric acid (E. Fischer, Ber., 1897, 30, p. 564) or by heating bromtheobrpmine with alkalis (Ber., 1895, 28, p. 2482). 3-9- Dimethyl uric acid is prepared by heating neutral lead urate with methyl iodide(H. B. HillandC. F. Mabery.^mer. Chem. Journ., 1880-1881,2, p. 308) and by methylating 3-methyl uric acid (E. Fischer, Ber., 1899, 32, p. 269). 7-9 or /J-Dimethyl uric acid is prepared by heating 7.9-dimethyl-8-oxy-2-6-dichlorpurin with hydrochloric acid to 130 C.
1'3'7-Tnmethyl uric acid or hydrpxycaffeine, may be prepared from caffeine, or by direct methylatipn of uric acid at o C. (E. Fischer). 1-3-9-Trimethyl uric acid is prepared by methylating l'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 l-y-dimethyl uric acid, above) and heating the resulting trimethyl dioxychlorpurin with concentrated hydrochloric acid to 110-115 C. (E. Fischer and F. Ach, Ber., 1899, 32, p. 256).
Tetramethyl uYic acid was first prepared (Ber., 1884, 17, p. 1784) by methylating 3-7-9-trimethyl 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- amino2-8-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-ch]or-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-ammopunn, is obtained from 2-4-dichlor-5- mtropyrimidine (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. Kriiger (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. linger (Ann., 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-8- chlorpurin with hydriodic acid. W. Traube (Ber., 1900, 33, p. 1371) condensed cyanacetic ester with guanidine and the resulting compound (I.) with caustic soda gives 2-4-diamino-6-oxypyrimidine (II.). 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-OH N:C-OH HN-CO HN:C CH 2 ->H 2 N-C CH -}H 2 N-C C-NH 2 -=>H 2 N.C C-NH.
H.NCN MNH, MNH, N-c-N> CH (I.) (H.) (HI.) (IV.)
It may also be obtained as follows [E. Merck, German Patents 158591 (1903); 162336 (1904)]. Dicyandiamide (I.) condenses with cyanacetic ester to form 2-cyanamino-4-aminp-6-oxypyrimidine (II.). This yields an isonitroso-derivative which on reduction gives 2-cyanamino-4.5-diamino-6-oxypyrimidine (III.). This compound when boiled with a 90% solution of formic acid gives guanine formate:
NH N-C-NH, N-C-NH 2 CN-NH-C -> CN-NH-C CH -> CN-NH-C C-NH 2 NH 2 - N:C-OH N:C-OH (I.) (H.) (HI.)
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-trichlorpunn, 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-8-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.).
7-Methyl guaninc is obtained from 7-mcthyl-6-oxy-2-chlorpurin (see above) by the action of aqueous ammonia at 150" C. It also results instead of the expected 7-methyl-2-oxy-6-aminopurin, when 7-methyl-6-amino-2-chlorpurin is treated with dilute alkalis (E. Fischer, Ber., 1808, 31, p. 542), owing to ring splitting in the l-6-position, followed; by eliminating of halogen acid.
Thiopurins. W. Traube (Ann., 1904, 331, pp. 66 seq.) has obtained many compounds of the purin group by using thiourea, which is condensed with cyanacetic ester, etc., to form thiopyrimidines. These in turn yield thiopurins, which on oxidation with dilute nitric acid are converted into purin compounds, thus:
H 2 N COjR HN-CO HX-CO HN-CO SC+CH, _, SC CH, ,SC C-NH, .SC C-NH.
>CH.
H.X CN HN-C:NH HN-C-NH, HN-C-N * Various thiopurins have been obtained by E. Fischer (Ber., 1898, 31, p. 431), principally by acting with potassium sulphydrate on chlorinated purin compounds.
2-6-8-Trithiopurin is obtained from the corresponding trichlorpurin and potassium sulphydrate. It forms a light yellow mass which carbonizes on heating. It is almost insoluble in water and alcohol; but readily dissolves in dilute solutions of the caustic alkalis and of ammonia.
Much work has been done by J. Tafel (Ber., 1900, seq.) on the electrolytic reduction of the members of the purin group. The substance to be reduced is dissolved in a 50-^75% solution of sulphuric acid and placed in a porous cell containing a lead cathode, the whole being then placed in a 20-60% solution of sulphuric acid in the anode cell. It is found that xanthine and its homologues take up four atoms of hydrogen per molecule and give rise to the llrd desoxy-compounds, which are stronger bases than the original substances. Uric acid takes up six hydrogen atoms per molecule and gives purone, CsHsNiOs, and it is apparently the <i\\xen atom attached to the carbon atom number 6 which is replaced by hydrogen, since when purone is heated with baryta, two molecules of carbon dioxide are liberated for one of purone. Consequently purone must contain two urea residues, which necessitates the presence of the > CO groups in positions 2 and 8. (F. G. P.*)
Note - this article incorporates content from Encyclopaedia Britannica, Eleventh Edition, (1910-1911)
