ORGANOHALIDES + Nucleophilic Reactions (SN1/2, E1/E2/E1cB)

CH21 PS CLASS

Preparation of Organohalides

• From ALKENES C=C [just review old lessons]• FOR TERTIARY ALCOHOLS, we can simply use

H-X (gas) X=Cl,Br in ether, 0°C

Preparation of Organohalides

• FOR TERTIARY ALCOHOLS, we can simply use H-X (gas) X=Cl,Br in ether, 0°C – Follows SN1 so a carbocation is formed, – be careful with rearrangements!

Preparation of Organohalides

• FOR PRIMARY/SECONDARY ALCOHOLS: SOCl2 / PBr3

Practice

Alkyl Fluorides

• Also from ALCOHOLS + • HF / Pryidine • (CH3CH2)2NSF3

Grignard Reagents

• Reaction of R-X with Mg over ether/THF to form R-Mg-X organometallic compound.

Grignard Reagents: reduction of R-X

More samples:

Nucleophilic Reactions

• R-X, alkyl halides are ELECTROPHILES (positive or electron-poor)

• They react with NUCLEOPHILES/BASES (negative or electron-rich)

• Either substitution – C-C-X becomes C-C-blah + X-

• or elimination reactions– C-C-X becomes C=C + X-

SUBSTITUTION REACTIONS

• S – substitution: R-X + Nu R-Nu + X- • N – Nucleophilic • 1 or 2 unimolecular or bimolecular rates• INVERSION (change of stereochemistry) CAN

HAPPEN!

Try this first…

SN2 BIMOLECULAR

• Bimolecular simply refers to the rate depending on BOTH reactants because of the nature of the mechanism

• Rate = k[RX][Nu]• Rate depends on both because there is

ONE SINGLE COLLISION BETWEEN RX and Nu to form a Nu-R-X transition state

SN2 BIMOLECULAR

100% INVERSION OF STEREOCHEMISTRY OCCURS!

SUBSTRATE

LEAVING GROUP

Factors that affect SN2 RXNS:

• STERIC EFFECTS TO INCOMING Nu:– C=C-X (vinylic) and Ar-X (aryl) TOTALL UNREACTIVE

Factors that affect SN2 RXNS:• THE NUCLEOPHILE

Factors that affect SN2 RXNS:• THE LEAVING GROUP

should be stable on its own as a free anion• Comparing halides, we go down the column

Factors that affect SN2 RXNS:

• Alcohols and fluorides usually do not undergo SN2 because OH- and F- aren’t good leaving groups

• This is why we use SOCl2 and PBr3 … THEY CONVERT THE –OH INTO A BETTER LEAVING GROUP

Factors that affect SN2 RXNS:• Reaction SOLVENT can also affect the reaction.• We prefer POLAR APROTIC SOLVENTS– POLAR but no –OH or –NH in the molecule (no

H2O, NH3, etc…)

• Polar protic solvents form a CAGE around Nu

Practice

Practice

Practice

Practice

SN1 UNIMOLECULAR

• Unimolecular: rate depends only on the substrate (mechanism), almost opposite of SN2

• Rate = k[RX]• Rate is only dependent on the slowest step

which is the spontaneous dissociation of your leaving group. (molecules just don’t easily dissociate!)

SN1 UNIMOLECULAR

SN1 UNIMOLECULAR

SN1 UNIMOLECULARSTEREOCHEM IS LOST, A RACEMATE FORM IS MADE, but usually not 50:50

SN1 UNIMOLECULARSTEREOCHEM IS LOST, A RACEMATE FORM IS MADE, but usually not 50:50

An ION PAIR BLOCKS THE OTHER SIDE!

Factors that affect SN1 RXNS:

• SUBSTRATE:

Factors that affect SN1 RXNS:

• LEAVING GROUP:

An –OH in acidic medium can become –OH2+ and leave as H2O which is very favorable

Factors that affect SN1 RXNS:

• NUCLEOPHILE: no effect, almost at all.

Factors that affect SN1 RXNS:

• SOLVENT: rates increase if you stabilize carbocation transition state.

• POLAR PROTIC!

Factors that affect SN1 RXNS:

• SOLVENT: rates increase if you stabilize carbocation transition state.

• POLAR PROTIC!

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE

Elimination Reactions

• More compliated (different mechanisms)• The loss of H-X can lead to a MIXTURE of

alkene products (C-C-X C=C + HX)• But we can predict the most stable/major

poduct• ZAITZEV’S RULE: base-induced eliminations

will form more stable alkene

E2 elimination• Again, bimolecular so a single collision

between your Base B: and the alkyl halide.

E2 elimination• Anti-periplanar is favored for transition state

E2 elimination• Anti-periplanar is favored for transition state

Practice

Practice

Practice

Practice

E1 reaction

• Unimolecular, ALSO spontaneously forms carbocation, but then followed by loss of H+ (taken by a base B: and not an attack by Nu:)

• COMPETES WITH SN1 reactions!

E1 reaction

E1 reactions

• No need for anti periplanar geometry

PRACTICE

PRACTICE

E1cB

• Unimolecular, but this time CARBANION formed because a proton H+ is first removed by a base.

• cB stands for “conjugate base” because you deprotonate your carbon C-H into a C- and H+

• Usually favored for poor leaving groups (e.g. –OH)

• Carbanion can be stabilized with C=O groups nearby

E1cB

E1cB

PRESENCE OF C=O NEARBY CAN GIVE RESONANCE STABILIZATION!

PREDICTING WHAT PREDOMINATES:

Slight Clarifications: BASE vs. NUCLEOPHILE

BASE• Affinity for a PROTON• Strong base like R-O- or OH-

NUCLEOPHILE• Usually a LEWIS BASE• In this context, how

attracted to a CARBON

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE

PRACTICE