chapter 2 organic reaction types

8/11/2019 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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A. AdditionsTwo reactants add together to form a single product without

side products.


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B. EliminationSingle reactant splits into 2 products with side product

water or HBr


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C. SubstitutionTwo reactants exchange parts to give two new

products.


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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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chapter 2 organic reaction types

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