Chapter 6 Nucleophilic Substitution

nucleophile

______ is a chemical species that forms bonds with electrophiles by donating an electron pair

nucleophiles

all molescules and ions wiith free pairs of electrons or atleast one pi bond can act as these

lewis bases

because nucleophiles donate electrons they are

nucleophilicity

_______ is the nucleophile strength and reveals the affinity of the atoms (related to basicity)

nucleophilic

_______ describes the affinity of a nucleophile to bond with positvely charged atomic nuclei

H2O and ROH (water and alcohols) (sometimes halides and azides (N3- or X-)

common nucleophilic functional groups are

• polar protic- solvents containing hydrogen atoms connected directly to an EN atom are capable of hydrogen bonding to the substrate (H2O, NH3, CH3OOH)

• polar aprotic: solvents unable to form hydrogen bonds with substrate - they have no hydrogen atoms that are directly connected to an EN atom and not capable of hydrogen bonding (CH2Cl2)

• nonpolar: liquids that do not have a dipole moment (alkanes, aromatics (benzene)

solvent infleuences nucleophilicity by

nucleophilic

the more EN the element is the less _____ (b/c high EN means less likely to donate their electrons)

I-

protic solvent favors the _____ halogen

F

aprotic solvent favors the ____ halogen (ion-dipole between solvent and nucleophile are weaker → the positive end of the solvents dipole is hidden and shielded from neg chaarge of nucleophile) (solvent is less important and F can be used)

• steric hindrance ie : tert-butanol is less potent as nucelohpile than methanol. the bulky methyl groups on the 3 degree alcohol block the route attack by the nuleophilic oxygen→ slowing reaction down.

steric effects and effect on nucleophilicity

• RO- (alkoxides)

• Carboxylates (RCOO-)

• Sulfhydryls (SH-)

• Cyanides (CN-)

• Azides (N3-)

• Iodides (I-)

common nucleophiles

reaction time

a bulkier nucleophile means a longer

• polar and protic (polar Helps stabilize ionic intermediates and the protic helps solvate leaving group)

• Water and Alcohols are examples and can act as nucleophiles

Sn1 Solvent effects

• 1 degree or methyl

• aprotic / nonpolar

• Uses acetone

SN2 solvent effects

3 is least reactive and the methyl is the most reactive

3 → Methyl (where the halogen is located)

Sn2 reaction rates

CH3 → 3

slowest → fastest

Sn1 reaction rates

H bonds with nucleophiles

protic solvents can form

E1

• 3 degree alkyl halides and alcohols (sometimes 2)

• Weak base

• Carbocation

E2

• 1 degree of CH3 (sometimes 2)

• Strong base used (OCH3-)

alkene preparation elimination → E1 vs E2

elimination, substitution

in general → alkyl halide as primary substrate and nucleophiles are lweis bases _____ preferred.

UNLESS 1) low levels of steric hindrance, nucleophiles that are weak, and low temp then use ______

SN2 and E2

strong nucleophiles/strong bases (HO, RO, R2N)

SN2

strong nucleophiles but weak bases (RS, RSH, X)

E2

strong bulky bases but weak nucleophiles (t-buto)

SN1 and E1

weak nucleophiles/weak bases (H2o, ROH, RNH2)

strong

tertiary substrate (SN1, E1, E2) ——> presence of _____ base E2

elimination preferred over substitution unless the reactant is strong nucleophile but weak base

secondary substrate (SN1, SN2, E1, E2) →

substitution over elimination unless strong bulky base

primary substrate (SN2 and E2) →

elimination products favored

heating reaction will result in ______ products favored over _____ products