Chapter 2 Organic Reaction Types
Transcript of Chapter 2 Organic Reaction Types
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ORGANIC REACTION
TYPESCHAPTER 2
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Kinds of Organic Reactions
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4 general types:A. Additions
B. Eliminations
C. Substitutions
D. Rearrangements
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Kinds of Organic Reactions
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A. AdditionsTwo reactants add together to form a single product without
side products.
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Kinds of Organic Reactions
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B. EliminationSingle reactant splits into 2 products with side product
water or HBr
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Kinds of Organic Reactions
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C. SubstitutionTwo reactants exchange parts to give two new
products.
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Kinds of Organic Reactions
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D. Rearrangementsingle reactant rearranges the bond and atoms to
yield an isomeric product.
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How Organic Reactions Occur: Mechanisms
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Reaction mechanismdescribe in detail everything thatoccurs during chemical reaction, which bonds are broken
or formed, and in what order, the relative rates of steps
involved.
All chemical reactions involve bond-breaking and bond-
making.
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Steps in Mechanisms
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We classify the types of steps in a sequence A step involves either the formation or breaking of a
covalent bond
Steps can occur in individually or in combination with
other steps When several steps occur at the same time they are said
to be concerted
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Types of Steps in Reaction Mechanisms
Symmetrical- homolytic Unsymmetrical- heterolytic
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Bond breaking (radical)
1 bonding electron
stays with each product
Bond-making (radical)
1 bonding electron is
donated by each
reactant
Bond-breaking (polar)
2 bonding electrons
stays with 1 product.
Bond-making (polar)2
bonding electrons are
donated by 1 reactant
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Indicating Steps in Mechanisms
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Curved arrows indicate breaking andforming of bonds
Arrowheads with a half head (fish-
hook) indicate homolytic and
homogenic steps (called radical
processes)
Arrowheads with a complete head
indicate heterolytic and heterogenic
steps (called polar processes)
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Radical Reactions
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Not as common as polarreactions
Radicalsreact to complete
electron octet of valence shell
A radical can break a bond inanother molecule and
abstract a partner with an
electron, giving substitution in
the original molecule
A radical can addto an
alkene to give a new radical,
causing an addition reaction
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Steps in Radical Substitution
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Three types of steps
Initiationhomolytic formation of two reactive species withunpaired electrons
Exampleformation of Cl atoms form Cl2and light
Propagationreaction with molecule to generate radical
Example - reaction of chlorine atom with methane to giveHCl and CH3
.
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Steps in Radical Substitution
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Terminationcombination of two radicals to form a stableproduct: CH3
.+ CH3.CH3CH3
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Polar Reactions
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Involve species with electron pairs in their orbitals.
More common reaction in organic chemistry.
Occur because of the electrical attraction between positive and
negative centersmost organic compounds are electrically neutral,
bonds in functional group are polar.
This causes a partial negative charge on an atom and acompensating partial positive charge on an adjacent atom
The more electronegative atom has the greater electron density such
as O, F, N, Cl more electronegative than carboncarbon atom has
partial positive charge (+)
Metal with lesser electronegativitycarbon atom has partialnegative charge (-)
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Polarizability
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Polarizationis a change in electron distribution as a
response to change in electronic nature of the
surroundings
Polarizability is the tendency to undergo polarization
Polar reactions occur between regions of high electrondensity and regions of low electron density
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Generalized Polar Reactions
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Nucleophile: nucleus
loving
Negatively polarised
Electron-rich atom
Donate pair of electrons to
electron poor atom
Neutral or negatively
charged
Example: NH4+ , H2O, OH
-,
Cl-
Electrophile: electron-
loving
Positively polarised
Electron-poor atom
Accepting a pair of
electrons from electron richatom
Neutral or positively
charged
Example: acids, alkylhalides, carbonyl
compounds
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An Example of a Polar Reaction: Addition of
HBr to Ethylene
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HBr adds to the part of C-C double bond
The bond is electron-rich, allowing it to function as a
nucleophile
H-Br is electron deficient at the H since Br is much more
electronegative, making HBr an electrophile
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Mechanism of Addition of HBr to Ethylene
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HBr electrophile is attacked
by electrons of ethylene(nucleophile) to form acarbocation intermediate andbromide ion
Bromide adds to the positivecenter of the carbocation,
which is an electrophile,forming a C-Br bond
The result is that ethylene andHBr combine to formbromoethane
All polar reactions occur by
combination of an electron-rich site of a nucleophile andan electron-deficient site of anelectrophile
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Using Curved Arrows in Polar Reaction
Mechanisms
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Curved arrows are a way to keep track of changes in
bonding in polar reaction
The arrows track electron movement
Electrons always move in pairs
Charges change during the reaction One curved arrow corresponds to one step in a reaction
mechanism
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Rules for Using Curved Arrows
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The arrow goes from the nucleophilic reaction site to theelectrophilic reaction site
The nucleophilic site can be neutral or negativelycharged
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The electrophilic site can be neutral or positivelycharged
The octet rule must be followed
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Organic reaction types:Nucleophilic Substitutions and Eliminations
Alk l H lid R t ith N l hil d
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Alkyl Halides React with Nucleophiles and
Bases
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Alkyl halides are polarized at the carbon-halide bond,
making the carbon electrophilic
Nucleophiles will replace the halide in C-X bonds of many
alkyl halides(reaction as Lewis base)
Nucleophiles that are Brnsted bases produce
elimination
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Why this Chapter?
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Nucleophilic substitution, base induced eliminationare among most widely occurring and versatile
reaction types in organic chemistry
Reactions will be examined closely to see:
- How they occur- What their characteristics are
- How they can be used
Th Di f N l hili
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The Discovery of Nucleophilic
Substitution Reactions
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In 1896, Walden showed that (-)-malic acid could beconverted to (+)-malic acid by a series of chemical stepswith achiral reagents
This established that optical rotation was directly relatedto chirality and that it changes with chemical alteration
Reaction of (-)-malic acid with PCl5gives (+)-chlorosuccinicacid
Further reaction with wet silver oxide gives (+)-malic acid
The reaction series starting with (+) malic acid gives (-) acid
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Reactions of the Walden Inversion
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Significance of the Walden Inversion
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The reactions alter the array at the chirality center
The reactions involve substitution at that center
Therefore, nucleophilic substitution can invert theconfiguration at a chirality center
The presence of carboxyl groups in malic acid led to
some dispute as to the nature of the reactions inWaldens cycle
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The SN2 Reaction
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Reaction is with inversion at reacting center
Follows second order reaction kinetics
Ingold nomenclature to describe characteristic step:
S=substitution
N (subscript) = nucleophilic 2 = both nucleophile and substrate in characteristic
step (bimolecular)
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Kinetics of Nucleophilic Substitution
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Rate(V) is change in concentration with time
Depends on concentration(s), temperature, inherentnature of reaction (barrier on energy surface)
Arate lawdescribes relationship between theconcentration of reactants and conversion to products
A rate constant (k) is the proportionality factor betweenconcentration and rate
Second order
process
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Reaction Kinetics
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The study of rates of reactions is called kinetics
Rates decrease as concentrations decrease but the rateconstant does not
Rate units: [concentration]/time such as L/(mol x s)
The rate lawis a result of the mechanism
The order of a reaction is sum of the exponents of theconcentrations in the rate lawthe example is secondorder
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SN2 Process
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The reaction involves a transition state in which both
reactants are together
Single step without intermediates when nucleophile react
with alkyl halide or tosylate (substrate) from the opposite
direction of the leaving group.
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SN2 Transition State
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The transition state of an SN
2 reaction has a planar
arrangement of the carbon atom and the remaining three
groups
R t t d T iti St t E L l
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Reactant and Transition State Energy Levels
Affect Rate
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Higher reactant energy
level (red curve) = faster
reaction (smaller G).
Higher transition stateenergy level (red curve) =
slower reaction (larger G).
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Characteristics of the SN2Reaction
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Sensitive to steric effects
Methyl halides are most reactive
Primary are next most reactive
Secondary might react
Tertiary are unreactive by this path
No reaction at C=C (vinyl halides)
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Steric Effects on SN2 Reactions
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The carbon atom in (a) bromomethane is readily accessibleresulting in a fast SN2 reaction. The carbon atoms in (b) bromoethane
(primary), (c) 2-bromopropane (secondary), and (d) 2-bromo-2-
methylpropane (tertiary) are successively more hindered, resulting in
successively slower SN2 reactions.
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Order of Reactivity in SN2
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The more alkyl groups connected to the reacting carbon,
the slower the reaction
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The Nucleophile
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Neutral or negatively charged species
Reaction increases coordination at nucleophile
Neutral nucleophile acquires positive charge
Anionic nucleophile becomes neutral
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Relative Reactivity of Nucleophiles
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Depends on reaction and
conditions
More basic nucleophiles
react faster
Better nucleophiles are
lower in a column of the
periodic table
Anions are usually more
reactive than neutrals
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The Leaving Group
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A good leaving group reduces the barrier to a reaction
Stable anions that are weak bases are usually excellent
leaving groups and can delocalize charge
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Poor Leaving Groups
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If a group is very basic or very small, it prevents reaction
Alkyl fluorides, alcohols, ethers, and amines do nottypically undergo SN2 reactions.
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The Solvent
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Solvents that can donate hydrogen bonds (-OH orNH)
slow SN2 reactions by associating with reactants Energy is required to break interactions between reactant
and solvent
Polar aprotic solvents (no NH, OH, SH) form weaker
interactions with substrate and permit faster reaction
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The SN1 Reaction
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Tertiary alkyl halides react rapidly in protic solvents by a
mechanism that involves departure of the leaving groupprior to addition of the nucleophile
Called an SN1 reactionoccurs in two distinct stepswhile SN2 occurs with both events in same step
If nucleophile is present in reasonable concentration (or itis the solvent), then ionization is the slowest step
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Rate-Limiting Step
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The overall rate of a
reaction is controlled bythe rate of the sloweststep
The rate depends on the
concentration of thespecies and the rateconstant of the step
The highest energytransition state point on
the diagram is that for therate determining step(which is not always thehighest barrier)
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SN1 Energy Diagram
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Rate-determining/ rate-limiting step is formation of
carbocation
First order
process
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Stereochemistry of SN1 Reaction
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The planar intermediate leads to loss of chirality
A free carbocation is achiral
Product is racemic or has some inversion
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SN1 in Reality
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Carbocation is biased to react on side opposite leaving
group Suggests reaction occurs with carbocation loosely
associated with leaving group during nucleophilicaddition
Alternative that SN2 is also occurring is unlikely
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Effects of Ion Pair Formation
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If leaving group remains associated, then product has
more inversion than retention
Product is only partially racemic with more inversion than
retention
Associated carbocation and leaving group is an ion pair
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Characteristics of the SN1Reaction
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Substrate
Tertiary alkyl halide is most reactive by thismechanism
Controlled by stability of carbocation
Hammond postulate, "Any factor that stabilizesa high-energy intermediate stabilizes transitionstate leading to that intermediate
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Allylic and Benzylic Halides
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Allylic and benzylic intermediates stabilized by
delocalization of charge
Primary allylic and benzylic are also more reactive in
the SN2mechanism
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Effect of Leaving Group on SN1
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Critically dependent on leaving group
Reactivity: the larger halides ions are better leavinggroups
In acid, OH of an alcohol is protonated and leaving groupis H2O, which is still less reactive than halide
p-Toluensulfonate (TosO-) is excellent leaving group
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Nucleophiles in SN1
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Since nucleophilic addition occurs afterformation of
carbocation, reaction rate is not normally affected by
nature or concentration of nucleophile
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Solvent in SN1
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Stabilizing carbocation
also stabilizes associatedtransition state andcontrols rate
Solvent effects in the SN1reaction are due largely tostabilization ordestabilization of thetransition state
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Polar Solvents Promote Ionization
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Polar, protic and unreactive Lewis base solvents facilitate
formation of R+ Solvent polarity is measured as dielectric polarization
(P) Nonpolar solvents have low P Polar solvents have high P values
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Biological Substitution Reactions
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SN1 and SN2 reactions are well known in biological
chemistry
Unlike what happens in the laboratory, substrate in
biological substitutions is often organodiphosphate
rather than an alkyl halide
Elimination Reactions of Alkyl Halides: Zaitsevs
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Elimination Reactions of Alkyl Halides: Zaitsev s
Rule
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Elimination is an alternative pathway to substitution
Opposite of addition
Generates an alkene
Can compete with substitution and decrease yield,
especially for SN1 processes
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Zaitsevs Rule for Elimination Reactions
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In the elimination of HX from an alkyl halide, the more
highly substituted alkene product predominates
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Mechanisms of Elimination Reactions
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E1: X-leaves first to
generate a carbocation
a base abstracts a
proton from the
carbocation
E2: Concerted transfer
of a proton to a base
and departure of
leaving group
The E2 Reaction and the Deuterium Isotope
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The E2 Reaction and the Deuterium Isotope
Effect
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A proton is transferred to base as leaving group begins to
depart
Transition state combines leaving of X and transfer of H
Product alkene forms stereospecifically
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Geometry of EliminationE2
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Antiperiplanar allows orbital overlap and minimizes steric
interactions
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Predicting Product
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E2 is stereospecific
Meso-1,2-dibromo-1,2-diphenylethane with base givescis 1,2-diphenyl
RR or SS 1,2-dibromo-1,2-diphenylethane gives trans1,2-diphenyl
The E2 Reaction and Cyclohexane
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y
Formation
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Abstracted proton and leaving group should align
trans-diaxial to be anti periplanar (app) inapproaching transition state
Equatorial groups are not in proper alignment
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The E1and SN1Reactions
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Competes with SN1 and E1 at 3 centers
V = k [RX], same as SN1
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Comparing E1 and E2
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Strong base is needed for E2 but not for E1
E2 is stereospecifc, E1 is not
E1 gives Zaitsev orientation
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E1cB Reaction
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Takes place through a carbanion intermediate
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Biological Elimination Reactions
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All three elimination reactions occur in biological
pathways
E1cB very common
Typical example occurs during biosynthesis of fats
when 3-hydroxybutyryl thioester is dehydrated tocorresponding thioester
Summary of Reactivity: SN1, SN2,
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E1,E1cB, E2
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Alkyl halides undergo different reactions in
competition, depending on the reacting moleculeand the conditions
Based on patterns, we can predict likelyoutcomes
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