REACTIVE INTERMEDIATES & ORGANIC NAME REACTIONS By Dr. Anand S Burange Ph.D. (ICT, Mumbai), CSIR-NET, GATE, CSIR-Nehru PDF (NCL, Pune), CSIR-RA Asst. Professor in Chemistry Wilson College, Mumbai 27th Sept- 2016 Suzuki coupling : Burange et al., ChemistrySelect, 2016, 1, 2673 – 2681 1

REACTIVE INTERMEDIATES Reactive intermediates The intermediates formed during the reactions: short lived, mostly non isolable, quickly converted into more stable molecule. Carbene Carbanion Reactive intermediates Nitrene Carbocation Radical Aryne 1

REACTIVE INTERMEDIATES:CARBOCATION For many years they were called as carbonium ions; in 1902 it was suggested inappropriate to use suffix ‘onium’ ion for lesser covalency which is often used for higher covalency than neutral atom. e.g. ammonium, hydronium ion. Finally accepted by IUPAC in 1987 after Olah’s discovery. Carbocation SP2 Hybridization CH5+ species: Possible???? Stability order of alkyl carbocation George Olah et al., found an intermediate of carbon where actually covalency of carbon is five (higher), i.e. CH5+ Methanonium ion (carbonium ion). Chemtech, 1971, 1, 566; JACS 1972, 94, 808 3o>2o >1o > methyl Reason: Hyperconjugation and Field effect Lot of literature availbale: work by Olah and his co-workers 1

CARBOCATION Can we prepare carbocation? YES Super Acid FSO3H + SbF5 dissolved in SO2 or SO2ClF is known as super acid. Alcohols, alkenes and even alkanes give carbocation when treated with super acid. JOC 1971, 36, 2354; JACS 1967, 89, 3576. Evidence for stability of carbocation? Both pentyl fluorides gave isopropyl cation. All four butyl fluorides gave tert-butyl cation. All seven pentyl fluorides gave tert-pentyl cation. To date no primary cation survived long enough for detection. Which gas evolves when alkanes are treated with super acid? JACS 1967, 89, 4739 1

CARBOCATION Allylic, benzylic and cyclopropyl carbocations Non classical Allylic, benzylic and cyclopropyl carbocations 7- Norbornenyl cation Benzylic are more stable than simple allylic cations Cyclopropyl methyl cations are even more stable than benzylic. Norbornyl cation Reason for extra stability of cyclopropyl methyl carbocation More the canonical forms; more is the stability. 1

CARBOCATION Acyl-cation Acyl or acetyl cation is as stable as tert-butyl cation. Q. Which of the following carbocations do not exist? Which one is more stable? It is impossible to form carbocation at bridgehead atoms in [2.2.1] systems since they can not be planar. Larger bridgehead carbocations can exist. Cyclopropyl group provides extra stability already discussed in previous slide. 1

Ph3C+BF4- CARBOCATION How they exist? Commercially available carbocation Ph3C+BF4- More stable ones can be prepared in solution and in some case they even exist as solid salts. In solution, carbocations may be free i.e. in case of polar solvents they are solavated. In non-polar solvents they exist as an ion pair i.e. closely associated with negative ion/counter ion/gegenion. Aryl methyl carbocations are further stabilized by electron donating groups at ortho and para postion (s). 1

Wagner-Meerwein Rearrangement and Friedel Crafts # Problems #1 How will you synthesize n-butyl benzene? #2 Predict the product The acid catalyzed nucleophilic 1,2 migration of alkyl, aryl or hydride group from an alcohol to alkene is known as Wagner-Meerwein Rearrangement 1

Problems Test your understanding........ ? ? ? ? 1

Pinacol-pinacolone rearrangement 1,2 diol (pinacol:trivial name), undergoes acid catalyzed rearrangemet which involve formation of carbocation, alkyl/aryl group migration to yield carbonyl compound. Spirocycles can be prepared by this reaction. ? ? ? 1

Semipinacol rearrangement In presence of base, less hindered hydroxyl group of pinaocol reacts with TsCl to form tosylate. Formed tosylate further gives carbonyl compound in non-acidic condition (basic/neutral). ? ? Less hindered 1

Tiffeneau-Demjanov rearrangement Anti pariplanar relationship Semipinacol rearrangement of diazonium salts derived from 2-amino alcohols sometimes called as Tiffeneau_Demjanov rearrangement. Anti pariplanar relationship Orbital Approach 1

Tiffeneau-Demjanov rearrangement-Problems ? ? ? ? 1

REACTIVE INTERMEDIATE: CARBENE How to distinguish between singlet Highly reactive species. Practically all having lifetime considerably under 1 sec. Carbenes have been isolated only by entrapment in matrices at low temperature (77K or less). Ex. :CH2 (methylene); :CCl2 (dichlorocarbene) Carbene Six electron species Types of Carbene How to distinguish between singlet and triplet carbene? Method developed by Skell, where different type of carbene on reaction with cis-2-butene give different stereoisomer. H-C-H bond angle 103o SP2 hybridized H-C-H bond angle 136o SP3 hybridized 1

CARBENE Reaction of singlet and triplet carbenes : Skell et al , JACS 1956, 78, 4496; Tetrahedron 1985, 41, 1427 1

SIMMONS SMITH CYCLOPROPANATION In Simmons-Smith, zinc carbenoid behaves like singlet carbene and its addition to alkene are stereospecific. ? ? 1

Reimer Tiemann Reaction ? ? 1

REACTIVE INTERMEDIATE: CARBANION Simple carbanion of R3C- could assume a pyramidal (SP3) or a planar (SP2) configuration or may be something between depending upon the nature of R. Carbanion SP3 or SP2 Stability order Why alpha hydrogen of carbonyls are acidic? Stabilized by electron withdrawing group. Methyl> 1o > 2o> 3o 1

Acetoacetic Ester Synthesis/Claisen Condensation Why α- hydrogen atoms are acidic? Mechanism? How many α- hydrogen atoms are present in acetoacetic ester? Acetoacetic ester Applications Concept of 1,3-dianion Which anion is more reactive? Less stable anion more stable anion 1

# PROBLEMS JACS, 1974, 96, 1082 Tet. Lett, 1996, 37, 471 1

Appel Reaction # PROBLEM 1

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