Chem 334 - Summer 1998 - Organic Chemistry I Dr. Carl C. Wamser

Chapter 7 - Haloalkanes. Substitution and Elimination

solvolysis - solvent as nucleophile

3° halides undergo nucleophilic substitution by solvolysis

the SN1 mechanism:

example - tBuBr ----> tBu+ + Br-

tBu+ + H2O ----> tBu-OH2+

tBu-OH2+ ----> tBu-OH + H+

rate-determining step: unimolecular (the first step)

kinetics: first-order ( Rate = k [RX] )

independent of the concentration of nucleophile

rate doesn't increase with added nucleophile (e.g., N3-)

reactivity: 3° > 2° > 1° > CH3

just the opposite of SN2

carbocation stabilities: 3° > 2° > 1° > CH3+

hyperconjugation stabilizes electron-deficient carbocation

relief of steric strain also enhances SN1 reaction

stereochemistry: not specific

planar carbocation intermediate, generally racemic products

slight excess of inversion if the leaving group is still nearby (ion pair)

cyclic compounds: either cis or trans gives cis + trans mixture

(not necessarily equal amounts)

solvent effects: polar protic solvent works best

need good H-bonding to get leaving group to leave

leaving group effects: (same as SN2)

RSO3- > I- > Br- > Cl- > F-

nucleophile effects: no effect of nucleophile on rate

product-determining step: step 2 determines the product(s)

competitive nucleophiles compete in step 2

borderline 2° cases:

favor SN2 with polar aprotic solvent, strong nucleophile

favor SN1 with polar protic solvent, weak nucleophile

synthetically, SN2 is usually much preferred due to its stereospecificity

(also carbocations undergo other competing reactions)

the E1 elimination mechanism:

H-C-C-X ----> H-C-C+ + X-

H-C-C+ ----> C=C + H+

product is an alkene, by loss of X- followed by loss of H+

X- is lost from the alpha-carbon, H+ is lost from a beta-carbon

usually there are several possible products (from different beta-carbons)

rate-determining step: unimolecular

the first step is identical to SN1

kinetics: first-order (same as SN1)

reactivity: 3° > 2° > 1° (same as SN1)

comparison between E1 and SN1:

carbocation reacts with a base (to lose H+) - E1

or reacts with a nucleophile (to form a new C-Nu bond) - SN1

note - a compound that can act as a nucleophile can also act as a base

E1 and SN1 reactions usually occur together

the E2 elimination mechanism:

concerted elimination of H+ and X-

rate-determining step: bimolecular

kinetics: 2nd-order ( Rate = k [RX] [base] )

stereochemistry: anti elimination

the H and X removed in one step must be anti with respect to one another

coplanar bond breaking facilitates formation of the new _ bond

(discussed further in Chapter 11)

halocyclohexanes must lose H and X from adjacent axial positions

isotope effect: rate with D (on the _-carbon) slower than with H (kH/kD)

indicates breaking of C-H (or C-D) bond is part of the rate-determining step

comparison between E2 and SN2:

substrate reacts with a nucleophile (while X- is leaving) - SN2

or with a base (at a _-C-H bond, while X- is leaving) - E2

E2 and SN2 reactions usually occur together

control of elimination vs. substitution depends on selection of the nucleophile/base

to favor substitution, use good nucleophiles that are weak bases

enhance nucleophilicity by using a polar, aprotic solvent

use high concentrations of nucleophile (SN2 is 2nd-order)

I- , Br- , CN- , N3- , RCOO- , RS- , R3P

to favor elimination, use strong bases that are poor nucleophiles

use high concentrations of base (E2 is 2nd-order)

KOtBu or LiN(iPr)2 (LDA)

with reagents that are both nucleophilic and basic, mixed reactivity results

elimination becomes more predominant as alkyl branching increases

(substitution is more sensitive to steric hindrance than elimination is)

summary of reaction possibilities for different haloalkanes

1° - SN2 works well with a good nucleophile

E2 works well with a hindered base (KOtBu or LDA)

2° - SN2 with a strong nucleophile in a polar aprotic solvent

E2 with a strong (especially hindered) base

SN1 & E1 mix with a polar protic solvent and weak nucleophile

(to control the reaction, SN2 or E2 is much more preferable)

3° - SN1 with a polar, protic solvent and no base (nucleophile must be a weak base)

E1 will compete with above reaction, can be enhanced by adding a weak base

E2 occurs with a strong base

(see also Table 7-4 in the text)

Nucleophilic Substitution Mechanisms

What's the difference between SN1 and SN2 ?

	SN2	SN1
Reaction	RX + Nu --> RNu + X	same
Mechanism	concerted	two steps
Intermediate	none	carbocation
Kinetics	second-order	first order
Stereochemistry	complete inversion	nonspecific
Nucleophile	important	unimportant
Leaving Group	important	important
Alkyl Group	CH3 > 1° > 2° > 3° (steric hindrance)	3° > 2° > 1° > CH3 (carbocation stability)
Occurrence	CH3 , 1° , some 2°	3° , some 2°
Solvent Effects	variable	polar, protic

Elimination Mechanisms

What's the difference between E1 and E2 ?

	E2	E1
Reaction	RX + base --> C=C	same
Mechanism	concerted	two steps
Intermediate	none	carbocation
Kinetics	second-order	first order
Stereochemistry	anti periplanar	nonspecific
Base	important	unimportant
Leaving Group	important	important
Alkene Produced	Zaitsev Rule	same

Substitution vs. Elimination

How can you make ... react in an ... mechanism ?

	SN1	SN2	E1	E2
CH3X	No	good nucl.	No	No
1° ( RCH2X )	No	good nucl., weak base	No	strong base, weak nucl.
2° (R2CHX )	No	good nucl., weak base	No	strong base
3° ( R3CX )	good nucl., weak base	No	polar solvent, no base or nucl.	strong base

What's most likely to happen when ... reacts with ... ?

	Good nucl., strong base, e.g., OH-	Good nucl., weak base, e.g., I-	Poor nucl., strong base, e.g., tBuO-	Poor nucl., weak base, e.g., H2O
CH3X	SN2	SN2	SN2	No reaction
1° ( RCH2X )	SN2	SN2	E2	No reaction
2° (R2CHX )	E2	SN2	E2	No reaction
3° ( R3CX )	E2	SN1	E2	SN1