[Organic Chemistry] Substitution Reaction

반응 용어 정리

• substrate: 기질 = starting material
• reagent: 반응물
• product: 생성물
• byproduct: 부산물 (desired)
• side product: 다른 반응으로 간 생성물 (undesired)

Nucleophilic substitution reaction(SN reaction)

• nucleophile (Nu-) : 양성자 선호, $\delta ^-$ or ($-$)
• electrophile (E-) : $\delta ^+$ or ($+$)

• Alkyl halide

  • halogen: 전기음성도 $\uparrow$ $\Rightarrow$ 좋은 electrophile
    

• synthesis from alkyl halides through SN reactions
  $\\$

• possible mechanisms for substitution reactions
  1) concerted (simultaneous) mechanism
  
  2) stepwise mechanism
  

SN2

• kinetics
  • rate = $k$[alkyl halide][nucleophile]
  • bimolecular process
• stereochemistry
  • 100% inversion of configuration (back-side attack)
  • stereospecific reaction
    
• factors determining a reactivity of SN2 reaction
  1. Leaving-Group's ability
     - acidity of H-X
     $\rightarrow$ 짝산 강산이면 짝염기 good LG
     - sulfonates
     

2. steric of $C_\alpha$ in electrophile
   - reactivity: methyl > 1$\degree$ > 2$\degree$ >> 3$\degree$ (3$\degree$: reaction (X))
3. nucleophilicity of nucleophile
   - same period: basicity ($\uparrow$) $\Rightarrow$ nucleophilicity ($\uparrow$)
   - same group: polarizability ($\uparrow$) $\Rightarrow$ nucleophilicty ($\uparrow$) (HSe$^-$ > HS$^-$ > HO$^-$, PH$_3$ > NH$_3$)
4. solvent effect
   - polar protic < polar aprotic
   $\because$ protic solvent가 X$^-$ 안정화

• Strong Nu	Weak Nu
  I$^-$ Br$^-$ Cl$^-$
  HS$^-$ HO$^-$ NC$^-$	H$_2$O ROH
  RS$^-$ RO$^-$

• aprotic solvents
  

SN1

• kinetics
  • rate = $k$[substrate]
  • unimolecular reaction
• reaction mechanism (1st step: rds)
  
• stereochemistry
  • racemization
    
• reactivity
  1. LG's ability
     - better LG $\Rightarrow$ faster SN1
  2. nucleophilicity: no effect
  3. steric of electrophile
     - $C_\alpha$: 3$\degree$ >> 2$\degree$ > 1$\degree$
     $\because$ HYPERCONJUGATION
  4. solvent effect
     - polar aprotic < polar protic
     $\because$ H-Nu & C-LG 전기적 중성 $\Rightarrow$ protic solvent 써도 안정화 (X)
• additional process
  • proton transfer: poor LG 경우, H$^+$ 넣어서 better LG로.
  • carbocation rearrangement

• protic solvents
  

[ SN2 vs. SN1 ]

• Nucleophile
  • Nu가 charge (O) $\rightarrow$ SN2
  • Nu가 charge (X), 용매겸 Nu $\rightarrow$ SN1
• Solvent effect
  • polar aprotic: SN2
  • polar protic: SN1

Reference

• Klein, D. R. (2021). Organic Chemistry. John Wiley & Sons.
• 2023-1 DGIST 유기화학1 수업자료
• The structures in this document were drawn by ChemDraw JS.