chapter 2 organic reaction types_2015
TRANSCRIPT
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
1/102
ORGANIC REACTION
TYPES
CHAPTER 2
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
2/102
Kinds of Organic Reactions
2
In general, we look at what occurs and try to learnhow it happens.
Common patterns describe the changes.
4 general types:A. Additions – two molecules combine
B. Eliminations – one molecule splits into two
C. Substitutions – parts from two molecules exchange
D. Rearrangements – a molecule undergoes changes in theway its atoms are connected
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
3/102
Kinds of Organic Reactions
3
A. AdditionTwo reactants add together to form a single productwithout side products.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
4/102
Kinds of Organic Reactions
4
B. EliminationSingle reactant splits into 2 products with side product – water or HBr.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
5/102
Kinds of Organic Reactions
5
Elimination is the opposite of addition .
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
6/102
Kinds of Organic Reactions
6
C. SubstitutionTwo reactants exchange parts to give two new products.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
7/102
Kinds of Organic Reactions
7
D. RearrangementSingle reactant rearranges the bond and atoms toyield an isomeric product.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
8/102
Exercises
8
Classify the following reactions as addition, elimination,substitution or rearrangement.
1)
2)
3)
4)
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
9/102
How Organic Reactions Occur: Mechanisms
9
In an organic reaction, we see the transformation that hasoccurred. The mechanism describes the steps behind thechanges that we can observe.
Reactions occur in defined steps that lead from reactant to
product. Reaction mechanism – describe in detail everything that
occurs during chemical reaction, which bonds are broken orformed, and in what order, the relative rates of steps
involved. All chemical reactions involve bond-breaking and bond-
making.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
10/102
Steps in Mechanisms
10
We classify the types of steps in a sequence.
A step involves either the formation or breaking of acovalent bond.
Steps can occur in individually or in combination with other
steps.
When several steps occur at the same time they are said tobe concerted.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
11/102
Types of Steps in Reaction Mechanisms
Symmetrical- homolytic Unsymmetrical- heterolytic
11
Bond breaking (radical) – 1
bonding electron stays witheach product
Bond-making (radical) – 1bonding electron is donatedby each reactant
Bond-breaking (polar) – 2
bonding electrons stays with1 product.
Bond-making (polar) – 2
bonding electrons aredonated by 1 reactant
Bond formation or breakage can be symmetrical orunsymetrical.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
12/102
Indicating Steps in Mechanisms
12
Curved arrows indicate breakingand forming of bonds.
Arrowheads with a “half” head(“fish-hook”) indicate homolyticand homogenic steps (called„radical processes‟) .
Arrowheads with a completehead indicate heterolytic and
heterogenic steps (called „polarprocesses‟)
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
13/102
13
Bond breaking forms particles called reaction
intermediates.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
14/102
Common Reaction Intermediates
Formed by Breaking a Covalent Bond
14
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
15/102
Radical Reactions
15
Not as common as polar reactions.
Radicals react to complete electron octet of valence shell.
A radical can break a bond in another molecule and abstract a
partner with an electron, giving substitution in the original
molecule.
A radical can add to an alkene to give a new radical, causing an
addition reaction .
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
16/102
Steps in Radical Substitution
16
Three types of steps: Initiation
- Radicals are formed.
- Light supplies the energy to split a molecule.
Propagation
- A radical reacts with molecule to generate another radical.
- Free radical species are constantly generated throughout
the reaction.
Termination
- Combination of any two radicals to form stable product.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
17/102
Steps in Radical Substitution
17
Example: Initiation
formation of Cl radicals form Cl2 and light
Propagation
reaction of chlorine radical with methane to give HCl and •CH3
methyl radical reacts with Cl2 to generate the product and Cl•
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
18/102
Steps in Radical Substitution
18
Termination reaction of any two radicals
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
19/102
Polar Reactions
19
Involve species with electron pairs in their orbitals.
More common reaction in organic chemistry.
Occur because of the electrical attraction between positive
and negative centers – most organic compounds areelectrically neutral, bonds in functional group are polar.
Molecules can contain local unsymmetrical electrondistributions due to differences in electronegativities.
This causes a partial negative charge on an atom and acompensating partial positive charge on an adjacent atom.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
20/102
20
The more electronegative atom has the greater electrondensity such as O, F, N, Cl more electronegative than carbon
carbon atom has partial positive charge (δ+).
Metal with lesser electronegativity carbon atom has partialnegative charge (δ-).
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
21/102
21
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
22/102
22
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
23/102
Polarizability
23
Polarization is a change in electron distribution as aresponse to change in electronic nature of the surroundings.
Polarizability is the tendency to undergo polarization.
Polar reactions occur between regions of high electron densityand regions of low electron density.
In the halogen family, for example, polarizability increases inthe order F < Cl < Br < I. F atom is the lowest because their electrons are very tightly held;
they are close to the nucleus.
I atom is the highest since their valence electrons are far fromnucleus.
Atoms with unshared pairs are generally more polarizable thanthose with only bonding pairs.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
24/102
Generalized Polar Reactions
24
Nucleophile: nucleus loving
Negatively polarized
Electron-rich species
Donate pair of electrons toelectron poor atom
Neutral or negatively charged
Example: NH4+ , H2O, OH
, Cl
Electrophile: electron loving
Positively polarized
Electron-poor species
Accepting a pair of electronsfrom electron rich atom
Neutral or positively charged
Example: acids, alkyl halides,carbonyl compounds
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
25/102
Generalized Polar Reactions
25
In general, electrons flow from nucleophile to electrophiles.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
26/102
26
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
27/102
27
Exercises
Answers:
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
28/102
An Example of a Polar Reaction: Addition
of HBr to Ethylene
28
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.
M h i f Addi i f HB
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
29/102
Mechanism of Addition of HBr to
Ethylene
29
HBr electrophile is attacked by electrons of ethylene
(nucleophile) to form a carbocation intermediate and bromide ion. Bromide adds to the positive center of the carbocation, which is
an electrophile, forming a C-Br bond.
The result is that ethylene and HBr combine to form
bromoethane. All polar reactions occur by combination of an electron-rich site
of a nucleophile and an electron-deficient site of an electrophile.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
30/102
30
U i C d A i P l R ti
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
31/102
Using Curved Arrows in Polar Reaction
Mechanisms
31
Curved arrows are a way to keep track of changes in bondingin 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 reactionmechanism.
The arrow goes from the nucleophilic reaction site to theelectrophilic reaction site.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
32/102
Rules for Using Curved Arrows
32
The nucleophilic site can be neutral or negatively charged.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
33/102
Rules for Using Curved Arrows
33
The electrophilic site can be neutral or positively charged
The octet rule must be followed
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
34/102
Organic Reaction Types:Nucleophilic Substitutions and Eliminations
Alk l H lid R t ith N l hil
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
35/102
Alkyl Halides React with Nucleophiles
and Bases
35
Alkyl halides are polarized at the carbon-halide bond, makingthe carbon electrophilic.
Nucleophiles will replace the halide in C-X bonds of manyalkyl halides(reaction as Lewis base).
Nucleophiles that are Brønsted bases produce elimination.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
36/102
Why this Chapter?
36
Nucleophilic substitution, base induced elimination areamong most widely occurring and versatile reaction typesin 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
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
37/102
The Discovery of Nucleophilic
Substitution Reactions
37
In 1896, Walden showed that (-)-malic acid could beconverted to (+)-malic acid by a series of chemical steps withachiral reagents.
This established that optical rotation was directly related to
chirality and that it changes with chemical alteration. Reaction of (-)-malic acid with PCl5 gives (+)-chlorosuccinic acid
Further reaction with wet silver oxide gives (+)-malic acid
The reaction series starting with (+) malic acid gives (-) acid
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
38/102
Reactions of the Walden Inversion
38
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
39/102
Significance of the Walden Inversion
39
The reactions alter the array at the chirality center.
The reactions involve substitution at that center.
Therefore, nucleophilic substitution can invert the configuration
at a chirality center. The presence of carboxyl groups in malic acid led to some
dispute as to the nature of the reactions in Walden‟s cycle.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
40/102
Nucleophilic Substitution Reactions
40
In this type of reaction, a nucleophile, a species with an
unshared electron pair , reacts with an alkyl halide byreplacing the halogen substituent.
A substitution reaction takes places and the halogensubstituent, called the leaving group, departs as a halide ion.
Because the substitution reaction is initiated by a nucleophile,it is called a nucleophilic substitution reaction.
Example:
Nucleophile Alkyl halide(substrate)
Product Halide ion
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
41/102
Mechanisms of Nucleophilic Substitution
41
In a nucleophilic substitution:
But what is the order of bond making and bond breaking?
In theory, there are three possibilities. Bond making and bond breaking occur at the same time
Bond breaking occurs before bond making
Bond making occurs before bond breaking
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
42/102
Mechanisms of Nucleophilic Substitution
42
Bond Making and Bond Breaking Occur at The Same Time
In this scenario, the mechanism is comprised of one step.
In such a bimolecular reaction, the rate depends upon the
concentration of both reactants. The rate equation is second order.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
43/102
43
Mechanisms of Nucleophilic Substitution
Bond Breaking Occurs Before Bond Making
In this scenario, the mechanism has two steps and acarbocation is formed as an intermediate.
Because the first step is rate-determining, the rate depends onthe concentration of RX only.
The rate equation is first order.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
44/102
44
Mechanisms of Nucleophilic Substitution
Bond Making Occurs Before Bond Breaking
This mechanism has an inherent problem.
The intermediate generated in the first step has 10 electronsaround carbon, violating the octet rule. Because two other mechanistic possibilities do not violate a
fundamental rule, this last possibility can be disregarded.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
45/102
Kinetics of Nucleophilic Substitution
45
The study of rates of reactions is called kinetics.
Rate (V) is change in concentration with time.
Rates decrease as concentrations decrease but the rateconstant does not.
Rate units: [concentration]/time such as molL-1/s.
The rate law is a result of the mechanism. A rate law describes relationship between the
concentration of reactants and conversion to products. A rate constant (k) is the proportionality factor between
concentration and rate.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
46/102
The SN2 Reaction
46
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)
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
47/102
SN2 Process
47
The reaction involves a transition state in which both reactantsare together.
Single step without intermediates when nucleophile react withalkyl halide or tosylate (substrate) from the opposite directionof the leaving group.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
48/102
SN2 Transition State
48
The transition state of an SN2 reaction has a planararrangement of the carbon atom and the remaining threegroups.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
49/102
49
Stereochemistry of The SN2 Reaction
All SN
2 reactions proceed with backside attack of the nucleophile,
resulting in inversion of configuration at a stereogenic center.
Reactant and Transition State Energy
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
50/102
Reactant and Transition State Energy
Levels Affect Rate
50
Higher reactant energy
level (red curve) = faster
reaction (smaller G‡).
Higher transition state
energy level (red curve) =
slower reaction (larger G‡).
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
51/102
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
52/102
52
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)
Characteristics of SN2 Reaction
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
53/102
Steric Effects on SN2 Reactions
53
The carbon atom in (a) bromomethane is readily accessible
resulting 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.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
54/102
54
The higher the Ea, the slower the reaction rate. Thus, any factor that
increases Ea decreases the reaction rate.
Two Energy Diagrams Depicting The Effect of Steric Hindrance in SN2 Reactions
Steric Effects on SN2 Reactions
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
55/102
Order of Reactivity in SN2
55
The more alkyl groups connected to the reacting carbon, the
slower the reaction.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
56/102
Order of Reactivity in SN2
56
Methyl and 1° alkyl halides undergo SN2 reactions with ease.
2° Alkyl halides react more slowly.
3° Alkyl halides do not undergo SN2 reactions. This order of reactivity can be explained by steric effects. Steric
hindrance caused by bulky R groups makes nucleophilic attack from
the backside more difficult, slowing the reaction rate.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
57/102
The Nucleophile
57
Neutral or negatively charged species.
Reaction increases coordination at nucleophile.
Neutral nucleophile acquires positive charge.
Anionic nucleophile becomes neutral.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
58/102
Relative Reactivity of Nucleophiles
58
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.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
59/102
The Leaving Group
59
A good leaving group reduces the barrier to a reaction.
Stable anions that are weak bases are usually excellent leavinggroups and can delocalize charge.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
60/102
Poor Leaving Groups
60
If a group is very basic or very small, it is prevents reaction.
Alkyl fluorides, alcohols, ethers, and amines do not typically undergoSN2 reactions.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
61/102
The Solvent
61
Solvents that can donate hydrogen bonds (-OH or – NH) 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 interactionswith substrate and permit faster reaction.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
62/102
The SN1 Reaction
62
Tertiary alkyl halides react rapidly in protic solvents by a mechanism
that involves departure of the leaving group prior to addition of thenucleophile.
Called an SN1 reaction – occurs in two distinct steps while SN2occurs with both events in same step.
If nucleophile is present in reasonable concentration (or it is the
solvent), then ionization is the slowest step.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
63/102
Rate-Limiting Step
63
The overall rate of a
reaction is controlledby the rate of theslowest step.
The rate depends onthe concentration of
the species and therate constant of thestep.
The highest energytransition state pointon the diagram is thatfor the ratedetermining step(which is not alwaysthe highest barrier).
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
64/102
SN1 Energy Diagram
64
Rate-determining/ rate-limiting step is formation of
carbocation.
First order process
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
65/102
Stereochemistry of SN1 Reaction
65
The planar intermediate leads to loss of chirality.
A free carbocation is achiral.
Product is racemic or has some inversion.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
66/102
SN1 in Reality
66
Carbocation is biased to react on side opposite leaving group.
Suggests reaction occurs with carbocation loosely associatedwith leaving group during nucleophilic addition.
Alternative that SN2 is also occurring is unlikely.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
67/102
Effects of Ion Pair Formation
67
If leaving group remains associated, then product has more
inversion than retention.
Product is only partially racemic with more inversion thanretention.
Associated carbocation and leaving group is an ion pair.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
68/102
Characteristics of the SN1 Reaction
68
Substrate
Tertiary alkyl halide is most reactive by this mechanism. Controlled by stability of carbocation.
Hammond postulate, "Any factor that stabilizes a high-energy intermediate stabilizes transition state leading to that
intermediate”.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
69/102
Allylic and Benzylic Halides
69
Allylic and benzylic intermediates stabilized by delocalization of
charge.
Primary allylic and benzylic are also more reactive in theSN2 mechanism.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
70/102
Effect of Leaving Group on SN1
70
Critically dependent on leaving group.
Reactivity: the larger halides ions are better leaving groups. In acid, OH of an alcohol is protonated and leaving group is
H2O, which is still less reactive than halide.
p-Toluensulfonate (TosO-) is excellent leaving group.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
71/102
Nucleophiles in SN1
71
Since nucleophilic addition occurs after formation of
carbocation, reaction rate is not normally affected bynature or concentration of nucleophile.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
72/102
Solvent in SN1
72
Stabilizing carbocationalso stabilizes associatedtransition state andcontrols rate.
Solvent effects in the SN1reaction are due largelyto stabilization ordestabilization of thetransition state.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
73/102
Polar Solvents Promote Ionization
73
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
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
74/102
74
Exercises
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
75/102
Biological Substitution Reactions
75
SN1 and SN2 reactions are well known in biological chemistry.
Unlike what happens in the laboratory, substrate in biologicalsubstitutions is often organodiphosphate rather than an alkylhalide.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
76/102
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
77/102
77
Factors in Predicting SN1 vs SN2 Mechanisms
Four factors are relevant in predicting whether a given reaction is
likely to proceed by an SN1 or an SN2 mechanism.
3o > 2oNucleophilicstrength notimportant
Good LGimportant to
form C+
Enhanced bymore polar
solvent
CH3 > 1o
> 2o Needs a strong
nucleophile
Not as important
but enhancesreaction
Enhanced by
less polarsolvent
SN1
SN2
Substrate Nucleophile Leaving Group Solvent
Predicting SN1 vs SN2 Mechanisms:
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
78/102
78
N N
The Substrate
The most important is the structure of the alkyl halide (substrate).
Predicting SN1 vs SN2 Mechanisms:
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
79/102
79
N N
The Nucleophile
The strong nucleophile favors an SN2 mechanism.
The weak nucleophile favors an SN1 mechanism.
Predicting SN1 vs SN2 Mechanisms:
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
80/102
80
The Leaving Group
A better leaving group increases the rate of both SN1 and SN2
reactions.
Predicting SN1 vs SN2 Mechanisms:
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
81/102
81
The Solvent
The nature of the solvent is the fourth factor.
Polar protic solvents like H2O and ROH favor SN1
reactions because the ionic intermediates (both
cations and anions) are stabilized by solvation.
Polar aprotic solvents favor SN2 reactions because
nucleophiles are not well solvated, and therefore, are
more nucleophilic.
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
82/102
82
Results of SN1 vs SN2 Mechanisms
Kinetics:SN1 rate = k[RX]
SN2 rate = k[RX][Nu:]
Stereochemistry:SN1 both inversion and retention (racemic)
SN2 inversion only
Rearrangements:SN1 rearrangements common
SN2 rearrangements not possible
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
83/102
83
Exercises
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
84/102
84
Exercises
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
85/102
85
Exercise
Eli i ti R ti f Alk l H lid
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
86/102
Elimination Reactions of Alkyl Halides
86
A widely used method for synthesizing alkenes is the elimination of HX
from adjacent atoms of an alkyl halide. When the elements of a hydrogen halide are eliminated from a haloalkane
in this way, the reaction is often called dehydrohalogenation:
A hydrogen atom attached to the carbon atom is called a hydrogen atom.
Since the hydrogen atom that is eliminated in dehydrohalogenation isfrom the b carbon atom, these reactions are often called
eliminations.
Eli i ti R ti f Alk l H lid
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
87/102
87
Elimination Reactions of Alkyl Halides
There are two idealized mechanisms for -eliminationreactions, E1 and E2.
E1 mechanism: at one extreme, breaking of the R-Lv
bond to give a carbocation is complete before
reaction with base to break the C-H bond. only R-Lv is involved in the rate-determining step (as in SN1)
E2 mechanism: at the other extreme, breaking of the
R-Lv and C-H bonds is concerted (same time).
both R-Lv and base are involved in the rate-determining step(as in SN2)
Mechanisms of Elimination Reactions:
E1 d E2
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
88/102
88
E1 Reaction (Unimolecular Elimination)
X- leaves first to generate a carbocation
E2 Reaction (Bimolecular Elimination)
Concerted transfer of a proton to a base and departure of leaving group
E1 and E2
E2 R ti M h i
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
89/102
89
E2 = Elimination, Bimolecular (2nd order). Rate = k [RX] [Nu:-]
E2 reactions occur when a 2° or 3° alkyl halide is treated with astrong base such as OH-, OR-, NH2
-, H-, etc.
E2 Reaction Mechanisms
Elimination Reactions of Alkyl Halides:
Z it ’ R l
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
90/102
Zaitsev’s Rule
90
Elimination is an alternative pathway to substitution.
Opposite of addition.
Generates an alkene.
Can compete with substitution and decrease yield, especiallyfor SN1 processes.
Z it ’ R l f Eli i ti R ti
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
91/102
Zaitsev’s Rule for Elimination Reactions
91
In the elimination of HX from an alkyl halide, the more highly
substituted alkene product predominates.
The E2 Reaction and the Deuterium
I t Eff t
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
92/102
Isotope Effect
92
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.
G t f Eli i ti E2
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
93/102
Geometry of Elimination – E2
93
Antiperiplanar allows orbital overlap and minimizes steric
interactions.
E2 Stereochemistry
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
94/102
E2 Stereochemistry
94
Overlap of the developing orbital in the transition state
requires periplanar geometry, anti arrangement.
Predicting Product
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
95/102
Predicting Product
95
E2 is stereospecific.
Meso-1,2-dibromo-1,2-diphenylethane with base gives cis 1,2-diphenyl. RR or SS 1,2-dibromo-1,2-diphenylethane gives trans 1,2-diphenyl.
The E2 Reaction and CyclohexaneFormation
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
96/102
Formation
96
Abstracted proton and leaving group should align trans-diaxial
to be anti periplanar (app) in approaching transition state. Equatorial groups are not in proper alignment.
E1 Reaction Mechanisms
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
97/102
97
Just as SN2 reactions are analogous to E2 reactions, so SN1 reactions
have an analog, E1 reaction. E1 = Elimination, unimolecular (1st order); Rate = k [RX]
E1 Reaction Mechanisms
Slow step Fast step
E1 Reaction Mechanisms
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
98/102
98
E1 eliminations, like SN1 substitutions, begin with unimolecular
dissociation, but the dissociation is followed by loss of a protonfrom the -carbon (attached to the C+) rather than by substitution.
E1 & SN1 normally occur in competition, whenever an alkyl halide istreated in a protic solvent with a nonbasic, poor nucleophile.
As with E2 reactions, E1 reactions also produce the more highly
substituted alkene (Zaitsev‟s rule). However, unlike E2 reactionswhere no C+ is produced, C+ rearrangements can occur in E1reactions.
Example:
E1 Reaction Mechanisms
Comparing E1 and E2
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
99/102
Comparing E1 and E2
99
Strong base is needed for E2 but not for E1.
E2 is stereospecifc, E1 is not.
E1 gives Zaitsev orientation.
A Comparison of E1 and E2
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
100/102
100
CH3
CH3CH3
Br H
H
H
H
H
Zaitsev
Anti-ZaitsevNaOEt
EtOH /
E2
stereospecific
anti
not
stereospecific
E1EtOH /
ant i
syn
major product
E1 doesn’t require
anti-coplanarity
A Comparison of E1 and E2
Correlation of Structure & Reactivity for
S 1 S 2 E1 E2
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
101/102
101
SN1, SN2, E1, E2
Halide
Type SN1 SN2 E1 E2
RCH2X
(primary)
Does not
occur
Highly
favored
Does not
occur
Occurs when
strong bases
are used
R2CHX
(secondary)
Can occur
with benzylic
and allylic
halides
Occurs in
competition
with E2
reaction
Can occur
with benzylic
and allylic
halides
Favored when
strong bases
are used
R3CX
(tertiary)
Favored in
hydroxylic
solvents
Does not
occur
Occurs incompetition
with SN2
reaction
Favored when
bases are
used
Mechanism Review:
Substitution vs Elimination
-
8/18/2019 Chapter 2 Organic Reaction Types_2015
102/102
Substitution vs Elimination