Physical Organic Chemistry CH-5 Addition & Rearrangement reactions

1. Islamic University in Madinah Department of Chemistry Physical Organic ChemistryCH-5 Addition & Rearrangement reactions Prepared By Dr. Khalid Ahmad Shadid

2. Addition to double bond • Alkene double bond contain sigma and pi, the bond is more reactive thane in alkane. • Can react through electrophilic addition. • Electrophilic addition • Bromine and chlorine can react with alkene, while Iodine doesn't react. Florin react very fast but no product. • General Mechanism: R2C=CR2   +   X2   ——>  R2CX-CR2X

3. Brominating Mechanism • Br+ adds to an alkene producing a cyclic ion • Bromonium ion, bromine shares charge with carbon • Gives trans addition • Electrophilic addition of bromine to give a cation is followed by cyclization to give a bromonium ion • This bromonium ion is a reactive electrophile and bromide ion is a good nucleophile • Stereospecific anti addition • Exclusively Trans Addition to alkene. Even when alkene contain bulky group like tertiary butyl.

4. Addition of strong Acids • Addition of proton to a double bond (rate determining step), then fast nucleophilic attack.

5. Addition of Hydrogen Halide to alkene • Addition of HX to alkene. Can cause carbocation rearrangement. • Carbocation rearrangement from secondary to more stable tertiary.

6. Addition of Hypohalous Acids to Alkenes: Halohydrin Formation • This is formally the addition of HO-X to an alkene to give a 1,2-halo alcohol, called a halohydrin • The actual reagent is the dihalogen (Br2 or Cl2 in water in an organic solvent) • (HO-X), X: CL or Br is electrophile, its less electronegative than Oxygen

7. Mechanism of Formation of a Bromohydrin • Br2 forms bromonium ion, then water adds • Orientation toward stable C+ species • Aromatic rings do not react

8. Addition sulfonyl chloride Here electrophile is a cation RS+ . Chlorine more electronegative than sulfur (CH3)2C=CH2   +   C6H5SCl   ——>  (CH3)2CCl-CH2SC6H5

9. Addition of Water to Alkenes • Hydration of an alkene is the addition of H-OH to to give an alcohol • Acid catalysts are used in high temperature industrial processes: ethylene is converted to ethanol

10. Oxymercuration Intermediates • For laboratory-scale hydration of an alkene • Use mercuric acetate in THF followed by sodium borohydride • Markovnikov orientation • via mercurinium ion

11. Addition of Water to Alkenes: Hydroboration • Herbert Brown (HB) invented hydroboration (HB) • Borane (BH3) is electron deficient and is a Lewis acid • Borane adds to an alkene to give an organoborane

12. Orientation in Hydration via Hydroboration • Regiochemistry is opposite to Markovnikov orientation • OH is added to carbon with most H’s • H and OH add with syn stereochemistry, to the same face of the alkene (opposite of anti addition) • STEREOSPECIFIC

13. Mechanism of Hydroboration • Borane is a Lewis acid • Alkene is Lewis base • Transition state involves anionic development on B • The components of BH3 are added across C=C • More stable carbocation is also consistent with steric preferences

14. Halogen Addition • Mixed Halogens are polarized: X+- X- • more electronegative halogen will carry partial negative charge • Rate of addition: BrCl > Br2 > ICl > IBr > I2 • Morkovinikov addition

15. Oxidation of Alkenes: Epoxidation and Hydroxylation • Oxidation is addition of O, or loss of H • Epoxidation results in a cyclic ether with an oxygen atom • Stereochemistry of addition is syn • MCPBA in CH2Cl2 are the usual conditions • Addition of acid results in a trans-1,2-diol • Treatment of the epoxide with aqueous acid give a trans diol

16. Hydroxylation - converts to syn-diol • Osmium tetroxide, then sodium bisulfate • Via cyclic osmate di-ester • Osmium is toxic, so catalytic amount and NMO are used Osmium Tetroxide Catalyzed Formation of Diols

17. What is Rearrangement Reactions? • The term of “rearrangements” is used to describe organic reactions which involve the migration of an H atom or of a larger molecular fragment. • Nucleophilic Rearrangements • Electrophilic rearrangements • Radical rearrangements 1. Nucleophilic Rearrangements • [1,2]-Rearrangements

18. Wagner-Meerwein rearrangements • Wagner-Meerwein Rearrangements are [1,2]-rearrangements of H atoms or alkyl groups in carbenium ions that do not contain any heteroatoms attached to the valence-unsaturated center C-1 or to the valence-saturated center C-2.

21. Wagner-Meerwein rearrangements • Carbenium ions: 1 °→2 °，1 °→3 ° 2 °→3 ° • Reactions include Wagner-Meerwein rearrangement step: 1. Electrophilic additions of alkenes 2. Nucleophilic substitutions (SN1) 3. E1 elimination 4. Friedel-Crafts alkylation reactions, etc

22. Example: Friedel-Crafts Alkylation • 1-Bromopropane isomerizes quantitatively to 2-bromopropane under Friedel-Crafts conditions. The [1,2]-shift A→B involved in this reaction again is an H-atom shift.

23. Example: Wagner-Meerwein rearrangement as part of an isomerizing E1 elimination Methyl shift

24. Example: Nucleophilic Substitution HNO2 Methyl shift Mechanism C H HNO2 3 + C H C C H 3 2 C H 3 + H O C H C 2 C H C H 3 2 3 + H C H 3

25. Example: E1 and Nucleophilic Substitution Mechanism

26. GOOD LUCK