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Química Orgânica I
2008/09
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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
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An Addition Reaction
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An Elimination Reaction
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A Substitution Reaction
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A Rearrangement Reaction
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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
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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
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Types of Steps in Reaction Mechanisms
• Formation of a covalent bond
– Homogenic or heterogenic
• Breaking of a covalent bond
– Homolytic or heterolytic
• Oxidation
• Reduction
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Homogenic Formation of a Bond
• One electron comes from each
fragment
• No electronic charges are involved
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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
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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
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Bond Making
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Homolytic Breaking of Covalent Bonds
• Each product gets one electron from the bond
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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
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Bond Breaking
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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
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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
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Radical Substitution
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Radical Addition
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Chlorination of methane: a radical substitution reaction
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Steps in Radical SubstitutionIntitiation
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Steps in Radical SubstitutionPropagation
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Steps in Radical SubstitutionTermination
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Polar Reactions
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Polarity is affected by structure changes:
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Polarity
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Polarity
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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
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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
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Polar Reactions:
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Electrophiles & Nuclephiles
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a Polar Reaction: Addition of HBr to Ethylene
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Addition of HBr to Ethylene
HBr
δ+
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Π-Bonds as Nucleophiles:
� Π-bonding electron pairs can function as Lewis bases:
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Mechanism of Addition of HBr to Ethylene
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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
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electrons move from Nu: to E
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Nu: can be negative or neutral
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E can be positive or neutral
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ELECTRONS AND CHARGES
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Describing a Reaction: Equilibria, Rates, and Energy Changes
aA + bB cC + dD
Keq = [Products]/[Reactants] = [C]c [D]d / [A]a[B]b
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Keq
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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
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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
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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
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Alkyl halides have relatively good leaving groups
How do alkyl halides react?
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Alternatively…
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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
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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
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A bulky substituent in the alkyl halide reduces thereactivity of the alkyl halide: steric hindrance
Tertiary alkyl halides cannot undergo SN2 reactions
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Reaction coordinate diagrams for (a) the SN2 reaction of methyl bromide and (b) an SN2 reaction of a stericallyhindered alkyl bromide
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Inversion of configuration (Walden inversion) in an SN2 reaction is due to back side attack
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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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An SN1 is a two-step reaction and the leaving groupdeparts before the nucleophile approaches
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Reaction Coordinate Diagram for an SN1 Reaction
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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
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When a reaction forms a carbocation intermediate,always check for the possibility of a carbocationrearrangement
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The Stereochemistry of SN2 Reactions
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The Stereochemistry of SN1 Reactions
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Sometimes extra inverted product is formed in an SN1reaction because…
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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
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Calculation of an Energy Change from Bond Dissociation Energies
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Describing a Reaction: Energy Diagrams and Transition States
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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‡)
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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
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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
• 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).
=>
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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).
=>
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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
=>
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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.”
=>
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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?
=>
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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
−= =>
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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
=>
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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).
=>
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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. =>
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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
=>
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Chlorination Energy Diagram
Lower Ea, faster rate, so more stable
intermediate is formed faster.
=>
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• 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
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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
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Bromination Energy Diagram
• BDE for HBr is 368 kJ, but 431 kJ for HCl
=>
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Bromination vs. Chlorination
=>
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Endothermic and
Exothermic Diagrams
=>
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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.
=>
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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.
=>
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Reactive Intermediates• Carbocations
• Free radicals
• Carbanions
• Carbene
=>
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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.
=>
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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. =>
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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. =>
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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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