Diethylamine-catalyzed environmentally benign synthesis of 1-oxo-hexahydroxanthenes and bis-coumarins at ambient temperature

Article abstract of DOI:10.1007/s11164-016-2464-4

Abstract: An extremely simple, economical and environmentally benign protocol has been described for one-pot synthesis of 1-oxo-hexahydroxanthenes by pseudo three-component condensation between salicylaldehydes and dimedone, cyclohexane-1,3-dione or 5-met

Full text of DOI:10.1007/s11164-016-2464-4

Res Chem Intermed
DOI 10.1007/s11164-016-2464-4
Diethylamine-catalyzed environmentally benign
synthesis of 1-oxo-hexahydroxanthenes and
bis-coumarins at ambient temperature
Ravindra V. Kupwade1 Kapil S. Pandit1
•
•
Uday V. Desai1 Makarand A. Kulkarni1
Prakash P. Wadgaonkar2
•
•
Received: 17 October 2015 / Accepted: 30 January 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract An extremely simple, economical and environmentally benign protocol has
been described for one-pot synthesis of 1-oxo-hexahydroxanthenes by pseudo three-
component condensation between salicylaldehydes and dimedone, cyclohexane-1,3-
dione or 5-methyl cyclohexane-1,3-dione using diethylamine as the catalyst. Based upon
the mechanism of the reaction, the protocol has been extended towards the synthesis of
tetraketones and bis-coumarins.
Graphical Abstract
R
OH
OH
2 (4-Hydroxycoumarin)
Diethylamine
X = H
O
O
O
O
CHO
X
R
R1
R2
OH
O
O
R = H, Cl, Br, OMe, NO2 , etc.
2 (Cyclic-1,3-diketone)
R2
R
Diethylamine
X = OH
O
R1
Keywords Domino reactions Á 1-Oxo-hexahydroxanthenes Á Bis-coumarins Á
Tetraketones Á Diethylamine
&
Uday V. Desai
uprabhu_desai@rediffmail.com; uvdchem2011@gmail.com
1
2
Organic Chemistry Division, Department of Chemistry, Shivaji University, Kolhapur 416004,
India
Polymer Science and Engineering Division, CSIR, National Chemical Laboratory,
Pune 411008, India
123

R. V. Kupwade et al.
Introduction
The main current issues in the synthesis of complex organic molecules are
improvement of efficiency, avoidance of toxic agents, reduction in waste and
responsible utilization of natural sources. In this context, use of domino reactions
involving the participation of two or more substrates is of relevance both from
economic and ecological points of view [1–4]. Amongst domino reactions,
Knoevenagel–Michael domino reactions have emerged as a powerful strategy in
the synthesis of various oxa- as well as aza-heterocycles [5, 6].
In recent years, construction of xanthene scaffolds has attracted much attention of
organic chemists due to their importance in the field of medicine as well as material
science [7–11]. Two important classes of compounds containing a xanthene
structural motif are 1,8-octahydroxanthenes and 1-oxo-hexahydroxanthenes.
Amongst these 1-oxo-hexahydroxanthenes are of particular interest to synthetic
organic chemists due to their important pharmacological properties such as,
antiestrogenic, antibacterial, antimicrobial as well as hypoglycemic activities [12–
15]. They also exhibit thrombin inhibitory activity and serve as a neuropeptide Y Y5
receptor antagonist [16, 17]. Apart from biological activities, Li et al. [18, 19]
recently explored the potential of 1-oxo-hexahydroxanthenes in the synthesis of
other heterocycles. Synthesis of 1-oxo-hexahydroxanthenes involving one-pot
pseudo three-component condensation between salicylaldehyde and two equivalents
of dimedone or 1,3-cyclohexanedione was reported earlier using a range of Bronsted
[20–23] heteropoly [24] as well as Lewis acid catalysts [25]. On the other hand, a
few catalyst-free protocols have also been reported using glycerol [26] as well as
water [27, 28] as a solvent. It is noteworthy that most of these reported protocols are
operable at the reflux temperature and although their synthesis has been known to
follow Knoevenagel–carba–Michael domino pathway, to the best of our knowledge,
except for KF-alumina [29], there are no reports on their synthesis using any other
basic catalyst. All these observations coupled with our continued interest in the
development of environmentally benign protocols for the synthesis of biologically
active compounds [30–34] prompted us to develop a base-mediated and easily
adaptable protocol for the synthesis of 1-oxo-hexahydroxanthenes.
Diethylamine is a non-toxic, inexpensive and easy to handle organic base
available commercially. The first report on the use of diethylamine as a catalyst in
Knoevenagel condensation appeared in the 1940s [35]. However, it was interesting
to note that it’s use in multicomponent reactions had remained unexplored. In fact,
we have demonstrated for the first time the use of diethylamine as an efficient
organocatalyst in one-pot synthesis of b-phosphonomalononitriles and in diastere-
oselective synthesis of 2-amino-3-cyano-4H-chromenes by pseudo three component
condensations between salicylaldehyde and two equivalents of active methylene
compounds containing nitrile functionality [30, 31]. These reactions typically
involved Knoevenagel–cyclization–carba–Michael domino pathway. Thinking
along the same line we envisaged that synthesis of 1-oxo-hexahydroxanthenes
could easily be achieved by pseudo three-component condensation between
salicylaldehyde and two equivalents of active methylene compounds devoid of
123

Diethylamine-catalyzed environmentally benign synthesis…
nitrile function viz. dimedone or 1,3-cyclohexanedione using diethylamine as the
catalyst (Scheme 1).
Results and discussion
In an initial exploratory reaction, to a well stirred solution of salicylaldehyde
(2 mmol) and dimedone (4 mmol) in ethanol (4 mL) was added diethylamine
(20 mol%). Stirring was continued at ambient temperature. Upon completion of the
reaction [monitored by thin layer chromatography (TLC)], water (10 mL) was
added and the resultant solid was filtered, washed with water, dried, washed with
hexane–chloroform (9:1, v/v) and dried again. On the basis of comparison of
physical and spectroscopic data of the resultant solid with that reported earlier, it
was identified to be the desired 1-oxo-hexahydroxanthene, 5a. During the studies on
this model reaction, as targeted 1-oxo-hexahydroxanthene, 5a, was obtained in
excellent yield as well as purity by avoidance of conventional isolation as well as
purification procedures and by using diethylamine as a less expensive catalyst,
further optimization of the reaction conditions, in particular screening of other basic
catalysts for the synthesis of 5a, was surmised to be unnecessary. However, in
pursuance of making this protocol still greener and economical, the model reaction
was repeated in water (100 %) as well as a water–ethanol medium (1:2 and 1:1, v/v,
respectively), when desired 5a was obtained in lower yields (63, 58 and 60 %,
respectively). Thus, ethanol was selected as the reaction medium for subsequent
H
NC
X
X
X
2 NC
H
O
Diethylamine
(Ref: 31)
NH
2
R
X = CN, COOEt, SO2Ph
CHO
OH
O
1
2
R
R
R
2
1
R
R = H, Cl, Br, OMe, NO2, etc.
O
1
OH
R
O
2: R1 = R2= CH3
3: R1 = R2 = H
O
4: R1 = H; R2 = CH3
2
R
O
1
R
R
5: R1 = R2 = Me 6: R1 = R2 = H
7: R1 = H, R2 = CH3
Scheme 1 Diethylamine-catalyzed synthesis of 1-oxo-hexahydroxanthenes
123

R. V. Kupwade et al.
studies. Next, we planned to examine the scope of the developed protocol. Thus, the
dimedone component from the aforementioned model reaction was replaced with
1,3-cyclohexanedione, 3, as well as 5-methylcyclohexane-1,3-dione, 4. The
reactions required slightly longer reaction times; however, upon completion of
the reaction, corresponding 1-oxo-hexahydroxanthenes, 6a and 7a, were obtained in
excellent yields as well as purity. Recently, a model reaction has been performed.
Encouraged with this initial success, we then planned to investigate the generality
of the reaction conditions in the synthesis of various 1-oxo-hexahydroxanthene
derivatives. Accordingly, under the established reaction conditions, salicylaldehy-
des bearing electron-withdrawing as well as electron-donating groups were allowed
to react with dimedone, cyclohexane-1,3-dione as well as 5-methylcyclohexane-1,3-
dione. In all the cases, corresponding 1-oxo-hexahydroxanthene resulted in
excellent yields as well as purity (Table 1).
Table 1 Diethylamine catalyzed synthesis of 1-oxo-hexahydroxanthenesa
R1
R2
R2
R1
CHO
OH
Diethylamine
EtOH, RT
O
O
2
R
+
OH
O
O
R1
R
1
5; R1 = R2 = CH3
6; R1 = R2 = H
2; R1 = R2 = CH3
3; R1 = R2 = H
O
R2
4; R1 = H & R2 = CH3
7; R1 = H & R2 = CH3
Product
Aldehyde (R=)
R1
R2
Time (h)
Yield (%)
Melting point (°C)
Observed
Lit. References
5a
5b
5c
5d
5e
5f
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
4.5
4.0
4.0
5.0
4.5
4.5
5.0
6.0
4.5
5.5
5.0
5.5
6.0
5.5
7.0
6.0
5.5
5.5
92
90
87
85
87
85
87
73
86
78
84
81
80
79
65
82
81
78
201–203
249–251
232–234
228–230
216–218
243–244
223–225
228–232
181–184
208–210
242–245
236–240
247–248
238–241
220–223
231–234
248–251
241–244
204–206 [21]
5-Br
251–253 [27]
5-Cl
234–236 [25]
3,5-Cl2
4-OCH3
3-OH
4-OH
3-Br-5-NO2
5-OCH3
4,6-Cl2
H
227–228 [21]
215–218 [28]
245–248 [23]
5g
5h
5i
225–228 [28]
–
177–181 [20]
5j
–
6a
6b
6c
6d
6e
7a
7b
7c
a
242–244 [21]
4-OCH3
3-OH
4-OH
4,6-Cl2
H
H
H
–
H
H
–
H
H
242 [23]
H
H
–
–
–
–
H
CH3
CH3
CH3
5-Br
H
5-Cl
H
Reaction conditions: salicylaldehyde, 1 (2 mmol) and 1, 3-dione (2/3/4, 4 mmol), ethanol (4 mL),
diethylamine (20 mol%); RT
123

Diethylamine-catalyzed environmentally benign synthesis…
Our primary aim to undertake this work was not limited towards the synthesis of
1-oxo-hexahydroxanthenes but was also to understand the mechanism involved
therein for the possible extension of the work towards the synthesis of other
biologically active organic compounds. Hence, we turned our attention towards the
mechanism of the reaction.
From the mechanistic view point, synthesis of 1-oxo-hexahydroxanthene by
pseudo three component condensation between salicylaldehyde and two equivalents
of dimedone is believed to proceed by a Knoevenagel–carba–Michael cyclization
pathway (Path B, Scheme 2). On the other hand, based upon our earlier success in
the synthesis of various 2-amino-4H-chromene derivatives [30, 31], we believed
that in basic medium the reaction follows a Knoevenagel–cyclization–carba–
Michael pathway (Path A, Scheme 2). We surmised that, if the reaction follows Path
A, a three-component reaction between salicylaldehyde, dimedone and thiophenol
(1 mmol, each) should furnish 8, as Knoevenagel–cyclization–thia–Michael addi-
tion product (Scheme 2c).
O
O
R1
CHO
O
R1
R1
OH
2 / 3 / 4
R1
O
OH
1
R1
R1
(Z)
O
O
O
-
O
R1
R1
(A)
R1
O-
O
O
R1
R1
R1
- H2O
HO
R1
R1
OH
O
R1
R1
O
O
O
-
R1
OH
O
- H2O
O
O
O
R1
R1
5 / 6
R1 = Me / H
R1
(B)
(C)
R1
O-
R1
O
OH
OH
-
PhS
Ph
Ph
O
S
O
O
S
+
- H2O
H
R1
1
R1
R
O-
O
R1
1
R1
R
O
OH
8
HO
R1 = Me / H
Scheme 2 Plausible pathways for the formation of 1-oxo-hexahydroxanthenes
123

R. V. Kupwade et al.
In an attempt to investigate the correct pathway, a model reaction was carried out
between salicylaldehyde, dimedone and thiophenol (1 mmol, each), employing the
reaction conditions established for the synthesis of 5a. Upon completion of the
reaction, the resultant product was noticed to be an easily separable mixture of
1-oxo-hexahydroxanthene, 5a, and 8 (7:3, isolated yields). Thus, it was concluded
that in this multicomponent reaction, after the formation of Knoevenagel
condensation product, Z (Scheme 2), addition of dimedone (carba–Michael) and
of thiophenol (thia–Michael) takes place competitively and amongst these,
dimedone being more nucleophilic than thiophenol, carba–Michael addition
proceeds at a faster rate than thia–Michael addition reaction. To give credence to
this supposition, another model reaction was carried out wherein to a stirred solution
of salicylaldehyde and thiophenol (1 mmol, each) in ethanol (2 mL) was added
dropwise a solution of dimedone (1 mmol) in ethanol (3 mL). The resultant product
was once again identified to be the mixture of 5a and 8 in a 3:2 proportion (isolated
yields). Although this success supports the possibility of competitive carba as well
as thia–Michael addition in synthesis of 5a and 8, respectively, it is not sufficient
enough to conclude that the reaction does not follow Path A. Hence, additional
experiments were carried out.
Sun and co-workers quite recently reported that in a piperidine-catalyzed reaction
between an aldehyde and dimedone, an initial Knoevenagel condensation product,
being short-lived, instantaneously undergoes 1,4-conjugate addition with an enoliz-
able ketone like dimedone [36]. With reference to this report, we speculated about
similar observation for the reaction between salicylaldehyde and dimedone. Hence,
under the established reaction conditions, another model reaction was carried out
between salicylaldehyde and dimedone (1 mmol, each). Upon completion of the
reaction, as against the Knoevenagel condensation product, we were startled to notice
the formation of 5a as the sole product (43 %, isolated yield). Thus, we concluded
that even in the presence of a basic catalyst, formation of 1-oxo-hexahydroxanthene,
5a, proceeds by Path B and not by Path A. A search of the literature in the context of
this reaction mechanism revealed that in ammonium chloride-catalyzed synthesis of
5a and 8, Khan and co-workers also proposed Path B [37].
Taking clues from these results, it was surmised that if the reaction follows
Path B, the reaction between an aromatic aldehyde devoid of an ortho hydroxyl
group, e.g. 4-methoxybenzaldehyde, 9a, with two equivalents of dimedone
should furnish 2,20-(4-phenylmethylene)-bis-(3-hydroxy-3,3-dimethyl-2-cyclo-
hexene-1-one, tetraketone, 10a, while the similar reaction with the choice of
another 1,3-diketone, 4-hydroxycoumarin, 11, should furnish 3,30-(4-phenyl-
methylene)-bis-(4-hydroxycoumarin), 12a, as Knoevenagel–carba–Michael domino
reaction product, respectively (Scheme 3).
In an effort to confirm these speculations, two model reactions were performed
employing the reaction conditions established for the synthesis of 5a, (1) between
4-methoxybenzaldehyde, 9a, (1 mmol) and dimedone (2 mmol), and (2) between
4-methoxybenzaldehyde, 9a, (1 mmol) and 4-hydroxycoumarin, 11 (2 mmol).
Upon completion of the reactions (monitored via TLC), it was truly gratifying to
notice the formation of anticipated tetraketone, 10a, as well as bis-coumarin, 12a, in
excellent yields. In each case, the resultant solid was simply filtered, washed with
123

Diethylamine-catalyzed environmentally benign synthesis…
OMe
OMe
O
O
O
OH
O
OH
O
2, Diethylamine
11, Diethylamine
EtOH, RT
H
EtOH, RT
MeO
O
9a
11: 4-hydroxy coumarin
HO
OH
O
2: Dimedone
10a
12a
Scheme 3 Diethylamine-catalyzed synthesis of bis-coumarins and tetraketones
water, dried and washed again with hexane–chloroform (9:1, v/v) to obtain pure 10a
and 12a.
As far as earlier protocols reported for the synthesis of tetraketones and bis-
coumarins are concerned, a few interesting reports are noteworthy. For instance,
synthesis of tetraketones employing the same reactants has been reported earlier in
aqueous medium under catalyst-free conditions at ambient temperature [38].
Logically, we did not pursue to establish generality of the reaction conditions for the
synthesis of other tetraketones. On the other hand, synthesis of bis-coumarins has
been reported earlier using a variety of catalysts under a range of experimental
conditions [39–50]. Interestingly, most of the reported protocols require elevated
temperature [39–45] or microwave (MW) irradiation [46–48], while a few of them
require the use of an expensive catalyst [49]. Furthermore, their synthesis has
although been known to follow a Knoevenagel–carba–Michael domino pathway, to
the best of our knowledge, except for piperidine [50], there are no reports on their
synthesis using any other basic catalyst. In light of these observations, it was quite
evident that development of a protocol that would circumvent the drawbacks
associated with most of the earlier reported protocols is essential. The other reason
to undertake the synthesis of bis-coumarins was concerned with their well-
established biological activities [51–54]. For instance, bis-coumarins are known to
exhibit urease inhibitor, anticoagulant as well as snake venom NPP1 inhibitory
activity [53]. A few naturally occurring bis-coumarins are known to serve as DNA
polymerase beta lyase inhibitor [54]. Hence, we planned to extend the scope of the
established reaction conditions towards the synthesis of various bis-coumarins.
Accordingly, aromatic aldehydes tethered with electron-withdrawing as well as
electron-donating groups and a few heterocyclic aldehydes were allowed to react
with 4-hydroxy coumarin. In all the cases, desired bis-coumarin, 12b–k, was
obtained in excellent yields following very simple work-ups as well as purification
methods. The results are summarized in Table 2.
Finally, a comparison was made between the protocol developed by us and those
reported earlier for the synthesis of 5a as a model compound. The results summarized
in Table 3 clearly reveal the superiority of the protocol developed by us over all other
protocols in terms of yield, cost, operational simplicity, etc. On the other hand, to the
best of our knowledge, piperidine is the only basic catalyst reported for the synthesis
of bis-coumarins, and compared to piperidine, use of diethylamine is certainly
advantageous in terms of cost, ease of handling and the toxicity of the catalyst.
123

R. V. Kupwade et al.
Table 2 Diethylamine-catalyzed synthesis of bis-coumarins, 12
OH
O
R
O
OH
O
OH
O
Diethylamine
+
R
H
EtOH, RT
O
O
O
12
9
8
Product Aldehyde (9)
Time (h) Yield (%) Melting point (°C)
Obs.
Lit. References
12a
12b
12c
12d
12e
12f
12g
12h
12i
4-Methoxybenzaldehyde
2,5-Dimethylbenzaldehyde
4-Bromobenzaldehyde
6-Nitropiperonal
3.0
4.0
3.5
3.0
4.0
5.0
4.0
5.0
83
84
87
83
86
81
78
80
81
79
89
138–140 140–141 [45]
198–200
260–262 265–267 [40]
153–156
–
–
4-Hydroxybenzaldehyde
4-Nitrobenzaldehyde
Thiophene-2-carbaldehyde
5-Methylfurfural
205–207 202–204 [51]
228–231 232–234 [45]
150–152 156–158 [49]
185–187
134–136
222–225
–
–
–
3-Methyl thiophen-2-carbadehyde 4.0
12j
12k
4-Allyloxybenzaldehyde
4-Cyanobenzaldehyde
4.0
4.0
238–241 240–242 [40]
Reaction conditions: aldehyde (2 mmol), 4-hydroxycoumarin (4 mmol), diethylamine (20 mol%), etha-
nol (6 mL), RT
Table 3 Comparison between the present protocol and the protocols reported earlier for the synthesis of
5a as a model compound
No. Catalyst
Reaction conditions Time (h) Yield (%) References
1
L-Proline
Ethanol, 60 °C
Water, 85 °C
SF, RT, grinding
Water, reflux
SF,120 °C
Water, reflux
Glycerol, 90 °C
Water, 100 °C
SF, 120 °C
1
98
95
96
92
93
90
84
89
95
86
83
92
[23]
2
[(CH2)4 SO3H HMIM] [HSO4]
Cellulose sulfuric acid
CeCl3-7H2O
3
[22]
3
30
3
[20]
4
[25]
5
2,4,6-Trichloro-1,3,5-triazine
Catalyst-free
3
[21]
6
3
[27]
7
Catalyst-free
3
[26]
9
CH3COOH
3
[17]
10
11
12
13
Heteropolyacid
30
3
[24]
Benzyltriethylammonium chloride Water, 90 °C
KF–Al2O3
[28]
EtOH, 80 °C
EtOH, RT
3
[29]
Diethylamine (20 mol%)
4.5
This work
Conclusion
In summary, we have developed an operationally simple and environmentally
benign protocol for the synthesis of 1-oxo-hexahydroxanthenes as well as bis-
coumarins using diethylamine as the catalyst. Excellent yields, easy commercial
123

Diethylamine-catalyzed environmentally benign synthesis…
availability of the catalyst at an extremely low cost, ambient reaction conditions and
avoidance of conventional work-ups as well as purification procedures are the
noteworthy advantages of this energy-efficient protocol.
Experimental
General experimental procedure for 5/6/7
To a well stirred solution of salicylaldehyde, 1 (2 mmol) and appropriate 1,3-dione
(2/3/4, 4 mmol) in ethanol (4 mL) was added diethylamine (20 mol%) and stirring
continued. Upon completion of the reaction (TLC), the resultant solid was filtered,
washed with water, dried, again washed with a hexane–chloroform mixture (9:1,
v/v) and dried. The resultant product, 5/6/7, was found to be pure for all practical
purposes.
General experimental procedure for 12
To a well stirred solution of an aldehyde 9 (2 mmol) and 4-hydroxycoumarin (11,
4 mmol) in ethanol (4 mL) was added diethylamine (20 mol%) and stirring was
continued at ambient temperature. Upon completion of the reaction (TLC), the
resultant solid was filtered, washed with water, dried, washed again with a hexane–
chloroform mixture (9:1, v/v) and dried. The resultant bis-coumarins, 12, were
found to be pure for all practical purposes.
Spectral data of new compounds
5-Bromo-3,4-dihydro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3-dimethyl-
7-nitro-2H-xanthen-1(9H)-one, 5h: pale yellow solid; M.P.: 228–232 °C; IR (KBr):
3499, 2991, 1720, 1655, 1544, 1487, 1340, 1167, 845 cm-1; [1H-NMR, 300 MHz,
deuterated chloroform (CDCl3)]: d 1.08 (s, 4H), 1.16 (s, 8H), 2.27–2.33 (m, 3H), 2.41
(s, 2H), 2.32–2.39 (m, 3H), 4.83 (s, 1H), 7.78 (s, 1H), 8.29 (s, 1H), 10.38 (brs, 1H);
(13C-NMR, 75 MHz, CDCl3): d 26.19, 27.27, 29.29, 30.00, 32.04, 32.26, 40.91, 46.33,
30.19, 113.23, 114.13, 113.10, 122.86, 124.00, 124.43, 126.13, 127.78, 141.23, 133.13,
137.47, 163.33, 189.90, 198.23 ppm.
6,8-Dichloro-3,4-dihydro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3-
dimethyl-2H-xanthen-1(9H)-one, 5j: White solid; M. P.: 208–210 °C; IR (KBr):
3455, 2990, 1724, 1644, 1523, 1475, 1323, 1140, 877 cm-1; 1H-NMR : (300 MHz,
CDCl3) : d 0.87 (s, 6H), 1.03 (m, 4H), 1.13 (m, 2H), 2.03–2.06 (m, 3H), 2.14–2.41
(m, 3H), 2.81 (brs, 1H), 4.97 (s, 1H), 6.83 (s, 1H), 6.96–7.01 (m, 1H); 13C-NMR:
(75 MHz, CDCl3) d 23.31, 26.63, 28.37, 29.32, 31.37, 31.98, 48.31, 48.71, 30.94,
31.23, 111.47, 114.41, 124.29, 131.31, 134.04, 143.10, 132.39, 197.13, 198.20 ppm.
3,4-Dihydro-9-(2-hydroxy-6-oxocyclohex-1-enyl)-6-methoxy-2H-xanthen-1(9H)-
one, 6b: White solid; M. P.: 236–240 °C; IR (KBr): 3455, 2990, 1724, 1644, 1523,
1475, 1323, 1140, 877 cm-1; 1H-NMR : (300 MHz, CDCl3) : d 1.84–1.96 (m, 2H),
2.03–2.14 (m, 4H), 2.41–2.63 (m, 3H), 2.72–2.78 (m, 1H), 3.78 (s, 3H), 4.39 (s, 1H),
123

R. V. Kupwade et al.
6.38–6.92 (m, 2H), 6.91 (d, 1H, J = 9.1 Hz), 10.80 (brs, 1H); 13C-NMR: (75 MHz
CDCl3) : d 19.63, 19.94, 27.47, 27.96, 36.02, 33.32, 110.92, 111.03, 112.63, 116.49,
119.79, 128.43, 131.42, 138.92, 170.94, 201.31 ppm.
3,4-Dihydro-5-hydroxy-9-(2-hydroxy-6-oxocyclohex-1-enyl)-2H-xanthen-1(9H)-
one, 6c: White solid; M. P.: 247–248 °C; IR (KBr): 3502, 2996, 1712, 1640, 1568,
1498, 1333, 1145, 878 cm-1 1H-NMR : (300 MHz, CDCl3) : d 1.71–1.73 (t, 2H,
J = 6.5 Hz), 1.92–1.96 (t, 2H, J = 3.5 Hz), 2.02 (s, 4H), 2.29–2.31 (m, 2H),
2.30–2.61 (m, 1H), 4.83 (s, 1H), 6.41 (d, 1H, J = 7.4 Hz), 6.61 (d, 1H, J = 8 Hz),
6.67 (t, 1H, J = 7.8 Hz); 13C-NMR : (75 MHz, CDCl3) : d 20.23, 20.40, 26.76,
27.88, 36.89, 112.31, 114.18, 116.39, 118.79, 119.77, 124.00, 126.26, 129.89,
139.06, 144.37, 148.32, 168.43, 198.67 ppm.
6,8-Dichloro-3,4-dihydro-9-(2-hydroxy-6-oxocyclohex-1-enyl)-2H-xanthen-1(9H)-
one, 6e: Solid; M. P.: 220–223 °C; IR (KBr): 3487, 2956, 1630, 1599, 1560, 1341,
1145, 898 cm-1; 1H-NMR : (300 MHz, CDCl3) : d 1.92–1.98 (m, 3H), 2.00–2.09 (m,
1H), 2.23–2.48 (m, 6H), 2.80 (m, 2H), 4.33 (s, 1H), 7.11(d, 1H, J = 2.4 Hz), 7.34 (d,
1H, J = 2.4 Hz); 13C-NMR : (75 MHz, CDCl3) : d 20.07, 20.31, 24.36, 27.46, 34.33,
36.33, 40.17, 49.13, 110.91, 113.98, 121.06, 126.74, 127.13, 127.61, 127.72, 144.94,
168.34, 193.28, 202.67 ppm.
9-(2-Hydroxy-4-methyl-6-oxo-cyclohex-1-enyl)-3-methyl-2,3,4,9-tetrahydro-xan-
then-1-one,7a: Solid; M. P.: 231–234 °C; IR (KBr): 3499, 2991, 1720, 1655, 1544,
1487, 1340, 1167, 845 cm-1; 1H-NMR: [300 MHz, deuterated dimethyl sulfoxide
(DMSO-d6)]: d 0.85 (d, 3H, J = 4.1 Hz), 0.95(d, 3H, J = 6.1 Hz), 1.87 (s, 4H),
2.03–2.26 (m, 6H), 5.04 (s, 1H), 6.75–6.81(m, 2H), 6.90–6.99 (m, 2H); 13C-NMR :
(75 MHz, CDCl3) : d 20.87, 21.38, 26.10, 27.77, 28.41, 36.00, 45.42, 113.05,
115.00, 117.77, 123.81, 126.03, 127.78, 128.96, 150.25, 197.89 ppm.
7-Bromo-9-(2-hydroxy-4-methyl-6-oxo-cyclohex-1-enyl)-3-methyl-2,3,4,9-tetrahy-
dro-xanthen-1-one, 7b: Solid; M. P.: 248–251 °C; IR (KBr): 3445, 2915, 1714, 1601,
1561, 1544, 1333, 1112, 840 cm-1; 1H-NMR : (300 MHz, DMSO-d6) : d 0.90 (d, 3H,
J = 3.1 Hz), 1.02 (d, 3H, J = 3.9 Hz), 1.89–2.02 (m, 4H), 2.13–2.30 (m, 4H),
2.50–2.64 (m, 2H), 4.96 (s, 1H), 6.39 (d, 1H, J = 7.1 Hz), 6.57 (d, 1H, J = 6.8 Hz),
6.66 (t, 1H, J = 7.7 Hz); 13C-NMR : (75 MHz, DMSO-d6) : d 20.84, 20.95, 26.13,
27.92, 28.06, 35.93, 45.31, 111.85, 113.98, 118.70, 119.30, 123.94, 126.68, 138.94,
144.61, 166.87, 197.07 ppm.
7-Chloro-9-(2-hydroxy-4-methyl-6-oxo-cyclohex-1-enyl)-3-methyl-2,3,4,9-tetrahy-
dro-xanthen-1-one, 7c: Solid; M. P.: 241–244 °C; IR (KBr): 3488, 2992, 1712, 1610,
1
1567, 1515, 1340, 11,122, 878 cm-1; H-NMR : (300 MHz, DMSO-d6) : d 0.90 (s,
3H), 1.01 (s, 3H), 2.04 (s, 4H), 2.27 (s, 4H), 2.51 (s, 2H), 5.04 (s, 1H), 6.92 (s, 1H),
7.01 (s, 1H), 7.16 (s, 1H), 10.71 (s, 1H); 13C-NMR : (75 MHz, DMSO-d6) : d 20.74,
20.86, 25.94, 28.11, 28.28, 35.47, 45.22, 111.53, 117.78, 127.32, 128.07, 128.37,
148.91, 166.44, 196.27 ppm.
2-Hydroxy-3-((2-hydroxy-4-oxo-4H-chromen-3-yl)(2,5-dimethylphenyl)methyl)-
4H-chromen-4-one, 12c, Solid; M. P.: 198–200 °C; IR (KBr): 3434, 2972, 1645,
1614, 1565, 1510, 1321, 1132, 876 cm-1; 1H-NMR: (300 MHz, DMSO-d6): d 2.03
(s, 3H), 2.18 (s, 3H), 5.60 (s, 1H), 6.09 (s, 1H), 6.88 (d, 1H, J = 7.5 Hz), 6.96 (d,
1H, J = 7.3 Hz), 7.03 (s, 1H), 7.30 (d, 1H, J = 7.3 Hz), 7.34 (s, 1H), 7.37 (s, 1H),
123

Diethylamine-catalyzed environmentally benign synthesis…
7.58 (t, 2H, J = 7.7 Hz), 7.62 (d, 1H, J = 8.0 Hz), 7.82 (d, 1H, J = 7.7 Hz), 7.91
(d, 2H, J = 7.8 Hz), 12.56 (brs, 1H); 13C-NMR : (75 MHz, DMSO-d6): d 19.56,
21.44, 36.19, 91.48, 104.84, 116.26, 116.47, 116.81, 117.88, 123.66, 124.19, 124.23,
124.36, 127.12, 128.72, 130.82, 132.29, 133.13, 133.36, 134.49, 152.56, 153.98,
162.35, 164.39, 164.62, 166.10 ppm.
2-Hydroxy-3-((2-hydroxy-4-oxo-4H-chromen-3-yl)(6-nitrobenzo[d] [1, 3] dioxol-
6-yl)methyl)-4H-chromen-4-one, 12d, solid; M. P.: 203–205 °C; IR (KBr): 3465,
1
2948, 1651, 1610, 1555, 1532, 1505, 1367, 1155, 865 cm-1; H-NMR: (300 MHz,
DMSO-d6): d 5.59 (s, 1H), 6.10 (s, 2H), 6.71 (d, 1H, J = 4.0 Hz), 6.88 (d, 1H,
J = 2.1 Hz), 7.20 (d, 1H, J = 2.5 Hz), 7.23 (s, 2H), 7.25 (d, 2H, J = 3.4 Hz), 7.28
(d, 1H, J = 2.6 Hz), 7.32 (d, 1H, J = 2.2 Hz), 7.52 (t, 2H, J = 8.3 Hz), 7.92 (d, 2H,
J = 8.0 Hz); 13C-NMR: (300 MHz, DMSO-d6) (75 MHz, DMSO-d6): d 39.78,
96.27, 107.99, 109.51, 110.51, 114.30, 121.09, 121.15, 121.68, 128.28, 128.57,
137.05, 137.24, 147.99, 151.20, 156.01, 157.27, 158.70, 168.59, 169.11,
170.82 ppm.
2-Hydroxy-3-((2-hydroxy-4-oxo-4H-chromen-3-yl)(5-methylfuran-2-yl)methyl)-
4H-chromen-4-one, 12h, solid, M. P.:185–187 °C; IR (KBr): 3445, 2943, 1654,
1
1621, 1532, 1499, 1353, 823 cm-1; H-NMR: (300 MHz, DMSO-d6): d 2.13 (s,
3H), 5.85 (s, 1H), 5.96 (s, 1H), 6.10 (d, 1H, J = 3.1 Hz), 7.27 (s, 1H), 7.29 (s, 2H),
7.31 (s, 1H), 7.54 (t, 2H, J = 7.6 Hz), 7.93 (d, 2H, J = 7.6 Hz), 11.50 (brs, 2H);
13C-NMR: (75 MHz, DMSO-d6): d 13.63, 32.00, 103.51, 106.32, 107.98, 116.46,
116.62, 124.17, 124.62, 132.71, 151.28, 152.31, 164.31, 166.54 ppm.
2-Hydroxy-3-((2-hydroxy-4-oxo-4H-chromen-3-yl)(3-methylthiophene-2-yl)methyl)-
4H-chromen-4-one, 12i, Solid, M. P.: 134–136 °C; IR (KBr): 3455, 2988, 1674, 1612,
1514, 1491, 1377, 888 cm-1; 1H-NMR: (300 MHz, DMSO-d6): d 2.13 (s, 3H), 5.85 (s,
1H), 5.96 (s, 1H), 6.10 (d, 1H, J = 3.1 Hz), 7.27 (s, 1H), 7.29 (s, 2H), 7.31 (s, 1H), 7.54
(t, 2H, J = 7.6 Hz), 7.93 (d, 2H, J = 7.6 Hz), 11.50 (brs, 2H); 13C-NMR: (75 MHz,
DMSO-d6): d 13.58, 32.95, 104.46, 107.27, 108.93, 117.41, 117.57, 125.12, 125.57,
133.66, 148.78, 152.53, 153.26, 165.26, 167.49 ppm.
3-((4-(Allyloxy)phenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)-4-hydroxy-
2H-chromen-2-one, 12j: Solid; M. P.: 230–232 °C; IR (KBr): 3435, 2917, 1640,
1
1612, 1545, 1490, 1342, 808 cm-1; H-NMR: (300 MHz, DMSO-d6): d 4.53 (d,
2H, J = 5.4 Hz),5.28 (dd, 1H, J = 9.2 & 10.5 Hz), 5.41 (dd, 1H, J = 17.1 &
15.4 Hz), 5.99–6.12 (m, 1H), 6.87 (d, 2H, J = 8.8 Hz), 7.12 (d, 2H, J = 8.2 Hz),
7.41 (s, 2H), 7.44 (s, 2H), 7.61–7.67 (m, 2H), 8.02 (d, 1H, J = 8.0 Hz), 8.09 (d, 1H,
J = 7.7 Hz), 11.31 (s, 1H), 11.50 (s, 1H); 13C-NMR: (75 MHz, DMSO-d6): d
35.53, 68.74, 104.20, 105.81, 114.80, 116.57, 117.59, 124.41, 124.74, 127.04,
127.57, 132.65, 133.31, 152.28, 157.46, 164.39, 165.51, 166.63 ppm.
Acknowledgements Authors KSP and UVD are thankful to the University Grants Commission (UGC),
New Delhi for financial assistance [F. 43-221-2014/SR]. We are also grateful to the Department of
Science & Technology (DST), New Delhi for financial assistance to the Department of Chemistry, Shivaji
University Kolhapur under the DST–FIST program.
123

R. V. Kupwade et al.
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