Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A6_7_react.pdf · 1 w3.ualg.pt\~abrigas...

$: Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A6_7_react.pdf · 1 w3.ualg.pt\~abrigas QOI 0809 A6 1 Química Orgânica I 2008/09 w3.ualg.pt\~abrigas QOI 0809 A6 2 Organic$
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w3.ualg.pt\~abrigas QOI 0809 A6 1

Química Orgânica I

2008/09


Organic Reactions

• Addition – two molecules combine

• Elimination – one molecule splits

• Substitution – parts from two molecules exchange

• Rearrangement reactions – a molecule undergoes changes in the way its atoms are connected

2


An Addition Reaction


An Elimination Reaction

3


A Substitution Reaction


A Rearrangement Reaction

4


Reactions Mechanisms

• The mechanism

describes the steps

behind the changes that

we can observe

• Reactions occur in defined steps that lead from reactant to product


5


Steps in Mechanisms

• A step usually involves either the

formation or breaking of a covalent

bond

• Steps can occur individually or in

combination with other steps

• When several steps occur at the same

time they are said to be concerted


Types of Steps in Reaction Mechanisms

• Formation of a covalent bond

– Homogenic or heterogenic

• Breaking of a covalent bond

– Homolytic or heterolytic

• Oxidation

• Reduction

6


Homogenic Formation of a Bond

• One electron comes from each

fragment

• No electronic charges are involved


Heterogenic Formation of a Bond

• One fragment supplies two electrons (Lewis Base)

• One fragment supplies no electrons (Lewis Acid)

• Combination can involve electronic charges

• Common in organic chemistry

7


Indicating Steps in Mechanisms

• Curved arrows indicate breaking and forming of bonds

• Arrowheads with a “half” head (“fish-hook”) indicate homolyticand homogenic steps (called ‘radical processes’)—the motion of one electron

• Arrowheads with a complete head indicate heterolytic and heterogenic steps (called ‘polar processes’)—the motion of an electron pair


Bond Making

8


Homolytic Breaking of Covalent Bonds

• Each product gets one electron from the bond


Heterolytic Breaking of Covalent Bonds

• Both electrons from the bond that is

broken become associated with one

resulting fragment

• A common pattern in reaction

mechanisms

9


Bond Breaking


Radicals

• A “free radical” is an “R” group on its

own:–

.CH3 is a “free radical” or simply “radical”

– Has a single unpaired electron, shown as: .CH3

.

– Its valence shell is one electron short of being

complete

10


Radical 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


Radical Substitution

11


Radical Addition


Chlorination of methane: a radical substitution reaction

12


Steps in Radical SubstitutionIntitiation


Steps in Radical SubstitutionPropagation

13


Steps in Radical SubstitutionTermination


Polar Reactions

14


Polarity is affected by structure changes:


Polarity

15


Polarity


Polarizability

• Polarization is 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

electron density and regions of low electron density

16


Generalized Polar Reactions

• an electrophile, an electron-poor species (Lewis acid)

combines with

• a nucleophile, an electron-rich species (Lewis base)

• The combination is indicated with a curved arrow from nucleophile to electrophile


Polar Reactions:

17


Electrophiles & Nuclephiles


a Polar Reaction: Addition of HBr to Ethylene

18


Addition of HBr to Ethylene

HBr

δ+


Π-Bonds as Nucleophiles:

� Π-bonding electron pairs can function as Lewis bases:

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Mechanism of Addition of HBr to Ethylene


Rules for Using Curved Arrows

• The arrow goes from the nucleophilic reaction site to the electrophilic reaction site

• The nucleophilic site can be neutral or negatively

charged

• The electrophilic site can be neutral or positively charged

20


electrons move from Nu: to E


Nu: can be negative or neutral

21


E can be positive or neutral


ELECTRONS AND CHARGES

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curved arrows?


Solution:

23


Describing a Reaction: Equilibria, Rates, and Energy Changes

aA + bB cC + dD

Keq = [Products]/[Reactants] = [C]c [D]d / [A]a[B]b


Keq

24


Numeric Relationship of Keq and Free

Energy Change

• The standard free energy change at 1 atm

pressure and 298 K is ∆Gº

• The relationship between free energy change and an equilibrium constant is:

� ∆∆∆∆Gº = - RT lnKeq where

– R = 1.987 cal/(K x mol) (gas constant)

– T = temperature in Kelvins

– ln = natural logarithm


Changes in Energy at Equilibrium

• Free energy changes (∆Gº) can be divided into– a temperature-independent part called entropy

(∆Sº) that measures the change in the amount of disorder in the system

– a temperature-dependent part called enthalpy

(∆Hº) that is associated with heat given off (exothermic) or absorbed (endothermic)

∆∆∆∆Gº = ∆∆∆∆Hº - T∆∆∆∆Sº

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Ethylene + HBr

∆Gº = ∆Hº - T∆Sº


Irene LeeCase Western Reserve University

Cleveland, OH

©2007, Prentice Hall

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The atom or group that is substituted or eliminated in these reactions is called a leaving group

substitution reaction


Alkyl halides have relatively good leaving groups

How do alkyl halides react?

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Alternatively…


The substitution is more precisely called a nucleophilicsubstitution because the atom or group replacing theleaving group is a nucleophile

The reaction mechanism which predominates depends on the following factors:

• the structure of the alkyl halide• the reactivity of the nucleophile• the concentration of the nucleophile

• the solvent of the reaction

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The Mechanism of an SN2 Reaction

Consider the kinetic of the reaction:

a second-order reaction


Three Experimental Evidences Support an SN2 Reaction Mechanism

1. The rate of the reaction is dependent on the concentration of the alkyl halides and the nucleophile

2. The rate of the reaction with a given nucleophiledecreases with increasing size of the alkyl halides

3. The configuration of the substituted product is inverted compared to the configuration of the reacting chiral alkyl halide

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As SN2 is a one-step reaction

A nucleophile attacks the back side of the carbon that isbonded to the leaving group

30


A bulky substituent in the alkyl halide reduces thereactivity of the alkyl halide: steric hindrance

Tertiary alkyl halides cannot undergo SN2 reactions


Reaction coordinate diagrams for (a) the SN2 reaction of methyl bromide and (b) an SN2 reaction of a stericallyhindered alkyl bromide

31


Inversion of configuration (Walden inversion) in an SN2 reaction is due to back side attack


Experimental Evidence for an SN1 Reaction

1. The rate of the reaction depends only on the concentration of the alkyl halide

2. The rate of the reaction is favored by the bulkiness ofthe alkyl substituent

3. In the substitution of a chiral alkyl halide, a mixture of stereoisomeric product is obtained

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33


An SN1 is a two-step reaction and the leaving groupdeparts before the nucleophile approaches


Reaction Coordinate Diagram for an SN1 Reaction

34


The carbocation reaction intermediate leads to the formation of two stereoisomeric products


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The Effect of the Leaving Group on an SN1 Reaction

The nucleophile has no effect on the rate of an SN1 reaction

The rate of the reaction is affected by:

1) the ease with which the leaving group dissociatesfrom the carbon

2) the stability of the carbocation that is formed


When a reaction forms a carbocation intermediate,always check for the possibility of a carbocationrearrangement

36


The Stereochemistry of SN2 Reactions


The Stereochemistry of SN1 Reactions

37


Sometimes extra inverted product is formed in an SN1reaction because…


Describing a Reaction: Bond Dissociation Energies

• Bond dissociation energy (D): Heat change that occurs when a bond is broken by homolysis

• The energy is mostly determined by the type of bond, independent of the molecule

– The C-H bond in methane requires a net heat

input of 105 kcal/mol to be broken at 25 ºC.

• Changes in bonds can be used to calculate net changes in heat

38


Calculation of an Energy Change from Bond Dissociation Energies


Describing a Reaction: Energy Diagrams and Transition States

39


Describing a Reaction: Energy Diagrams and Transition States

• The highest energy

point in a reaction step is called the

transition state

• The energy needed

to go from reactant to transition state is the activation

energy (∆G‡)


First Step in the Addition of HBr

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Formation of a CarbocationIntermediate

• HBr, a Lewis acid, adds to

the π bond

• This produces an intermediate with a positive charge on carbon - a carbocation

• This is ready to react with bromide


Carbocation Intermediate Reactions with Anion

• Bromide ion adds an electron pair to the carbocation

• An alkyl halide produced

• The carbocation is a reactive intermediate

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• Chlorination of Methane

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Chlorination of Methane

• Requires heat or light for initiation.

• The most effective wavelength is blue, which

is absorbed by chlorine gas.

• Many molecules of product are formed from absorption of only one photon of light (chain reaction).

=>


Initiation Step

A chlorine molecule splits homolytically into

chlorine atoms (free radicals).

=>

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Propagation Step (1)

The chlorine atom collides with a methane

molecule and abstracts (removes) a H,

forming another free radical and one of the

products (HCl).

=>


Propagation Step (2)

The methyl free radical collides with another

chlorine molecule, producing the other

product (methyl chloride) and regenerating

the chlorine radical.

=>

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Overall Reaction

=>


Termination Steps

• Collision of any two free radicals.

• Combination of free radical with

contaminant or collision with wall.

Can you suggest others? =>

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Equilibrium Constant

• Keq = [products]

[reactants]

• For chlorination Keq = 1.1 x 1019

• Large value indicates reaction “goes to

completion.”

=>


Free Energy Change

• ∆G = free energy of (products - reactants), amount of energy available to do work.

• Negative values indicate spontaneity.

• ∆Go = -RT(lnKeq)where R = 8.314 J/K-moland T = temperature in kelvins

• Since chlorination has a large Keq, the free energy change is large and negative.

=>

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Problem

• Given that -X is -OH, the energy difference for the following reaction is -4.0 kJ/mol.

• What percentage of cyclohexanol molecules will be in the equatorial conformer at equilibrium at 25°C?

=>


Kinetics

• Answers question, “How fast?”

• Rate is proportional to the concentration of

reactants raised to a power.

• Rate law is experimentally determined.

=>

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Reaction Order

• For A + B → C + D, rate = k[A]a[B]b

– a is the order with respect to A

– b is the order with respect to B

– a + b is the overall order

• Order is the number of molecules of that reactant which is present in the rate-determining step of the mechanism.

• The value of k depends on temperature as given by Arrhenius:

RTEaAek

/

r

−= =>


Activation Energy

• Minimum energy required to reach

the transition state.

• At higher temperatures, more molecules have the

required energy.

C

H

H

H

H Cl

=>

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Energy Diagram

• Reactants → transition state → intermediate

• Intermediate → transition state → product

=>


Rate, Ea, and Temperature

X + CH4 HX + CH3

X E a Rate @ 300K Rate @ 500K

F 5 kJ 140,000 300,000

Cl 17 kJ 1300 18,000

Br 75 kJ 9 x 10-8

0.015

I 140 kJ 2 x 10-19

2 x 10-9

=>

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Conclusions

• With increasing Ea, rate decreases.

• With increasing temperature, rate

increases.

• Fluorine reacts explosively.

• Chlorine reacts at a moderate rate.

• Bromine must be heated to react.

• Iodine does not react (detectably).

=>


Chlorination of Propane

• six 1° H’s; two 2° H’s.

• We expect 3:1 product mix,– 75% 1-chloropropane

– 25% 2-chloropropane.

• Typical product mix: – 40% 1-chloropropane

– 60% 2-chloropropane.

• Therefore, not all H’s are equally reactive.

=>

1°°°° C

2°°°° CCH3 CH2 CH3 + Cl2

hννννCH2

Cl

CH2 CH3 + CH3 CH

Cl

CH3

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compare hydrogen reactivity

• find amount of product formed per hydrogen: – 40% 1-chloropropane from 6 hydrogens

– 60% 2-chloropropane from 2 hydrogens.

• 40% ÷÷÷÷ 6 = 6.67% per primary H• 60% ÷÷÷÷ 2 = 30% per secondary H

• Secondary H’s are 30% ÷÷÷÷ 6.67% = 4.5 times more reactive toward chlorination than primary H’s. =>


Free Radical Stabilities• Energy required to break a C-H bond

decreases as substitution on the carbon

increases.

• Stability: 3° > 2° > 1° > methyl

∆H(kJ) 381, 397, 410, 435

=>

51


Chlorination Energy Diagram

Lower Ea, faster rate, so more stable

intermediate is formed faster.

=>


• six 1° H’s and two 2° Η’s.

– We expect 3:1 product mix, or

– 75% 1-bromopropane

– 25% 2-bromopropane.

• Typical product mix:



• Bromination is more selective than chlorination. =>

1°°°° C

2°°°° C

CH3 CH2 CH3 + CH2

Br

CH2 CH3 +Br2

heatCH3 CH

Br

CH3

Bromination of Propane

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• find amount of product formed per H:

– 3% 1-bromopropane from 6 hydrogens

– 97% 2-bromopropane from 2 hydrogens.

• 3% ÷÷÷÷ 6 = 0.5% per primary H97% ÷÷÷÷ 2 = 48.5% per secondary H

• Secondary H’s are 48.5% ÷÷÷÷ 0.5% = 97 times more reactive toward bromination than primary H’s.

compare hydrogen reactivity


Bromination Energy Diagram

• BDE for HBr is 368 kJ, but 431 kJ for HCl

=>

53


Bromination vs. Chlorination

=>


Endothermic and

Exothermic Diagrams

=>

54


Hammond Postulate

• Related species that are similar in energy are also similar in structure. The structure of a transition state resembles the structure of the closest stable species.

• Endothermic reaction: transition state is product-like.

• Exothermic reaction: transition state is reactant-like.

=>


Radical Inhibitors

• Often added to food to retard spoilage.

• Without an inhibitor, each initiation step will cause a chain reaction so that many molecules will react.

• An inhibitor combines with the free radical to form a stable molecule.

• Vitamin E and vitamin C are thought to protect living cells from free radicals.

=>

55


Reactive Intermediates• Carbocations

• Free radicals

• Carbanions

• Carbene

=>


Carbocation Structure

• Carbon has 6 electrons, positive charge.

• Carbon is sp2 hybridized with vacant p orbital.

=>

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Carbocation Stability

• Stabilized by alkyl substituents 2 ways:

• (1) Inductive effect:

donation of electron density

along the sigma bonds.

• (2) Hyperconjugation: overlap of sigma bonding orbitals with empty p orbital.

=>


Free Radicals

• Also electron-deficient

• Stabilized by alkyl substituents

• Order of stability:3° > 2° > 1° > methyl =>

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1. New derivatives or alcohols


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Free Radicals and Human Disease(Peter H. Proctor, PhD, MD)

http://www.general.info/crcpap2.htm

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Carbenes• Carbon is neutral.

• Vacant p orbital, so can be electrophilic.

• Lone pair of electrons, so can be

nucleophilic. =>


Carbanions

• Eight electrons on C:6 bonding + lone pair

• Carbon has a negative charge

• Destabilized by alkyl substituents

• Methyl >1° > 2 ° > 3 °

=>

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Carbenes

• Carbon is neutral.

• Vacant p orbital, so can be electrophilic.

• Lone pair of electrons, so can be nucleophilic. =>


Adaptado de:

• Organic Chemistry, 6th Edition; L. G.

Wade, Jr.

• Organic Chemistry, 6th edition; McMurry’s

• Organic Chemistry, 5th Edition; Paula

Yurkanis Bruice

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