Chapter 6 Flashcards
Alkyl halides
Halogen, X, is directly bonded to sp3 carbon
Vinyl halides
X is bonded to sp2 carbon of alkene
Aryl halides
X is bonded to sp2 carbon on phenyl ring
CH2X2
methylene halide
CHX3
haloform
CX4
carbon tetra halide
Geminal dihalide
two halogen atoms are bonded to the same carbon
Vicinal dihalide
two halogen atoms are bonded to adjacent carbons
Allylic Halogination
- Allylic radical is resonance stabilized
- Bromination occurs with good yield at the allylic position (sp3 C next to C=C)
SN2 Reaction
- Bimolecular nucleophilic substitution
- Concerted reaction: new bond forming and old bond
breaking at same time
- Rate is first order in each reactant
- Inversion at carbon
SN2 Energy Diagram
- The SN2 reaction is a one-step reaction
- Transition state is highest in energy
What does SN2 stand for?
SN2 stands for: substitution, nucleophilic, bimolecular
Bimolecular
TWO species are involved in rate determining step
SN2 Mechanism Favored When:
Substrate is PRIMARY and UNHINDERED
GOOD (strongly basic) Nucleophile
GOOD (weakly basic) Leaving Group
POLAR, APROTIC Solvent
Kinetics of SN2 Reaction
Second order reaction: Rate = k [:Nu] [substrate]
Suggests that C-Nu bond forms as C-X bond breaks
Requires backside attack of nucleophile
Trigonal bipyramidal transition state
SN2 and Stereochemistry
- Backside attack of nucleophile results in INVERSION of configuration
- The stereochemistry is always reversed, but the R/S does not always switch. Depends on the priority of the nucleophile and substituents on the stereocenter.
SN2 Orbital Inversion
Inversion of Configuration Required by Orbitals
Relative Reactivity of Halides via SN2
methyl > primary > secondary >> tertiary (doesn’t happen)
Steric Effects of the Substrate on SN2 Reactions
As substitution increases, steric crowding increases.
Approach of the nucleophile is increasingly hindered.
Nucleophilicity across a period
Nucleophilicity increases
across a period (R to L).
Nucleophilicity in groups
Nucleophilicity increases down a group.
Nucelophilicity in acids vs bases
Neg. charged species a stronger nucleophile than its conjugate acid.
Why? Ability to donate electrons.
What makes a good leaving group in SN2 reactions?
More stable anion = better leaving group
Leaving Groups
Good leaving groups: I -, Br -, sulfonates
Modest leaving group: Cl -
Poor leaving groups: F -, - OH, CH3CO2 -, PhO -
Are strong bases good leaving groups in SN2 reactions?
No, strong bases are poor leaving groups
The SN2 Mechanism – Solvent Effects
SN2 reactions favored (faster) in polar, aprotic solvents
SN2 reactions disfavored (slower) in protic solvents: water, alcohols, acetic acid
Solvent Effects: Protic Problems
Polar protic solvents have acidic hydrogens (O—H or N—H) which can solvate the nucleophile reducing their nucleophilicity.
Nucleophile strength and rate of the reaction
- Stronger nucleophile = faster reaction
Stability of leavin group and rate of the reaction
More stable leaving group = faster reaction
What are the steps in an SN1 reaction?
1) formation of carbocation by loss of leaving group
2) attack (substitution) of nucleophile
When is SN1 favorable?
Substrate is tertiary, allylic / benzylic or sterically hindered
PROTIC / MILDLY ACIDIC Solvent
Rate determining step in SN1
Formation of carbocation is the rate determining step
Racemization in SN1
The lobes of the empty p-orbital are on both sides of the trigonal plane
Nucleophile can attack the carbocation from either side – leads to racemization of optically active S.M.
Hydrogen Shift
Hydrogens adjacent to a 1° or 2° halide can shift over to form a more stable cation
Methyl Shift
Since a primary carbocation cannot form, the methyl group on the adjacent carbon can move (along with both bonding electrons) to the primary carbon displacing the bromide and forming a tertiary carbocation.
Relative Reactivity of Halides via SN1
tertiary > secondary > primary >> methyl
Do nucleophiles have an effect on the rate of SN1 reactions?
Carbocation formation is rate determining:
Thus, different nucleophiles do not change rate in SN1
Poor nucleophiles better to avoid side reactions
Leaving groups in SN1 reactions
Better leaving groups lead to faster carbocation formation
I - > Br - ~ - OTs > Cl –
Typically need good leaving groups for SN1
In what type of solvent do SN1 reactions work best?
SN1 reactions work best in POLAR PROTIC solvents:
H2O, CH3CO2H, CF3CH2OH, CH3OH, etc.
Elimination reactions
The halogen and one hydrogen are eliminated from the molecule resulting in a double bond
E1 Reaction
Unimolecular elimination
Two groups lost: a hydrogen and the leaving group
Nucleophile can act as a base
The E1 and SN1 reactions have similar conditions so a mixture of products often observed
Step 1 of E1 reaction
Step 1: Leaving group leaves, forming a carbocation
Step 2 of E1
Step 2: Base abstracts H+ from adjacent carbon forming the double bond
E1 and SN1 are competing reactions because their first steps both for a carbocation. What conditions favor elimination over substitution?
High temperature and weak/bulky bases will favor elimination over substitution.
In E1, which step is the rate-determining step?
The first step (just like SN1)
Zaitsev’s Rule
More substituted double bonds are more stable
In elimination reactions, the major product of the reaction is the more substituted double bond: Zaitsev’s Rule
The E2 reaction
Elimination, bimolecular
Requires a strong base
Concerted reaction: the proton is abstracted, the double bond forms and the leaving group leaves, all in one step
E1 Mechanism
•Order of reactivity for alkyl halides:
3° > 2 ° > 1°
Mixture may form, but Zaitsev product
predominates
E2 Stereochemistry
- The halide and the proton to be abstracted must be anti-coplanar (q=180º) to each other for the elimination to occur
- The orbitals of the hydrogen atom and the halide must be aligned so the s bond overlaps with s*
- The anti-coplanar arrangement minimizes any steric hindrance between the base and the leaving group
E2 Reactions on Cyclohexanes
- An anti-coplanar conformation (180°) can only be achieved when both the hydrogen and the halogen occupy trans diaxial positions.
- The chair must flip to the conformation with the axial halide in order for the elimination to take place.
How does the strength of the nucleophile determine order?
Strong nucleophiles or bases promote bimolecular reactions (E2 or Sn2)
What type of Alkyl halides usually undergo SN2?
1° alkyl halides usually undergo SN2
What type of reactions do tertiary alkyl halides usually undergo?
3° alkyl halides mixture of SN1, E1 or E2. They cannot undergo SN2
What type of reactions do secondary alkyl halides usually undergo?
2° alkyl halides: mix of substitution and elimination. Look at nucleophile / base strength
_____ temperature favors elimination
High temperature favors elimination
______ bases favor elimination
Bulky bases favor elimination
NaOC(CH3)3
Common polar, aprotic solvents
acetone, DMF, DMSO, acetonitrile, HMPA
