experimental background 4. geometrical and energetic bases of reaction mechanisms 5. typical...
TRANSCRIPT
Experimental background
4. Geometrical and Energetic Bases of reaction mechanisms
5. Typical reaction mechanisms- free radical halogenations of methane and other saturated hydrocarbons- conditions for competing reactions such as substitution and elimination- spatial arrangement of MO and reaction stereochemistry- hard and soft acids and bases- thermodynamic and kinetic control of competing mechanism- potential energy surface
Geom. & Energ. BasesGeometrical and Energetic Bases of reaction mechanisms
Solomons 269Bruckner I-220March’s 1300
+ ClHO
H2C CH2
H
Cl
HO
H2C CH2
HO H
Cl
H2C CH2
H
Cl
H2C CH2
H OH
SN2
E2
H
X
HO:
HO:
E2
SN2
Competing reactions: two types of second order reactions can be distinguished:
E2
SN2
Geom. & Energ. Bases
EtCl + OH major product EtOH minor product (1%) CH2=CH2
E2
SN2
-538.13151999
-75.3265988-154.07574482
-458.91415079
-78.03171814-76.01074643
0
E2
SN2
293,8 kcal/mol
314.7 kcal/mol
RHF/6-31G(d)
memo: at RHF/6-31G(d) gas phasethe major product is EtOH (SN2)~21 kcal/mol!
However the reaction will not takeplace in the gas phase ~300 kcal/mol?
Geom. & Energ. Bases
H
XH
HO
+ H2O + X
+ XSN2
E2
+OH:
The energetics of the reactions,may be measured by reaction kinetics determines which one of two mechanism dominates.
Both reactions follow second order kinetics:
HO:-+
H
Cl
+H2O + Cl-
vE2 = kE2[R-Cl][OH-]
C C
H
Cl
+ :OH(-) C C
H
OH
+ Cl(-)kSN2
vSN2 = kSN2[R-Cl][OH-]
the goal is to demonstrate thatfor parallel or competing mechanisms, the product ratio in the reaction mixture, at any time during the reaction, is equal to the rate constant ratio
kSN2
kE2
C C OHH
C C
]
]
[
[=
Geom. & Energ. BasesGeom. & Energ. Bases
C Ck'E2
C C
H
OH
k'SN2
C C
H
Cl
k'SN2 = kSN2 [OH(-)] and k'E2 = kE2 [OH(-)]where
Experimentally measured concentrations as function of the reaction time
d[A]dt
- = k1[A] + k2[A] = (k1 +k2)[A] = k[A] [A] = [A]0 exp(-kt)
the rates of consumption of A:
differential rate equ. integrated rate equ.
d[X]dt
= k1[A] = [A]0k1e-kt
d[Y]dt
= k2[A] = [A]0k2e-kt
individual rates of product formation:
kk1
[X] = [A]0(1-e-kt)
kk2
[Y] = [A]0(1-e-kt)
with the initial conditions:[X]0 = [Y]0 = 0
[X][Y] =
k2
k1
Experimental background
4. Geometrical and Energetic Bases of reaction mechanisms
5. Typical reaction mechanisms- free radical halogenations of methane and other saturated hydrocarbons- conditions for competing reactions such as substitution and elimination- spatial arrangement of MO and reaction stereochemistry- hard and soft acids and bases- thermodynamic and kinetic control of competing mechanism- potential energy surface
Typical reaction mech.
OMe
O2N NO2
NO2
OEt
O2N NO2
NO2
EtO K
MeO K
2-Methoxy-1,3,5-trinitro-benzene
2-Ethoxy-1,3,5-trinitro-benzene
Typical reaction mech.
HO: XC HO C + XOH X
#
HO: + XC HO CHO: X + X
Transition State
Reaction Intermediate
SN2
SN1
H2C Br + OH C2H5 OH + BrCH3
C Br HO C4H9 + BrHO
CH3
CH3
H3C
General equations for the various mechanisms
Nucleophil Substitutionon saturated carbon atoms:
Nucleophil Substitutionon aromatic carbon atoms:
X
OMe
X X
OEtMeO OEt
EtO K
H
MeO K
H
K
where X electron withdrawing group
example:
Typical reaction mech.Electrophilic Substitutionon saturated carbon atom:
SE2: Y-R + E Y + R-E
SE1: Y-R + E Y + + E Y + R-ER
BrHg-R + Br-Br + HgBr2R-Br
H3C C CH3
O
H3C C CH2
O
+ Hbáziskatal.
H3C C CH2
O
Br Br+
H3C C CH2Br
O
+ Br+
Electrophilic Substitutionon aromatic carbon atom :
O
N
O
H +
NO2
+
H
Benzene Nitro-benzene
HX H X X
H
example:
Typical reaction mech.
H RaH
Ra
+ Ra H
slow
Ra
fast Ra
Typical reaction mech.Radical Substitutionon saturated carbon atom:
Radical Substitutionon aromatic carbon atom :
H3C:H + Cl H3C + HCl
H3C + Cl : Cl H3C-Cl + Cl
H PhPhH
+ Ph-HPh Ph
intermediate biphenyl
Ph C
O
O O C
O
Ph Ph C
O
O O C
O
Ph80oC
Ph C
O
O Ph + O C O
benzoyl peroxide at relatively low temperature
2 benzoyloxy radicalsspontaneous decarboxylation
initiaiton: Ra Cl OCMe3 Ra Cl OCMe3+
R H OCMe3 R H OCMe3
R ClOCMe3 +
chain reaction
example:
memo: Ra := initiator radicalR := radicalR-Cl := the looked-for alkyl halogenid
alkyl hypochlorite forming “stable” alkoxy radical
Sykes 57
Sykes 61
Typical reaction mech.
C C
Br
H
C C
H
Br
C C
Br
BrH
H
H
H
H
H
H
H HH
HH
slow fast
Typical reaction mech.
Br
Me CH CH2
Br
H
H
Me CH CH2secondary carbocation
Me CH CH2primery carbocation
H
H
Me CH CH2
Me CH CH2
H
H
Br
Br
propene
2-Bromo-propane
1-Bromo-propane
Typical reaction mech.Nucleophil additionon unsaturated carbon atom:
AN2
Nu : C O Nu C O
Nu : +O
O
Nu
example:
+ -H2C CH C N H2C CH
EtO
C N
H
EtOH 3-Ethoxy-propionitrileAcrylonitrile
C O+ -
EtOH
C
HOEt
OC
OEt
OHEtOH
hemiacetal
Solomons 734Electrophil additionon unsaturated carbon atom:
Sykes 75
Typical reaction mech.Radical additionon unsaturated carbon atom:
Me+ Br
Br
R
Br
Me
HO + H-Br H2O + Br
H-Br
2,3,4,5-Tetramethyl-hexa-2,4-diene
2-Bromo-2,3,4,5,5-pentamethyl-hex-3-ene
example:
R CH CH2
HBr
HBr
R CH CH2
H Br
R CH CH2
Br H
radical addition
electrophylicaddition
R:= alkyl group
Sykes 88
Typical reaction mech.
CH2 CR2
H2O O H
Br
H
CH2
Br
H
Br
CH2 CR2slow fast
H
H
R
R
O HBr
CH2 CMe2
Br
H
CH2 CMe2
H
H
2-Bromo-2-methyl-propane Isobutene
Typical reaction mech.Base induced (nucleophilic) eliminationon saturated carbon atom:
HO:
H
Z
H2O +
+ Z
Bimolecular (E2)
Unimolecular:E1cB
+ Br
H2C CH2
H
Br
HOH2C CH2
HO H
Br
H2C CH2
H OH
SN2
E2
X2C CH2
Y
X2C CH2
HO H
Y
X2C CH2
H
Y
HOHO H
conjugated base
Unimolecular:E1
Cl2C CF2
HO H
F
C CF2
H
F
HO
ClCl
1,1-Dichloro-2,2-difluoro-ethene2,2-Dichloro-1,1,1-trifluoro-ethane
Typical reaction mech.Acid induced (electrophilic) eliminationon saturated carbon atom:
- H2OH2C CR2
OH
HH2SO4
H2O
H
H2C CR2
HOH
H
H2C CR2
H- H
H2C CR2
H- H2O
H2C CMe2
OH
HH2SO4
H
H2C CMe2
H OHH
2-Methyl-propan-2-ol Isobutene
H
SMe
Ph
PhH + SMe
2,3-Dimethyl-2-methylsulfanyl-butane
2,3-Dimethyl-but-2-ene
Radical eliminationon saturated carbon atom:
H2C CH2
Y
H
H2C CH2
Y
HRaRa
Sykes 156
Typical reaction mech.Free radical halogenations of methane and other saturated hydrocarbons
Homolytic bond dissociation energies
How to determine whether a reaction is endo- and exothermic? Determine the corresponding bond dissociation energies (BDE).
H + H + Cl + Cl
H2 + Cl2
2 HCl
-206+162
-44
at B3LYP/6-311++G(d,p)no vibrational corr.
157 kcal/mol -207 kcal/mol
-49 kcal/mol
HH + ClCl2 HClBDE(kcal/mol): 104 + 58 +(-103 x 2) = 162+(- 206)
H of reaction = -206 - ( -162 ) = -44 kcal/mol
Typical reaction mech.Homolytic and heterolytic bond dissociation energies
H:Cl
H(+) + Cl(-)
H + Cl
heterolytic
or ionic
homolytic
or free radical
Note that: the heterolytic (ionic) dissociation requires (103 + 230.4 = 333.4 kcal/mol)is more than three times that of the homolytic (free-radical) dissociation (103 kcal/mol).
Furthermoer: This holds for organic molecules also:
Conclusion: direct contrast with the experiencethere must be an explanation!
Answer: the effect of the solvent
Typical reaction mech.Typical reaction mech.Answer: Both cations and anions are strongly solvatedby polar solvents such as H2O.
Therefore 1. ionic reactions are energetically more favourable in polar solvent
Bond type BDEkcal/mol
Bond type
BDEkcal/mol
Bond type
BDEkcal/mol
Bond type BDEkcal/mol
H3C-H 104 F-F 38 H-F 136 H3C-F 108
10 C-H 98 Cl-Cl 58 H-Cl 103 H3C-Cl 83.5
20 C-H 94.5 Br-Br 46 H-Br 87.5 H3C-Br 70
30 C-H 91 I-I 36 H-I 71 H3C-I 56
Typical textbook values of selected BDE values in kcal/mol.
2. free-radical reactions are energetically more preferred, in the gas phase or in a non-polar solventswhere the above stabilizationis not possible,
Typical reaction mech.Free-radical reactions: halogenation of hydrocardons
In ionic reactions electrons moved in pairs
In free-radical reactions, only one electron moves in a given step
In stable organic molecules electrons are always paired.Thus, a free-radical needs to be generated to initiate a radical mechanism.
If the free-radical is generated thermally, then BDE is the energy requirement
If the free-radical is generated photochemically,then more than the BDE is needed
Typical reaction mech.
an example: the chlorination of methane
Cl:Cl 2 Cl chain initiation
H3C:H + Cl H3C + HClH3C + Cl:Cl H3C–Cl + Cl
chain propagation
2 CH3 H3C–CH3
2 Cl Cl–Cl
H3C + Cl H3C–Cl
chain termination
energy requirement is the BDE Cl2 +58 kcal/mol.
bond- breaking
bond-making
overall reaction
Hreaction Ereaction
= BDEproduct - [-BDEreactant] -104 - (-103) =1
H3C:H + Cl H3C + HClH3C + Cl:Cl H3C–Cl + Cl
chain propagation
Hreaction = BDECl2 - [-BDECl-CH3] -58 - (-83.5) = -25.2
BDEF–F2 F = +38 kcal/mol BDECl–Cl2 Cl = +58 kcal/mol
BDEBr–Br2 Br= +46 kcal/mol
BDEI–I2 I = +36 kcal/mol
BDEF-CH3 = +108 kcal/mol
BDECl-CH3 = +83.5 kcal/mol BDEBr-CH3 = +70kcal/mol BDEI-CH3
= +56 kcal/mol
H = -70 kcal/mol
H = -25.2 kcal/mol H = -24kcal/mol H = -20 kcal/mol
BDEH-CH3 = +104 kcal/mol BDEH-CH3 = +104 kcal/mol
BDEH-CH3 = +104 kcal/mol
BDEH-CH3 = +104 kcal/mol
BDEH-F = +136 kcal/mol
BDEH-Cl = +103 kcal/mol BDEH-Br = +87.5 kcal/mol BDEH-I = +71 kcal/mol
H = -32 kcal/mol
H = 1 kcal/mol H = 16.5 kcal/mol H = 33 kcal/mol
Hreaction = BDEC-CH3 - [-BDEH-Cl] -104 - (-103) = 1
Typical reaction mech.H = -32 kcal/mol + H = 1 kcal/mol +H = 16.5 kcal/mol +H = 33 kcal/mol +
H = -70 kcal/mol H = -25.2 kcal/mol H = -24kcal/mol H = -20 kcal/mol
= -102.0 kcal/mol F= -24.2 kcal/mol C l= -7.5 kcal/mol Br= +13.0 kcal/mol I
Energy profile for the methane halogenation chain propagation steps(H3CH + X H3C + HX and XX + CH3 X + XCH3) for X = F, Cl, Br and I.
Reaction with fluorine is very exothermic (-102 kcal/mol) Explosion!
Reaction with iodine is very endothermic (+13 kcal/mol) It doesn’t occur!
Reaction with chlorine is rather exothermic (-24.2 kcal/mol) Ferocious, not very selective reagent.
Reaction with bromine is slightly exothermic (-7.5 kcal/mol) Sluggish, selective reagent.
Typical reaction mech.Example for selectivity: chlorination is not really selective (-24.2 kcal/mol)
bromination is more selective (-7.5 kcal/mol)
H3C CH2 CH3
H3C CH2 CH2Cl
H3C CH2 CH2Br + H3C CHBr CH3
H3C CHCl CH3Cl2
Br2
+45% 55%
<1% >99%six H atoms attached to primary carbon atom two H atoms attached to
secondary carbon atom
Hreaction (kcal/mol)
Bond X = Cl X = Br
H3C H -103.0 - (-104.0) = + 1.0 -87.5 - (-104.0) = + 16.5
1 C H (primer) -103.0 - (- 98.0) = - 5.0 -87.5 - (- 98.0) = + 10.5
2 C H (secondary) -103.0 - (- 94.5) = - 8.5 -87.5 - (- 94.5) = + 7.0
3 C H (tertiary) -103.0 - (- 91.0) = -12.0 -87.5 - (- 91.0) = + 3.5
Calculation of Hreaction for [9.10] using the thermochemical equation [9.7]
Chlorine bites off H atom from almost any CH bond
Bromine can bite off only H atoms from sec. and tert. C atoms
Typical reaction mech.
Example for stereochemistry
if a chiral centre is formed during halogenation then the reaction will yield a racemic mixture
if the molecule have an optically active compound,then the resulting compound will be diastereomeric.
C
C
Ph
CH3
Cl
HBr
H C
C
Ph
CH3
H
H Br
Cl
C
C
Ph
CH3
H
H H
Cl
C
C
Ph
H Cl
H3C H
SS
SR
Br
chiral centre
prochiral centre
Diastereomeric
S
Br2Br2
Typical reaction mech.
Ea(Cl) < Ea(Br)1o-2o
1o-2o
Typical reaction mech.Reactivity and Selectivity
HCH3C CH2
H H
1o 2o
CH3–CH2–CH2 + HBr
CH3–CH–CH3 + HBr
CH3–CH2–CH2 + HCl
CH3–CH–CH3 + HCl
Br
Cl
For H attached to primer C atomEa(Cl)1 < Ea(Br)1
Cl. is more reactive than Br.
For H attached to sounder C atomEa(Cl)2 < Ea(Br)2
Br. is more selective than Cl.
Typical reaction mech.
Conditions for competing reactions such as substitution and elimination
SN2 and E2 as well as SN1 and E1 mechanisms may occur in competition
The structure of the substrate can discriminate between SN2 or the SN1
HO: X
R
C
RH
HO: X
R
C
HH
HO: X
R
C
RR
The polarity of the solvent can discriminate between SN2 or the SN1
lesspolar
morepolar
highlypolar
H2O + R-Clk1
k2H2O + R(+) + Cl(-)
R-OH + HCl
H3O+ + + Cl(-)C C
k2subst
k2elim
polarity stabilizes carbocations (and haloids)thus give chance to E1
C C
[ROH] k2subst
k2elim=
SN1 E1
=
product ratio
rate const. ratio
Typical reaction mech.
C C
[ROH] k2subst
k2elim=
SN1 E1
=
product ratio
rate const. ratio
The relative magnitude of the rate constantsis determined by the basicity of the nucleophile used
Strong Bronsted bases is more effective inremoving a proton from the intermediate carbocation than weak ones.
C C
E1 > SN1
> [R–Nuc]
k2elim > k2
subst
for strong bases for weak bases
C C
E1 < SN1
< [R–Nuc]
k2elim < k2
subst
An examples
EtO- stronger basethan EtOH
C C
H
Br
CH3
H
CH3
H
C C
CH3
CH3
H
H
C C
CH3
CH3
H
H
+ Br(-)
+ H-Br
tBuOEt +
tBuOEt +
~ 10% ~ 90%
~ 20% ~ 80%
SN1 E1
EtOH
EtO-
conclusion
E1 > SN1
Typical reaction mech.Examples
CH Cl
H3C
H3CCH I
H3C
H3CNaI
Na2CO3+ NaCl
CH Br
H3C
H3C
CH Cl
H3C
H3C
CH OEt
H3C
H3C
C H
H2C
H3C
C H
H2C
H3C
~ 100% ~ 0%
~ 75%
SN1 E2
~ 25%
Cl(-)
EtO(-)
CH
X
C C
H
HH
H
H3CH
CH3 CH CH CH3
CH3 CH2 CH CH2
small base
Zaitsev`s rule
bulky base
Hoffman`s rule
The two second-order rate constantskSN1 and kE2 reflect the difference in basicity of the nucleophile used
stronger bases
weaker bases
E1 > SN1
E1 < SN1
Typical reaction mech.Spatial arrangement of MO and reaction stereochemistry
The Frontier Molecular Orbital (FMO), (HOMO/LUMO) approach
Spatial arrangements of molecular orbitals are crucial for the stereochemistry of a reaction: e.g. SN2.
backside attack on the C - Cl bond is due to the orientation of the LUMO of the R-Clalong the C - Cl axis, pointing away from the carbon
the HOMO of the nucleophile
the LUMO of the substrate interact the HOMO of the substrate breaks up during the reaction when a new bond is formed
SN2
Solomons 235 & movie
Typical reaction mech.Spatial arrangements of molecular orbitals are crucial for the stereochemistry of a reaction: e.g. E2.
Solomons 267, 288 & movie
Typical reaction mech.
C C
H(+) C C
H
(+)
Typical reaction mech.Spatial arrangements of molecular orbitals are crucial for the stereochemistry of a reaction: e.g. SN1 and E1.
The first step for the SN1 and E1 is common.
It is a reverse Lewis acid-base reaction
N
H
HH
B
F
FF
N B
H
F
F
H
F
H+ (-)
(+)
C C
H
C C
H
OH
CC
H
HO
(+) + (-):OH +
In SN1 the simple Lewis acid-base reaction,the collapse of the carbocation and hydroxide ion follows:
C C
H
C CHO:(-) + H2O +(+)
In E1, the carbocation behaves as a Bronsted acidand a proton is transferred from carbon to the basesuch as HO:(-)
the carbocation is a -protonatedcarbon-carbon double bond:
C C
Cl
C C
Cl
C OB:(-) + + A(+)(+) B C O
A
Lewis orBronsted acidLewis base
Typical reaction mech.The HOMO/LUMO involvement is a general principle of organic reactions.e.g. the addition reaction to a carbon-oxygen double bond (carbonyl compound):
The acid, A(+), attaches the HOMO and the base, :B(-), attaches the LUMOof the carbonyl compound.
The orbital level diagram of H2C = O
RHF/6-31G(d)
Typical reaction mech.
Further examples for FMO
Overlaps between the HOMO of the reactant andthe LUMO of the reagent is as follows:the positive lobe of overlaps with an other positive lobeand a negative only with an other negative lobe
Conservation of orbital symmetry (Fukui, Woodward and Hoffmann) is usedto predict whether a reaction is allowed or forbidden.
Diels-Alder reaction March’s 1068
Electrocycling rearrangement March’s 1428
Ring closure of dienes March’s 1429
Sigmatropic rearrangement March’s 1438
Typical reaction mech.hard and soft acids and bases
Bronsted acidity: the proton donating ability in aqueous solution.(The pKa of an acid is related to the pH value of the aqueous solution)
H2O + HA H3O(+) + A(-) pKa = pH - log[A(-)][HA]
Bronstedacid
Bronstedbase
proton is transferred
Problem: the same type of simplicity is not present for defining Lewis acidity and basicity.
electron pair is transferred
+A B
A B
Lewis acid
Lewis base
Lewiscomplex
HOMO LUMO
N
H
HH
+ B
F
FF
N B
H
F
F
H
F
H
RHF/6-31G(d)
Solomons 97,
Etymology:the “dative bond” of the Lewis comp. was donated by the base
Typical reaction mech.the strengths of Lewis acids depend on the structure (polarizability) of the bases (acceptor) employed.
BX3 AlX3 FeX3 GaX3 SbX5 SnX4 AsX5 ZnX2 HgX2
Lewis Characteristics Hard Soft
size small large
(+) charge density high low
Acid electronegativity high low
polarizability low high
lone pair no yes
valence electrons bonded strongly loosely
(-) charge density high low
Base electronegativity high low
polarizability low high
oxidation hard easy
Some characteristics of Lewis acids and bases
The softness of bases increases from left to the right according to rows and going dawn along the columns of the periodic table
CH3- NH2
- OH- F- or I- Br- Cl- F-
softer harder or softer harder
[i]
Typical reaction mech.
Hard bases Borderline bases Soft bases
NH3,RNH2,H2O,OH
R2O,ROH,RO-,F-,AcO-
C6H5NH2,C5H5N,N3-
Br-,NO2-,SO3
2-
R2S,RSH,RS-,R3P,
(RO)3P,RNC,CO,C2H4,
PO43-,SO4
2-,Cl-,CO32- C6H6,I
-,SCN-,S2O32-,CN-
CIO4-,NO3
- H-,R-
Hard acids Borderline acids Soft acids
H+,Li+,Na+,K+, Fe2+,Co2+,Ni2+Cu2+ Cu+,Ag+,Hg+,Pd2+
Mg2+,Ca2+,Mn2+, Zn2+,Sn2+,Sb3+,Pb2+, Pt2+,Hg2+,RS+,I+,Br+,
Al3+,Cr3+,Co3+,Fe3+, Bi3+,NO+,R3C+,C6H5
+, HO+,RO+,I2,Br2,BH3,GaCl3,
RCO+,BF3,B(OR)3,AlMe3, BMe3,SO2,GaH3 1,3,5-(NO2)3C6H3,
AlCl3,AlH3, SO3, quinones, (NC)2C=C(CN)2
CO2,HX (hydrogen- CH2, carbenes
bonded molecules)
Selected hard and soft Lewis acids and bases
Ruff, Csizmadia 361
Examples:
F- is a stronger base with respect to H+ I- is a stronger base with respect to Ag+
H+ is a stronger acid with respect to RNH2
Ag+ is a stronger acid with respect to phosphines (R3P)
Typical reaction mech.The principle of similarity:hard acids react favorably with hard bases
andsoft acids react favorably with soft bases.
Lewis complex to be formed is more stable if both the acid and base components are of the same hardness
The interaction in terms of frontier orbitals:
hard acids have a high-energy LUMO
hard bases have a low-energy HOMO E(HOMO-LUMO) is relatively large
soft acids have a low-energy LUMO
soft bases have a higher-energy HOMO E(HOMO-LUMO) is relatively small
stable but weaker bond of ionic nature e.g. H+ and F- → HF
strong covalent bond is formede.g. Br+ and CH3
- →CH3Br
mismatches: “hard and soft”e.g. H+ and I- → HI low stability complexes are formed
Typical reaction mech.Nucleophiles and electrophiles
neutral or negatively charged compoundcontaining lone electron pairs
electron pair accepting molecules
Lewis base as well as nucleophilic reagent
Lewis acidas well as electrophilic reagent
base strength measured by the protonation equilibrium,nucleophilicity by the rate of nucleophilic reaction.
thermodynamic property
kinetic property
RCH CH2R(+)
RCH CHR RHC CHR
Br Br
H(+) Br(-)
Example 1:
alkenesoft nucleophile
brominesoft electroeophile
protonhard
electroeophile
because of the principle of similarity for the above reactions: k < kH+ Br2
Typical reaction mech.
Example 2:
hard nucleophile
brominesoft electroeophile
protonhard
electroeophile
H(+)
H2O HO(-) HOBr + Br(-)
because of the principle of similarity for the above reactions: k > kH+ Br2
Br2
nucleophiles with soft electrophiles:
same nucleophiles with hard electrophiles:
HS- CN- Br- Cl- OH- F-
faster reaction slower reaction
OH- > CN- > HS- > F- > Cl- > Br- > I-
Conclusion:
soft nucleophiles +
soft electrophiles
hard nucleophiles +
hard electrophiles
driving force: HOMO-LUMO
driving force:attraction of opposite charges
orbital-controlled reaction
charge-controlled reaction
Example:
SN1 reaction: rate-determining step the formation of the carbocation
orbital-controlled reaction
charge-controlled reaction
SN2 reaction: rate-determining step is te HOMO LUMO overlap
Application:
fluoride ion is a hard nucleophile, thus, prepare fluoro compounds via SN1 reaction,enhance the reaction by choosing a good leaving group such as tosylate
Typical reaction mech.Nucleophilicity and solvation
Small sized, hard bases with a large negative charge density e.g. F-, Cl-, RO-
their reactivity is decreased.
form hydrogen bonds in protic solvents
extensive solvation
Large sized, soft nucleophiles,with a small negative charge density e.g. I-, SCN-
very weakly involved in hydrogen bonding
their reactivity is enhanced
Example: if the electrophile is methyl iodide, then the order of nucleophilicity is as follows:
I- > SCN- CN- > N3- Br- > Cl- > AcO-
in protic solvents
in dipolar aprotic solvents
CN- AcO- Cl- Br- N3- > I- > SCN-
Typical reaction mech.Electron supply and demand
The effect of substituents on the FMO energies of Lewis acids and bases and their effect on the subsequent Lewis complex stability.
The electronic effects of substituents:electron withdrawing groups (EWG) make a molecule less basic or more acidic
electron donating groups (EDG) make a molecule more basic or less acidic.
Typical reaction mech.Typical reaction mech.Thermodynamic and kinetic control of competing mechanism
Z
[Y]
[X]
TS
[Y]
[X]
product
transition state stability andproduct stability predetermine X:a clear situation
Question: what will be the major product ?
transition state stability indicate Ybutproduct stability predetermine X:a bias situation
C C
H3C
H3C
CH3
CH3C C
H3C
H3C
H2C
H
>CH3
C C
H3C
CH2
H2C
H>
CH3
H3C
C C
H
(CH2)3
H
H>
H3C
Example: which of the isomers will be formed during a ER and an EN?
more EDGhigher stability
less EDGlower stability
Zaitsev rule Hoffman rule
Typical reaction mech.
The size of the nucleophile (base) plays a dominant role in determining whether the Zaitsev or the Hofmann product is formed:
C C C
H R
H H
X
H H
H
only small nucleophiles
can attack here leading to
Zaitsev product
large nucleophiles
can attack here leading to
Hoffmann product
CH
X
C C
H
HH
H
H3CH
CH3 CH CH CH3
CH3 CH2 CH CH2
small base
Zaitsev`s rule
bulky base
Hoffman`s rule
Typical reaction mech.Potential Energy Surface (PES) representation of chemical reaction
3 translational coordinates and 3 rotational coordinates of a generaln-atomic molecule leave (3n – 6) internal coordinates.