Alkyl Halides
Name the following alkyl halides
How are alkyl halides prepared? From alkanes Free radical halogenation From alkenes Hydrohalogenation Halogenation From alcohols
Free Radical Chlorination
Experimental Evidence Helps to Determine Mechanism Chlorination does not occur at room temperature in the dark. The most effective wavelength of light is blue that is strongly absorbed by Cl2 gas. The light-initiated reaction has a high quantum yield (many molecules of product are formed from each photon of light).
Free Radical Species are Constantly Generated Throughout the Reaction Propagation
Termination: Reaction of any 2 Radicals
Chlorination of Propane
Chlorination of Methylpropane
3o Radicals are Easiest to Form
Stability of Free Radicals
(1) Consider the free radical monochlorination of 2,2,5-trimethylhexane. Draw all of the unique products (Ignore stereoisomers). (2) Consider the free radical monochlorination of 1,4-dimethylcyclohexane. The reaction affords three different products (all C8H15Cl). Draw the three products (Ignore stereoisomers).
Conversion of Alkenes into Alkyl Halides
Conversion of Alcohols into Alkyl Halides Reactions with HX, SOCl2, PBr3
Conversion of Alcohol into a Leaving Group Form Tosylate (p-TsCl, pyridine) Use strong acid (H3O+) Convert to Alkyl Halide (HX, SOCl2, PBr3)
Alcohols to Alkyl Halides
What the **** is SN1? Unimolecular Nucleophilic Substitution
Lucas Test
Qualitative test for Alcohol Characterization
1o and 2o Alcohols: best to use SOCl2, PBr3, or P/I2
Thionyl chloride mechanism
How would you prepare the following RX from the appropriate alcohols?
7.25] Draw and name the monochlorination products of the reaction of 2-methylpentane with chlorine gas. Which are chiral? 7.36] How would you prepare the ff cpds, starting from cyclopentene and any other reagents needed? Chlorocyclopentene Cyclopentanol Cyclopentylmagnesium chloride cyclopentane
Reactions of Alkyl Halides Grignard Reagents
What’s special with Grignard reagents?
Outline a synthetic scheme from the appropriate alkyl halide
Reactions of Alkyl Halides Substitution and Elimination
Substitution, Nucleophilic, Bimolecular – SN2
Reaction Profile for SN2 Reaction (Wade)
Stereochemistry of SN2 Reaction Inversion of Configuration
Proof of Inversion of Configuration at a Chiral Center
Acetate Approaches from 180o Behind Leaving Group
Inversion on a Ring is often more Obvious: Cis Trans
Substrate Reactivity Since the energy of the transition state is significant in determining the rate of the reaction, a primary substrate will react more rapidly than secondary (which is much more rapid than tertiary).
1o > 2o >> 3o Bulkiness of Substrate
Polar, Aprotic Solvents favor SN2
Nucleophilicity
Iodide vs. Fluoride as Nucleophiles
Nucleophiles (preferably non-basic)
Good Leaving Groups are Weak Bases
Common Leaving Groups
SN2 and E2
Bimolecular Elimination - E2 Nucleophile acts as Bronsted Base
SN2 Competes with E2
SN2 Competes with E2
SN2 Competes with E2
Stereochemistry of E2
Anti-Coplanar Conformation
3(R),4(R) 3-Bromo-3,4-dimethylhexane
H and Br Anti-coplanar orientation
In a Cyclohexane, Leaving Group must be Axial
Zaitsev’s Rule
More Stable Alkene Predominates
Hyperconjugation p bond associates with adjacent C-H s bond
With Bulky Base, Hofmann Product Forms
Which will react more rapidly?
Reactive Conformations
E2 Reaction of (R,R) 2-iodo-3-methylpentane
Stereochemistry is Important
Unimolecular Substitution and Elimination – SN1 and E1
SN1 mechanism (Wade) 1st step is rate determining
Reaction Profiles (Wade) SN1 SN2
SN1 Transition State
SN1 Solvent Effects
Partial Racemization in SN1
Carbocation Stability more highly substituted, lower energy
Carbocation Stability
Carbocations can Rearrange 1,2-Hydride Shift
Hydride shift
E1 Mechanism
E1 and SN1 Compete
Dehydration of Alcohols – E1
Draw the Major Product & Predict the Mechanism
Which Reacts More Rapidly in E2 Reaction?
Cis Reacts more Rapidly
What is an E1CB reaction? Poor LG 2 carbons away from a carbonyl carbon (beta alcohol) Proceeds via a carbanion intermediate stabilized by resonance. Step 1: Abstraction of alpha proton Step 2: Ejection of leaving group.