Expeditious reaction of ninhydrin with active methylene compounds on montmorillonite K10 clay

Article abstract of DOI:10.1007/s00706-008-0066-6

Ninhydrin reacted expeditiously with thirteen active methylene compounds on montmorillonite K10 clay at room temperature to furnish, in 5 min, a Knoevenagel condensate in one case, aldols in six cases, aldol-derived cyclic hemiketals in three cases, and interesting products in the remaining three cases. Almost identical results were obtained, but faster, when the reactions were carried out in water on steam-bath. The structures of two novel products were also confirmed by single-crystal X-ray diffraction analysis. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-008-0066-6

Monatsh Chem (2009) 140:189–197
DOI 10.1007/s00706-008-0066-6
ORIGINAL PAPER
Expeditious reaction of ninhydrin with active methylene
compounds on montmorillonite K10 clay
Manas Chakrabarty Æ Ajanta Mukherji Æ
Shiho Arima Æ Yoshihiro Harigaya Æ
Guillaume Pilet
Received: 3 September 2008 / Accepted: 11 September 2008 / Published online: 14 October 2008
Ó Springer-Verlag 2008
Abstract Ninhydrin reacted expeditiously with thirteen
active methylene compounds on montmorillonite K10 clay
at room temperature to furnish, in 5 min, a Knoevenagel
condensate in one case, aldols in six cases, aldol-derived
cyclic hemiketals in three cases, and interesting products in
the remaining three cases. Almost identical results were
obtained, but faster, when the reactions were carried out in
water on steam-bath. The structures of two novel products
were also confirmed by single-crystal X-ray diffraction
analysis.
to furnish the Knoevenagel condensates in wide-ranging
yields, milder catalysts and conditions continue to be
developed for this reaction [5–11]. The so-called ‘‘solvent-
free’’ synthesis on solid supports [12, 13], often promoted
by infrared [14] and microwave irradiation [15–17], cata-
lyst-free reactions in water alone [18–20], and, most
importantly, catalyst-free and solvent-free stoichiometric
conversion of reactants to products using ‘‘reactive mill-
ing’’ (recently by use of commercial ball mills) known as
‘‘mechanochemistry’’ [21] or ‘‘tribochemistry’’ [22], and
also as ‘‘melt reactions’’ [23, 24] have been successfully
applied to Knoevenagel reactions in recent years [13, 25].
Our ongoing interest in carrying out useful reactions
either in the so-called solvent-free manner on environment-
friendly solids as catalysts or in water with or without the
use of microwave irradiation (MWI) [26–28], drew our
attention to the fact that most of the Knoevenagel reactions
reported so far were studied with benzaldehydes. We were
interested in the Knoevenagel reaction of ninhydrin (1),
which bears a masked carbonyl group at C-2, because of
the synthetic potential of the corresponding Knoevenagel
condensates, e.g. as ‘‘ene’’ components in Diels–Alder
reactions [29, 30] and as synthons for complex molecules
[31–34]. Surprisingly, 1 has been reported to undergo
successful Knoevenagel reaction with only one active
methylene compound, viz. malononitrile (2a) under three
different conditions [30, 35, 36]. The Knoevenagel con-
densates of 1 with several other active methylene
compounds were prepared by the base (trifluoroacetic
anhydride, pyridine)-catalysed or acid (concentrated sul-
furic acid)-catalysed dehydration of the corresponding
preformed aldols [37, 38]. The aldols had, in turn, been
prepared from 1 and the various active methylene com-
pounds by heating in dilute sulfuric acid [39] and at room
temperature or beyond in dimethoxyethane (DME) (with
Keywords Ninhydrin ꢀ Active methylene compounds ꢀ
Montmorillonite K10 clay ꢀ Water ꢀ Aldolization
Introduction
The Knoevenagel reaction is an important C–C bond-
forming reaction [1, 2], carried out classically in solutions
heated under reflux in the presence of acids or bases as
catalysts [3, 4]. In view of the harsh conditions and long
periods of these reactions, which involve tedious work-ups
M. Chakrabarty (&) ꢀ A. Mukherji
Department of Chemistry, Bose Institute, 93/1, A. P. C. Road,
Kolkata 700009, India
e-mail: chakmanas@yahoo.co.in
S. Arima ꢀ Y. Harigaya
School of Pharmaceutical Sciences, Kitasato University,
Minato-ku, Tokyo 108, Japan
G. Pilet
Laboratoire des Multi-materiaux et Interfaces,
´
Groupe de Cristallographie et Ingenierie Moleculaire,
´
UMB 5615 CNRS–Universite Claude Bernard, Lyon 1, France
´
´
123

190
M. Chakrabarty et al.
˚
molecular sieve, MS 3 A) [35, 40], ethanol [41], water
[42], or acetic acid [43, 44] or by using a ball mill [45]. All
but the last named grinding method suffered from disad-
vantages, for example use of acid or solvents, long reaction
periods (e.g. up to 22 h), tedious work-ups for isolation of
the pure products, and often low yields of the aldols (e.g.
46%, 51/58%, etc). Only the ball mill method furnished the
aldol from 1 and dimedone in quantitative yield.
Results and discussion
When a mixture of equimolar amounts of 1 and each of
thirteen active methylene compounds (2a–2m) was uni-
formly adsorbed on clay and kept at room temperature, the
reactions were complete (TLC) in 5 min, except for 2g
which required 30 min when heated at 60–70 °C in an
oven (Table 1). In all these examples, except for Mel-
drum’s acid (2m), a single product was formed; 2m
furnished two products, which were separated by column
chromatography. Throughout, the products were leached
from the clay with methanolic ethyl acetate except for 2c,
for which dichloromethane was used, because the product
was thermally labile. The known products were identified
But because the ball mill method has been applied to the
reaction of 1 with dimedone only and because ball mills are
undeniably expensive equipments, we wondered if the
initial condensation of ninhydrin with active methylene
compounds and subsequent acid-catalysed dehydration of
the resulting aldols to form the corresponding Knoevenagel
condensates could be accomplished together in one pot by
using commercially available montmorillonite K10 clay
(hereinafter referred to as clay) because it is highly acidic,
has a large specific area, and yet is environment-friendly
[46], hence enjoying widespread use in organic synthesis
[47]. Accordingly, 1 was treated with several active
methylene compounds separately on clay at room temper-
ature. The results, albeit contrary to our expectation, were
quite diverse and interesting. For comparative evaluation,
the reactions were also carried out in water, which fur-
nished nearly the same results. Our experiments and their
outcome are presented herein.
1
by comparison (melting point, IR, and/or supportive H
NMR data) and the new products by thorough spectro-
scopic analysis and, in two cases, also by single-crystal X-
ray diffraction analysis.
The product from 1 and malononitrile (2a), despite
having a somewhat higher (by ca 10 °C) melting point than
that reported earlier for the corresponding Knoevenagel
condensate (3a) prepared from indane-1,2,3-trione and 2a
1
˚
in DME/MS 3 A [35], was identified as 3a from its IR, H,
and 13C NMR spectroscopic data (Scheme 1).
Each of the products from ethyl cyanoacetate
(2b), diethyl malonate (2c), cyclohexane-1,3-dione (2d),
Table 1 Reaction of 1 with 2 on clay at rt and in H2O on a steam-bath
Entry
Educt
Clay
H2O
Time (min)
Yield (%)a
Product
Time (min)
Yield (%)a
Product
1
2a
2b
2c
2d
2e
2f
5
5
85
94
82
80
83
91
97
68
86
90
89
92
40
–
3a [35]
3b [35]
3c [35]
3d [42]
3e [42]
3fc
1
1
–
1
1
1
1
1
1
1
1
1
5
1d
–
1d
91
97
–
3a
2
3b
3
5
–
4
5
83
90
98
98
98
96
93
98
92
93
–
3d
5
5
3e
6
5
30b
3f
7
2g
2h
2i
3gc
3g
3h0 [35]
8
5
3h [44]
3i [35]
3j [42]
3kc
3lc
3mc
9
5
3i
3j
3k
3l
3l
–
10
11
12
13
14
15
16
a
2j
5
2k
2l
5
5
2m
2n
2o
2p
5
–
–
–
–
–
–
–
–
–
–
–
–
Refers to isolated yield
b
c
d
Reactants on clay were heated at 60–70 °C in an oven
New compounds
Products underwent decomposition
123

Expeditious reaction of ninhydrin with active methylene compounds
191
O
O
O
O
O
O
OH
OH
OH
CN
CN
clay, rt
5 min
O
OH
OH
CN
CN
Me
Me
+
3'
5'
3'
ca. 2:1
Me
Me
O
4'
O
4'
O
HO
1
5'
2a
3a
Minor
Major
Scheme 1
Fig. 1 Equilibrium of 3f in DMSO-d6
dimedone (2e), 4,4-dimethylcyclohexane-1,3-dione (2f),
and oxindole (2g) displayed significantly, inter alia, IR
absorption bands for the hydroxyl and an uncoupled, de-
shielded (d = 4.06–5.74 ppm) proton signal in their 1H
NMR spectra. They thus appeared to be the corresponding
aldols (3b–3g) (Scheme 2), which received full support
from their 13C NMR data. But some snags we encountered
while trying to identify them, and some of their additional
structural characteristics are as follows.
product of tandem Knoevenagel–Michael addition reac-
tions. This reportedly bioactive compound [48] had been
prepared earlier from 2h and 3h0 in acetic acid–sulfuric
acid [44] and also by electrolysis of 2,2-dibromoindane-
1,3-dione using a graphite cathode [48]. The lack of
melting point of 3h in the two previous reports precluded
direct comparison. We, therefore, prepared 3h0 from 1 and
2h in acetic acid, converted it to 3h [44] and compared
it with the product obtained from 1 and 2h on clay.
Our product was unambiguously characterized as 3h
(Scheme 3).
The product 3b had a higher melting point (by ca 15 °C)
than had earlier been reported for the corresponding aldol
(3b) prepared from indane-1,2,3-trione and 2b in DME/MS
˚
3 A [35]. The product 3c could not be crystallized by us
The products stemming from 1 and, separately, acetyl-
acetone (2i) and ethyl acetoacetate (2j) were identified as
the dihydroxydihydrofuroindanones 3i and 3j, respectively
(i.e. the cyclic hemiketals formed from the enols of the
initially formed, unisolable aldols), prepared earlier from
the same reactants from reactions in warm water; their
depicted stereostructures were established by NOE studies
and single-crystal X-ray crystallographic analyses [42] and
separately in acetic acid [43]. The reaction of 1 with methyl
acetoacetate (2k), not studied earlier, resulted in a similar
formation of the third cyclic hemiketal 3k, which was
unequivocally identified from its similar spectroscopic data
(Scheme 4).
even from petroleum ether bp 60–70 °C which had previ-
ously been reported as the solvent used for crystallization of
this compound [35]. The product 3e, which had earlier been
prepared from 1 and 2e under four different conditions [39,
42, 43, 45], contained a trace of the corresponding enol
(d = 11.18 ppm, \1H) in CDCl3-DMSO-d6. The product
1
3f, a new chemical entity, displayed in its H NMR spec-
trum (DMSO-d6) two sets of signals for the methylene and
methyl groups (vide Experimental), suggesting that this
product exists in DMSO as a ca 2:1 mixture of the two
tautomers (Fig. 1). The products from 2b–2g are shown in
Scheme 2.
The reaction of 1 with malonic acid (2l) on clay fur-
nished, in high yield, the hydroxyacid (3l), the product of
decarboxylation of the initially formed, unisolated hy-
droxydicarboxylic acid, i.e. the aldol (3l0) (Scheme 5).
Decarboxylation during the attempted Knoevenagel reac-
tion, although documented previously for reactions carried
out under reflux in solution [49], is hitherto unreported for
The product from 1 and indane-1,3-dione (2h) appeared
not to be the corresponding aldol (3h0) from its much
higher melting point than previously reported for 3h0 [35]
1
and from its IR and H NMR spectra. Indeed, the latter
contained a two-proton singlet at d = 5.02 ppm, which,
with its mass spectrometrically derived molecular formula,
C27H14O6, suggested it to be ‘‘trisindanedione’’ (3h), the
O
O
O
O
O
O
OH
CO Et
clay, rt
5 min
clay, rt
5 min
2b-2c
2d-2f
+
+
+
CO Et
2
1
+
)
2
2
R
R
O
O
2b: R=CN
O
3b-3c
3d-3f
2c: R=CO Et
2
2h
3h
[44]
OH
O
clay, rt
5 min
R
3'
1
R
O
R
R
R'
O
4'
R'
O
O
OH
[44]
O
R'
R'
O
O
O
N
OH
2d: R=R'=H
2e: R=H; R'=Me
2f: R=Me; R'=H
clay, 60-70°C
30 min
H
O
3'
2'
2g
O
O
N
O
3g
3h'
H
Scheme 2
Scheme 3
123

192
M. Chakrabarty et al.
O
O
O
O
OH
3a
4
O
OH
clay, rt
5 min
CO2H
CO2H
Me
Me
clay, rt
5 min
COR
1
+
+
COR
Me
CH2CO2Me
O
1
+
O
3
COMe
8b
3m: 40%
2m
2l: major (TLC)
Not isolated
O
2
HO
2i: R=Me
2j: R=OEt
2k: R=OMe
3i-3k
Scheme 6
Scheme 4
O
O
OH
CH2CO2H
clay, rt
5 min
CO2H
CO2H
1
+
2l
3l
O
_
OH
CO2
CO2H
CO2H
O
3l'
Fig. 3 X-ray crystal structure of 3m
Scheme 5
Conceivably, 3m originated from the clay-catalysed
esterification of 3l (methanol used for extraction being the
source of the alcohol part of 3m), which, in turn, must have
originated from 3l0. The latter may have been formed in
either of two possible ways. Reaction of 1 with 2m may
lead to the aldol 3m0, which may undergo hydrolytic
cleavage to 3l0 with concomitant loss of acetone (route
‘‘A’’). Alternately, 2m itself may undergo a similar
cleavage on clay to furnish acetone and malonic acid (2l),
and the latter may then undergo aldol condensation with 1
to form 3l0 (route ‘‘B’’) (Scheme 7). When, in a separate
experiment, only 2m was uniformly adsorbed on clay and
kept at room temperature for 30 min, it remained
unchanged (TLC), which ruled out route ‘‘B’’. The other
end product, i.e. malonic acid (2l) is likely to have been
formed by a competitive retro-aldolization of 3l0—a
process presumably faster than the decarboxylative meth-
ylation of 3l0 to 3m, because 2l was the major product
(Scheme 7).
reactions carried out at room temperature. The structure of
3l was, therefore, additionally supported by single-crystal
X-ray diffraction analysis (Fig. 2).
Reaction of Meldrum’s acid (2m) on clay indicated
(TLC) the formation of malonic acid (2l) and the hydrox-
yacid 3l as the major and the minor components. When,
however, the clay containing the products was leached with
10% methanolic ethyl acetate, the extract showed (TLC)
the presence of 2l (not isolated by us) and, instead of 3l,
another less polar product identified spectroscopically as
the new compound 3m, i.e. the methyl ester of 3l
(Scheme 6). Because formation of 3m was unexpected, its
structure was also consolidated by single-crystal X-ray
crystallography (Fig. 3).
In order to confirm the source of the alcohol part of 3m,
an equimolar mixture of 1 and 2m was dissolved in a
minimum volume of ethanol (and not methanol), adsorbed
uniformly on clay and kept at room temperature until
(5 min) the reactants were fully consumed (TLC). The
resulting products were leached from the clay with 10%
ethanolic (and not methanolic) ethyl acetate, and the
extract showed (TLC) the presence of 2l and a product
which was more polar than 3m. This second product was
separated and identified spectroscopically as 3m00, i.e. the
Fig. 2 X-ray crystal structure of 3l
123

Expeditious reaction of ninhydrin with active methylene compounds
193
O
water (5 min; 70% yield) [36]. The reactions of 2d, 2e, 2i,
and 2j in water at room temperature had reportedly fur-
nished the aldols 3d and 3e and the aldol-derived cyclic
hemiketals 3i and 3j in 82–86% yields but required 15–
22 h for completion [42]. We, therefore, investigated the
catalyst-free reactions of 1 with 2a–2p in water but on a
steam-bath. All the reactions were complete in 1 min,
except for 2m (5 min) and 2c (which did not react)
(Table 1). The substrates, except for 2h and 2m, furnished
the corresponding products that were obtained from the
clay-mediated reactions but in better yields, 83–98%.
While 2h resulted in the formation of the expected
aldol 3h nearly quantitatively, 2m efficiently furnished the
hydroxyacid 3l, which was not unexpected, because its
isolation did not involve any extractive work-up. Among
the substrates 2n–2p, only 2n and 2p reacted with 1 and
were fully consumed in 1 min, but the products underwent
decomposition during isolation.
OH
O
O
O
1
+
+ H2O
O
_
clay
Me2CO
Me
Me
O
"A"
3m'
2m
O
"B"
_
OH
+ H2O
Me2CO
CO2H
CO2H
1
+
CO2H
clay
CO2H
O
3l'
2l
Retro-
aldolization
_
CO2
O
MeOH
2l
(major unisolated)
3m: 40%
OH
CH2CO2H
EtOH
O
3m'': 25%
3l
Scheme 7
To conclude, montmorillonite K10 clay was unable to
bring about the desired Knoevenagel condensation of nin-
hydrin (1) with the active methylene compounds 2b–2p.
But it was proved to be quite efficient and expeditious in
their aldolization and formation of some novel compounds
with interesting mechanisms of formation. Water was found
to be somewhat better suited, which furnished somewhat
different results but much faster and more efficiently.
Because montmorillonite K10 clay is commercially avail-
able, inexpensive, and harmless to the environment, and
because the reactions were carried out in a manner
involving use of substantially lesser amounts of solvents,
the present method should be considered as a viable alter-
native to the best method(s) available for the purpose.
ethyl ester of 3l, thereby consolidating the origin of the
alcohol part of 3m and also of 3m00 (Scheme 7).
Interestingly, although methanolic ethyl acetate was used
for leaching the product(s)-on-clay in the reaction of 1 with
both malonic acid (2l) and Meldrum’s acid (2m), sepa-
rately, 3m, i.e. the methyl ester of 3l, was obtained only in
the latter case. This strongly suggested that both 2m (itself a
strong acid) and clay have a role to play in the esterification
process. In order to verify this possibility, an equimolar
mixture of the acid 3l and 2m in methanol was uniformly
adsorbed on clay, kept at room temperature for 30 min, and
leached with methanolic ethyl acetate, when the extract was
found to contain 3m (not detailed in the Experimental
section). Our assumption thus turned out to be true.
Ninhydrin (1) was also allowed to react with cyano-
acetamide (2n), hydantoin (2o), and thiazolidine-2,4-dione
(2p) in a similar manner on clay. All three failed to react at
room temperature or at elevated temperature (60–70 °C).
In order to check the recyclability of clay, the reaction of 1
with each of 2b, 2d, and 2i, separately, was carried out
twice more using clay recovered and reactivated after the
first and the second set of experiments. Clay recovered
from the first cycle was found to furnish 3b, 3d, and 3i in
the same time (5 min) and in slightly lower yields (84, 72,
and 78%) than in the first cycle. However, clay recovered
from these experiments, when used in the second recycle,
led to the starting materials remaining largely unconsumed
(not detailed in the Experimental section). Clay is thus
recyclable at best up to the second cycle.
Experimental
Montmorillonite K10 clay was procured from Fluka.
Melting points were determined on a Toshniwal apparatus.
FTIR spectra were recorded on a Nicolet Impact 410
spectrophotometer, 1H (500/300 MHz) and 13C (125/
75 MHz) NMR spectra, including DEPT 135, on Bruker
DRX 500/300 NMR spectrometers, LR EIMS on a Jeol
JMS-AX505HA, and HR EI/FAB and ESI-MS on Jeol
JMS-700 MStation and Waters Qtof Micro YA263 mass
spectrometers, respectively. In FABMS spectra, m-nitro-
benzyl alcohol was used as the liquid matrix. The six new
compounds (3f, 3g, 3k, 3l, 3m, and 3m00) were subjected to
elemental analyses on a Perkin Elmer 2400 Series II C, H,
N Analyzer and the results were found to be in good
agreement with the calculated values. Thin-layer chroma-
tography (TLC) was carried out on silica gel G plates
(Merck, India) and column chromatography (CC) was
carried out on silica gel (60–120 mesh; Qualigens, India).
Pertinently, the reaction of 1 with 2a and the four 1,3-
dicarbonyl compounds 2d, 2e, 2i, and 2j had earlier been
carried out in water [36, 42]. Of these, only 2a furnished
the corresponding Knoevenagel condensate 3a in boiling
123

194
M. Chakrabarty et al.
2-Dicyanomethyleneindane-1,3-dione (3a)
For known compounds, only data not reported elsewhere
have been furnished here. PE refers to petroleum ether, bp
60–80 °C. The yields of the products have been rounded to
the nearest integers.
Golden yellow crystals; mp 267–268 °C (dec) (EtOAc)
([35] 258–260 °C); yield 0.18 g, 85% (clay)/0.19 g, 91%
(water); Rf = 0.28 (EtOAc–MeOH, 19:1); 13C NMR
(125 MHz, DMSO-d6): d = 125.1, 138.5 (both Ar–CH),
87.0, 111.7 (92), 142.1, 154.5, 183.6 (92) (all C) ppm.
General procedure for reaction on montmorillonite
K10 clay
Ethyl cyano(20-hydroxyindane-10,30-dione-20-yl)
acetate (3b)
A mixture of 1 mmol 1 and 1 mmol 2 was dissolved in
0.5–1.0 cm3 MeOH, adsorbed uniformly on 1.0 g clay, and
kept inside a hood at rt. The reactants were consumed
(TLC) in 5 min (except for 2g). The clay was then leached
with 3 9 15 cm3 5–10% MeOH–EtOAc, solvent was
removed from the pooled extracts by distillation, and the
resulting residue was purified either by CC (for 3m) or
directly by crystallization (for the rest) to furnish 3a–3f,
3h–3m. The purity of these products was checked by TLC
White crystals; mp 140–142 °C (dec) (n-hexane–EtOAc)
([35] 123–125 °C); yield 0.25 g, 94% (clay)/0.26 g, 97%
(water); Rf = 0.50 (C6H6–MeOH, 19:1); 1H NMR
(500 MHz, CDCl3 ? DMSO-d6): d = 1.09 (t, J = 7.0 Hz,
3H), 4.05 (q, J = 7.0 Hz, 2H), 4.55 (s, 1H), 7.51 (s, 1H),
7.90–7.94 (m, 2H), 8.01–8.05 (m, 2H) ppm; 13C NMR
(125 MHz): d = 13.8 (CH3), 63.7 (CH2), 41.9, 124.3,
124.5, 136.6 (all CH), 72.4, 113.7, 140.9, 141.3, 163.7,
195.86, 195.87 (all C) ppm.
1
and H NMR spectroscopy.
Diethyl (20-hydroxyindane-10,30-dione-20-yl)
malonate (3c)
In the reaction with 2g, the reactants remained largely
unconsumed (TLC) even after 4 h. A fresh batch of the
reactants-on-clay was, therefore, prepared in a similar
manner and heated in an oven at 60–70 °C when the
starting materials were consumed in 30 min. The clay was
then cooled to rt, leached with 5% MeOH–EtOAc and the
product, obtained after a similar work-up, was purified by
crystallization to furnish pure 3g.
Gummy material ([35] 76–78 °C); yield 0.26 g, 82%
(clay); Rf = 0.50 (C6H6–EtOAc, 2:1); 1H NMR
(300 MHz, CDCl3): d = 1.23 (t, J = 7.2 Hz, 6H), 4.17
(s, 1H), 4.13–4.33 (m, 4H), 5.06 (s, 1H), 7.84–7.93 (m,
2H), 7.99–8.07 (m, 2H) ppm.
2-(Cyclohexane-20,60-dione-10-yl)-2-hydroxyindane-1,
3-dione (3d)
General procedure for reaction in water
White crystals; mp 173–175 °C (dec) (PE–EtOAc) ([42]
174–175 °C); yield 0.22 g, 80% (clay)/0.23 g, 83%
(water); Rf = 0.37 (EtOAc–MeOH–AcOH, 96:3:1).
A suspension of a mixture of 1 mmol 1 and 1 mmol 2 in
2 cm3 water was heated on steam-bath until the reactants
were consumed (TLC). For each of 3a, 3b, 3e, 3f, 3h0, 3i,
3j, and 3l, the precipitated solid was isolated by filtration,
washed with water, dried, and purified by crystallization.
For 3d, 3g, and 3k the resulting gummy material was
extracted with 3 9 15 cm3 EtOAc, the solvent was
removed from the pooled extracts by distillation, and the
resulting residue was purified by crystallization. The purity
2-(40,40-Dimethylcyclohexane-20,60-dione-10-yl)-2-
hydroxyindane-1,3-dione (3e)
White crystals; mp 208 °C (dec) (n-hexane–EtOAc) ([42]
208 °C); yield 0.25 g, 83% (clay)/0.27 g, 90% (water);
Rf = 0.40 (EtOAc–MeOH, 9:1); 1H NMR (500 MHz,
CDCl3 ? DMSO-d6): d = 1.05 (s, 6H), 2.21 (s, 4H), 5.74
(br s, 1H), 7.32 (brs, 1H), 7.58–8.06 (m, 4H), 11.18 (br
s,\1H).
1
of the final products was checked by TLC and H NMR
2-(30,30-Dimethylcyclohexane-20,60-dione-10-yl)-2-
hydroxyindane-1,3-dione (3f, C17H16O5)
spectroscopy.
Alternative preparation of 3h0 and 3h
White crystals; mp 168–170 °C (dec) (n-hexane–EtOAc);
yield 0.27 g, 91% (clay)/0.29 g, 98% (water); Rf = 0.44
Following a reported procedure [44], 3h0 was prepared
from 1 and 2h on a 2-mmol scale in 86% yield (0.52 g) as
light yellow crystals, mp 238–240 °C (dec) ([35] 238–
240 °C).
ꢀ
(EtOAc–MeOH, 9:1); IR (nujol): m ¼ 3302; 3,191, 1,741,
1,720, 1,647, 1,600, 1,342, 1,256, 1,149, 1,096, 976, 870,
764, 724 cm-1; 1H NMR (500 MHz, CDCl3 ? DMSO-d6):
d = 1.04 (br, 6H), 1.79 (s, 2H), 2.40 (br s, 2H), 5.54 (br,
1H), 6.84 (br, 1H), 7.54–8.03 (m, 4H) ppm; 1H NMR
(500 MHz, DMSO-d6; major:minor = ca. 2:1): d = 0.84
and 0.99 (s each, 4H:2H, 2 9 CH3), 1.23 and 1.63 (s each,
1.3H:0.7H, 40-CH2), 1.71 and 2.20 (s each, 1.3H:0.7H, 50-
CH2), 6.15 (s, 1H), 7.63 (br s, 1H), 7.69 (br s, 1H), 7.85 (s,
2H), 8.23 (s, 1H) ppm; 13C NMR (125 MHz): d = 25.0,
Following the same reference, 3h was prepared from 3h0
and 2h on a 1-mmol scale in 65% yield (0.28 g) as pale
yellow crystals, mp 282–284 °C (dec) ([44]; mp not
reported). The identity of this compound and the product
3h obtained from clay was verified by direct comparison
(mp, mixed mp, TLC, co-TLC).
123

Expeditious reaction of ninhydrin with active methylene compounds
195
25.2 (both CH3), 34.9, 36.2 (both CH2), 123.8, 125.5,
132.1, 136.9 (all Ar–CH), 41.5, 83.7, 135.0, 147.5, 175.4,
181.9, 192.7, 197.8 (all C) ppm; LR EI-MS: m/z
(%) = 300 (M?, 63), 285 (9), 284 (15), 282 (9), 272
(11), 229 (21), 216 (20), 203 (40), 167 (27), 160 (10), 140
(29), 132 (39), 112 (16), 105 (27), 104 (100), 76 (73); HR
ESI-MS calcd for C17H16O5Na, 323.0895 (M ? Na)?,
found 323.0897.
Methyl (3a,8b-cis)-3a,8b-dihydroxy-2-methyl-4-oxo-3a,
8b-dihydro-4H-indeno[1,2-b]furan-3-carboxylate
(3k, C14H12O6)
White crystals; mp 107–108 °C (dec) (PE–CH2Cl2); yield
0.25 g, 89% (clay)/0.27 g, 98% (water); Rf = 0.32 (C6H6–
ꢀ
EtOAc, 1:1); IR (nujol): m ¼ 3569, 3,476, 3,270, 1,732,
1,606, 1,255, 1,182, 1,155, 1,135, 1,102, 970, 937, 890,
777, 731 cm-1; 1H NMR (500 MHz, DMSO-d6): d = 2.12
(s, 3H), 3.59 (s, 3H), 6.15 (s, 1H), 7.63 (dt, J1 = 8.0 Hz,
J2 = 3.0 Hz, 1H), 7.71 (d, J = 7.5 Hz, 1H), 7.81–7.85 (m,
2H), 8.04 (br s, 1H) ppm; 13C NMR (125 MHz): d = 15.6
(CH3), 51.4 (OCH3), 123.7, 125.6, 132.1, 136.9 (all Ar–
CH), 85.0, 105.4, 110.5, 135.0, 147.7, 165.2, 170.3, 198.3
(all C) ppm; LR EI-MS: m/z (%) = 276 (M?, 32), 258
(10), 244 (100), 234 (35), 226 (16), 202 (94), 201 (15), 174
(41), 173 (25), 149 (24), 146 (30), 132 (14), 104 (25), 76
(17), 43 (51); HR EI-MS calcd for C14H12O6, 276.0634
(M)?, found 276.0637.
2-Hydroxy-2-(oxindol-30-yl)indane-1,3-dione
(3g, C17H11NO4)
Light brown crystals; mp 195 °C (dec) (PE–EtOAc); yield
0.285 g, 97% (clay)/0.287 g, 98% (water); Rf = 0.30
ꢀ
(C6H6–MeOH, 19:1); IR (nujol): m ¼ 3432, 3,184, 1,759,
1,719, 1,698, 1,619, 1,593, 1,272, 1,226, 1,180, 1,145,
1
1,081, 1,016, 963, 764, 720 cm-1; H NMR (500 MHz,
CDCl3 ? DMSO-d6): d = 4.06 (s, 1H), 6.63 (s, 1H), 6.70
(dt, J1 = 7.5 Hz, J2 = 1.0 Hz, 1H), 6.80 (d, J = 7.5 Hz,
1H), 6.85 (d, J = 7.5 Hz, 1H), 7.09 (tt, J1 = 7.5 Hz,
J2 = 1.0 Hz, 1H), 7.81 (ddd, J1 = 7.5 Hz, J2 = 1.5 Hz,
J3 = 1.0 Hz, 1H), 7.84 (dt, J1 = 7.5 Hz, J2 = 1.0 Hz, 1H),
7.89 (dt, J1 = 7.5 Hz, J2 = 1.5 Hz, 1H), 8.05 (dt,
J1 = 7.5 Hz, J2 = 1.0 Hz, 1H), 10.27 (s, 1H) ppm; 13C
NMR (125 MHz): d = 47.6, 110.9, 122.3, 124.0, 124.1,
125.2, 129.1, 136.8, 137.0 (all CH), 76.5, 123.2, 141.3,
141.5, 143.1, 177.6, 197.4, 198.6 (all C) ppm; LR EI-MS:
m/z (%) = 293 (M?, 49), 275 (8), 160 (13), 133 (100), 132
(35), 104 (26), 76 (13); HR EI-MS calcd for C17H11NO4,
293.0688 (M)?, found 293.0689.
(20-Hydroxyindane-10,30-dione-20-yl)acetic acid
(3l, C11H8O5)
Colourless crystals; mp 181–182 °C (dec) (EtOAc–
MeOH); yield 0.20 g, 92% (clay)/0.20 g, 92% (water);
ꢀ
Rf = 0.49 (EtOAc–MeOH, 17:1); IR (nujol): m ¼ 3331,
1,743, 1,709, 1,587, 1,341, 1,274, 1,182, 1,155, 1,082, 943,
735 cm-1
;
1H NMR (500 MHz, CDCl3 ? DMSO-d6):
d = 3.16 (s, 2H), 4.47 (br, 1H), 7.83–7.89 (m, 2H), 7.95–
8.02 (m, 2H) ppm; 13C NMR (125 MHz): d = 38.7 (CH2),
124.0, 136.0 (both Ar–CH), 72.6, 141.5, 172.0, 199.6 (all
C) ppm; LR EI-MS: m/z (%) = 220 (M?, 6), 202 (100),
174 (43), 160 (8), 146 (28), 132 (42), 104 (84), 76 (29); HR
EI-MS calcd for C11H8O5, 220.0372 (M)?, found
220.0374; HR FAB-MS calcd for C11H9O5, 221.0450
(M ? H)?, found 221.0441.
2,2-Bis(indane–10,30-dione-20-yl)indane-1,3-dione (3h)
White crystals; mp 282–283 °C (dec) (PE–CHCl3) ([44],
mp not reported; mp of 3h prepared by us following [44]
282–284 °C); yield 0.29 g, 68% (clay); Rf = 0.61
ꢀ
(EtOAc–MeOH, 19:1); IR (nujol): m ¼ 1739, 1,707,
Methyl (20-hydroxyindane-10,30-dione-20-yl)acetate
(3m, C12H10O5)
1,586, 1,348, 1,265, 1,238, 817, 761 cm-1; HR EI-MS
calcd for C27H14O6, 434.0791 (M)?, found 434.0794.
Colourless crystals; mp 95–96 °C (n-hexane–CH2Cl2); yield
0.09 g, 40% (clay); Rf = 0.28 (PE–C6H6–EtOAc, 2:2:1); IR
2-Hydroxy-2-(indane-10,30-dione-20-yl)indane-1,3-dione
(3h0)
ꢀ
(nujol): m ¼ 3383, 1,752, 1,712, 1,593, 1,215, 1,076, 1,000,
943, 751, 731 cm-1; 1H NMR (500 MHz, CDCl3 ? DMSO-
d6): d = 3.21 (s, 2H), 3.48 (s, 3H), 6.47 (s, 1H), 7.87–7.91
(m, 2H), 7.98–8.03 (m, 2H) ppm; LR EI-MS: m/z (%) = 234
(M?, 17), 202 (100), 175 (43), 174 (36), 160 (7), 146 (28),
132 (38), 104 (61), 76 (20); HR FAB-MS calcd for
C12H11O5, 235.0606 (M ? H)?, found 235.0614.
Light yellow crystals; mp 238–240 °C (dec) (PE–CHCl3)
([35] 238–240 °C); yield 0.3 g, 98% (water); Rf = 0.41
(EtOAc–MeOH, 19:1).
(3a,8b-cis)-3-Acetyl-3a,8b-dihydroxy-2-methyl-3a,8b-dihy-
dro-4H-indeno-[1,2-b]furan-4-one (3i)
White crystals; mp 168 °C (dec) (PE–CH2Cl2) ([35] 167–
169 °C); yield 0.22 g, 86% (clay)/0.25 g, 96% (water);
Rf = 0.35 (C6H6–EtOAc, 1:1).
Preparation of ethyl (20-hydroxyindane-10,30-dione-
20-yl)acetate (3m00, C13H12O5)
Ethyl (3a,8b-cis)-3a,8b-dihydroxy-2-methyl-4-oxo-3a,
8b-dihydro-4H-indeno[1,2-b]furan-3-carboxylate (3j)
White crystals; mp 93–95 °C (dec) (PE–CH2Cl2) ([42] 93–
103 °C); yield 0.26 g, 90% (clay)/0.27 g, 93% (water);
Rf = 0.36 (C6H6–EtOAc, 1:1).
A mixture of 1 mmol 1 and 1 mmol 2m was dissolved in
1.0 cm3 EtOH, adsorbed uniformly on 1.0 g clay and kept
in a hood at rt. The reactants were consumed in 5 min
(TLC). The clay was then leached with 3 9 15 cm3 10%
123

196
M. Chakrabarty et al.
6. Abaee MS, Mojtahedi MM, Zahedi MM, Khanalizadeh G (2006)
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EtOH–EtOAc, the solvent was removed from the pooled
extracts by distillation and the resulting residue purified by
preparative TLC in C6H6–EtOAc (1:1) to furnish 0.06 g
1
(25%) pure (TLC, H NMR) 3 m00 as colourless crystals.
Mp 107–108 °C (PE–CH2Cl2); Rf = 0.37 (PE–C6H6–
ꢀ
EtOAc, 2:2:1); IR (nujol): m ¼ 3365, 1,753, 1,719, 1,593,
1,410, 1,340, 1,210, 1,081, 1,029, 943, 753 cm-1; 1H NMR
(500 MHz, CDCl3 ? DMSO-d6): d = 1.01 (t, J = 7.0 Hz,
3H), 3.20 (s, 2H), 3.89 (q, J = 7.0 Hz, 2H), 6.45 (s, 1H),
7.87–7.90 (m, 2H), 7.99–8.02 (m, 2H) ppm; 13C NMR
(125 MHz): d = 14.0 (CH3), 38.9 (CH2), 61.2 (OCH2),
124.0, 136.2 (both Ar–CH), 72.5, 141.6, 169.9, 199.6 (all
C) ppm.
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X-ray diffraction data for compounds 3l and 3m
3l (CCDC-689405): C11H8O5, M = 220.18 g mol-1
monoclinic, a = 6.2035(3), b = 18.263(1), c = 8.6388(5)
;
´
˚
3
˚
A, b = 97.290(3); V = 978.2(1) A ; T = 293 K; space
group P21/n (no. 14), Z = 4,4176 reflections measured,
2,318 unique (Rint = 0.034); R(F, I/r(I) [ 1) = 0.0576,
Rw (F, I/r(I) [ 1) = 0.0485; S = 1.16; Dqmax = 0.24
´
´
˚
e-
-3, Dqmin = -0.23 e-
˚
A A
-3; 1,404 reflections used to
˚
refine 163 parameters. Mo-Ka radiation (k = 0.71073 A);
colourless cubes, 0.20 9 0.21 9 0.24 mm3, densitycalc
1.495, l = 0.120 mm-1
3m (CCDC-689404): C12H10O5, M = 234.21 g mol-1
monoclinic, a = 9.9333(5), b = 21.051(1), c = 10.7673(6)
=
24. Trotzki R, Hoffmann MM, Ondruschka B (2008) Green Chem
10:767
.
;
25. Kaupp G (2005) Top Curr Chem, vol 254. Springer, Berlin, p 95
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Monatsh Chem 138:1279 and references cited therein
29. Chatterjee S (1967) Science 157:314
´
´
3
˚
˚
A, b = 97.290(3); V = 2233.3(2) A ; T = 293 K; space
group P21/a (no. 14), Z = 8,7385 reflections measured,
5,037 unique (Rint = 0.025); R(F, I/r(I) [ 1) = 0.0572,
Rw (F, I/r(I) [ 1) = 0.0554; S = 1.15; Dqmax = 0.30
´
´
˚
e-
-3, Dqmin = -0.25 e-
˚
A A
-3; 3,635 reflections used to
˚
30. Chatterjee S (1969) J Chem Soc (B):725
´
refine 361 parameters. Mo-Ka radiation (k = 0.71073 A);
31. Pita B, Sotelo E, Suarez M, Ravin˜a E, Ochoa E, Verdecia Y,
Novoa H, Blaton N, de Ranter C, Peeters OM (2000) Tetrahedron
56:2473
colourless plates, 0.20 9 0.70 9 0.73 mm3, densitycalc
1.393, l = 0.110 mm-1
=
.
32. Nair V, Beneesh PB, Sreekumar V, Bindu S, Menon RS, Deepthi
A (2005) Tetrahedron Lett 46:201
33. Elinson MN, Feducovich SK, Starikova ZA, Vereshchagin AN,
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Acknowledgments We sincerely thank Professor S. Raha, Director,
Bose Institute, for laboratory facilities, the C.S.I.R., Govt. of India for
providing a fellowship (A.M.), Mr B. Majumder, NMR facilities, and
Mr P. Dey, Microanalytical Laboratory, both of the Bose Institute, for
recording the spectra.
¨
35. Schonberg A, Singer E (1970) Chem Ber 103:3871
36. Bryce MR, Davies SR, Hasan M, Ashwell GJ, Szablewski M,
Drew MGB, Short R, Hursthouse MB (1989) J Chem Soc Perkin
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