Liquid-Phase Organic Synthesis Based On Poly (Ethylene Glycol)-Supported Carboxylic Acid Ester Reagents

In this dissertation, the progress of liquid-phase synthesis on poly (ethylene glycol) (PEG) support for the latest ten years was introduced. Some reactions in the liquid-phase synthesis on poly(ethylene glycol) supported carboxylic acid ester reagents were investigated.Firstly, a new liquid-phase synthesis of trans-cinnamic acids and their derivatives was described. Difunctional PEG 4000 with acryloyl chloride in anhydrous dichloromethane in the presence of K₂CO₃ readily gave rise to the corresponding PEG bound acrylate, which was reacted with aryl iodides in the presence of catalytic amounts of palladium acetate and tetra-n-butylammonium bromide in pure water using potassium carbonate as a base, and subsequent cleavage from the PEG by hydrolysis of resin using sodium hydroxide aqueous solution and subsequently acidified with hydrochloric acid solution or Treatment of the resin with 0.1 N MeONa in methanol to afford trans-cinnamic acid and their ester derivatives with good yields (81-86 %) and high purities (>93 % by ¹H NMR analysis) of the crude products.Secondly, liquid-phase synthesis of 2-methyl-2-aryloxypropanoic acid derivatives using 2-bromo-2-methylpropanoic acid as a link was described. Treatment of soluble PEG 4000 with 2-bromo-2-methylpropanoic acids in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) in anhydrous CH₂Cl₂ at room temperature readily funished the corresponding PEG-bound 2-bromo-2-methylpropanoates, which were further treated with phenoxides in the presence of a catalytic amount of NBu₄I and KI, and subsequent cleavage from the PEG by hydrolysis of resin using sodium hydroxide aqueous solution and subsequently acidified with hydrochloric acid solution afforded 2-methyl-2-aryloxypropanoic acid derivatives with good yields (81-91%) and high purities (>93% by ¹H NMR analysis) of the crude products. On the other hand, resin cleaved with 0.1 N EtONa in ethanol at room temperature could afford ethyl 2-methyl-2-aryloxypropanoates in good yields and purity.