Synthesis and Cleavage of the Cyclic Oxalates of 1,2-Glycols.

Research Project

Project/Area Number	06672095
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Chemical pharmacy
Research Institution	Kanazawa University
Principal Investigator	ITAYA Taisuke Kanazawa University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (20019657)
Project Period (FY)	1994 – 1995
Project Status	Completed (Fiscal Year 1995)
Budget Amount *help	¥2,100,000 (Direct Cost: ¥2,100,000) Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000) Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywords	Oxalyl chloride / Cycloalkane-1,2-diol / Cyclic oxalate / Highly selective synthesis / Stereospecific cyclocondensation / Hydrolysis rate / 付加-脱離機構 / X-線解析 / 1,2‐グリコール / 環状炭酸ジエステル / 立体電子効果 / 反応機構 / 縮合環化反応
Research Abstract	We have already disclosed that oxalyl chloride reacts with acyclic 1,2-glycols in tetrahydrofuran in the presence of triethylamine to afford a different type of compound as a major product, depending on the structure of the glycol : unsubstituted, monosubstituted, and erythro-disubstituted ethylene glycols provided the cyclic oxalates or polymeric oxalates, while the threoisomers and pinacol afforded the cyclic carbonates. 1.The only exception we found was trans-cyclohexane-1,2-diol, which exclusively afforded the cyclic oxalates. This reaction probably proceeded through the tetrahedral intermediate with a boat form, avoiding steric interference between the bridge-head hydrogen and carbonyl oxygen. 2.The dramatic reversal of the product ratio was realized in the reaction with pinacol or the threo-compounds by the use of pyridine instead of triethylamine to afford the cyclic oxalates. 1,1'-Oxalyldiimidazole was found to be a good choice for the exclusive formation of the cyclic oxalates. The formation of the polymeric oxalates from the erythro-compounds was completely suppressed by the use of 2,4,6-collidine. 3.The cyclic oxalates thus obtained underwent hydrolytic cleavage of the acyl-alkoxy linkage to afford the monoester of oxalic acid at pH 5 at the rate of 200-1000 times faster than the cyclic oxalate of pinacol. The three-dimensional structure elucidated by X-ray crystal analysis shows that the carbonyl carbons of the cyclic oxalate of pinacol are effectively blocked by two of the four methyl groups.