CH 9a - Substitutions

nucleophilic substitution

any reaction in which one nucleophile substitutes for another at a sp3 carbon

NaN3 =

sodium azide

nucleophilic substitution mechanism differ on

timing of bond-breaking and bond-forming step

if steps are simultaneous =

designated Sn2

Sn2 - bond-breaking and forming are both

in the rate-determining step

Sn2 stereochemistry - backside attack of nucleophile leads to

inversion of configuration at chiral carbon

• R → S or S→ R

if bond to leaving group breaks first -

designated Sn1

SN1 - rate-determining step

the leaving group (halogen) leaving

SN1 stereochemistry

reaction at chiral carnation gives racemic product (both R and S enantiomers)

SN1 reactions covered by electronic factors

the relatively stabilities of the carbocation intermediates

SN2 reactions covered by steric factors

the relative ease of approach of a nucleophile to the reaction site

SN1 carbocation

3 > 2 > 1 (doesn't really occur) > methyl (does not occur)

SN2 carbocation

methyl > 1 > 2 > 3 (does not occur)

stability of carbocations

allylic and benzylic are more stable than alkyl

SN2 B-branching

the more B-branches slows the relative rate of reaction

the better the leaving group can stabilize the electron pair, the

better the leaving ability

the most stable anions and best leaving groups are the

conjugate bases of strong acids

leaving group

I- > Br- > Cl- > H2O » F-

• based on size and not electronegativity

solvents are classified as

polar and non polar

the most common measure of a solvent polarity is

dielectric constant

dielectric constant

measure of a solvent’s ability to insulate opposite charges from one anther

the greater the value of the dielectric constant of a solvent, the

smaller the interaction between ions of opposite charge dissolved in that solvent

protic solvent

solvent that is a hydrogen bond donor

• the most common contain -OH groups

aprotic solvent

solvent that cannot serve as a hydrogen bond donor

• no -OH or -NH groups

common protic solvents

water (H2O), formic acid (HCOOH), methanol (CH3OH), ethanol (CH3CH2OH), acetic acid (CH3COOH)

common aprotic solvents - polar

DMSO, acetonitrile, DMF, acetone

common aprotic solvents - moderately polar

dichloromethane and THF

common aprotic solvents - non polar

diethyl ether, toluene/benzene, and hexane

Sn1 reactions involves the reaction and separation of unlike charges in

the transition state of the rate-determining step

SN1 rate depends on the ability of

the solvent of keep these charges separated and to solvate both the anion and the cation

SN1 most effective solvents are

polar protic

• combination of high dielectric constant and hydrogen bonding

most common SN2 reactions involves

charged transition state of the rate-determining step and charged nucleophiles/leaving groups

SN2 - weaker salvation of nucleophile means

easier to reaction

SN2 most effective solvent is

polar aprotic

• combination of high dielectric constant and no hydrogen bonding

structure of nucleophile is only a factor in

SN2 reactions

nucleophilicity

a kinetic property measured by the rate at which a nu: causes a nucleophilic substitution under a standardized set of experimental conditions

basicity

an equilibrium property measure by the position of equilibrium in an acid-base reaction

other factors of nucleophiles in Sn2

• solvation (protic vs aprotic)

• polarizability (larger electron cloud)

• shape

structure of nucleophile - when comparing same element

look at basicity

• negative > neutral

• further down the row the better

structure of nucleophile - when comparing elements in the same group

look at polarizability

• further down the column the better

rearrangements only occur in

Sn1 reactions

Sn2 - methyl (CH3X)

favored

SN2 - primary (RCH2X)

favored

Sn2 - secondary (R2CHX)

favored in aprotic solvents with good nucleophiles

Sn2 - tertiary (R3CX)

does not occur

Sn1 - methyl (CH3X)

does not occur

sn1 - primary (RCH2X)

rarely occurs

sn1 - secondary (R2CHX)

favored in protic solvents with poor :nu

• rearrangments may occur

sn1 - tertiary (R3CX)

favored

sn2 - substiution at a chirla center

inversion of configuration

sn1 - substitution at a chiral center

racemization is favored