Reference of 1193-24-4 , The common heterocyclic compound, 1193-24-4, name is 4,6-Dihydroxypyrimidine, molecular formula is C4H4N2O2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
4,6-Dichloropyrimidine-5-carbaldehyde (9).; In a 5 L 4-neck flask equipped with mechanical stirrer, addition funnel, condenser, thermocouple, and a N2 sweep into an aqueous NaOH scrubbing solution, phosphorous oxychloride (1 L, 10.572 mol, 4.82 equiv) was cooled in an ice/salt bath. N,N-Dimethylformamide (DMF, 320 mL, 4.138 mol, 1.85 equiv) was added dropwise at 0+/-2 C. After addition of 100 mL of DMF (0.5 hr) crystallization occurred and the reaction temperature was increased from 0 to 10 C. Addition was stopped and the mixture was allowed to recool to 2 C. The remaining DMF was added over 2.5 hr at <8 C. The suspension became very thick making stirring difficult. When addition of DMF was complete, the mixture was stirred 0.5 hr at 3-5 C. 4,6-dihydroxypyrimidine (8, 250 g, 2.232 mol) was added portion wise as a solid. After about one third of 4,6-dihydroxypyrimidine was added the reaction mixture became more mobile and a slow exothermic phenomena occurred with the reaction temperature increasing to 12 C. over 0.5 hr. The remaining 4,6-dihydroxypyrimidine was added portion wise over 0.25 hr with the reaction temperature increasing from 12 to 27 C. The reaction temperature was maintained at 25-27 C. with intermittent cooling during which time the yellow suspension became thinner, then thicker once again. After the exothermic phenomenon subsided in about 1 hr, the reaction mixture was heated slowly. At about 55 C. the reaction mixture became extremely thick and the second mild exothermic phenomenon was occurred. The heating mantle was removed while the reaction temperature continued to increase to about 63 C. and remained at this temperature for several minutes before dropping. Heating of the mixture was resumed until gentle reflux (about 100 C.) was attained. At about 95 C. a steady, fairly rapid evolution of HCl began and the reaction mixture gradually thinned and darkened. After about 0.5 hr a clear, brown solution developed with the reflux temperature slowly increasing to 115 C. over 1.25 hr. After a total of 2.5 hr at reflux, the reaction mixture was cooled to room temperature and stirred overnight. Excess POCl3 (as much as possible) was removed under reduced pressure (bath temperature 45-50 C.). The thick residual brown oil was poured very slowly into cold H2O (5 L) in a 20 L separation funnel, adding ice as needed to maintain the aqueous mixture near room temperature. The aqueous mixture was extracted with EtOAc (2×3 L, 1×2 L). The combined EtOAc extracts were washed with H2O (2×2.5 L), saturated NaHCO3 aqueous solution (1 L), brine (1 L), dried over Na2SO4, filtered, and concentrated under reduced pressure (bath temperature at 35 C.) to afford the crude 4,6-dichloropyrimidine-5-carbaldehyde (9, 270 g, 395 g theoretical, 68.4%) as yellow-orange solid. A 20 g portion of this crude material was purified by Kugelrohr distillation (oven temperature at 90-100 C., 225 mTorr) to give 15.3 g of pure 4,6-dichloropyrimidine-5-carbaldehyde (9) as a white solid that turned yellow on standing at room temperature. (On standing crude 9 undergoes slow hydrolysis with formation of HCl. Prior to use in the next step crude 9 was dissolved in a mixture of EtOAc and toluene and filtered to remove insoluble material. The filtrate washed with H2O, saturated NaHCO3 solution, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure and the resulting yellow solid used the following day.) For 9: 1H NMR (CDCl3, 300 MHz) delta ppm 10.46 (s, 1H), 8.89 (s,1H).
The synthetic route of 1193-24-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Zhou, Jiacheng; Liu, Pingli; Lin, Qiyan; Metcalf, Brian W.; Meloni, David; Pan, Yongchun; Xia, Michael; Li, Mei; Yue, Tai-Yuen; Rodgers, James D.; Wang, Haisheng; US2010/190981; (2010); A1;,
Pyrimidine | C4H4N2 – PubChem,
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