《5-Arylpyrimidines. II. 4,6-Disubstituted 5-phenylpyrimidines》 was published in Collection of Czechoslovak Chemical Communications in 1965. These research results belong to Budesinsky, Z.; Roubinek, F.; Svatek, E.. Formula: C11H11NO6 The article mentions the following:
cf. Cesk. Farm. 11, 345(1962). HCO2Et gave with RCH(CONH2)2 (I) compounds of type II, yielding with P2S5 the corresponding 4,6-dimercapto and with POCl3 the resp. 4,6-dichloro derivatives which were converted to products of type III. I were obtained from the corresponding malonic esters by the method of Dox and Yoder ( CA 16, 2846) [R, % yield, and m.p. (H2O) given]: 2-ClC6H4, 72, 171°; 4-ClC6H4, 81, 211°; 4-AcNHC6H4, 59.5, 247-8°. Me p- acetamidophenylmalonate, m. 185-6° (MeOH), was obtained in 36-g. yield by hydrogenation and subsequent acetylation of 105.5 g. Me p-nitrophenylmalonate, m. 95-8° (MeOH), prepared, in turn, by treating 166.4 g. Me phenylmalonate in 500 ml. H2SO4 at 0° portionwise with 88 g. KNO3. Refluxing 2 hrs. 1 mole I with 2 g.-atoms Na in 1500 ml. EtOH and 2 moles HCO2Et, adding more 0.4 mole HCO2Et and refluxing another 2-3 hrs., keeping overnight, dissolving the separated product in 1000 ml. hot H2O, decolorizing with C and making acid with HCl gave II (R2 OH) (R1, % yield, m.p., and solvent given): Bu, 39.2, 282-4°, EtOH; 2-ClC6H4, 53.2, 349°, H2O; 4-ClC6H4, 62.2, >360°, AcOH; 4-AcNHC6H4, 39.3, >360°, HCONH2. II (R1 4-NO2C6H4, R2 OH), m. >360°, was obtained in 88.3% yield by the nitration of II (R1 R2 OH) with KNO3 as above, II (R1 4-NH2C6H4, R2 OH) was prepared by deacetylation of II (R1 4-AcNHC6H4, R2 OH). II (R2 OH) (0.1 mole) yielded, when refluxed 4-7 hrs. with 120 ml. POCl3 and 7 ml. PhNMe2, II (R2 Cl) (R1, % yield, m.p., and solvent given): Bu, 82, b11 128°, -; Ph, 84.2, 112-14°, AcOH; 2-ClC6H4, 71.8, 113-14°, EtOH; 4-ClC6H4, 74.7, 92°, EtOH; 4-NO2C6H4, 91.8, 143-4°, EtOH, was obtained by nitration of II (R1 Ph) as above. II (R1 Ph, 2 Cl) (20 g.) was dissolved in 50 ml. hot EtOH and kept with 30 ml. aqueous NH4OH in a sealed Carius tube 2 hrs. at 100° to yield 17.5 g. 4-amino-5-phenyl-6-chloropyrimidine, m. 195-7° (C6H6). Analogously was obtained 76.6% 4-amino-5-(2-chlorophenyl)-6-chloropyrimidine, m. 173° (MeOH). Refluxing 3 hrs. II (R2 OH) 1 with pyridine 15 and P2S5 6 weight parts gave 4,6-dimercapto derivatives of II which yielded, when kept (0.01 mole) with 0.022 g.-atom Na in 25 ml. MeOH and 0.04 mole ClCH2CO2Me 8-12 hrs., the solution filtered, evaporated in vacuo, the product crystallized from MeOH and refluxed 15 min. with 0.05 mole KOH, the corresponding 4,6-bis(carboxymethylthio)pyrimidines II (R1, R2, % yield, m.p., and solvent given): Ph, SH, 74.1, 238-42°, H2O; 2-ClC6H4, SH, 37, 247-50°, EtOH; 4-ClC6H4, SH, 45.9, 240-8°, H2O; 4-NO2C6H4, SH, 41.4, 193-5°, H2O; Ph, SCH2CO2H, 67.2, 204-6°, H2O; 2-ClC6H4, SCH2CO2H, 37.4, 204°, AcOH; 4-ClC6H4, SCH2CO2H, 76, 214°, H2O; 4-NO2C6H4, SCH2CO2H, 79, 90-2°, MeOH. 4-NH2C6H4, SCH2CO2H, 76.5, >360°, was obtained by hydrogenation of II (4-NO2C6H4, SCH2CO2Me) over Pd-C in MeOH and subsequent saponification of the resulting II (4-NH2C6H4, CH2CO2Me). II (R2 Cl) yielded, when kept (0.02 mole) in EtOH solution of 0.04 mole KHS overnight, III (Z H), which gave with ClCH2CO2Me upon saponification III (Z CH2CO2H). The following III were obtained (R, Z, % yield, m.p., and solvent given): Bu, H, -, 176-8°, EtOH; Ph, H, 63.1, 220-5°, EtOH; 2-ClC6H4, H, 61.5, 210-20°, C6H6; 4-ClC6H4, H, 72.5, 230-40°, EtOH; Bu, CH2CO2H, 87, 104-5°, MeOH; Ph, CH2CO2H, 72.5, 161°, EtOH; 2-ClC6H4, CH2CO2H, 62.1, 135°, EtOH; 4-ClC6H4, CH2CO2H, 71, 104-5°, EtOH. II (R1 4-NO2C6H4, R2 Cl) gave with KHS bis[4-mercapto-5-(4-nitrophenyl)-6-pyrimidyl]sulfide, m. 225°. 4-Mercapto-5-phenyl-6-aminopyrimidine, m. 232-5° (EtOH), was obtained by heating 5.0 g. III (R Ph, Z H), with 20 ml. aqueous NH4OH and 20 ml. EtOH 16 hrs. at 150°. II (R1 Ph, R2 SCH2CO2Me) (0.5 g.) gave, when heated with 8 ml. aqueous NH4OH 8 hrs. at 100°, 4,6-bis(carbamidomethylthio)-5-phenylpyrimidine, m. 189-91° (H2O); and on refluxing 1 hr. with 0.25 ml. 85% N2H4.H2O in 10 ml. MeOH, quant. yield of 4,6-bis(carbohydrazidomethylthio)-5-phenylpyrimidine, m. 200-2° (H2O). 2-Carboxymethylthio-4,6-dihydroxy-5-phenylpyrimidine (IIIa), obtained in 8.7-g. yield by refluxing 3 hrs. 20 g. 2-thio-5-phenylbarbituric acid (IV), 11 ml. ClCH2CO2Me, and 1.8 g. Na in 50 ml. MeOH and saponifying the resulting ester (9.3 g.), gave crystals, m. 161-3° (H2O). 2,4,6-Trimercapto-6-phenylpyrimidine, obtained in 68.6% yield as above from IV and P2S5 in pyridine, m. 242-4° (H2O). A solution of 4.0 g. 2,4,6-trithio-5-phenylbarbituric acid in 20 ml. MeOH containing 1.11 g. Na afforded, on boiling 30 min. with 6.8 g. ClCH2CO2Me and alk. saponification of the ester, 2.8 g. 2,4,6-triscarboxymethylthio-5-phenylpyrimidine, m. 221-3° (H2O). Some uv spectroscopical data on the above-mentioned compounds are given which prove sterical hindrance of coplanarity in the benzene and pyrimidine nuclei, effected by substituents in the position 4 and 6 of the pyrimidine nucleus and in the position 2 of the benzene nucleus, and the resulting hindrance of the conjugation. IIIa raised markedly blood pressure in mice and II (R1 Ph, R2 SCH2CO2H) showed a virus-inhibiting effect on influenza pneumonia in mice. The experimental process involved the reaction of Dimethyl 2-(4-nitrophenyl)malonate(cas: 4033-88-9Formula: C11H11NO6)
Dimethyl 2-(4-nitrophenyl)malonate(cas: 4033-88-9) belongs to esters. They are important in biology, being one of the main classes of lipids and comprising the bulk of animal fats and vegetable oils. They perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market.Formula: C11H11NO6
Referemce:
Ester – Wikipedia,
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