Synthesis Of Coumarin Derivatives Under Solvent-free Condition

The typical organic synthesis has long been carried out in organic solvents because reactions in solvents proceed homogeneously and exchange energy smoothly. However, most of organic solvents are volatile, flammable, toxic and unrecoverable. Solvent-free reactions, avoiding the use of organic solvents, are clean, effective and economical reactions, in which the safety is largely increased, workup procedure is considerably simplified and the cost is greatly reduced. Therefore, solvent-free organic reactions have attracted many interests in chemical industry. Indeed, most of solvent-free organic reactions occur in solid state, the tightly and regularly arranged structures of solids make the reactions proceed more efficiently and selectively than solution ones. Furthermore, due to the simplicity in process and handling, solvent-free reactions can be accelerated by means of grinding, microwave irradiation and ultrasonic irradiation.As the development of the combinatorial chemistry, polymer-supported reagents become more popular in recent years. Organic reactions of polymer-supported reagents have many advantages over small molecular reactions: ease of separation of products by filtration make the workup procedure be simplified; more stable and safe property make the reactions be more available; enhanced selectivity make the reactions be suitable to unsymmetrical synthesis. Thus, the combinatorial synthesis of heterocycle compounds and screenning of biologically active compounds have extensively conducted using polymer-supported reagents.Coumarin derivatives have attracted much attention due to their antibacterial, anticoagulants, antiallergic, hypotensive, anti-HIV and anticancer activities. Furthermore, coumarin derivatives have also been extensively used as optical bleaching agents, luminescent probes, active media for tunable dye lasers, and non-linear opitical materarial since their excellent opitical properties. Coumarin derivatives bearing 1,3,4-oxadiazole, 1,3,4-thiadiazole and thiourea moieties may be good active compounds or optical materials possessing high fluorescence quantum yields and laser quantum yields.In this thesis, we designed and synthesized three series of coumarin derivatives from coumarin 3-carboxylic acid using room-tempreture grinding, microwave irradiation and polymer-supported reagent under solvent-free condition.Part I: N-Aryl-coumarin-3-carboxamides and coumarin-3-carboxylates were rapidly synthesized under solvent-free condition and room-temperature grinding. In addition, the mixture of coumarin-3-carboxylic acid chloride and potassium thiocyanate in the presence of poly(ethylene glycol)-400 (PEG-400) was ground to first give N-coumaroyl isocyanate as an intermediate. This intermediate was further ground with a variety of aryl amines to afford N-coumaroyl-N'-arylthioureas. N-Coumaroyl-N -arylthioureas were further ground with wet potassium permanganate to produce corresponding N-coumaroyl-N -arylureas in high yield. This solvent-free method has advantages of no use of organic solvents, fast rate, high yield and simple work-up procedure.Part II: 2-Aryl-5-(coumarin-3'-yl)-l,3,4-oxadiazoles were efficiently synthesized by microwave accelerated solvent-free procedure in high yield via the condensation of coumarin-3-carboxylic acid with (un)substituded benzoic acid hydrazides using poly(ethylene glycol) (PEG) supported dichlorophosphate as dehydration reagent. Meanwhile 2-amino-5-aryloxymethyl-l,3,4-thiadiazoles were also rapidly synthesized via the condensation of thiosemicarbazide with (un)substituded aryloxyacetic acid using the same dehydration reagent. The further reactions of 2-amino-5-aryloxymethyl-l,3,4 -thiadiazoles with coumarin-3-carboxylic acid chloride or benzofuran-2-carboxylic acid chloride to afford 2-aryloxymethyl-5-(coumarin-3'-carbamido)-l,3,4-thiadiazoles or 2-aryloxymethyl-5-(benzo-furan-2'-carbamido)-l,3,4-thiadiazoles by means of solvent-free grinding orsolvent-freemicrowave irradiation. This is an environmentally-friendly, readily operated, and safe protocol and suitable to...