”The Physics and Chemistry of Water”
10 – Chemical reactions in aqueous
solutions
Effects of water in reactions
• Hydration of reactants cause steric barriers
• Increases attraction between nonpolar reactants
• Strong cohesive energy promotes volume-reducing
reactions
• Surface-adsorbed water affects bulk/surface composition ratios
• May swell polymers
• Necessary for acid-base reactions
Water as a medium for organic reactions
• Increasingly used for environmental reasons.
• Efficient in many situations where the transition state or other intermediates are polar.
• Sometimes strong reaction promotors at low
concentrations.
Elementary reaction dynamics I
(After Atkins)
• The activated complex is an energetic cluster
of reactants, near the region of the reaction
rearrangement, where some vibrational mode
is replaced by a translation along the reaction
coordinate.
• The transition state is the configuration at the
peak (saddle point) in the potential energy
curve (surface).
• The reaction rate is the frequency of activated
complexes passing over the energy barrier.
Elementary reaction dynamics II
Consider a bimolecular reaction:
A + B → [AB]‡ → products
The equilibrium constant for formation of the activated complex is
‡
K =
[AB]‡
[A][B]
The rate of the reaction is
d[A]
−
= [AB]‡ × (rate of passage over barrier)
dt
The rate of passage equals the frequency ν with
which the complex separates as products, i.e. when
one of its vibrations becomes a translation. This
is a thoroughly excited vibration at temperature
T , with classical energy ² = kT , and ν = ²/h, so
that ν = kT /h, and the reaction rate is therefore
d[A]
‡
kT
= k2[A][B] = K [A][B]
dt
h
where the rate constant is (the Eyring equation):
−
k2 = K ‡
kT
h
Elementary reaction dynamics III
Some thermodynamic quantities:
• The activation free energy is
∆‡G = −RT ln K ‡
• Since ∆‡G = ∆‡H − T ∆‡S, the Eyring equation becomes
kT −∆‡G/RT
kT ∆‡S/R −∆‡H/RT
k2 =
e
=
e
e
h
h
Now ∆‡H = ∆‡E + ∆(P V ‡), but in liquids
(and solids) the P V ‡ term is negligible, so that
d ln k2
dT
=
Ea
RT 2
=
∆H ‡ + RT
RT 2
, and Ea = ∆‡H+RT
• ∆r Gª is the standard reaction free energy.
Diels-Alder reactions I
A nonpolar ”4+2 cycloaddition”, forming a 6membered ring from from two unsaturated fragments, via an ordered transition state, where the
reactant’s π-electrons form a common cloud.
• Outcome generally predictable even for complicated cases.
• Usually does not require catalyst or initiator.
• The ”aromatization” of the transition state
decreases its energy, so the activation barrier
is low.
This is a reaction that can be considerably enhanced by hydrophobic effects!
Diels-Alder reactions II
(Rideout & Breslow, J. Am. Chem. Soc. 102, 7817 (1980))
Cyclopentadiene + Butenone
Rate constants at 20◦ C
Solvent
Additive
k2 (10−5 M−1 s−1 )
Isooctane
5.94
MeOH
75.5
H2 O
4400
H2 O
LiCl (4.86 M)
10800
+
−
H2 O
C(NH2 )3 Cl (4.86 M)
4300
• The rate is higher in MeOH than isooctane,
where the former is slightly more polar.
• LiCl is expected to increases the hydrophobic
interaction between nonpolar molecules, due
to the strong tendency of Li+ to induce order in water. (In old style terminology it is a
”structure maker”, and ”salts out” nonpolar
material dissolved in water).
−
• Guanidinium chloride (C(NH2)+
3 Cl ) disrupts
the organized water strcture (a ”structure breaker”),
and is expected to reduce hydrophobic association, though the effect on the rate is only
small.
Diels-Alder reactions III
(Rideout & Breslow, J. Am. Chem. Soc. 102, 7817 (1980))
Anthracene-9-carbinol + N -Ethylmaleimide
Rate constants at 30◦ C
Solvent
k2 (10−5 M−1 s−1 )
Isooctane
796
1-butanol
666
MeOH
344
CH3 CN
107
H2 O
22600
• The reaction is fastest in the least polar of the
organic solvents.
• The dramatic rate increase in water remains.
Hydrophobic interaction, driving the reactants
together at a rate higher than in organic solvents,
causes the rate increase, rather than just the polarity of the solvent!
Carboxymethylation of starch in
isopropanol-water media I
(Kooijman et al., Starch/Stärke 55, 495 (2003))
Native starch (above) is insoluble in cold water,
but carboxymethylated starches are, provided that
the degree of substitution is higher than ∼0.2.
The reaction is carried out with sodium monochloroacetate (SMCA) in the presence of a strong base, to
enhance nucleophilicity of the hydroxyl groups,
and to swell the starch particles.
R–OH + NaOH *
) R–ONa + H2 O
R–ONa + ClCH2 COONa → R–O-CH2 COONa + NaCl
NaOH also participates in undesired side-reactions,
reducing the selectivituy of SMCA:
NaOH + ClCH2 COONa → H–O-CH2 COONa + NaCl
The reaction medium is typically a 9:1 mixture of
alcohol:water, where alcohol is required for solubility, and water for efficiency.
Water has a clear influence on the degree of substitution (DS) and the selectivity of SMCA for
the reaction with starch (rather than NaOH).
DS for arrowroot (solid line) and potato (dashed line) starch.
Conversion (solid line) and SMCA selectivity (dashed line).
• Water swells the starch particles to make them
more accessible for the reagents.
• Water also hydrates the starch, thus affecting
the distribution of the various components between the bulk liquid and the starch particles.
Water in radical reactions I
(Yorimitsu et al., J. Am. Chem. Soc. 122, 11041 (2000))
Radical cyclization of allyl iodoacetate in various
solvents
solvent
yield dielectric
ET
cohesive energy
(%) constant (kcal/mol) density (cal/mol)
H2 O
78
78.39
63.1
550.2
DMSO
37
46.45
45.1
168.6
formamide
24
111.0
55.8
376.4
DMF
13
36.71
43.2
139.2
acetonitrile 13
35.94
45.6
139.2
methanol
6
32.66
55.4
208.8
ethanol
3
24.55
51.9
161.3
THF
<1
7.58
37.4
86.9
benzene
<1
2.27
34.3
83.7
hexane
<1
1.88
31.0
52.4
Radical reactions are generally rather insensitive
to the medium, so why does water improve the
yield?
Water in radical reactions II
(Yorimitsu et al., J. Am. Chem. Soc. 122, 11041 (2000))
• The large dielectric constant of water reduces
the activation energy for the rotation 1 → 3,
and the cyclization 3 → 5, relative to other
solvents.
• The high cohesive energy density assists in the
rotation 1 → 3, in that the size of the cavity
required for the reactant is reduced.
• The dipole moment has a minor effect, but
from 1 to 4, the dipole moment increases, thus
being promoted by highly polar solvents.
Solvation effects on reactions
(Bergsma et al., J. Chem. Phys. 86, 1356 (1967))
MD simulation of a nucleophilic displacement reaction in water
Cl− + CH3Cl → ClCH3 + Cl−
Contrast between reactions in gas and water –
free energy profile along the reaction coordinate:
• The polar solvent will stabilize the higher charge
density reactants and products more than the
lower charge density transition state complex.
• The energy wells in the gas phase are characteristic of metastable charge dipole complex
forming close to the transition barrier.
Solvation effects on reactions
(Bergsma et al., J. Chem. Phys. 86, 1356 (1967))
MD simulation of a nucleophilic displacement reaction in water
Cl− + CH3Cl → ClCH3 + Cl−
Contrast between reactions in gas and water –
free energy profile along the reaction coordinate:
• The polar solvent will stabilize the higher charge
density reactants and products more than the
lower charge density transition state complex.
• The energy wells in the gas phase are characteristic of metastable charge dipole complex
forming close to the transition barrier.
Solvation effects on reactions
(Bergsma et al., J. Chem. Phys. 86, 1356 (1967))
MD simulation of a nucleophilic displacement reaction in water
• The results of the reaction simulation differs
significantly from a description with equilibrium solvation, where the free energy of the
solvent is equilibrated to the reaction system
along the reaction coordinate.
• The outcome of the reaction is highly dependent on (or determined by) the local configuration of the solvent at the transition state.
• The reaction in the transition barrier is characterized by a frozen solvent configuration, i.e.
nonadiabatic solvation.
• A significant fraction of the transtion states
reappear as reactants again.
There are two reasons for this:
1. The time scale of the reaction is much shorter
than the characteristic time scale of solvent
reorientation.
2. There is rapid variation of charge distribution
along the reaction coordinate near the transition barrier, leading to a pronounced coupling
between the reacting system and the solvent,
in addition to the ion-dipole-forces present for
fixed charges.
H-bond effects
(Yin et al., Organometallics 20, 1216 (2001))
Transition-metal-catalyzed hydrogenation of CO2
to formic acid is accelerated by small amounts of
added water in organic solvents.
Free energy profiles (kcal/mol) for the reactions
of TpRu-(PH3)(CH3CN)(H) with CO2, without (top)
and with (bottom) water.
H-bonding of H2O to CO2 enhances the electrophilicity at the carbon, resulting in significant reduction of the reaction barrier.
General references
• G. Wilse Robinson et al., Water in biology, chemistry
and physics, Singapore: World Scientific 1996.
• W. A. Smit et al., Organic synthesis, Cambridge: Royal
Society of Chemistry 1998.