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Elimination
Elimination:
One molecule is cleavaged into two molecule
PT: Proton Transfer, LGE: Leaving Group Explusion
Mechanisms
• E1 : leaving group (X) cleavage first)
• E2 : The H and the X is cleavaging simultaneously
• E1cb : H cleaved first (cb: conjugated base)
H
H
C
C
C
C
L
C
C
C
C
L
The elimination reactions are often competing with
substitution because of tight similarity
Compiting reaction ways
B
H
+
CR2
CR2
1,2 E
L
SN2
H
C
CR2
CR2 +
CR2
B
L
L
+
C
C
C
C
RC-L
L
C
H
H + CR2
E1
C
rC-H
B
C
rC-L
H
H
C
C
L
L
A schematic illustration of two extreme cases: E2 is favoured over E1
(left hand side) and E1 is favoured over E2 (right hand side). It is
assumed that under ordinary circumstances E1cb is the least favoured
mechanism.
O2
N
O2N
O2N
H
C
H
H
C
H
HO
HO
C
H
NR3
+ H2O
NO2
O2N
OMe
H
H
Ph
OMe
H
H
H
C
Ph
Ph
H
C
H
NR3
H
C
H2O
H
H
+ :OMe
NO2
H
Cl
Cl
OH
+ H2O
+ Cl
OH
H
Ar
NC
CN
Ar
NC
Ar
CN
CN
CN
+ H2O
CN
CN
CN
CN
CN
The more heavily an olefin is substituted, the greater its stability:
H3C
CH3
H3C
H
>
>
H3C
CH3
H3CH2C
H3C
CH2CH3
H
H3C(H2C)3
H
>
H3C
CH2CH3
H
H
The size of the nucleophile plays a dominant role in determining whether the
Zaitsev or the Hofmann product is formed thus, constitutional isomer may
also be formed.
X
H
CH
H3C
Small base
Zaitsev's rule
H
H
H
Bulky base
Hoffman's rule
H
H X
R
H
H H
H H
Only small nucleophilescan
attack here leading to
Zaitsev product
Large nucleophiles
can attack here leading
to Hoffman product
H3C
C
H
C
H
CH3
H3C
C
H2
C
H
CH2
Ionic reactions in gas phase
Double-well potential curve : The ion-molecule complexes are at
lower energy level (Even more the energy of TS could be lower )
than the starting species and product.
Theoretical and experimental
examples
Degradation of hydroxy-carbonic acids in gas phase
(Domingo et al. (1997), J. Am. Chem. Soc. 119, 6415-6422.)
General considerations
a-Hydroxy-propinic acid RRC(OH)COOH where R,R is H and their
homologons derivates(eg lacticid where R,R is H,Me) have 4 unique
conformations in which the two OH groups assume special
conformational relationships with respect to each other. These involve
two internal rotations(dihedrals) associated with the two/OH groups with
a unique carbnyl orientations.
Conformation D is sufficiently destabilized so only A, B and C are
expected to show decarbonylation reaction
The following 3 families of mechanisms may be anticipated
A: Unimolecular Internal SN2 type reactionmechanism (SNi) with alactone formation
B: Unimolecular Internal Addition/elimination mechanism with alactone formation
C: Bimolecular elimination (E2) reaction mechanism with the involved
of a base catalyst
Degradation of hydroxy-carbonic acids in gas phase
(Domingo et al. (1997), J. Am. Chem. Soc. 119, 6415-6422.)
„A” path
[TS1]
k1
H
O
O
C
R2
C
-H2O
[TS4]
k4
R1
R2
C
OH
R1
R1 +
O
R2
C
C
O
CO
O
„B” path
H
O
O
C
R2
C
OH
R1
[TS2]
k2
[TS4]
k4
O
C
R2
-H2O
R1
C
R1
R2
C
O
+
CO
O
„C” path
H
O
C
R2
R1
O
C
OH
[TS3]
k3
R1
H 2O +
R2
+ CO
C
O
Degradation of hydroxy-carbonic acids in gas phase
(Domingo et al. (1997), J. Am. Chem. Soc. 119, 6415-6422.)
Based on experimental data (Chuciani és mtsi.) these reactions
follows homogen, unimolecular and first order way
Shcism:
R1R2COHCOOH  R1R2CO + CO + H2O
I.
R1=R2=H:
II.
R1=H, R2=CH3:
III.
R1=R2=CH3:
Three possible reaction paths were
computed:
TS2
TS1
TS4
TS3
G
IN
R
P
x
Degradation of hydroxy-carbonic acids in gas phase
(Domingo et al. (1997), J. Am. Chem. Soc. 119, 6415-6422.)
Results
Energies
Data of all components after ZPVE and temperature
correction
The intermediers are far stable than any of starting and
product species
Degradation of hydroxy-carbonic acids in gas phase
(Domingo et al. (1997), J. Am. Chem. Soc. 119, 6415-6422.)
Kinetics
As the k2 is very high the rate constant was calculated as
follows
kap=k1+k2+k3
Results at MP2/6-31G++G** level are in better
correlation with the experimental data
The rate constans derived from experiments are closer to
the computed k1 : „A” path is dominating
Degradation of hydroxy-carbonic acids in gas phase
(Domingo et al. (1997), J. Am. Chem. Soc. 119, 6415-6422.)
Results
TS geometies
In the case of TS1 and TS2 hydroxyl group is leaving, and
with the carboxylic protont form a water molecule
Difference is in the attacking carboxilic group and its direction
TS3: The hydrogen of carboxilic group and one of its oxygen
and the hydrogen of hydroxilic group leave as a water
Investigation of E2 model systems to characterize
kinetic isotope effects
(Schrøder és Jensen (1997), J. Org. Chem. 62, 253-260.)
Methods
MP2/6-31+G*
5 leaving group and 6 nucleophil agent: 30 reactions were
investigated
Calculating of kinetic isotope effects :
kH / kD  exp(( GD  GH ) / RT )
Reaction scheme:
Nu
Nu
H
H
X
+ Nu
+ XX
Investigation of E2 model systems to characterize
kinetic isotope effects
(Schrøder és Jensen (1997), J. Org. Chem. 62, 253-260.)
Results
Three typical TS
Br-/NH2Reactant like
Cl-/FE2
TS
F-/Clproduct like
The proton transfer occurs along a linear in most cases, only two
structures deviate from 180 degrees (both of them are reactant-like with
NH3 leaving group. The departure of the leaving group and the proton
transfer are coordinated but not coincident, the former depends on the
initial compound, the latter on the nuclepohile.
Base-induced 1,4-elimination
(Bickelhaupt (2001) Mass Spetrom. Rev.. 20, 347-361.)
Introduction
Competing reaction paths:
B
+
H
CR2
CR
CH
CR2
L
1,4-E
B
H
R2C
C
H
CR2
L
B
SN2’
1,2-Evin
CR
B
H
R2HC
CR
C
H
CR2
R2HC
C
R
C
CR2
Using different reaction systems, 1,4-elimination dominates
over 1,2 E. The real competitor is SN2: the greater the
electronegativity of the leaving group, the more likely SN2 is
(the LUMO of the substrate localizes more on Ca).
L
L
Base-induced 1,4-elimination
(Bickelhaupt (2001) Mass Spetrom. Rev.. 20, 347-361.)
Reaction mechanisms
In the case of 1-alkoxy-2-butenes (Bickelhaupt et al., 1995, J. Am.
Chem. Soc. 117: 9889) the reaction mechanism is E1cb with the
formation of S-H- ions (S=CH3CHCHCH2Oet, CH3CHCHCH2OMe).
H3C
CH2
HC
O
CH3
CH
With cis-metoxy substrates, F- and OH- yields a barrierless proton
transfer, moreover, the allyl cation is stable after dissociation of the BH
conjugated acid. The bond between Ca and the leaving group is intact
and only slightly longer than in the reactant.
Base-induced 1,4-elimination
(Bickelhaupt (2001) Mass Spetrom. Rev.. 20, 347-361.)
Reaction of protonated alcohols with water
(Uggerud and Bache-Andreassen (1999), Chem. Eur. J. 5, 1917-1930.)
Alcohols in acidic water solution can either reform by
water exchange or yield an alkene with water elimination.
This group focused on substitution.
R
R
H2O
H 2O
R
H 2O
R
OH2
R
OH2
R
SN1
OH2
OH2
H2O
SN2 (Walden-inversion)
Methods:
FT-ICR
Theoretical methods
HF/6-31G(d) optimization and MP2/6-31G(d) energy calculation
for each critical point (reactants, transition states, intermediates,
products)
Geometry optimization at MP2/6-31G(d) and B3LYP/6-31G(d)
level of theory was performed for all reactions but those
including water clusters (see below)
Zero-point energy correction was performed. reaction rates were
calculated with the method ’microcanonical variation RiceRamsperger-Kassel-Marcus” (RRKM)
Reaction of protonated alcohols with water
(Uggerud and Bache-Andreassen (1999), Chem. Eur. J. 5, 1917-1930.)
Results
Proton affinity of water clusters (aggregates of several water molecules,
not really great clusters) increases with their size (MP2 calculations tend
to overestimate it).
The reaction takes place only if it is exothermic or only slightly
endothermic. This means that the proton affinity of water involved
should be greater than that of alkenes.
CH3 CH2 OH2
H2C
CH2
H3O
The ethanol  ethene reaction pathway is energetically favoured.
However, the bound water molecule increases the activation barrier. The
reaction is observable experimentally but very slow.
H2C
CH3
CH
CH3
CH
OH2
H3O
H3C
The isopropanol  propene reaction is observable experimentally in
spite of being slighltly less favoured thermodynamically than the former
as the energy barrier is lower.
H2C
CH3
H3C
C
CH3
OH2
H3C
C
H3O
CH3
The tert-butanol  isobutene reaction is endothermic and les favoured
energetically than the substitution. In spite of these this is the dominant
reaction. It is explained on the basis of the infavoured formation of the
buthyl cation (in the case of the elimination TS is intramolecular). It is
not clear from the article whether they have actually calculated anything
for carbocations but they reason using their stability.
Reaction of protonated alcohols with water
(Uggerud and Bache-Andreassen (1999), Chem. Eur. J. 5, 1917-1930.)
Results:
Reaction of protonated alcohols with water
(Uggerud and Bache-Andreassen (1999), Chem. Eur. J. 5, 1917-1930.)
Results
Energy diagram1
Reaction of protonated alcohols with water
(Uggerud and Bache-Andreassen (1999), Chem. Eur. J. 5, 1917-1930.)
Results
Energy diagram2
„Symmetrical” TSs
Reaction of protonated alcohols with water
(Uggerud and Bache-Andreassen (1999), Chem. Eur. J. 5, 1917-1930.)
Results
The slightly endothermic reactions do not agree well with expectations
but are explainable. The covibrational energy of the reactant was
possibly underestimated and the experimental heats of formation bear
also some uncertainity.
Proton affinities (literature data vs. MP2 calculations): H2O (691, 704),
(H2O)2 (806, 839), (H2O)3 (871, 888), valamint CH2CH2 (681, 681),
CH3CHCH2 (752, 748), (CH3)2CCH2 (796, 806)
Solvatation: water cluster models. In these reactions the proton affinity
of the medium is an important factor (the water in the medium does not
participate in the reaction but has a catalytic role by promoting water
excision from the protonated alcohol). Naturally, the solvation of the
species is also important.
Structures correspondig to TSs are solvated less well than reactants and
products. Even considering this, the order of activation energies is the
reverse of that for nuclepophilic substitution: CH3CH2 > (CH3)2 >
(CH3)3C.
While for SN2 the reactivity order is reversed when shifting from the
gas phase to water, this does not occur in the case of elimination (this is
not emphasised by the authors but this is what they got).
Acid catalysed elimination
Dehydration of carbohydrates [2]
Models:
alcohols (ethanol, isopropanol, ethylene-glycol
Methods:
1. B3LYP/6-311G(d,p) and CBS-QB3 (the authors state that the
latter is more suitable for energy calculations of transition
states)
2. Estimation of reaction rates with TST (transition state theory)
method
Aims:
1. Determination of activation energies for the alcohols and
comparing the obtained values. Conclusions for carbohydrates.
2. Investigation of the effects of alkali metals and protons.
Results:
1. Elimination reaction of ethanol (uncatalyzed)
Activation energy is 67.4 kcal/mol which is in agreement with the
experimental value. According to bond angles, he four-centered TS is
closer to the product than the reactant.
H
C
H
H
H
OH
C
H
H
C
H
H
OH
C
H
H
H2C
CH2 + H2O
Elimination reaction of ethanol in presence of
alkali metals (Lewis acid catalysis)
Li+ and Na+ significanlty reduce the activation barrier (by 12 and 7
kcal/mol, respectively). Lithium ion is more effective because of the
long Na-O bond (the radius of Na is too big). Formation of carbocations
may occur as a side reaction, but this is fortunately not significant.
Li+
Li+
H
C
H
C
H
OH
H
H
H
C
H
H
OH
C
H
H
Li+
OH
H
H
C
H
H
C
H2C
H
CH2 + H2O * Li+
Elimination reaction of protonated ethanol (Brønsted acid
catalysis)
Activation E is greatly reduced (20.7 kcal/mol) in the presence of
protons, which is in accordance with experimental results. The reaction
is endothermic because the proton affinity of the alcohol is greater than
that of water. TS is stable and has lower energy than the product.
Formation of carbocation occurs as a side reaction.
C
H
H
OH2+
H
C
H
C
H
H
H
H
OH2+
C
H
H
OH2+
H
H
C
H
C
H
H2C
CH2 + H3O+
H
H
OH2+
C
H
H
C
H
H
CH3CH2+
+ H 2O
Energy profile of the elmination reaction of ethanol
80
OH
H
67.4
C
C
H
H
H
H
Li
Relatív E0
(kcal/mol)
C
H
H
55.3
OH
H
C
H
H
H3C
40
OH2
H
C
OH
H
H
H
30.7
20.7
H3C
C
CH2
C
H
CH2
H
11.4
OH2*Li
8.8
C
C
H
H
H
H
H2C
10.1
H2C
CH2
0
CH2 + H3O
16.4
H
H
OH2
H3C
H2C
OH3
OHLi
H3C
+ H2O
32.8
C
H
CH2
CH2 + H2O
CH2 + H2O*Li
Elimination reaction of isopropanol
Isobutanol is a secunder alcohol, nevertheless, the reaction mechanism is
the same as in the case of ethanol with a practically identical activation
energy. The only difference is that the TS is more product-like.
OH
H
H
CH3
C
H
C
H
C
H
H
H
OH
C
H
H
CH3
H
C
+
C
H
H 2O
CH3
Elimination reaction of isopropanol in the presence of alkali
ions
The barrier heigth decreases more markedly than for ethanol (49,5
kcal/mol).Carbocation formation occurs (a secunder one is more stable)
but not in a significant quantity.
Li+
Li+
H
C
H
C
H
O
H
H
CH3
C
H
OH
C
H
H
CH3
+
Li
OH
H
H
C
H
H
H
H
C
C
CH3
H
+
C
CH3
H2O* Li+
Elimination reaction of protonated isopropanol
Similarly to alkali field metals, the barrier height decreases more than
for ethanol (12.5 kcal/mol). However, the TS is much more than the
product (36.9 kcal/mol) thus activation energy should be calculated for
the second step. Carbocation is also formed and is thermodynamically
more stable than the elmination product.
C
H
C
H
OH2+
H
OH2+
H
C
H
CH3
H
C
H
H
CH3
OH2+
H
H
H
C
H
C
H
H
C
CH3
+ H3O+
C
H
CH3
Carbocation formation
OH2
H
OH2+
H
C
H
H
C
H
CH3
H
C
H
+
H
CH3CHCH3+ + H2O
C
CH3
Energy profile of the elimination recation of protonated isopropanol
CH3
40
H2C
+ H3O
C
H
36.9
Relatív E0
(kcal/mol)
CH3
H3C
C
H
+ H2O
23.5
20
H
O
H
C
H
H
C
H
H
CH3
12.5
H
H
OH2
H
H
C
C
H
CH3
13.2
OH2
OH2
C
H
12.5
H
H
C
C
H
CH3
H
H
C
H
CH3
0
Elimination reaction of ethylene glycol
The barrier height is only slighltly altered relative to that of ethanol, thus
it can be concluded that it is uniformly 67-69 kcal/mol for all alcohols
investigated. This indicates that a similar value for carbohydrates can be
expected. This is supported by the investigation of levoglucosan (a
sterically hindered carbohydrate).
Elimination reaction of ethylene glycol in the presence of
alkali metals
As Na+ and Li+ form a complex with the compound, the activation
energy is high and the reaction is slower than for ethanol
Li
HO
C
H
Li+
+
OH
H
H
H C
HO
C
H
H
OH2
H
+
Li
H
C
O
OH
C
H
H
H
C
C
H
H
+
C
H2O*Li+
H
HO
H
Elimination reaction of protonated ethylene glycol
The barrier height is low, the major product is protonated formaldehyde.
Similar oxonium cations may be important in reactions occuring at the
pyrolysis of carbohydrates
H
H2O
OH
C
H
C
H
H
H
H
H
O
C
H
C
H
H
OH
H2O
H
OH
C
H
H
H
C
OH
C
H
H
H
+
C
H
H2O
Energy profile of the elimination reaction of ethylene glycol
100
72.1
H
H
O
C
H
H
C
H
OH
H
50
H
H
O
C
C
H
H
H
OH
27.6
OH
H2C
OH
6.3
H2O
C
H2O
CH
C
H
H
H
-0.1
H
0
OH
H2O
OH
C
C
H
OH
H
H
H
-12.5
H3C
CH
OH
H3C
CH
H2O