4
M. Suresh et al. / Tetrahedron 75 (2019) 130573
Table 5
the carbonyl compound.
Reaction with hypervalent iodine reagents.
In conclusion, we have developed multiple approaches
involving various oxidants for the oxidative cleavage of C]C of
arylidene Meldrum's acid and malononitrile derivatives to the
corresponding aldehyde. The advantages of these methods are as
follows: (1) the cleavage of C]C bond proceeds under mild con-
dition with various oxidants in short reaction time; (2) the C]C
bond can be cleaved without addition of any transition metal
catalyst; (3) PIDA cleaves the C]C bond of malononitrile de-
rivatives effectively.
Entry
oxidants
Co-oxidants
Solvent
Time (mins)
Yield (%)
1
2
3
4
5
PIDA
PIDA
PIDA
DMP
p-IBA
e
DCM
THF
120
45
120
360
360
56
89
80
nr
nr
4
. Experimental section
e
e
CH
THF
DCM
3
CN
e
Reagents and solvents were purchased from commercial sour-
NMO
ces and used without further purification. All the reactions were
monitored by TLC, performed on 0.25 mm silica gel coated
aluminium sheets (F-254) and visualized by UV light and KMnO
solution. Column chromatography was carried out using silica gel
4
generated iodoxobenzoic acid [5a,17] (i.e mixture of p-IBA and 2 eq.
of NMO) 2g were ineffective. Further, we decided to explore the
oxidative cleavage of malononitrile derivatives with PIDA in THF. To
our delight, the PIDA involved C]C bond scission of malononitrile
derivative provided comparatively better yield than other oxidants
and the results are summarized in Table 6.
1
(100e200 mesh). H NMR spectra were recorded in solvent CDCl
3
on 300, 400 MHz Bruker-AVANCE and 400 MHz JEOL spectrometers
with TMS as an internal standard.
4.1. Synthesis of substrate
3
. Plausible mechanism
Starting materials arylidene Meldrum's acid, malononitrile de-
rivatives were synthesized by a modified procedure reported by
Bigi et al. [20,21] Thus the mixture of aldehyde and Meldrum's acid
or malononitrile in H O was stirred at room temperature for 12 h to
2
afford the corresponding product. Diethylmalonate derivatives,
cinnamic acid and chalcones were prepared according to reported
procedure [22e24].
From various experiments, we observed that the C]C bond of
arylidene Meldrum's acid derivatives can be effectively cleaved
with peroxides, NaClO , and PIDA to afford selectively the corre-
2
sponding benzaldehydes. The C]C bond cleavage with these oxi-
dants quickly furnished the aldehydes. Controlled experiments by
lowering the oxidants and the reaction time minimize the imme-
diate C]C bond cleavage to aldehyde. Unluckily, while purification
we found that the intermediate was decomposed and afforded the
aldehyde. However, the available literature sources have supported
to develop the plausible mechanism [5b,7,8,18]. Commonly, the
oxidation of double bond of all substrates with peroxides proceed
via epoxidation and further the oxirane ring cleavege to form the
diol under the developed reaction conditions. However, we assume
that the C]C bond cleavage of arylidene Meldrum's acid with
4.2. General procedure for oxidative cleavage by oxone to afford
acid 3
To a heterogeneous mixture of arylidene meldrum's acid or
malononitrile derivatives in distilled water, Oxone (3 eq) was added
ꢀ
and heated at 80 C for 2 h. The progress of the reaction was
monitored by the TLC and after completion saturated NH
tion was added and extracted with ethyl acetate. The organic layer
was dried over anhydrous Na SO and purified by column chro-
matography to isolate the pure product.
4
Cl solu-
oxone in CH
3 2
CNeH O proceeds via diol formation and followed by
2
4
the CeC single bond cleavage as shown by the Moorthy et al
Scheme 3). [5b].
(
In case of PIDA mediated reaction [19], first it activates benzylic
4
.3. General procedure for oxidative cleavage by oxone to afford
position of arylidene Meldrum's acid by interacting with carbonyl
oxygen and followed by the Michael addition generates the
aldehyde 2
b
-
acetylated species (Scheme 4). Further attack by carbonyl oxygen of
acetyl group leads to intramolecular cyclization and form the ace-
tyloxonium ion of Meldrum's acid derivative. Presence of water in
the reaction medium support to provide the a-actylated-b-hydroxy
alkylidene Meldrum's acid. Further cleavage of CeC bond provides
To a heterogeneous mixture of arylidene meldrum's acid or
malononitrile derivatives in distilled water, Oxone (2.5 eq) was
ꢀ
added and heated at 45 C for 2 h. The progress of the reaction was
monitored by the TLC. After 2 h, saturated NaHCO
added to the reaction mixture and extracted with ethyl acetate. The
organic layer was dried over anhydrous Na SO and purified by
column chromatography to isolate the pure aldehyde.
3
solution was
2
4
Table 6
Reaction of PIDA with arylidenemalononitrile derivative.
4
H
.4. General procedure for oxidative cleavage by oxone in CH
3
CN/
Substrate
Substitution
Time (mins)
Yield of aldehyde
2
O to afford aldehyde 2
4
4
3
2
2
-Cl
-Me
,4-di-OMe
,5-di-OMe
-OMe
45
45
60
60
60
2b, 89%
2f, 91%
2 h, 82%
2j, 78%
2k, 77%
Oxone (2.5 eq) was added to the solution of Arylidene mel-
drum's acid or malononitrile derivatives in CH
3
CN/H
2
O (1:1) and
ꢀ
heated the reaction mixture at 45 C for 1 h. The progress of the
reaction was monitored by the TLC. After completion, ethyl acetate
was added to the reaction mixture and separated the organic layer.
H
300
No reaction
The organic layer was washed thrice with saturated NaHCO
tion and followed by distilled water. The organic layer was dried
over anhydrous Na SO and filtered through silica gel plug. The
3
solu-
2
4