Chang, P.; Wu, Shao-Lan published the artcile< 5-Hydroxypyrimidines. I. Synthesis of 2-substituted 4,5,6-trihydroxypyrimidines>, Application In Synthesis of 15837-41-9, the main research area is .
Et benzyloxymalonate (I) condenses with various amidine derivatives to 2-substituted 5-benzyloxy-4,6-dihydroxypyrimidines (II, R, PhCH2O), converted to the corresponding 4,5,6-(HO)3 analogs (III, R, HO) by Pd-catalyzed hydrogenation; Raney Ni converts II (SH, PhCH2O) to II (H, PhCH2O) the PhCH2 group being unaffected. [In this abstract N:CR.N:C(OH).CR’:COH (II) and N:CR.N:C(OH).C(OH):COH (III) are designated by the Roman numeral, followed by R and R’, and by R, resp.] All III give pos. color reactions with FeCl3-NH4OH (blue-violet), Ba(OH)2 (violet-blue), and phosphomolybdic acid (deep blue), and decolorize (reduce) 2,6-dichlorophenolindophenol at various rates. PhCH2OCH2CO2H (IV) [20 g., b0.4 142-4°, prepared in 84% yield according to Fischer and Gohlke (C.A. 28, 1337) except that the mixture is acidified immediately with cooling instead of after removing the large excess of PhCH2OH], refluxed 2 hrs. with 25 ml. EtOH, 30 ml. C6H6, and 2 ml. concentrated H2SO4, the volatiles distilled, the residue neutralized with aqueous Na2CO3, extracted with Et2O, and the extract dried and distilled gives 74% PhCH2OCH2CO2Et (V), b8 135-7°, also prepared via PhCH2OCH2CN (VI); 50 ml. each of MeOH and 40% aqueous HCHO ice-cooled, stirred with 32.5 g. KCN until homogeneous, 57 g. PhCH2Cl in 100 ml. MeOH slowly stirred in at room temperature, the mixture heated 4 hrs. at 40°, cooled, poured into 100 ml. H2O, and the organic layer worked up give some PhCH2Cl, a small unidentified fraction, b. 110-25°, n25D 1.5073, d2020 1.081, and crude VI, b. 130-45°, redistilled to give 58-60% purified VI, b14 136-7°, which becomes progressively yellower on exposure to air, analyzes 1% low for N, and always leaves on redistillation a black residue shown to contain PhCH2OCONH2 [also prepared (m. 90.5-1.0°) by mixing 1 g. V with 5 ml. concentrated NH4OH and recrystallizing the product from hot H2O], and IV, b6 180°. Redistilled VI (74 g.) treated at 0° with 55 g. 95% EtOH previously saturated with HCl (33 g.), refluxed 4 hrs., yields 70% V, b5 125-6°, b10 138°, b12 145-6°; if the crude VI is only freed of more volatile materials and alcoholized undistd., 48% V (based on unrecovered PhCH2Cl) is obtained. No IV was obtained by dissolving 9.2 g. Na in 100 ml. hot PhCH2OH, adding 46.6 g. ClCH2CO2Na, and heating 5 hrs. at 160°, nor was VI identified among the products of reaction of 18 g. CuCN in 40 ml. anhydrous Et2O with 35 g. PhCH2OCH2Cl at 30°. Na (6.9 g.) in 90 ml. anhydrous EtOH treated with 68.7 g. (CO2Et)2 at room temperature, stirred 10 min., 58.2 g. V added dropwise, the mixture heated 4-5 hrs. at 50-60°, kept overnight at room temperature, acidified with glacial HOAc, poured into H2O, extracted with Et2O, the extracts dried, freed of Et2O, the residual liquid heated at 180-200°/15-20 mm. until evolution of CO ceases (2-3 hrs.), and the residue distilled gives 49% I, b0.4 127-9°, n20D 1.4900. I with concentrated NH4OH gives PhCH2OCH(CONH2)2, needles from H2O, m. 222°. Na (1.4 g.) in 30 ml. anhydrous EtOH treated with 16 g. I, then 8 g. EtBr, refluxed until neutral to litmus, cooled, poured into H2O, extracted with Et2O, and the extract dried and distilled gives 56% PhCH2OCEt(CO2Et)2 (VII), b0.4 133-4°, n20D 1.4862. Urea (3 g.) dissolved in a solution of 1.5 g. Na in 40 ml. anhydrous EtOH, 9 g. I added, the mixture refluxed 6 hrs. at 105-7°, cooled, the Na salt dissolved in a small amount of H2O, and the solution acidified with concentrated HCl precipitates 67% II (OH, PhCH2O), needles from H2O or 50% aqueous EtOH, decompose 202-3° after turning red at 180°. II (OH, PhCH2O) also gradually reddens on standing exposed to air, recrystallization of the red material from H2O yielding a colorless, air-stable, more H2O-soluble product (VIII), decompose 202-55°, believed to be II(OH, HO). VII condenses with NH2CONH2 in the presence of NaOEt to give 20% II(OH, Et), needles from EtOH, m 186-7°, stable in air. Similarly, 6.6 g. I, 3 g. NH2C(:NH)NH2.HNO3 (IX), and 1.2 g. Na in 30 ml. EtOH react (6 hrs.) to give 83% II(NH2, PhCH2O), needles from EtOH, m. 220-1° (decomposition); which also reddens in air, but is stabilized by recrystallization VII condenses with IX to 68% II(NH2, Et), recrystallized from EtOH, stable, m. 308-9° (decomposition). I condenses similarly with CH3C(:NH)NH2.HCl to give 54% II(Me, PhCH2O), needles from H2O, m. 263-4° (decomposition); with NH2CSNH2 to give 78% II(SH, PhCH2O), needles from EtOH, m. 140-1° (decomposition), reddens in air; and with NH2C(:NH)SEt.HBr to give 51% II(SEt, PhCH2O), needles from EtOH, m. 164-5° (decomposition), turning red-violet in air. II(SH, PhCH2O) (1 g.) in hot dilute NH4OH (2 ml. concentrated NH4OH cut with 16 ml. H2O) is heated 2 hrs. on steam with 3 g. Raney Ni, the mixture filtered hot, concentrated until crystals appear, and cooled gives 86% II(H, PhCH2O), m. 223-4° (decomposes) (from H2O). II(OH, PhCH2O) (1 g.) in 60 ml. HCO2H shaken with 0.1 g. PdO and H at room temperature and atm. pressure until 1 mol. equivalent H is taken up (20 min.) and the filtered mixture concentrated gives 98% dialuric acid (III, HO), m. 213-14° (decomposition) after reddening from 180°, readily air-oxidized. Similarly, II (NH2, PhCH2O) gives a quant. yield of III(NH2), which turns brown at 293-4° but remains solid up to 320°; this substance also turns red in air. Hydrogenation of II(Me, PhCH2O) in glacial HOAc gives 100% III(Me), stable in air, blackens at 290-1°, but is not molten at 320°. Similarly, II(H, PhCH2O) is reduced to III(H), air-stable, blackens at 284-5°, but does not m. at 320°.
Scientia Sinica (English Edition) published new progress about Color reaction. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Application In Synthesis of 15837-41-9.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia