Expeditious Syntheses to Pharmochemicals 1,3-Dihydroxyacetone, 1,3-Dichloro-, 1,3-Dibromo- and 1,3-Diiodoacetone from Glycerol 1,3-Dichlorohydrin Using Homogenous and Heterogenous Medium

New efficient and reproductive routes to production of 1,3-dihydroxyacetone (1), 1,3-dichloroacetone (6), 1,3-dibromoacetone (7) and 1,3-diiodoacetone (8) from glycerol 1,3-dichlorohydrin (3) were developed. The synthesis of 1 was processed in three steps from glycerol 2 (1,3-selective chlorination of 2 to 3, oxidation of 3 to 6 and subsequent di-hydroxylation) in 51% overall yield. On the other hand, 7 and 8 were produced from3, via a trans-bromination and trans-iodination, respectively, followed by oxidation and hydroxylation steps, in 38-52% overall yield. It was used homogeneous media with different reagents (HCl/AcOH, pyridinium chlorochromate (PCC), PCC-HIO4) and heterogeneous media with reagents supported on polymer resins such as Amberlyst® A26-HCrO4– form, PV-PCC (polyvinyl-pyridinium chlorochromate) and Amberlyst® A26-OH- form or reagents supported on alumina such as KI/Al2O3, KBr/Al2O3, in solvent free conditions.

本研究开发了以甘油1,3-二氯丙醇（3）为原料，高效且可重现的1,3-二羟基丙酮（1）、1,3-二氯丙酮（6）、1,3-二溴丙酮（7）及1,3-二碘丙酮（8）的合成路线。化合物1的合成以甘油（2）为起始原料，经三步反应完成：首先对甘油（2）进行1,3-选择性氯化得到化合物3，随后将3氧化为1,3-二氯丙酮（6），最后经二羟基化反应，总收率达51%。另一方面，化合物7与8均以化合物3为原料，分别经溴代置换、碘代置换反应，再依次完成氧化与羟基化步骤制得，总收率为38%~52%。本研究使用了多种反应体系：涵盖以HCl/乙酸、氯铬酸吡啶鎓（pyridinium chlorochromate, PCC）、PCC-高碘酸为试剂的均相体系；以Amberlyst® A26-铬酸氢根型、聚乙烯基氯铬酸吡啶鎓（PV-PCC, polyvinyl-pyridinium chlorochromate）、Amberlyst® A26-氢氧根型等聚合物树脂负载试剂构成的非均相体系；以及以碘化钾/氧化铝（KI/Al₂O₃）、溴化钾/氧化铝（KBr/Al₂O₃）等氧化铝负载试剂构成的反应体系，所有反应均在无溶剂条件下进行。