Reagents in Organic Synthesis

REAGENTS IN ORGANIC SYNTHESIS Mr Anand S Burange, Institute Of Chemical Technology, Matunga , Mumbai-400019 E-mail: asgburange@gmail.com Lecture at KTHM College, Nashik on 15th September 2012 WHAT IS A CHEMICAL REACTION? Chemical reaction is an effective interaction between two or more molecules/atoms /ions leading to the formation of new compound(s) Reagents to be covered…… Entry Reagent NaNH2/NH3 1,3-propan-dithiol Methylmethyl thiomethyl sulfoxide OsO4, KMnO4 NaIO4 LTA m-CPBA, Hydrogen peroxide Ozone LAH/NaBH4 10 DIBAL-H and solvent effect 11 Diethyl oxalate 12 Simmon’s Smith Vs Stabilized sulphur ylid 13 Abnormal Witting 14 NaNO2/HCl (Semi-pinacolone rearrangement) Role of anti-pariplanar relationship 15 Organoborane and hyperconjugation 16 Pph3 or P(OEt)3 and organosilane reagent 17 Diazomethane 18 PhSeBr 19 MeLi Lecture at KTHM College, Nashik on 15th September 2012 NaNH2/NH3  Sodamide can be prepared by adding sodium metal to ammonia  Sodium metal can easily react with any active proton donor with the release of hydrogen gas  NaNH2/NH3 obtained can be used for benzyne mechanism while NaNH2/NH3 in ethanol is used for Birch reduction Lecture at KTHM College, Nashik on 15th September 2012 Lecture at KTHM College, Nashik on 15th September 2012  i NaNH2/NH3 ii -CH(CO2Et)2  OH-/340o C  NaNH2/NH3 i Cl-PO(OEt)2/NaH ii NaNH2/NH3 (Via Benzyne) Lecture at KTHM College, Nashik on 15th September 2012 1,3-propan-dithiol 1,3-propan-dithiol is used to change the polarity of carbonyl carbon of aldehydes in order to make it nucleophilic by using LDA as a base This change in polarity is called as umpolung Using this concept, we can easily prepare any cyclic ketones like cyclopropanone, cyclobutanone, etc Protected form of formaldehyde Again LDA is used to get which on deprotection using acid/ Hg 2+ yields Lecture at KTHM College, Nashik on 15th September 2012 Predict alkyl halide required with eq of LDA… BrCH2CH2CH2CH2CH2Br BrCH2CH2CH2CH2Br BrCH2CH2Br BrCH2CH2CH2Br Lecture at KTHM College, Nashik on 15th September 2012 Methylmethyl thiomethyl sulfoxide -CHO group can be introduced at a beta position of enone system can be asses by using methylmethyl thiomethyl sulphoxide i LDA iii H3O+/Hg2+ Lecture at KTHM College, Nashik on 15th September 2012 Baeyer- Villiger Oxidation and migratory aptitude Per acid Why electrophilic ? Stable carboxylate anion Lecture at KTHM College, Nashik on 15th September 2012 10 In Polar solvent Lecture at KTHM College, Nashik on 15th September 2012 19 In non-polar solvent H2O Stable at low temperature and recovered at -78oC H3O+ Lecture at KTHM College, Nashik on 15th September 2012 20 NaBH4 Vs LAH Lecture at KTHM College, Nashik on 15th September 2012 21 Simmons-Smith Cyclopropane Synthesis It has been developed by H.E Simmons and R.D Smith of the DuPont Company During this synthesis diiodomethane and zinc-copper couple are stirred together with alkene The diiodomethane and zinc react together to produce carbene like species called as carbenoid which brings stereospecific addition of CH2 directly to the double bond Simplest carbene : Methylene :CH2 Can be easily prepared by thermolysis or by irradiating diazomethane gas Lecture at KTHM College, Nashik on 15th September 2012 22 Lecture at KTHM College, Nashik on 15th September 2012 23 Epoxidation and cyclopropanation of alpha-beta unsaturated enone systems H2O2/OH- Me2SOCH2- Lecture at KTHM College, Nashik on 15th September 2012 24 Unstabilized sulphur ylids are useful to convert carbonyls to respective epoxides + Me2S Application of unstabilized sulphur ylid Lecture at KTHM College, Nashik on 15th September 2012 25 Diazomethane for ring expansion CH2N2 Diazomethane is a poisonous gas It must be handled with great care Structure: Needle like nucleophile Lecture at KTHM College, Nashik on 15th September 2012 26 Epoxide is a product of side-reaction occurs during this reaction Lecture at KTHM College, Nashik on 15th September 2012 27 !!ANTI PERIPLANAR RELATIONSHIP!! / Elimination reaction Lecture at KTHM College, Nashik on 15th September 2012 28 NaNO2/HCl (Semi-pinacolone rearrangement) 29 Lecture at KTHM College, Nashik on 15th September 2012 Predict the suitable reagents for the following examples… CH3-O-CH=Pph3 i.Base ii PhSeBr iii Oxidant (e.g H2O2) ph3P=CH2 OR i Me3SiCH2MgCl ii H+ iii KH or HF Peterson olefinating agent better than P-ylid BF3/DMSO (solvent) 30 i Base/ ii H+/heat Diethyl oxalate Ph3P: /(EtO)3P: MeLi(Excess) Lecture at KTHM College, Nashik on 15th September 2012 31 Organoborane and hyper-conjugation From Boron, the alkyl group contributing less hyperconjugation effect migrates to carbonyl carbon 32 Lecture at KTHM College, Nashik on 15th September 2012 33