6. an overview of organic reactions
DESCRIPTION
6. An Overview of Organic Reactions. Why this chapter?. To understand organic and/or biochemistry, it is necessary to know: -What occurs -Why and how chemical reactions take place We will see how a reaction can be described. 6.1 Kinds of Organic Reactions. - PowerPoint PPT PresentationTRANSCRIPT
6. An Overview of Organic 6. An Overview of Organic ReactionsReactions
Why this chapter?Why this chapter?To understand organic and/or biochemistry, it is necessary to know:-What occurs-Why and how chemical reactions take place
We will see how a reaction can be described
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6.1 Kinds of Organic Reactions6.1 Kinds of Organic Reactions In general, we look at what occurs and try to learn
how it happensCommon patterns describe the changes
◦ Addition reactions – two molecules combine
◦ Elimination reactions – one molecule splits into two
3
◦ Substitution – parts from two molecules exchange
◦ Rearrangement reactions – a molecule undergoes changes in the way its atoms are connected
What kind of reaction is the transformation shown What kind of reaction is the transformation shown below? below?
1. an elimination reaction
2. a rearrangement reaction
3. a substitution reaction
4. an addition reaction5. none of these
+ HClCl
Learning Check:Learning Check:
What kind of reaction is the transformation shown What kind of reaction is the transformation shown below? below?
1. an elimination reaction
2. a rearrangement reaction
3. a substitution reaction
4. an addition reaction5. none of these
+ HClCl
Solution:Solution:
6
6.2 How Organic Reactions 6.2 How Organic Reactions Occur: MechanismsOccur: Mechanisms In a clock the hands move but the mechanism behind the face is what causes the movement
In an organic reaction, 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
7
Steps in MechanismsSteps in MechanismsWe classify the types of steps in a sequenceA step involves either the formation or
breaking of a covalent bondSteps can occur in individually or in
combination with other stepsWhen several steps occur at the same time
they are said to be concerted
8
Types of Steps in Reaction MechanismsTypes of Steps in Reaction MechanismsBond formation or breakage can be symmetrical or
unsymetrical Symmetrical- homolyticUnsymmetrical- heterolytic
Bond Breaking
Bond MakingBond Making
9
Indicating Steps in MechanismsIndicating Steps in MechanismsCurved arrows indicate breaking
and forming 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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6.3 Radical Reactions6.3 Radical ReactionsNot as common as polar reactionsRadicals 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
11
Three types of steps◦ Initiation – homolytic formation of two reactive species
with unpaired electrons Example – formation of Cl atoms form Cl2 and light
◦ Propagation – reaction with molecule to generate radical Example - reaction of chlorine atom with methane to
give HCl and CH3.
◦ Termination – combination of two radicals to form a stable product: CH3
. + CH3. CH3CH3
Steps in Radical SubstitutionSteps in Radical Substitution
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Steps in Radical Substitution: Steps in Radical Substitution: Monochlorination of MethaneMonochlorination of Methane
Initiation
Propagation
13
Steps in Radical SubstitutionSteps in Radical SubstitutionTermination
With excess concentration of Cl2 present continued reaction is probable with formation of dichloro, trichloro, and tetrachloro methanes.
p. 141
Radical Substitution Example:Radical Substitution Example:Biosynthesis of ProstaglandinsBiosynthesis of Prostaglandins
p. 142
Radical Example:Radical Example:
p. 142
Learning Check:Propose a mechanism. Add curved arrows to indicate the flow of electrons:
p. 142
Solution:Propose a mechanism. Add curved arrows to indicate the flow of electrons:
In a radical chain reaction, what would In a radical chain reaction, what would be the best description of the following be the best description of the following reaction?reaction?HH33C• + •Cl → CHC• + •Cl → CH33ClCl
1. propagation2. elimination3. initiation4. termination5. substitution
Learning Check:
In a radical chain reaction, what would In a radical chain reaction, what would be the best description of the following be the best description of the following reaction?reaction?HH33C• + •Cl → CHC• + •Cl → CH33ClCl
1. propagation2. elimination3. initiation4. termination5. substitution
Solution:
20
Radical Substitution: Radical Substitution: With >1 kind of HWith >1 kind of H
When there is • >1 type of H then there is • >1 option for radical formation and therefore • >1 option for a monohalogenation product.
C
H
H
H
C C
H
H
H
H
H
C
H
H
H
C
H
H
C
Cl
H
H
C
H
H
H
C
Cl
H
C
H
H
H+ Cl2 hv +
1-chloropropane 2-chloropropane
In the reaction of ClIn the reaction of Cl22 with 2-methylbutane, with 2-methylbutane, how many how many monochlorinatedmonochlorinated isomers are isomers are produced?produced?
1. 22. 33. 44. 55. 6
C
H
C C
H
H
H
H
H
C
H
H
H
CHH H
+ Cl2 hv
Learning Check:
In the reaction of ClIn the reaction of Cl22 with 2-methylbutane, with 2-methylbutane, how many how many monochlorinatedmonochlorinated isomers are isomers are produced?produced?
1. 22. 33. 44. 55. 6
C
H
C C
H
H
H
H
H
C
H
H
H
CHH H
+ Cl2 hv
Solution:
23
6.4 Polar Reactions6.4 Polar ReactionsMolecules can contain local unsymmetrical
electron distributions due to differences in electronegativities
This causes a partial negative charge on an atom and a compensating partial positive charge on an adjacent atom
The more electronegative atom has the greater electron density
Elements such as O, F, N, Cl more electronegative than carbon
p. 143
25
26
PolarizabilityPolarizabilityPolarization 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
p. 144
PolarizabilityPolarizabilityBonds inherently polar already can be made more polar by reactions with acids or bases.
p. 144
PolarizabilityPolarizability
2.55
2.58
2.55
2.66
Bonds not inherently polar can be polarizable as interactions with solvent or other polar molecules effect the electron distribution.
Large atoms with loosely held electrons are more polarizable than small atoms with few tightly held electrons.So: SS is more polarizable than OO
II is more polarizable than ClCl
29
Generalized Polar ReactionsGeneralized Polar ReactionsAn electrophileelectrophile, an electron-poor species,
combines with a nucleophilenucleophile, an electron-rich species
An electrophile is a Lewis acidA nucleophile is a Lewis baseThe combination is indicate with a curved arrow from
nucleophile to electrophile
Fig. 5-1a, p. 145
p. 146
Learning Check:Which of the following is likely to be a nucleophile and which an electrophile?
p. 146
Solution:Which of the following is likely to be a nucleophile and which an electrophile?
E EN N
p. 146
Is BF3 is likely to be a nucleophile or an electrophile?
Learning Check:
p. 146
Is BF3 is likely to be a nucleophile or an electrophile?
Solution:
E
Which of the following is expected Which of the following is expected to be the worst nucleophile?to be the worst nucleophile?
1. NH3
2. H2O3. BH3
4. ethylene5. (CH3) 3P
Learning Check:
Which of the following is expected Which of the following is expected to be the worst nucleophile?to be the worst nucleophile?
1. NH3
2. H2O3. BH3
4. ethylene5. (CH3) 3P
Solution:
37
6.5 An Example of a Polar Reaction: 6.5 An Example of a Polar Reaction: Addition of HBr to EthyleneAddition of HBr to Ethylene
HBr adds to the part of C-C double bondThe bond is e- rich, allowing it to function as a nucleophileH-Br is electron deficient at the H since Br is much more
electronegative, making HBr an electrophile
38
Mechanism of Addition of HBr to EthyleneMechanism of Addition of HBr to Ethylene 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
Fig. 5-2a, p. 148
p. 142
Learning Check:What product would you expect?
p. 142
Solution:What product would you expect?
Br
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6.6 Using Curved Arrows in Polar 6.6 Using Curved Arrows in Polar Reaction MechanismsReaction MechanismsCurved arrows are a way to keep track
of changes in bonding in polar reactionThe arrows track “electron movement” Electrons always move in pairsCharges change during the reactionOne curved arrow corresponds to one
step in a reaction mechanism
43
Rules for Using Curved ArrowsRules for Using Curved ArrowsThe arrow (electrons) goes from the
nucleophilic reaction site (Nu: or Nu:Nu: or Nu:-- ) to the electrophilic reaction site (sink, E or Esink, E or E++)
The nucleophilic site can be neutral or negative
44
The nucleophilic site can be negative or neutralRules for Using Curved ArrowsRules for Using Curved Arrows
45
The electrophilic site can be positive or neutral
46
The octet rule must be followed
The hydrogen already has two e-s so when another pair moves in the 2 already owned have to leave.
What is the role of the alkene in the What is the role of the alkene in the reaction above? reaction above?
1. electrophile2. nucleophile3. free radical4. catalyst5. Lewis acid
+ H3O + H2O
Learning Check:
What is the role of the alkene in the What is the role of the alkene in the reaction above? reaction above?
1. electrophile2. nucleophile3. free radical4. catalyst5. Lewis acid
+ H3O + H2O
Solution:
p. 151
Learning Check:Add curved arrows to indicate the flow of electrons:
p. 151
Solution:Add curved arrows to indicate the flow of electrons:
p. 152
Add curved arrows to indicate the flow of electrons:Learning Check:
52
Add curved arrows to indicate the flow of electrons:Solution:
p. 152
Predict the products of the following reaction:Learning Check:
p. 152
Predict the products of the following reaction:Solution:
CH CO2-
OHH
C
HCO2
-CH2
-O2C OH
H+
1. x
2. x
3. x
4. x
5. x
Br + OH2
Br
O HH
Br + OH2
Br
O H
Br + OH2
Br
O HH
Br + OH2
Br
O HH
Br + OH2
Br
O H
Learning Check: Which of the following Which of the following represents a correctly represents a correctly drawn reaction drawn reaction mechanism?mechanism?
1. x
2. x
3. x
4. x
5. x
Br + OH2
Br
O HH
Br + OH2
Br
O H
Br + OH2
Br
O HH
Br + OH2
Br
O HH
Br + OH2
Br
O H
Solution: Which of the following Which of the following represents a correctly represents a correctly drawn reaction drawn reaction mechanism?mechanism?
p. 142
Learning Check:What carbocation intermediate is consistent with the product formed? Propose a mechanism. (Add curved arrows to indicate the flow of electrons.)
p. 142
Solution:
+ C CH2
H3C
H3CH Br CH3C
CH3
CH3
Br
C CH2
H3C
H3C
H
C CH2
H3C
H3C
Hor
Br
1o carbocation 3o carbocation
What carbocation intermediate is consistent with the product formed? Propose a mechanism. (Add curved arrows to indicate the flow of electrons.)
Not formed
59
6.7 Describing a Reaction: 6.7 Describing a Reaction: Equilibria, Rates, and Energy ChangesEquilibria, Rates, and Energy Changes
Reactions can go either forward or backward to reach equilibrium◦The multiplied concentrations of the products
divided by the multiplied concentrations of the reactant is the equilibrium constant, Keq
◦Each concentration is raised to the power of its coefficient in the balanced equation.
aA + bB cC + dD
p. 153
61
Magnitudes of Equilibrium ConstantsMagnitudes of Equilibrium Constants
If the value of KKeqeq >1 >1, this indicates that at equilibrium most material is present as productsproducts◦ If Keq = 10, then the concentration of the product is ten times that
of the reactant
A value of KKeqeq < 1 < 1 indicates that at equilibrium most material is present as the reactantreactant◦ If Keq = 0.10, then the concentration of the reactant is ten times
that of the product
aA + bB cC + dD
62
Free Energy and EquilibriumFree Energy and EquilibriumThe ratio of products to reactants is controlled
by their relative Gibbs free energyThis energy is released on the favored side of
an equilibrium reactionThe change in Gibbs free energy between
products and reacts is written as “G”
If Keq > 1, energy is released to the surroundings (exergonic reaction)
If KKeqeq < 1 < 1, energy is absorbed from the surroundings (endergonicendergonic reaction)
63
Numeric Relationship of KNumeric Relationship of Keqeq and Free Energy and Free Energy ChangeChange
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 ln Keq where◦R = 1.987 cal/(K x mol)◦T = temperature in Kelvin◦ln Keq = natural logarithm of Keq
p. 154
ΔHo is the heat, or enthalpy, of reaction.ΔHo < 0 ; The reaction is exothermic.ΔHo > 0 ; The reaction is endothermic.
ΔG, the Gibbs free energy change, determines Keq and whether the reaction is spontaneous or nonspontaneous.
ΔGo < 0 ; The reaction is spontaneous.ΔGo > 0 ; The reaction is nonspontaneous.
ΔGo < 0 ; Keq > 1ΔGo = 0 ; Keq = 1ΔGo > 0 ; Keq < 1
This reaction is exothermic
This reaction is spontaneous
The equilibrium lies toward product
65
6.2
Which of the following equations is Which of the following equations is correct?correct?
1. ∆G = ∆H – T∆S2. ∆G = ∆s + T∆H3. ∆H = T∆G – T∆S4. ∆G = ∆H + T∆S 5. ∆S = T∆H – ∆G
Learning Check:
Which of the following equations is Which of the following equations is correct?correct?
1. ∆G = ∆H – T∆S2. ∆G = ∆s + T∆H3. ∆H = T∆G – T∆S4. ∆G = ∆H + T∆S 5. ∆S = T∆H – ∆G
Solution:
68
6.8 Describing a Reaction: Bond 6.8 Describing a Reaction: Bond Dissociation EnergiesDissociation Energies
Bond dissociation energy (D): amount of energy required to break a given bond to produce two radical fragments when the molecule is in the gas phase at 25˚ C
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 (438 kJ/mol) to be broken at 25 ºC.◦ Table 5.3 lists energies for many bond types
Changes in bonds can be used to calculate net changes in heat
Table 5-3a, p. 156
Bond Dissociation EnergiesBond Dissociation Energies
Table 5-3b, p. 156
Bond Dissociation EnergiesBond Dissociation Energies
p. 157
Calculate the Calculate the HHoo for the chlorination of for the chlorination of methane :methane :
ClCl22 + CH + CH44 → CH → CH33Cl + HClCl + HClbond CH3–H CH3–Cl H–Cl H–H Cl–Cl
BDE (kJ/mol) 438 351 432 436 243
Bond Dissociation EnergiesBond Dissociation Energies
Bonds Broken Bonds MadeCl-Cl +243 kJ/mol
H3C-H +438 kJ/mol
H3C-Cl -351 kJ/mol
H-Cl -432 kJ/mol
+681 kJ/mol -783 kJ/mol
Ho = + 681 - 783 = -102 kJ/mol
p. 157
Consider the following reaction:Consider the following reaction:CHCH33I + HI + H22O → CHO → CH33OH + HIOH + HI
1. CH3–I2. HO–H3. H–I4. CH3O–H5. CH3–OH
If BDEs are used to estimate the enthalpy of this reaction, which bond’s BDE is not needed?
Learning Check:
Consider the following reaction:Consider the following reaction:CHCH33I + HI + H22O → CHO → CH33OH + HIOH + HI
1. CH3–I2. HO–H3. H–I4. CH3O–H5. CH3–OH
If BDEs are used to estimate the enthalpy of this reaction, which bond’s BDE is not needed?
Solution:
The BDE’s for some bonds are collected in the table The BDE’s for some bonds are collected in the table below:below:
An alternative step in chlorination of methane might be An alternative step in chlorination of methane might be as follows:as follows:Cl• + CHCl• + CH44 → CH → CH33Cl + H•Cl + H•
1. Cl• cannot approach the carbon atom close enough to form a bond because of steric interference from hydrogens
2. H• is not among the products of methane chlorination
3. Cl• can only bond to hydrogen atoms4. this step is too endothermic as compared to
alternatives5. this step is too exothermic
What is the reason that this step is not observed?
bond CH3–H CH3–Cl H–Cl H–H Cl–Cl
BDE (kJ/mol) 438 351 432 436 243
Learning Check:
The BDE’s for some bonds are collected in the table The BDE’s for some bonds are collected in the table below:below:
An alternative step in chlorination of methane might be An alternative step in chlorination of methane might be as follows:as follows:Cl• + CHCl• + CH44 → CH → CH33Cl + H•Cl + H•
1. Cl• cannot approach the carbon atom close enough to form a bond because of steric interference from hydrogens
2. H• is not among the products of methane chlorination
3. Cl• can only bond to hydrogen atoms4. this step is too endothermic as compared to
alternatives5. this step is too exothermic
What is the reason that this step is not observed?
bond CH3–H CH3–Cl H–Cl H–H Cl–Cl
BDE (kJ/mol) 438 351 432 436 243
Solution:
The following reaction is an The following reaction is an example of:example of: H H33CC++ + Cl + Cl– – → CH → CH33ClCl
1. a termination step2. a heterolytic
process3. an initiation step4. a homogenic
process5. an exergonic
reaction
Solution:
78
6.9 Describing a Reaction: Energy Diagrams 6.9 Describing a Reaction: Energy Diagrams and Transition Statesand Transition States
The highest energy point in a reaction step is called the transition statetransition state
The energy needed to go from reactant to transition state is the activation energy (G‡)
79
First Step in AdditionFirst Step in AdditionIn the addition of
HBr the (conceptual) transition-state structure for the first step
The bond between carbons begins to break◦The C–H bond
begins to form◦The H–Br bond
begins to break
Fig. 5-6a, p. 159
Fast exergonic Slow exergonic
Slow endergonicFast endergonic
Which part of the following energy Which part of the following energy diagram indicates whether the overall diagram indicates whether the overall reaction is exergonic or endergonic?reaction is exergonic or endergonic?
1. I2. II3. III4. IV5. V
Learning Check:
Which part of the following energy Which part of the following energy diagram indicates whether the overall diagram indicates whether the overall reaction is exergonic or endergonic?reaction is exergonic or endergonic?
1. I2. II3. III4. IV5. V
Solution:
Which statement about free energy is Which statement about free energy is correct?correct?
1. The ∆G of a reaction depends on the reaction mechanism (path).
2. The ∆G‡ of a reaction depends on the mechanism (path).
3. The ∆G of a reaction may be changed by adding a catalyst.
4. The bigger the ∆G value, the faster the reaction.
5. For exergonic reactions ∆G >0.
Learning Check:
Which statement about free energy is Which statement about free energy is correct?correct?
1. The ∆G of a reaction depends on the reaction mechanism (path).
2. The ∆G‡ of a reaction depends on the mechanism (path).
3. The ∆G of a reaction may be changed by adding a catalyst.
4. The bigger the ∆G value, the faster the reaction.
5. For exergonic reactions ∆G >0.
Solution:
85
6.10 Describing a Reaction: 6.10 Describing a Reaction: IntermediatesIntermediates If a reaction occurs in
>1step, it must involve species that are neither the reactant nor the final product
These are called reaction intermediates or simply “intermediates”
Each step has its own free energy of activation
The complete diagram for the reaction shows the free energy changes associated with an intermediate
On the reaction energy profile shown On the reaction energy profile shown below, which of the species is the highest below, which of the species is the highest energy intermediate?energy intermediate?
1. I2. II3. III4. IV5. V
Learning Check:
On the reaction energy profile shown On the reaction energy profile shown below, which of the species is the highest below, which of the species is the highest energy intermediate?energy intermediate?
1. I2. II3. III4. IV5. V
Solution:
Which of the following statements Which of the following statements is true?is true?
1. Transition states can be observed and sometimes isolated.
2. Transition states can not be observed and never isolated.
3. Intermediates can be observed and sometimes isolated.
4. Intermediates can be observed but never isolated.
5. Intermediates can never be observed.
Learning Check:
Which of the following statements Which of the following statements is true?is true?
1. Transition states can be observed and sometimes isolated.
2. Transition states can not be observed and never isolated.
3. Intermediates can be observed and sometimes isolated.
4. Intermediates can be observed but never isolated.
5. Intermediates can never be observed.
Solution:
Consider the reaction profile shown below. If Consider the reaction profile shown below. If there is a sufficient amount of thermal energy there is a sufficient amount of thermal energy available to overcome the highest activation available to overcome the highest activation energy and sufficient time for all molecules to do energy and sufficient time for all molecules to do that multiple times, what is the main structure that multiple times, what is the main structure present under such conditions?present under such conditions?
1. A2. B3. C4. D5. E
Learning Check:
Consider the reaction profile shown below. If Consider the reaction profile shown below. If there is a sufficient amount of thermal energy there is a sufficient amount of thermal energy available to overcome the highest activation available to overcome the highest activation energy and sufficient time for all molecules to do energy and sufficient time for all molecules to do that multiple times, what is the main structure that multiple times, what is the main structure present under such conditions?present under such conditions?
1. A2. B3. C4. D5. E
Solution:
Which energy difference corresponds to Which energy difference corresponds to the activation energy of the rate-the activation energy of the rate-limiting step for A to E transformation? limiting step for A to E transformation?
1. B – A2. C – A3. D – A4. E – A5. D – C
Learning Check:
Which energy difference corresponds to Which energy difference corresponds to the activation energy of the rate-the activation energy of the rate-limiting step for A to E transformation? limiting step for A to E transformation?
1. B – A2. C – A3. D – A4. E – A5. D – C
Solution:
Which of the following statements is Which of the following statements is incorrectincorrect??
1. Polar reactions must have ionic intermediates.
2. Initiation in radical-chain reactions must generate species with unpaired electrons.
3. Polar reactions occur between electrophiles and nucleophiles.
4. Lewis bases generally behave as nucleophiles.
5. Electrophiles can be neutral as well as positively charged.
Learning Check:
Which of the following statements is Which of the following statements is incorrectincorrect??
1. Polar reactions must have ionic intermediates.
2. Initiation in radical-chain reactions must generate species with unpaired electrons.
3. Polar reactions occur between electrophiles and nucleophiles.
4. Lewis bases generally behave as nucleophiles.
5. Electrophiles can be neutral as well as positively charged.
Solution:
97
6.11 A Comparison between Biological Reactions 6.11 A Comparison between Biological Reactions and Laboratory Reactionsand Laboratory Reactions
Laboratory reactions usually carried out in organic solvent
Biological reactions in aqueous medium inside cellsThey are promoted by catalysts that lower the
activation barrierThe catalysts are usually proteins, called enzymesEnzymes provide an alternative mechanism that is
compatible with the conditions of life
Fig. 5-8, p. 161
Table 5-4, p. 164
6.4
Which of the following Which of the following does notdoes not describe describe the role that the role that can becan be played by an played by an enzyme in a biological reaction?enzyme in a biological reaction?
1. It changes the mechanism of the reaction.
2. It lowers the energy of a transition state.3. It changes the free-energy of the
reaction.4. It changes the rate of the reaction.5. It increases the specificity of the
reaction.
Learning Check:
Which of the following Which of the following does notdoes not describe describe the role that the role that can becan be played by an played by an enzyme in a biological reaction?enzyme in a biological reaction?
1. It changes the mechanism of the reaction.
2. It lowers the energy of a transition state.3. It changes the free-energy of the
reaction.4. It changes the rate of the reaction.5. It increases the specificity of the
reaction.
Solution: