Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI4a_REACT.pdf · Bromine must be heated to...
Transcript of Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI4a_REACT.pdf · Bromine must be heated to...
1
AFB QO I 2007/08 1
Química Orgânica I
Ciências Farmacêuticas
Bioquímica
Química
AFB QO I 2007/08 2
Adaptado de:
� Organic Chemistry, 6th Edition; L. G. Wade, Jr.
� Organic Chemistry, 6th edition; McMurry’s
2
AFB QO I 2007/08 3
5.1 Kinds of Organic Reactions
� Addition reactions – two molecules combine
� Elimination reactions – one molecule splits into two
� Substitution – parts from two molecules exchange
� Rearrangement reactions – a molecule undergoes changes in the way its atoms are connected
AFB QO I 2007/08 4
An Addition Reaction
3
AFB QO I 2007/08 5
An Elimination Reaction
AFB QO I 2007/08 6
A Substitution Reaction
4
AFB QO I 2007/08 7
A Rearrangement Reaction
AFB QO I 2007/08 8
How Organic Reactions OccurMechanisms
� In a clock the hands move but the mechanism behind the face is what causes the movement
� In an organic reaction, by isolating and identifying the products, we see the transformation that has occurred.
� The mechanism describes the steps behind the changes that we can observe
� Reactions occur in defined steps that lead from reactant to product
5
AFB QO I 2007/08 9
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
AFB QO I 2007/08 10
Types of Steps in Reaction Mechanisms
� Formation of a covalent bond
� Homogenic or heterogenic
� Breaking of a covalent bond
� Homolytic or heterolytic
� Oxidation of a functional group
� Reduction of a functional group
6
AFB QO I 2007/08 11
Homogenic Formation of a Bond
�One electron comes from each fragment
�No electronic charges are involved
AFB QO I 2007/08 12
Homogenic Formation of a Bond
7
AFB QO I 2007/08 13
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
AFB QO I 2007/08 14
Heterogenic Formation of a Bond
8
AFB QO I 2007/08 15
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
AFB QO I 2007/08 16
Bond Making
9
AFB QO I 2007/08 17
Homolytic Breaking of Covalent Bonds
�Each product gets one electron from the bond
AFB QO I 2007/08 18
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
10
AFB QO I 2007/08 19
Bond Breaking
AFB QO I 2007/08 20
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
11
AFB QO I 2007/08 21
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
AFB QO I 2007/08 22
Radical Substitution
12
AFB QO I 2007/08 23
Radical Addition
AFB QO I 2007/08 24
Chlorination of methane: a radical substitution reaction
13
AFB QO I 2007/08 25
Steps in Radical SubstitutionIntitiation
AFB QO I 2007/08 26
Steps in Radical SubstitutionPropagation
14
AFB QO I 2007/08 27
Steps in Radical SubstitutionTermination
AFB QO I 2007/08 28
Polar ReactionsPolarity
15
AFB QO I 2007/08 29
Polarity is affected by structure changes:
AFB QO I 2007/08 30
16
AFB QO I 2007/08 31
AFB QO I 2007/08 32
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
17
AFB QO I 2007/08 33
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
AFB QO I 2007/08 34
Polar Reactions:
18
AFB QO I 2007/08 35
Electrophiles & Nuclephiles
AFB QO I 2007/08 36
a Polar Reaction: Addition of HBr to Ethylene
19
AFB QO I 2007/08 37
Addition of HBr to Ethylene
HBr
δ+
AFB QO I 2007/08 38
Π-Bonds as Nucleophiles:
� Π-bonding electron pairs can function as Lewis bases:
20
AFB QO I 2007/08 39
Mechanism of Addition of HBr to Ethylene
AFB QO I 2007/08 40
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
21
AFB QO I 2007/08 41
electrons move from Nu: to E
AFB QO I 2007/08 42
Nu: can be negative or neutral
22
AFB QO I 2007/08 43
E can be positive or neutral
AFB QO I 2007/08 44
ELECTRONS AND CHARGES
23
AFB QO I 2007/08 45
curved arrows?
AFB QO I 2007/08 46
Solution:
24
AFB QO I 2007/08 47
Describing a Reaction: Equilibria, Rates, and Energy Changes
aA + bB cC + dD
Keq = [Products]/[Reactants] = [C]c [D]d / [A]a[B]b
AFB QO I 2007/08 48
Keq
25
AFB QO I 2007/08 49
Numeric Relationship of Keq and Free Energy Change
� The standard free energy change at 1 atmpressure 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
AFB QO I 2007/08 50
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
26
AFB QO I 2007/08 51
Ethylene + HBr
∆Gº = ∆Hº - T∆Sº
AFB QO I 2007/08 52
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
27
AFB QO I 2007/08 53
Calculation of an Energy Change from Bond Dissociation Energies
AFB QO I 2007/08 54
Describing a Reaction: Energy Diagrams and Transition States
28
AFB QO I 2007/08 55
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‡)
AFB QO I 2007/08 56
First Step in the Addition of HBr
29
AFB QO I 2007/08 57
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
AFB QO I 2007/08 58
Carbocation Intermediate Reactions with Anion
� Bromide ion adds an electron pair to the carbocation
� An alkyl halide produced
� The carbocation is a reactive intermediate
30
AFB QO I 2007/08 59
AFB QO I 2007/08 60
� Chlorination of Methane
31
AFB QO I 2007/08 61
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).
=>
AFB QO I 2007/08 62
Initiation Step
A chlorine molecule splits homolyticallyinto chlorine atoms (free radicals).
=>
32
AFB QO I 2007/08 63
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).
=>
AFB QO I 2007/08 64
Propagation Step (2)
The methyl free radical collides with another chlorine molecule, producing the other product (methyl chloride) and regenerating the chlorine radical.
=>
33
AFB QO I 2007/08 65
Overall Reaction
=>
AFB QO I 2007/08 66
Termination Steps� Collision of any two free radicals.
� Combination of free radical with contaminant or collision with wall.
Can you suggest others? =>
34
AFB QO I 2007/08 67
Equilibrium Constant
� Keq = [products][reactants]
� For chlorination Keq = 1.1 x 1019
� Large value indicates reaction “goes to completion.”
=>
AFB QO I 2007/08 68
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.
=>
35
AFB QO I 2007/08 69
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?
=>
AFB QO I 2007/08 70
Kinetics
� Answers question, “How fast?”
� Rate is proportional to the concentration of reactants raised to a power.
� Rate law is experimentallydetermined.
=>
36
AFB QO I 2007/08 71
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
−= =>
AFB QO I 2007/08 72
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
=>
37
AFB QO I 2007/08 73
Energy Diagram� Reactants → transition state → intermediate
� Intermediate → transition state → product
=>
AFB QO I 2007/08 74
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
=>
38
AFB QO I 2007/08 75
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).
=>
AFB QO I 2007/08 76
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
39
AFB QO I 2007/08 77
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. =>
AFB QO I 2007/08 78
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
=>
40
AFB QO I 2007/08 79
Chlorination Energy DiagramLower Ea, faster rate, so more stable
intermediate is formed faster.
=>
AFB QO I 2007/08 80
� 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: � 3% 1-bromopropane
� 97% 2-bromopropane
� 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
41
AFB QO I 2007/08 81
� 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
AFB QO I 2007/08 82
Bromination Energy Diagram
� BDE for HBr is 368 kJ, but 431 kJ for HCl
=>
42
AFB QO I 2007/08 83
Bromination vs. Chlorination
=>
AFB QO I 2007/08 84
Endothermic and Exothermic Diagrams
=>
43
AFB QO I 2007/08 85
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.
=>
AFB QO I 2007/08 86
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.
=>
44
AFB QO I 2007/08 87
Reactive Intermediates� Carbocations
� Free radicals
� Carbanions
� Carbene
=>
AFB QO I 2007/08 88
Carbocation Structure
� Carbon has 6 electrons, positive charge.
� Carbon is sp2 hybridized with vacant porbital.
=>
45
AFB QO I 2007/08 89
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 porbital.
=>
AFB QO I 2007/08 90
Free Radicals
� Also electron-deficient
� Stabilized by alkyl substituents
� Order of stability:3° > 2° > 1° > methyl =>
46
AFB QO I 2007/08 91
Carbanions� Eight electrons on C:
6 bonding + lone pair
� Carbon has a negative charge
� Destabilized by alkyl substituents
� Methyl >1° > 2 ° > 3 °
=>
AFB QO I 2007/08 92
Carbenes
� Carbon is neutral.
� Vacant p orbital, so can be electrophilic.
� Lone pair of electrons, so can be nucleophilic. =>