Pharmaceutical Organic Chemistry

1. MR.DHIRAJKUMAR S.NIKAM
ASST.PROFESOR
Pharmaceutical Chemistry
Bharati Vidyapeeth College of
Pharmacy Navi Mumbai
India
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SN1 Reaction

2. SN1 Reaction
 Contents :
• Features of SN1 reaction
• SN1 Mechanism
• Stereochemistry
• Carbocation stability
• Carbocation rearrangement
• Factors affecting SN1 reaction
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3. SN1 Reaction
 Features:
• Follows first order kinetics
• Racemization
• Non-stereospecific
• Carbocation rearrangement
• Reactivity sequence of substrate 3o > 2o > 1o > CH3W
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4. SN1 Reaction Mechanism
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Example
Rate= k[RBr] follows first order kinetics
Mechanism

5. SN1 Stereochemistry
Step 1
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Step 2

6. SN1 Reaction Mechanism
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Energy diagram

7. Carbocation stability
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Structure of carbocation : Trigonal Planar
Stability of carbonations

8. Carbocation stability
• Three factors affects carbocation stability:
1. Inductive effect
2. Hyper conjugation effect
3. Resonance
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9. Carbocation stability
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Stability order
Resonance

10. Carbocation Rearrangement
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Alkyl Shift
Hydride Shift

11. Carbocation Rearrangement
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Alkyl shift ring expansion
Aryl Shift

12. Factors affecting SN1 reaction
All carbocations are very good electrophiles and even weak
nucleophile will react quickly with them.
e.g. H2O and CH3OH
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SN1 relative reactivity
R3CX >R2CHX > RCH2X > CH3
3o 2o 1o Methyl
Relative rate >106 1 < 10-4 < 10-5
I. Nature of substrate
II. Nature of nucleophile

13. Factors affecting SN1 reaction
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III. Effect of leaving group
IV. Solvent effect

14. Factors affecting SN1 reaction
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V. Order of leaving group
H
O
H
water
CH3
O
HO
acetic acid
H3C OH
methanol
H2
C
CH3
HO
ethanol
H
C
O
HO
formic acid
> > > >
V. Order of polar protic solvents

15. Summary SN1 reaction
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Overall summary
Kinetics Follow first order kinetics
Rearrangement Undergoes carbocation rearrangement
Product 50 % Inversion
50 % Retention
Forms racemic mixture
Nucleophile Unimportant, any weak nucleophile can perform
reaction
Leaving group Important , requires best leaving group
Solvents Important , requires polar protic solvent

16. References
1. Organic Chemistry by R.T. Morrison and R. N.
Boyd, 7th edition.
2. Organic Chemistry by Pine, Stanley H.;
Hendrickson, James B.; Cram, Donald J.;
Hammond, George S., 5th edition.
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