COUPLING OF HALOARENES WITH TERMINAL ALKYNES BY USING COPPER, IT’S COMPLEXES THEIR SYNTHESIS AND ITS APPLICATION IN SYNTHETIC ORGANIC CHEMISTRY

Abstract

The first part of my thesis describes the preparation of different copper catalyst for the Sonoghashira reaction and exploration of its activity for Sonoghashira reaction. It include optimization of reaction condition like right solvent selection for reaction, temperature of reaction, base selection for reaction, purification of product and synthesis or selection of starting materials for reaction. Here in we have prepared following catalyst and explored its activity for Sonoghashira reaction. We have developed first time industrial process of preparation for Iodo(tristriphenylphosphine)copper(I). We have prepared 25-30 compounds for each catalyst and characterized using H1NMR, C13 and C13 Dept. Spectroscopy. 1. Iodo (tristriphenylphosphine)copper(I): 2. Bromotris(triphenylphosphine)copper(I) 3. Di-μ-iodidobis[2,2'-bis(diphenylphosphanyl)-1,1'-bina phthyl,]copper(I) 4. (Z)-5-((2-mercaptophenylimino)methyl)-2-methoxy phenol Copper(I) In addition to this have explored the catalytic activity of copper carbonate for Sonoghashira reaction in legand and base free condition (Copper carbonate itself act as base and legand), the specificity of the Sonoghashira reaction is the mild reaction condition. Use of copper catalyst for this reaction makes milder condition for this reaction. The use of copper catalyst in place of palladium catalyst makes this synthesis more economical and environment friendly and closes to green approch. Second part describes the application of Sonoghashira reaction 1. Preparation of 2-Vinyl phenols: This is new protocol we have developed and reporting first time using simple reagent copper powder. Generally in Sonoghashira the terminal alkyne proton get substituted by alkyl or aryl group. But here we got addition product. in nucleophilic addition also generally addition takes place according to markovnikov's rule and nucleophile will attach to less substituted carbon atom but Here in reported protocol substitution takes place according to anti markovnikov's rule. 2. Preparation of Isocumarin: synthesis of isocumarin involves two steps. Preparation of 2- alkyne benzoic acid from alkyne and 2-Iodobenzoic acid and its cyclization to form 5 isocumarin. We have prepared isocumarin derivative in single step (one pot synthesis) using simple reagent copper powder and 2-iodobenzoic acid and alkyne as a starting materials. We have also prepared isocumarin 2- iodobenzoate as a starting material using copper powder as a reagent. We have prepared isocumarin using catalyst CuI(PPh3)3. Third Part descries Industrial application of Sonoghashira reaction. 1. Synthesis of Keto and Oxazoline: Developed a new protocol for synthesis of Keto Oxazoline in this protocol formation of oxazoline and oxidation of alkyne group to ketone occur in single step using simple and mild reagent copper powder. We are reporting this new rearrangement with formation of oxazoline ring and oxidation of triple bond for the first time. We have filed Indian patent application for this process and product using copper powder. 2. Induction of Chirality in organic molecule: In literature there is no method available using simple starting material for the preparation of chiral isoindolinone. We have developed the method for preparation of isoindolinone using simple starting material 2- Iodo benzoic acid, and alkynes. Developed a process for chiral purification (chiral resolution) using simple single solvent in single purification up to enantiomeric excess 95%. Here also the copper metal used for coupling and cyclization making this synthesis more economic and approaches towards the green synthesis.