Salt effect on the endo/exo ratio of the reaction of cyclopentadiene with methyl methacrylate

Article abstract of DOI:10.1016/S0040-4020(02)01055-4

The salt effect on the stereoselectivity of the reaction of cyclopentadiene with methyl methacrylate has been investigated. CaCl₂, Na₂SO₄, KCl and LiCl enhance the endo/exo ratios, while guanidinium chloride (GnCl) and LiClO₄ decrease them. The results are supported by independent calculations of salting-out and in coefficients.

Full text of DOI:10.1016/S0040-4020(02)01055-4

Tetrahedron 58 (2002) 8759–8762
Salt effect on the endo/exo ratio of the reaction of cyclopentadiene
with methyl methacrylate
Suvarna S. Deshpande,a Usha D. Phalguneb and Anil Kumara
,
*
aPhysical Chemistry Division, National Chemical Laboratory, Pune 411 008, India
bOCS Division, National Chemical Laboratory, Pune 411 008, India
Received 27 June 2002; revised 26 July 2002; accepted 22 August 2002
Abstract—The salt effect on the stereoselectivity of the reaction of cyclopentadiene with methyl methacrylate has been investigated. CaCl2,
Na2SO4, KCl and LiCl enhance the endo/exo ratios, while guanidinium chloride (GnCl) and LiClO4 decrease them. The results are supported
by independent calculations of salting-out and in coefficients. q 2002 Published by Elsevier Science Ltd.
1. Introduction
In the past, the research work from this laboratory has been
focussed on delineating the origin of the forces responsible
for rate variations in salt solutions.3,7 The salt effect on the
kinetics of the reaction of anthracene-9-carbinol with
N-ethylmaleimide has recently been demonstrated in
detail.7b The present paper deals with the study of endo/
exo ratios for the reaction of cyclopentadiene with methyl
methacrylate in different salt solutions. To the best know-
ledge of the authors, no reports exist in the literature
describing the salt effect on this reaction. As more exo (less
endo) product has been reported for this reaction in organic
solvents, this investigation explores the possibility of
altering the endo/exo ratio in salt solutions.
The rates and stereoselectivities of Diels–Alder reactions
can be greatly varied in the presence of water, non-aqueous
solvents and salt solutions. The use of solvent manipulation
for enhancing the rates, stereoselectivities and endo/exo
ratios was based upon the classic work from the laboratories
of Breslow1 and Grieco.2 Whereas Breslow and co-workers
demonstrated the spectacular effect of water and its salt
solutions on Diels–Alder reactions,1 the use of 5 M
LiClO4–diethylether, LPDE was established by Grieco
and co-workers in accelerating sluggish Diels–Alder
reactions and in obviating the high pressure conditions
during the synthesis of cantharidin.2 The developments in
this area have been reviewed recently from this laboratory.3
2. Results and discussion
As a part of the efforts being made in this laboratory it was
shown that the endo/exo ratios for the reaction of
cyclopentadiene with methyl acrylate increased in aqueous
LiCl, NaCl, NaBr and CaCl2, while LiClO4 and guani-
dinium chloride (GnCl) lowered them.4 As shown several
years ago, the reaction of cyclopentadiene with methyl
methacrylate (Scheme 1) in organic solvents yields more
exo product.5,6
Fig. 1 shows the (endo/exo)rel ratios obtained for the title
reaction in LiCl, KCl, Na2SO4, CaCl2, LiClO4 and GnCl up
to a concentration of 3 M. The (endo/exo)rel is defined as the
endo/exo obtained in salt solution over that in water alone.
As the reaction in water serves as a reference reaction, the
reaction in this laboratory was carried out in each batch
containing 18 mmol of cyclopentadiene and 15 mmol of
Scheme 1.
Keywords: salting-out; Diels–Alder reaction; salt solution.
*
Corresponding author. Tel./fax: þ91-20-5893044; e-mail: akumar@ems.ncl.res.in
0040–4020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd.
PII: S0040-4020(02)01055-4

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Table 1. Contributions of ka, kb and kc, and total salting coefficients, kS for
the reaction of cyclopentadiene with methyl methacrylate in salt solutions
Salt
ka
kb
kc
kS
CaCl2
Na2SO4
KCl
LiCl
GnCl
LiClO4
0.568
0.461
0.313
0.239
0.078
0.048
20.051
20.041
20.029
20.017
20.373
20.483
0.016
0.008
0.004
0.003
20.029
20.055
0.533
0.428
0.288
0.225
20.324
20.490
solubilities of diene and dienophile as compared to the
solubilities in water. The reverse effect takes place in
presence of salting-in agents. An effort was made to
compute the solubility of methyl methacrylate in different
salt solutions by using the method based on Universal
Functional Group Contribution Model, UNIFAC as modi-
fied in this laboratory and tested for different cases.4,9 Fig. 2
shows the relative solubility of methyl methacrylate,
(S/S 0)MMA in different salt solutions. The quantity
(S/S 0)MMA is defined as the solubility of methyl methacryl-
ate in salt solution over that in water. The agreement
between the computed10a and experimental solubilities10b
confirms the validity of our computational methodology.
As seen in Fig. 2, CaCl2, Na2SO4, KCl and LiCl lower the
solubility of methyl methacrylate as compared to in water
and thus methyl methacrylate salts-outs. On the other hand,
GnCl and LiClO4 increase the solubility of methyl
methacrylate through the salting-in effect.
Figure 1. (endo/exo)rel as a function of salt concentration, [salt] for the
reaction of cyclopentadiene with methyl methacrylate; (X) CaCl2, (A)
Na2SO4, (D) KCl, (W) LiCl, (O) GnCl, (L) LiClO4.
methyl methacrylate in 10 ml of water for about 9 h to reach
completion. The reaction in water was repeated four times
with the average value of endo/exo being 0.40^0.02
(endo¼29%, exo¼71%) showing that water alone cannot
reverse the endo/exo value of this reaction, in agreement
with the earlier report.6d
From the above plot, it is clear that CaCl2, Na2SO4, KCl and
LiCl increase the (endo/exo)rel ratios, indicating that these
salts enhance the amount of endo product. Of these salts,
CaCl2 is the most effective additive. This suggests that the
endo product is preferred over exo in the presence of CaCl2.
On the other hand, both GnCl and LiClO4 decrease the
endo/exo ratios, thereby increasing the dominance of the exo
product. From Fig. 1, it is clear that endo products in water
can be greatly enhanced if the reaction is carried in CaCl2,
Na2SO4, KCl and LiCl. The endo product can be increased
by 1.3 times in a 1.5 M CaCl2 solution. The order in which
the these salts increase the endo/exo values is: CaCl2.
Na2SO4.KCl.LiCl. Similarly, LiClO4 is a more effective
salt than GnCl in decreasing the endo/exo ratios for this
reaction.
In order to rationalize the salting effects in this reaction, the
salting-out and in coefficients were computed using scaled
particle theory11a because of its successful application to
a variety of properties, including solubilities.4,11b,c The
salting coefficients, kS obtained from the computational
methodology advanced by Shoor and Gubbins,12 and
Pierotti11d are listed in Table 1. In essence, kS is a
combination of three terms: ka accounting for cavity
formation by the diene or dienophile, kb introducing the
diene or dienophile in the cavity and kc giving the number
density of solution species.
The increase and decrease of endo/exo values and rates of
Diels–Alder reaction in salt solutions are attributed to the
salting-out and in phenomena.1,3,8 The salts that enhance
rates also increase the hydrophobic effect operating in the
solvent medium. Thus, CaCl2, Na2SO4, KCl and LiCl are
the salting-out agents and GnCl and LiClO4 the salting-in
ones. Accordingly, the salting-out agents lower the
As seen from Table 1, positive kS (salting-out) values are
observed for CaCl2, Na2SO4, KCl and LiCl, while negative
(salting-in) for GnCl and LiClO4. The kS values follow the
order, in which the salts affect the endo/exo values. For all
the endo/exo ratio-enhancing salts, the ka values are high
and positive suggesting that cavitation is not easier in the
presence of these salts. Thus, the effect of these salts stems
from the salting-out. The small magnitude of kb in these
salts suggest that solvation of diene and dienophile is not
possible. On the other hand, highly negative kb values in
GnCl and LiClO4 indicate strong solute–solvent inter-
actions leading to the salting-in effect. The resultant kS is a
product of competition between ka and kb. Scaled particle
theory is noted to predict the correct sign and magnitude of
kS in this reaction unlike the simplified Debye–McAulay
theory.13
The cavity formation and solvation phenomena in relation
to endo/exo ratios can also be independently supported by
the Gibbs free energy computations.14 The relative change
in the Gibbs free energy on addition of a salt in a reaction
Figure 2. Relative solubilities of methyl methacrylate, (SMMA/S 0MMA) in (1)
CaCl2, (2) Na2SO4 (3) KCl (4) LiCl (5) GnCl (6) LiClO4; lines are
calculated, points experimental.

S. S. Deshpande et al. / Tetrahedron 58 (2002) 8759–8762
8761
3. Experimental
Cyclopentadiene was freshly cracked from its dimer
(Merck) just before its use. Methyl methacrylate obtained
from Merck was used immediately after its distillation. High
purity AR grade salts were used for preparing solutions in
de-ionized water.
In a typical run, 1.5 ml (18 mmol) of freshly cracked
cyclopentadiene was transferred into 5 ml of salt solution.
Then, 1.5 ml (15 mmol) of methyl methacrylate was
dissolved in 5 ml of the salt solution. The solution
containing cyclopentadiene was added to the solution
having methyl methacrylate. The reaction mixture was
magnetically stirred at 308C for about 9 h.
The endo and exo-products were determined using NMR as
described in the literature.21 Each reaction was carried out
three times and the endo/exo ratios were reproducible to
within 5%. GC and NMR were used to check the
dimerization of cyclopentadiene, which was found to be
negligible.
Figure 3. Plots of d(DG 0)solvn against d(DG 0)cavn for the reaction of
cyclopentadiene with methyl methacrylate in CaCl2, GnCl, LiClO4, see
Fig. 2 for symbols.
Acknowledgements
d(DG 0)soln can be given as that in Gibbs free energies of
cavitation, d(DG 0)cavn and solvation, d(DG 0)solvn as:
The authors thank Sanjay Pawar for his technical help
during this work. The Department of Science and
Technology, New Delhi is acknowledged for funding this
research through a grant-in-aid (SP/S1/G19/99).
dðDG0Þsoln ¼ dðDG0Þcavn þ dðDG0Þsolvn
The computed d(DG 0)cavn and d(DG 0)solvn values from
scaled particle theory11,12 are plotted in Fig. 3. For GnCl and
LiClO4, the d(DG 0)solvn is larger than d(DG0)cavn confirm-
ing that the salting-in effect by these salts originates from
solvation effects. On the other hand, due to the electro-
striction effect14,15 in CaCl2, Na2SO4, KCl and LiCl, less
empty space is available for accommodating the diene and
dienophile leading to salting-out. This is consistent with the
trend of ka values shown in Table 1 for these salts.
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