Química Orgânica I 2008/09 w3.ualg.pt\~abrigas QOI 0809 A6 1 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 w3.ualg.pt\~abrigas QOI 0809 A6 2 1
An Addition Reaction w3.ualg.pt\~abrigas QOI 0809 A6 3 An Elimination Reaction w3.ualg.pt\~abrigas QOI 0809 A6 4 2
A Substitution Reaction w3.ualg.pt\~abrigas QOI 0809 A6 5 A Rearrangement Reaction w3.ualg.pt\~abrigas QOI 0809 A6 6 3
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 w3.ualg.pt\~abrigas QOI 0809 A6 7 w3.ualg.pt\~abrigas QOI 0809 A6 8 4
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 w3.ualg.pt\~abrigas QOI 0809 A6 9 Types of Steps in Reaction Mechanisms Formation of a covalent bond Homogenic or heterogenic Breaking of a covalent bond Homolytic or heterolytic Oxidation Reduction w3.ualg.pt\~abrigas QOI 0809 A6 10 5
Homogenic Formation of a Bond One electron comes from each fragment No electronic charges are involved w3.ualg.pt\~abrigas QOI 0809 A6 11 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 w3.ualg.pt\~abrigas QOI 0809 A6 12 6
Indicating Steps in Mechanisms Curved arrows indicate breaking and forming of bonds Arrowheads with a half head ( fish-hook ) indicate homolytic and 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 w3.ualg.pt\~abrigas QOI 0809 A6 13 Bond Making w3.ualg.pt\~abrigas QOI 0809 A6 14 7
Homolytic Breaking of Covalent Bonds Each product gets one electron from the bond w3.ualg.pt\~abrigas QOI 0809 A6 15 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 w3.ualg.pt\~abrigas QOI 0809 A6 16 8
Bond Breaking w3.ualg.pt\~abrigas QOI 0809 A6 17 Radicals A free radical is an R group on its own:. CH 3 is a free radical or simply radical Has a single unpaired electron, shown as:. CH 3. Its valence shell is one electron short of being complete w3.ualg.pt\~abrigas QOI 0809 A6 18 9
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 w3.ualg.pt\~abrigas QOI 0809 A6 19 Radical Substitution w3.ualg.pt\~abrigas QOI 0809 A6 20 10
Radical Addition w3.ualg.pt\~abrigas QOI 0809 A6 21 Chlorination of methane: a radical substitution reaction w3.ualg.pt\~abrigas QOI 0809 A6 22 11
Steps in Radical Substitution Intitiation w3.ualg.pt\~abrigas QOI 0809 A6 23 Steps in Radical Substitution Propagation w3.ualg.pt\~abrigas QOI 0809 A6 24 12
Steps in Radical Substitution Termination w3.ualg.pt\~abrigas QOI 0809 A6 25 Polar Reactions w3.ualg.pt\~abrigas QOI 0809 A6 26 13
Polarity is affected by structure changes: w3.ualg.pt\~abrigas QOI 0809 A6 27 Polarity w3.ualg.pt\~abrigas QOI 0809 A6 28 14
Polarity w3.ualg.pt\~abrigas QOI 0809 A6 29 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 w3.ualg.pt\~abrigas QOI 0809 A6 30 15
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 w3.ualg.pt\~abrigas QOI 0809 A6 31 Polar Reactions: w3.ualg.pt\~abrigas QOI 0809 A6 32 16
Electrophiles & Nuclephiles w3.ualg.pt\~abrigas QOI 0809 A6 33 a Polar Reaction: Addition of HBr to Ethylene w3.ualg.pt\~abrigas QOI 0809 A6 34 17
Addition of HBr to Ethylene δ+ Br H w3.ualg.pt\~abrigas QOI 0809 A6 35 Π-Bonds as Nucleophiles: Π-bonding electron pairs can function as Lewis bases: w3.ualg.pt\~abrigas QOI 0809 A6 36 18
Mechanism of Addition of HBr to Ethylene w3.ualg.pt\~abrigas QOI 0809 A6 37 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 w3.ualg.pt\~abrigas QOI 0809 A6 38 19
electrons move from Nu: to E w3.ualg.pt\~abrigas QOI 0809 A6 39 Nu: can be negative or neutral w3.ualg.pt\~abrigas QOI 0809 A6 40 20
E can be positive or neutral w3.ualg.pt\~abrigas QOI 0809 A6 41 ELECTRONS AND CHARGES w3.ualg.pt\~abrigas QOI 0809 A6 42 21
curved arrows? w3.ualg.pt\~abrigas QOI 0809 A6 43 Solution: w3.ualg.pt\~abrigas QOI 0809 A6 44 22
Describing a Reaction: Equilibria, Rates, and Energy Changes aa + bb cc + dd K eq = [Products]/[Reactants] = [C] c [D] d / [A] a [B] b w3.ualg.pt\~abrigas QOI 0809 A6 45 Keq w3.ualg.pt\~abrigas QOI 0809 A6 46 23
Numeric Relationship of K eq 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 lnk eq where R = 1.987 cal/(k x mol) (gas constant) T = temperature in Kelvins ln = natural logarithm w3.ualg.pt\~abrigas QOI 0809 A6 47 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 w3.ualg.pt\~abrigas QOI 0809 A6 48 24
Ethylene + HBr Gº = Hº - T Sº w3.ualg.pt\~abrigas QOI 0809 A6 49 Irene Lee Case Western Reserve University Cleveland, OH 2007, Prentice Hall w3.ualg.pt\~abrigas QOI 0809 A6 50 25
substitution reaction The atom or group that is substituted or eliminated in these reactions is called a leaving group w3.ualg.pt\~abrigas QOI 0809 A6 51 Alkyl halides have relatively good leaving groups How do alkyl halides react? w3.ualg.pt\~abrigas QOI 0809 A6 52 26
Alternatively w3.ualg.pt\~abrigas QOI 0809 A6 53 The substitution is more precisely called a nucleophilic substitution because the atom or group replacing the leaving 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 w3.ualg.pt\~abrigas QOI 0809 A6 54 27
The Mechanism of an S N 2 Reaction Consider the kinetic of the reaction: a second-order reaction w3.ualg.pt\~abrigas QOI 0809 A6 55 Three Experimental Evidences Support an S N 2 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 nucleophile decreases 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 w3.ualg.pt\~abrigas QOI 0809 A6 56 28
w3.ualg.pt\~abrigas QOI 0809 A6 57 As S N 2 is a one-step reaction A nucleophile attacks the back side of the carbon that is bonded to the leaving group w3.ualg.pt\~abrigas QOI 0809 A6 58 29
A bulky substituent in the alkyl halide reduces the reactivity of the alkyl halide: steric hindrance Tertiary alkyl halides cannot undergo S N 2 reactions w3.ualg.pt\~abrigas QOI 0809 A6 59 Reaction coordinate diagrams for (a) the S N 2 reaction of methyl bromide and (b) an S N 2 reaction of a sterically hindered alkyl bromide w3.ualg.pt\~abrigas QOI 0809 A6 60 30
Inversion of configuration (Walden inversion) in an S N 2 reaction is due to back side attack w3.ualg.pt\~abrigas QOI 0809 A6 61 Experimental Evidence for an S N 1 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 of the alkyl substituent 3. In the substitution of a chiral alkyl halide, a mixture of stereoisomeric product is obtained w3.ualg.pt\~abrigas QOI 0809 A6 62 31
w3.ualg.pt\~abrigas QOI 0809 A6 63 w3.ualg.pt\~abrigas QOI 0809 A6 64 32
An S N 1 is a two-step reaction and the leaving group departs before the nucleophile approaches w3.ualg.pt\~abrigas QOI 0809 A6 65 Reaction Coordinate Diagram for an S N 1 Reaction w3.ualg.pt\~abrigas QOI 0809 A6 66 33
The carbocation reaction intermediate leads to the formation of two stereoisomeric products w3.ualg.pt\~abrigas QOI 0809 A6 67 w3.ualg.pt\~abrigas QOI 0809 A6 68 34
The Effect of the Leaving Group on an S N 1 Reaction The rate of the reaction is affected by: 1) the ease with which the leaving group dissociates from the carbon 2) the stability of the carbocation that is formed The nucleophile has no effect on the rate of an S N 1 reaction w3.ualg.pt\~abrigas QOI 0809 A6 69 When a reaction forms a carbocation intermediate, always check for the possibility of a carbocation rearrangement w3.ualg.pt\~abrigas QOI 0809 A6 70 35
The Stereochemistry of S N 2 Reactions w3.ualg.pt\~abrigas QOI 0809 A6 71 The Stereochemistry of S N 1 Reactions w3.ualg.pt\~abrigas QOI 0809 A6 72 36
Sometimes extra inverted product is formed in an S N 1 reaction because w3.ualg.pt\~abrigas QOI 0809 A6 73 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 w3.ualg.pt\~abrigas QOI 0809 A6 74 37
Calculation of an Energy Change from Bond Dissociation Energies w3.ualg.pt\~abrigas QOI 0809 A6 75 Describing a Reaction: Energy Diagrams and Transition States w3.ualg.pt\~abrigas QOI 0809 A6 76 38
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 ) w3.ualg.pt\~abrigas QOI 0809 A6 77 First Step in the Addition of HBr w3.ualg.pt\~abrigas QOI 0809 A6 78 39
Formation of a Carbocation Intermediate 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 w3.ualg.pt\~abrigas QOI 0809 A6 79 Carbocation Intermediate Reactions with Anion Bromide ion adds an electron pair to the carbocation An alkyl halide produced The carbocation is a reactive intermediate w3.ualg.pt\~abrigas QOI 0809 A6 80 40
w3.ualg.pt\~abrigas QOI 0809 A6 81 Chlorination of Methane w3.ualg.pt\~abrigas QOI 0809 A6 82 41
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). w3.ualg.pt\~abrigas QOI 0809 A6 83 => Initiation Step A chlorine molecule splits homolytically into chlorine atoms (free radicals). => w3.ualg.pt\~abrigas QOI 0809 A6 84 42
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). w3.ualg.pt\~abrigas QOI 0809 A6 85 => Propagation Step (2) The methyl free radical collides with another chlorine molecule, producing the other product (methyl chloride) and regenerating the chlorine radical. => w3.ualg.pt\~abrigas QOI 0809 A6 86 43
Overall Reaction w3.ualg.pt\~abrigas QOI 0809 A6 87 => Termination Steps Collision of any two free radicals. Combination of free radical with contaminant or collision with wall. Can you suggest others? w3.ualg.pt\~abrigas QOI 0809 A6 88 => 44
Equilibrium Constant K eq = [products] [reactants] For chlorination K eq = 1.1 x 10 19 Large value indicates reaction goes to completion. => w3.ualg.pt\~abrigas QOI 0809 A6 89 Free Energy Change G = free energy of (products - reactants), amount of energy available to do work. Negative values indicate spontaneity. G o = -RT(lnK eq ) where R = 8.314 J/K-mol and T = temperature in kelvins Since chlorination has a large K eq, the free energy change is large and negative. => w3.ualg.pt\~abrigas QOI 0809 A6 90 45
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? => w3.ualg.pt\~abrigas QOI 0809 A6 91 Kinetics Answers question, How fast? Rate is proportional to the concentration of reactants raised to a power. Rate law is experimentally determined. => w3.ualg.pt\~abrigas QOI 0809 A6 92 46
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 ratedetermining step of the mechanism. The value of k depends on temperature as given by Arrhenius: k E a / RT r = Ae => w3.ualg.pt\~abrigas QOI 0809 A6 93 Activation Energy Minimum energy required to reach the transition state. At higher temperatures, more molecules have the required energy. H H C H H Cl => w3.ualg.pt\~abrigas QOI 0809 A6 94 47
Energy Diagram Reactants transition state intermediate Intermediate transition state product w3.ualg.pt\~abrigas QOI 0809 A6 95 => Rate, E a, and Temperature X + CH 4 HX + CH 3 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 => w3.ualg.pt\~abrigas QOI 0809 A6 96 48
Conclusions With increasing E a, 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). => w3.ualg.pt\~abrigas QOI 0809 A6 97 Chlorination of Propane 1 C CH 3 CH 2 C 2 CH 3 + Cl hν 2 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. Cl CH 2 w3.ualg.pt\~abrigas QOI 0809 A6 98 => Cl CH 2 CH 3 + CH 3 CH CH 3 49
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. => w3.ualg.pt\~abrigas QOI 0809 A6 99 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 => w3.ualg.pt\~abrigas QOI 0809 A6 100 50
Chlorination Energy Diagram Lower E a, faster rate, so more stable intermediate is formed faster. w3.ualg.pt\~abrigas QOI 0809 A6 101 => 1 C Br CH 3 CH 2 CH 3 + Br 2 heat CH 2 2 C 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. w3.ualg.pt\~abrigas QOI 0809 A6 102 => Bromination of Propane CH 2 CH 3 + CH 3 Br CH CH 3 51
compare hydrogen reactivity 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 H 97% 2 = 48.5% per secondary H Secondary H s are 48.5% 0.5% = 97 times more reactive toward bromination than primary H s. w3.ualg.pt\~abrigas QOI 0809 A6 103 Bromination Energy Diagram BDE for HBr is 368 kj, but 431 kj for HCl => w3.ualg.pt\~abrigas QOI 0809 A6 104 52
Bromination vs. Chlorination w3.ualg.pt\~abrigas QOI 0809 A6 105 => Endothermic and Exothermic Diagrams => w3.ualg.pt\~abrigas QOI 0809 A6 106 53
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. => w3.ualg.pt\~abrigas QOI 0809 A6 107 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. => w3.ualg.pt\~abrigas QOI 0809 A6 108 54
Reactive Intermediates Carbocations Free radicals Carbanions Carbene => w3.ualg.pt\~abrigas QOI 0809 A6 109 Carbocation Structure Carbon has 6 electrons, positive charge. Carbon is sp 2 hybridized with vacant p orbital. => w3.ualg.pt\~abrigas QOI 0809 A6 110 55
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. => w3.ualg.pt\~abrigas QOI 0809 A6 111 Free Radicals Also electron-deficient Stabilized by alkyl substituents Order of stability: 3 > 2 > 1 > methyl => w3.ualg.pt\~abrigas QOI 0809 A6 112 56
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1. New derivatives or alcohols w3.ualg.pt\~abrigas QOI 0809 A6 115 w3.ualg.pt\~abrigas QOI 0809 A6 116 58
w3.ualg.pt\~abrigas QOI 0809 A6 117 w3.ualg.pt\~abrigas QOI 0809 A6 118 59
w3.ualg.pt\~abrigas QOI 0809 A6 119 Free Radicals and Human Disease (Peter H. Proctor, PhD, MD) http://www.general.info/crcpap2.htm w3.ualg.pt\~abrigas QOI 0809 A6 120 60
Carbenes Carbon is neutral. Vacant p orbital, so can be electrophilic. Lone pair of electrons, so can be nucleophilic. => w3.ualg.pt\~abrigas QOI 0809 A6 121 Carbanions Eight electrons on C: 6 bonding + lone pair Carbon has a negative charge Destabilized by alkyl substituents Methyl >1 > 2 > 3 => w3.ualg.pt\~abrigas QOI 0809 A6 122 61
Carbenes Carbon is neutral. Vacant p orbital, so can be electrophilic. Lone pair of electrons, so can be nucleophilic. => w3.ualg.pt\~abrigas QOI 0809 A6 123 Adaptado de: Organic Chemistry, 6th Edition; L. G. Wade, Jr. Organic Chemistry, 6th edition; McMurry s Organic Chemistry, 5th Edition; Paula Yurkanis Bruice w3.ualg.pt\~abrigas QOI 0809 A6 124 62