Reagents in Organic synthesis March 27, 2017 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 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

What is a chemical reaction? March 27, 2017 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). NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Reagents to be covered…… Entry Reagent 1 NaNH2/NH3 2 1,3-propan-dithiol 3 Methylmethyl thiomethyl sulfoxide 4 OsO4, KMnO4 5 NaIO4 6 LTA 7 m-CPBA, Hydrogen peroxide 8 Ozone 9 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 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 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 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 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 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 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/ Hg2+ yields Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Predict alkyl halide required with 2 eq. of LDA…. BrCH2CH2CH2CH2CH2Br BrCH2CH2CH2CH2Br BrCH2CH2Br BrCH2CH2CH2Br Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 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 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

? Baeyer- Villiger Oxidation and migratory aptitude Per acid March 27, 2017 Baeyer- Villiger Oxidation and migratory aptitude Per acid ? Why electrophilic Stable carboxylate anion Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Various per acids used for Baeyer Villiger oxidation and epoxidation reactions Migratory aptitude in Baeyer-Villiger Oxidation Reaction H> phenyl > tert-alkyl> sec-alkyl > primary alkyl > methyl Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Bartlett has proposed one step mechanism for epoxidation of alkene using per-acid Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 OsO4 OR KMnO4 OR OsO4/ NMO OR K2OsO4 /NMO m-CPBA CH2I2/ Zn-Cu (Simmon’s Smith) I2/ AgOAc (Prevost) OR m-CPBA followed by hydrolysis Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Some selectivity aspects during epoxidation reactions….. Stereoselectivity 50:50 both stereo-isomers are formed Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 Cleavage of 1,2-diols March 27, 2017 Vs No Cleavage NaIO4 is selective for only cis-diol LTA breaks both cis and trans diols Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Ozonolysis at different conditions… O3 , CH2Cl2 Zn, Me2S O3 , CH2Cl2 NaBH4 OR LAH O3 , CH2Cl2 H2O2 Mechanism involves formation of primary ozonoid which on homolysis gives carbonyl oxide radical. Carbonyl oxide radical on dimerization gives tetraoxane which on breaking yields corresponding carbonyl. Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 DIBAL-H and Solvent-Effect It’s a neutral aluminium hydride containing only one hydride species. It’s a convenient reagent for reducing carboxylic acids to alcohols. It can reduce esters to alcohols and aldehydes selectively. Amides and nitriles also yields aldehydes Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 In Polar solvent Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 In non-polar solvent H2O Stable at low temperature and recovered at -78oC H3O+ Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 NaBH4 Vs LAH Lecture at KTHM College, Nashik on 15th September 2012

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 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 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Epoxidation and cyclopropanation of alpha-beta unsaturated enone systems H2O2/OH- Me2SOCH2- Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 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 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Diazomethane for ring expansion Diazomethane is a poisonous gas. It must be handled with great care. CH2N2 Structure: Needle like nucleophile Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 Epoxide is a product of side-reaction occurs during this reaction Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

!!ANTI PERIPLANAR RELATIONSHIP!! / Elimination reaction March 27, 2017 !!ANTI PERIPLANAR RELATIONSHIP!! / Elimination reaction Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 NaNO2­/HCl (Semi-pinacolone rearrangement) Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

ph3P=CH2 OR i. Me3SiCH2MgCl ii. H+ iii. KH or HF 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)

Lecture at KTHM College, Nashik on 15th September 2012 March 27, 2017 i. Base/ ii. H+/heat Diethyl oxalate Ph3P: /(EtO)3P: MeLi(Excess) Lecture at KTHM College, Nashik on 15th September 2012 NET/SET Guidance Lecture under UGC merged scheme at Patkar College, Goregaon, Mumbai

Lecture at KTHM College, Nashik on 15th September 2012 Organoborane and hyper-conjugation From Boron, the alkyl group contributing less hyperconjugation effect migrates to carbonyl carbon Lecture at KTHM College, Nashik on 15th September 2012

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