SUBSTITUTION AND ELIMINATION REACTIONS
OF HALIDES, ALCOHOLS, ETC

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Table 1 shows the general patterns of reactivity for substitution and elimination at sp3 carbon, Table 2 has details on substrate types, Table 3 has details on nucleophiles and leaving groups, and Table 4 has details on solvents. All of this data was compiled from review articles and advanced texts.

Table 1a. Properties of Nucleophilic Substitution Reactions: Rates and Outcomes

Property

SN2

SN1
substrate effect on rate rate: p>s>>t cause: steric rate: t>>s>>p cause: steric and carbocation stability
products substitution plus a little E2 substitution plus at lot of E1 rearrangement possible
stereochemistry stereospecific, inversion racemization (some excess inversion)
kinetics 2nd order (substrate, base) 1st order (substrate)
leaving group weaker base faster weaker base faster
nucleophile most basic if same atom,
largest & least solvated (most polarizable) if different atom 		no effect on rate
solvent   polar or non-polar OK, may be nucleophilic polar fastest, may be nucleophilic

Table 1b. Properties of Elimination Reactions: Rates and Outcomes

Property

E2 (halide)

E1 (halide)

E1 (alcohol)
substrate effect on rate halide C t>s>p, CH t>s>p, cause: mostly steric halide C t>>s>p, cause: carbocation stability alcohol C t>s>>p, cause: carbocation stability
products alkene, halide C becomes sp2; get some SN2 if p,s most stable alkene, rearrangements common (H>R) most stable alkene, rearrangements common (H>R)
stereochemistry stereospecific, H and X must be anti most stable alkene most stable alkene
kinetics 2nd order (substrate, base) 1st order (substrate) 1st order (substrate) and acid-catalyzed (1st order)
leaving group anions, weaker base faster anions, weaker base faster neutral, weaker base faster
base strongest base fastest, more hindered gives more E2 and less substit. no base necessary in acid solution - no good base available
solvent polar, aprotic polar polar

Table 2: Relative Reactivities of Substrate Types, Fastest First

X can be any leaving group - for comparisons between substrates close in reactivity, you can predict more reliably if X remains constant. Elimination reactions can occur if there is an H which can be lost to form the alkene; E1 and E2 rates are in the same order as SN1

Table 2a. Reactivitiy via SN2

Table 2b. Reactivity via SN1

ArCH2X

Ar3CX

RC(=0)CH2X

ArCHX

C = C - CH2X

ROCH2X

RCH2X

R3CX

R2CHX

ArCH2 X

Approx. limit for SN2. Below here, SN1 is faster or the substrate unreactive

C = C - C H2X

R3CX

R2CHX

R3CCH2X

 Approx. limit for SN1. Below here, SN1 faster or the substrate unreactive

C = C - X

RCH2X

ArX

RC(=O)CH2X

 

C = C - X

 

ArX

Table 3: Relative Reactivities of Nucleophiles and Leaving Groups, Fastest First

Table 3a.
Nucleophile (SN2 only)
(form before attack)

Table 3b.
Leaving Group (SN1, SN2, E1, E2)
(form after leaving)

RS -

N2

ArS - a

CO2

S2O3 -

RSO3 - (TsO -)

R2O

I -

HS -

Br -

I -

H2O

NC -

S(CH3)2

SCN -

Cl -

R2NH

HOR

ArNH2 a

NO3 -

R3N a

NR3

EtO -(RO -)

CH3CO2 -

HO -

Below: almost never observed as leaving groups

Py(C5H5N)

F -

N3 -

HO -

Br -

RO -

ArO - a

H -

NH3

R2N -

R2S

Ar -

Cl -

R -

CH3CO2 -

H2O

ROH

Below: almost never observed as nucleophiles

F -

ArNR2 a

NO3 -

TsO -

ClO4 -

  

aElectronic and steric effects in R or Ar can affect the relative reactivity, and may vary with substituent on the substrate.

Table 4: Solvent Effects on the Rate of Nucleophilic Substitution and Elimination

Table 4a. Relative Rates of SN1, and E1 in Different Solvents, Fastest First

Generally polar solvents accerate SN1, and E1 compared to E2. The order below is about the same as that of their dielectric constants

H2O

HCO2H

CH3OH

CH3CH2OH

CH3COCH3

CH3CO2H

Below: SN1 impossible

Py(C5H5N)

CHCl3

CH3CH2OCH2CH3

C6H6

Table 4b. Relative Rates of SN2 and E2 in Different Solvents, Fastest First

Aprotic (di)polar solvents accelerate SN2 and E2, compared to protic solvents of the same dielectric constant, and reverse the relative reactivity of the halides. The order below is that of their dielectric constants.

CH3SOCH3 (DMSO)

CH3CN

HCON(CH3)2 (DMF)

O = P(N(CH3)2)3 (HMPA)

CH3COCH3

C5H5N(Py)

ORGANIC ENRICHMENT 1998

E-mail me at: lsweeting@towson.edu

Last update Aug 17, 1998