1. REACTIVE INTERMEDIATES & ORGANIC NAME REACTIONSBy
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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. Problems
Test your understanding ? ? ? ? 1

10. 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

11. 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

12. 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

13. Tiffeneau-Demjanov rearrangement-Problems? ? ? ? 1

14. 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

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

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

17. Reimer Tiemann Reaction? ? 1

18. 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

19. 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

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

21. Appel Reaction
# PROBLEM 1

22. Contact: asgburange@gmail.com
Thank you
Contact: 1