MITSUNUBU REACTION.pptx

MITSUNUBU REACTION.pptx

• 1.
  Presentation on Advanced organicchemistry-I Topic-Mitsunobu reaction Presented by Tapas Majumder M.Pharma, 1st Sem Enrollment no-2106240007 Department of pharmacy Tripura University(a central University) Presented to Dr. Pratap ch. Acharya HOD, Dept of pharmacy
• 2.
  CONTENT 1. INTRODUCTION 2. SALIENTFEATURES 3. BASIC REACTION 4. MECHANISM 5. EXAMPLES 6. APPLICATIONS 2
• 3.
  INTRODUCTION  The Mitsunobureaction was discovered by a professor in Japan, Oyo Mitsunobu(1934-2003).  The Mitsunobu reaction is an organic reaction that converts an alcohol(R-OH, primary or secondary) into a variety of functional groups (Esters, Phenyl ethers, thioethers) using Triphenylphosphine(PPh3) and Azodicarboxylate such as diethyl azo dicarboxylate(DEAD) or di isopropyl azodicarboxylate(DIAD) in the presence of Nucleophile(Carboxylic acid, hydrazoic acid, imide. Phenol, sulphonamide)  The main attraction of the reaction is the inversion of stereogenic centre. The alcohol reacts with the phosphine to create an excellent leaving group then undergoes an inversion of stereochemistry in a SN2 reaction as the nucleophile displaces it.  The Mitsunobu reaction proceeds under mild, mostly neutral conditions and typically at zero degree to room temperature. 3
• 4.
  Salient features  Condensationof an alcohol and a nucleophile using Triphenyl phosphine and di aryl azodicarboxylate.  Substrate: Primary or Secondary alcohols(chiral alcohol gives inversion product)  Nucleophile: normally acidic compound containing an –H,-OH,SH,-NH-  Reagents: Trialkyl/Triaryl Phosphine and Dialkyl azodicarboxylate  Solvents: THF, toluene, benzene, DMF, diethyl ether, acetonitrile. 4
• 5.
  Basic reaction Alcohol Ester 5 DEAD(diethyl azo dicarboxylate) PPh3 (Triphenyl phosphine)
• 6.
  6 PPh3 + NN COOEt EtOOC PPh3 N EtOOC N – COOEt Ph3P Ph-COOH -PhCOO- (Nu-) Ph3P N NH EtOOC COOEt + R 1 R 2 OH PPh3 R 1 R 2 O + H N N H COOEt COOEt R 1 R 2 O + PPh3 + + NH NH COOEt EtOOC Alkoxy phosphonium ion Diethyl-1,2-hydrazine dicarboxylate(Biproduct) -PhCOO - R 1 R 2 O O Ph Ester + O PPh3 Phosphine Oxide
• 7.
  7 Examples: C H3 CH3 OH + O OH C H3 CH3 O O 2-Octanol Benzoicacid 2-Octyl benzoate pph3 DEAD C H3 C2H5 O H H C H3 C2H5 H OH OH OH CH3 CHO PPh3 +DEAD/THF(- 50°C) CH3 COOH,LiAlH4 Ph-COOH DEAD+PPh3/THF(-50°C) OH CH3 CH2OH PPh3 +DIED PhCOOH/THF(- 50°C) O O
• 8.
  APPLICATION 8 The Mitsunobu reactionhas found widespread use in many fields because of its high reliability and extensive versatility.  It is mostly used in the total synthesis of biologically active natural products such as (+) catechin(antioxidant) ,(+) vinblastine (anti neoplastic agent used to treat number of types of cancer bladder cancer, melanoma, testicular cancer).  This reaction has been used to synthesize quinine, colchicine(used in the treatment of Gout), morphine, Strychnine(a toxic ,crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents). .
• 9.
  9 THANK YOU