62
KISELEV ET AL.
v-complexes between the Lewis acids and dienophiles
increases the reaction rate by up to 6 orders of magni-
tude without changing the equilibrium constants [1,2].
Carrying out cycloaddition reactions under high exter-
nal pressure leads to an increase of both their rate and
equilibrium constants [1,3]. Changing the solvent can
also influence the rate constants. Unlike organic sol-
vents, until recently the reactions in water had no prac-
tical use because of the low solubility of reactants and
products. However, observations of unexpected accel-
erations of the nonpolar DARs in water in comparison
with organic solvents have arisen a considerable inter-
est to this solvent because of its availability and the
nature of the acceleration effect [4–12].
Currently many types of reactions with significant
rate increases in water are known [13]. Novel meth-
ods of further acceleration and alteration of selectivity
of these reactions have been developed. For example,
DARs of inert aromatic compounds were accelerated
in water by placing them into self-assembled coor-
dination cages [12]. New microfluidic devices allow
to facilitate molecules to come to and to be removed
from aqueous–organic interfaces, creating a quasi-
homogeneous medium [14,15]. A number of hetero-
geneous reactions “on water” with rapid stirring in
aqueous suspensions and emulsions proceed faster than
in pure organic solvents and even faster than under
homogeneous solvent-free conditions [16]. Some of
these processes are effective combinations of click-
chemistry and green-chemistry approaches [17]. Such
an increase in the rate of heterogeneous reactions “on
water” with rapid stirring is likely to be driven by the
strong interactions at the interface between water and
hydrophobic reactants [18].
The effects of hydrophobic promotion [4,10,11], the
influence of the solvent’s cohesive energy [19], and a
sharp rise in the energy level of the reactants in com-
parison with a smaller rise of the energy of the acti-
vated complex [10,11] have been named as possible
causes of the rate acceleration in water. Accumula-
tion of the kinetic data allows to clarify the mecha-
nism of homogeneous reactions “in water” and het-
erogeneous reactions “on water” [20]. The extensive
studies of the DAR of 9-(hydroxymethyl)anthracene
(1) with N-ethylmaleimide in water, in the presence
of inorganic salts, and in binary aqueous–organic sol-
vents have been carried out [4–11]. 1 is a good choice
as diene to study the hydrophobic promotion due to
its large hydrophobic surface. Its aqueous solubility is
only about 10−4 mol·L−1. However, it is sufficient for
UV/vis spectrophotometric monitoring of the reaction
rate thanks to its high UV light absorption coefficient.
Most of the dienophiles having heteroatomic activating
groups are better soluble in water than dienes.
Hydrogen-bond formation between reactants and
water can also be one of the reasons for the re-
action rate enhancement in water. On the other
hand, it has been noted that 2,2,2-trifluoroethanol
forms stronger H bonds than water, but the reac-
tion rate of 1 with N-ethylmaleimide in water is
almost 60 times higher than that found in 2,2,2-
trifluoroethanol [10,11].
In fact, many explanations of the solvent-induced
rate acceleration can be reduced to the same phys-
ical basis. The relative strength of interactions be-
tween the reactants and solvent in comparison with
the strength of solvent–solvent interactions is gov-
erning the reaction rates. In all DARs in solution,
it is always necessary to remove some solvent (S)
molecules surrounding the reaction centers of diene
and dienophile before they form an activated complex
(Eq. (1)):
(Diene) · Sn + (Dienophile) · Sm
→ (Activated complex)= · Sp + S(n+m−p) (1)
If the energy of interactions of reactants with the
solvent is higher than the solvent–solvent interaction
energy, it will be difficult to desolvate the reactants
and the reaction rate will be reduced [21,22]. The rates
of DARs will be increased in two cases: (1) the sol-
vent is rather weakly interacting with the reactants, and
formation of the activated complex is accompanied by
an easy desolvation followed by formation of strong
intermolecular solvent–solvent interactions, which is
the case for hydrophobic reactants in water; (2) weak
interactions of reactants with solvents such as alka-
nes and perfluoroalkanes, when the activated complex
formation is accompanied by an easy release of the
solvent molecules with subsequent formation of weak
solvent–solvent interactions (S–S). In solutions in alka-
nes and, especially, in perfluoroalkanes, intermolecu-
lar interactions of diene–dienophile couples are gen-
erally stronger than those between solvent molecules
[23]. Therefore, in both cases an increase in the DAR
rate can be expected, but this effect is stronger in
water.
In this work, we study and compare the influence
of organic and binary aqueous–organic solvents con-
taining 1,4-dioxane as a cosolvent on the rates of the
Diels–Alder reactions of 1 with N-phenylmaleimide
(3e) as well as 9,10-bis(hydroxymethyl)anthracene (2)
with maleic anhydride (3a) and N-ethylmaleimide (3b)
(Scheme 1).
International Journal of Chemical Kinetics DOI 10.1002/kin.21057