Acid-base catalysts derived from weakly acidic ion exchange resin: Efficiency in the Knoevenagel condensation

Article abstract of DOI:10.1016/S0040-4039(00)60817-1

Weakly acidic cation-exchange resins in H⁺ form, partially neutralized with H₂N(CH₂)(n)N⁺Me₃ OH^- (n = 2-5), have been shown to catalyze the Knoevenagel condensation. The efficiency of catalysis depends on the aminoalkyl chain length and extent of neutralization.

Full text of DOI:10.1016/S0040-4039(00)60817-1

Acid-Base Catalysts Derived from Weakly Acidic Ion Exchange
Efficiency in the Knoevenagel Condensation
Resin:
Tohru Saito,* Hitoshi
Keiko Honda, and
Faculty of
Sciences,
Weakly acidic
catalyze
and extent of
H+
OH-
=
catalysis
on
A combination of acid and base components often exhibits an efficient catalytic effect in some synthetically
useful reactions. The well-known instances are successful uses of
acid salts for certain
In these cases, the catalysts
condensations such as the Knoevenagel’ and intramolecular aldol condensations.*
seem to activate carbonyl substrates usually through
reaction of carbonyl compounds with a nucleophile containing an ionizable hydrogen can be catalyzed, in
principle, by both the base and acid that function by assisting of the nucleophile and by hydrogen
or
formation. Meanwhile, the addition
bonding or protonation at the carbonyl oxygen, respectively. If the two catalysts, acidic and basic, act
concurrently as shown in Scheme 1, a great catalytic advantage would be expected’ In practice, promising
results have been obtained for systems consisting of one intermolecular general base and one intramolecular
general acid catalyst.’ Moreover, bifunctional tautomeric catalysis can be regarded as a special case of acid-base
. . . . .
. . . . . A-
H - A
l+
Scheme 1
Recently, silica gel functionalixed with amino
Knoevenagel condensation and a concerted, acid-base-catalyzed mechanism has been
has been shown to be a useful catalyst for the
In seeking
efficient acid-base catalysts for this type of condensation, we designed the catalysts (type 1) that contain
aminoalkyl groups bound (with regulating the fraction of amine) to a carboxylic acid-type cation exchange resin
ion pairs with the intramolecular
amino alkyl chain length should vary the interaction between substrates and the amino and
affecting catalytic nature. Here we describe the preparation of
condensations of several aklehydes and ketones with active methylene compounds.
The catalysts ‘la-e prepared as follows.
(quimolar
resin was filtered off, washed successively with
Similarly, the catalysts lb-e
were prepared by the use of the corresponding
(0.5 molar equiv).
groups.
It was
that a change in the
groups in 1,
1
and its catalytic effect on the Knoevenagel
A
of Amberlite IRC-50 in
was allowed to stand at temperature
and
and aqueous
The resulting
24 h.
and dried to give the catalyst la
= 2, c:
=
=
d:
=
e:
7535

7536
Amberlite IRC-50
(la-e)
l a
2
0.73
0.31
4
5
l e
The
Amberlite IRC-50 resins la-e thus obtained were tested for catalytic activity in the
condensation of benxaldehyde with ethyl cyanoacetate. As summarized in Table I, all la-e manifested the
catalytic activity even at room
used. The catalysts la and lb,
The
was greatly affected by the
of the resin catalyst
the former, showed notably high efficiency, whereas the catalysts
holding a longer alkyl chain of amine tended to lower catalytic activity. Interestingly, replacement of the primary
amino groups in lb by the dimethylamino resulted in considerable retention of activity. Umnodifled
Amberlite IRC-50 resin showed no catalytic activity. In contrast with the catalysis by the modified
a sulfonic acid-type cation exchange resin, in
Amberlite IRC-50 resins, Amberlyst
form exhibited no catalytic effect on the condensation at room temperature. On the other
hydroxide and n-caproic acid showed only a poor
hand, a mixture of
catalytic effect on the condensation.
4
3
2
Scheme 2
Table L Condensation of
Catalyst
with Ethyl Cyanoacetate Using la-e and Related Catalysts
lime
Temp.
temp.
room temp.
5
5
100 min
58
temp.
room temp.
room temp.
temp.
7
5
46
0
room temp.
temp.
containing 0.01 mol of
and 0.10 g of catalyst in 3 ml of
stated.
mp
mp
1).
carried out with 0.60 g of catalyst In
farm
of 0.24 mmol of the hydroxide and 0.53
of the acid.

7537
Table II. Knoevenagel Condensation of2 with Using the Catalyst
2
3
X
Y
Temp.
R e f .
12.13
12
82.5-83.5
temp.
mom temp.
room temp.
temp.
113-114
126128
12.13
14
room temp.
15, 16
17
92.e93.5
49-50
mom temp.
room temp.
16. 19
15.19-21
oil
12.22
23.24
oil
room temp.
containing 2.0 mmol of
of
2.0-2.1
of active
0.020 of catalyst in
0.6-1.5
The successful demonstration of catalysis by the modified Amberlite IRC-50 resins la-e, particularly by
in the above with ethyl cyanoacetate prompted us to examine the efficiency of
the catalyst in the Knoevenagel condensations of several other aldehydes or ketones with active methylene
compounds. am in Table IL aromatic aldehydes. when reacted at
room temperature, were all converted to the
yields (entries l-3). Benxaldehyde
was also found to condense with diethyl malonate and with ethyl
but in lower yields (entries 12 and
13). In the
of clnnamaldehyde with
the Knoevenagel condensation product was obtained
without the Michael addition
(entry 4).
condensation of cyclohexanone with
very
(entry
(entry 5). The same ketone also reacted
but smoothly at the boiling point of
ethyl cyanoacetate rather slowly at room temperature
(entry 9). The reactions
(entries and 11).
much more difficult to
accomplish with the aromatic ketones than
To our knowledge, this is the
example of the use of a weakly acidic resin as a catalyst in the
Knoevenagel condensation.” It is uncertain as to whether or not the mechanism of the Knoevenagel
condensation
50
by 1 involves a concerted acid-base catalysis. However, the efficiency of Amberlite
observed in the Knoevenagel condensation of
with ethyl
cyanoacetate seems to eliminate the possibility of the
in this
intermediate for the reaction. Further studies in
catalysis.
to delineate the scope and limitations of the modified
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(Received in Japan 7 August