Zn[(L)Proline]2: An eligible candidate for the synthesis of xanthenediones in water

Article abstract of DOI:10.1002/aoc.2895

An efficient route for the condensation of aldehydes with dimedone in the presence of Zn[(L)Proline]₂ in water has been reported. Hydrophilicity of the catalyst is the main attribute of this reaction. The water-mediated reaction using catalytic

Full text of DOI:10.1002/aoc.2895

Full Paper
Received: 5 May 2012
Revised: 29 May 2012
Accepted: 3 June 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2895
Zn[(L)Proline]2: an eligible candidate for the
synthesis of xanthenediones in water
Mazaahir Kidwai* and Arti Jain
An efficient route for the condensation of aldehydes with dimedone in the presence of Zn[(L)Proline]2 in water has been
reported. Hydrophilicity of the catalyst is the main attribute of this reaction. The water-mediated reaction using catalytic
amounts of recyclable catalyst avoids the use of expensive, corrosive reagents and toxic solvents and provides operational
simplicity. Moreover, column chromatography and recrystallization of product are not required as the crude products itself
are very pure and hence can be used for target-oriented synthesis on a large scale. Copyright © 2012 John Wiley & Sons, Ltd.
Keywords: Zn(proline)2; xanthenedione; water; environmentally benign; recyclability
The design and synthesis of organometallic complexes have
Introduction
recently been the subject of intense interest,[31] not only because
Solvents define a major part of the environmental performance
of their fascinating structural topology but also their potential
of processes in chemical industry and also have an impact on
applications as functional materials in magnetism, molecular
absorption, fluorescence, catalysis and chemical separation.[32,33]
cost, safety and health issues. The idea of ’green’ solvents
expresses the goal to minimize environmental impacts resulting
As a part of our ongoing research program aimed at developing
from the use of solvents in chemical production. As clearly stated
ecofriendly methods for carrying out various organic transforma-
tions,[34–36] we report herein the recently explored Zn[(L)Proline]2
by Sheldon, ’the best solvent is no solvent and if a solvent
(diluent) is needed it should preferably be water’.[1]
complex as an efficient catalyst for the synthesis of xanthenediones.
Zn[(L)Proline]2 is an efficient, stable, inexpensive, recyclable,
Water is a lingua franca of the life on our planet and is the
solvent of choice for nature to carry out her synthesis.[2]
water-compatible, Lewis acid catalyst which is not dissociated
Reactions in aqueous media are environmentally benign, easy
under reaction conditions. This complex is soluble in water but
to handle and are devoid of any corrosive or carcinogenic effects.
insoluble in organic solvents, which allows simple and quantita-
Moreover, reactions in water lead to shorter reaction time with
tive recovery of the catalyst.
enhanced yield and greater ease of manipulation. Therefore, the
Ever since the exploration of water-soluble Zn[(L)Proline]2
complex by Darbre’s group[37] only few reports have appeared
development of an efficient synthetic methodology in aqueous
media appears to be necessary.[3] The use of water as a solvent
to date employing Zn[(L)Proline]2 as a Lewis acid catalyst for
different organic reactions.[38–49] Thus there is much scope for
has been accepted for a wide range of organic transformations,
including stereoselective Diels–Alder reaction,[4] Claisen rearrange-
further exploration of this catalyst for its application in the syn-
ment,[5] Aldol reaction,[6] allylation reaction,[7] oxidation including
thesis of various privileged medicinal heterocyclic rings.
asymmetric epoxidation[8] and hydrogenation of alkenes.[9]
Xanthenediones occupy an important place in the realm of
natural and synthetic organic chemistry. They have been used as sen-
Experimental
sitizers in photodynamic therapy[10] and have several medicinal uses,
such as antiviral,[11] antibacterial and anti-inflammatory agents,[12,13]
General
in antagonism of the paralyzing action of zoxazolamine,[14] and can
Some chemicals were purchased from Sigma-Aldrich and Lancaster
act as versatile synthons because of the inherent activity of the inbuilt
and were used as such. All reactions and purity of products were
pyran ring.[15,16] Furthermore, because of their useful spectroscopic
monitored by thin-layer chromatography (TLC) using aluminum
properties,[17] they are used as dyes, in laser technologies[18] and in
plates coated with silica gel (Merck) employing ethyl acetate and
hexane (3:7). The isolated products were further purified by
fluorescent material for visualization of biomolecules.[19]
Conventional synthesis of xanthenediones usually involves acid- or
column chromatography using silica gel (Sigma-Aldrich 24,
217–9, 70, 35–70, mesh 40 Aꢀ surface area 675 m2 gꢁ1). IR spectra
were recorded on a PerkinElmer FT-IR 1710 spectrophotometer
base-catalyzed condensation of appropriate active methylene
carbonyl compounds with aldehydes.[20]
Recently, several reports have been put forward in which
xanthenedione derivatives were synthesized.[21–30] Each of these
methods has its own advantages but also suffers from one or
more disadvantages, such as prolonged reaction time, tedious
workup processes, expensive reagents, usage of volatile
solvents, low yield, lack of easy availability of the catalyst,
preparation of starting materials, hazardous reaction condition
and non-reusability of the catalyst.
*
Correspondence to: M. Kidwai, Green Research Laboratory, Department of Chem-
istry, University of Delhi, Delhi 110 007, India. E-mail: kidwai.chemistry@gmail.com
Green Research Laboratory, Department of Chemistry, University of Delhi,
Delhi 110 007, India
Presently Vice-chancellor of Jiwaji University, Gwalior (MP) India
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.

M. Kidwai and A. Jain
using Nujol film and KBr pellet. 1 H NMR and 13 C NMR
were recorded on a JEOL JNMECX 400P FT NMR system using tet-
ramethylsilane as an internal standard. The chemical shift values
are recorded on a d scale. Elemental analysis was performed on a
Hereaus CHN rapid analyzer. Electrospray ionization mass spectra
1364, 1199 cmꢁ1
.
1 H NMR (400 MHz, CDCl3): d 7.27 (d, J= 8.0 Hz,
2 H, H-20, H-60), 7.17–7.26 (m, 2 H, H-30, H-50), 7.07–7.15(m, 1 H,
H-40), 4.72 (s, 1 H, CH-90), 2.43 (s, 4 H, 2H-2, 2 H-7), 2.18
(q, J= 16.4 Hz, 4 H, 2 H-4, 2 H-5), 1.07 (s, 6 H, equatorial 2CH3), 0.96
(s, 6 H, axial 2CH3). 13 C NMR (100 MHz, CDCl3): d C-1, C-8; 196.36,
C-11, C-13; 162.22, C-1’; 144.04, C-30, C-50; 128.34, C-20, C-60; 128.01,
C-40; 126.33, C-10, C-12; 115.63, C-2, C-7; 50.70, C-9; 40.84, C-4, C-5;
32.16, C-3, C-6; 31.81, C-14, C-16; 29.23, C-15, C-17 27.29. EI-MS
(m/z): 350 (M+). Anal. Calcd for C23H26O3: C, 78.83; H, 7.47. Found:
C, 78.98; H, 7.43.
were recorded on
a Waters LCT Micromass instrument.
The melting point of the compounds was measured through a
Thomas-Hoover melting point apparatus and was uncorrected.
General Procedure for the Synthesis of Zn[(L)proline]2
The zinc amino complex was prepared by adding Et3N (0.6 ml) to
the amino acid (4.34 mmol) in MeOH (10 ml), followed by
addition of zinc acetate (2.17 mmol) after 10 min. After stirring
for 45 min, a white precipitate was collected by filtration
(23–95% yield). The complex was characterized by 1 H NMR, 13 C
NMR, IR, transmission electron microscopy, powder X-ray diffrac-
tion and electron impact (EI) mass spectrometry.[35,37]
General Procedure for the Synthesis of Xanthenediones
In a 50 ml round-bottom flask, dimedone (0.02 mol) and aldehydes
(0.01mol) in 5 ml water were mixed. To this, Zn[(L)Proline]2 was
added and refluxed. The progress of the reaction mixture was mon-
itored by TLC. After completion of the reaction, the reaction mixture
was cooled at room temperature, and ethyl ether (2ꢂ 4 ml) was
added to the mixture to extract the product. The combined organic
layers were washed with water and brine, dried with anhydrous
Na2SO4 and evaporated under reduced pressure. The catalyst was
recovered by simple separation of aqueous and organic phases.
The catalyst present in the aqueous layer was recovered by
precipitating the aqueous layer by addition of acetone and used
for the subsequent cycle. The structures of all the products were
unambiguously established on the basis of their spectral analysis
(IR, 1 H NMR, 13 C NMR, CHN and EI mass spectral data).
9-(40-Chlorophenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
anthene-1,8-dione (3b). NMR (400 MHz, CDCl3): d 7.42 (d, 2 H,
J = 8.1 Hz, H-20, H-60), 7.36 (d, 2 H, J = 8.1 Hz, H-30, H-50), 4.64
(s,1H, CH-9), 2.32 (s, 4 H, 2CH-2, 2CH-7), 2.31 (q, J = 16.5 Hz, 2 H-4,
2H-5, 4H), 1.10 (s, 6H, equatorial 2CH3), 0.98 (s, 6 H, axial 2CH3).
13 C NMR (100 MHz, CDCl3): d C-1, C-8; 195.28, C-11, C-13; 162.19,
C-10; 140.77, C-40; 135.67, C-30, C-50; 128.11, C-20, C-60; 128.45, C-10,
C-12; 115.21, C-2, C-7; 50.63, C-9; 40.16, C-4, C-5; 32.45, C-3, C-6;
31.27, C-14, C-16; 29.13, C-15, C-17; 27.2. EI-MS (m/z): 366 (M+). Anal.
Calcd for C23H26O4: C, 71.77; H, 6.54. Found: C, 71.88; H, 6.44.
Procedure to Recover Zn[(L)Proline]2
After completion of the reaction the crude product was extracted
with ethyl ether and the catalyst was recovered by separation of
aqueous and organic phases. The catalyst was recovered by precip-
itating the aqueous layer by simple addition of acetone. Then, the
catalyst was dried at 80ꢀC for 2 h and used for the next cycle.
Spectral Data of the Synthesized Compounds
9-(40 -Nitrophenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
anthene-1,8-dione (3c). White solid. M.p. 222–224 ꢀC. IR (KBr):
9-Phenyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydroxanthene-1,8-
dione (3a). White solid. M.p. 204–205 ꢀC. IR (KBr): 2954, 1664,
2956, 1671, 1650, 1520, 1362, 1206, 870 cm cmꢁ1 1 H NMR
.
(400 MHz, CDCl3): d 8.11 (d, J = 8.4 Hz, 2 H, H-20, H-60), 7.44
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Zn(proline)2 for the synthesis of xanthenediones in water
(d, J = 8.4 Hz, 2 H, H-30, H-50), 4.80 (s, 1 H, CH-9), 2.49 (s, 4 H, 2CH-2,
2CH-7), 2.22 (q, J= 16.1 Hz, 4 H, 2 H-4, 2 H-5), 1.10 (s, 6 H, equatorial
2CH3), 0.99 (s, 6 H, axial 2CH3). 13 C NMR (75 MHz, CDCl3): d C-1,
C-8; 196.14, C-11, C-13; 162.29, C-10; 151.33, C-40; 146.61, C-30,
C-50; 129.34, C-20, C-60; 123.55, C-10, C-12; 114.52, C-2, C-7;
50.53, C-9; 40.88, C-4, C-5; 31.3, C-3, C-6; 31.1, C-14, C-16; 29.16,
C-15, C-17; 29.20. EI-MS (m/z): 395 (M+). Anal. Calcd for
C23H25NO5: C, 69.85; H, 6.37; N, 3.54. Found: C, 69.86; H 6.40; N, 3.40.
2CH3). 13 C NMR (100 MHz, CDCl3): d Cꢁ 1, C ꢁ 8; 196.11, C-11, C-13;
162.26, C-20; 148.40, C-40; 126.67, C-50; 125.28, C-30; 123.33, C-10,
C-12; 115.24, C-2, C-7; 50.70, C-9; 40.89, C-2, C-6; 32.01, C-14, C-16;
29.23, C-15, C-17; 27.34. EI-MS (m/z): 356 (M+). Anal Calcd for
C21H24O3S: C, 70.78; H, 6.74. Found: C, 70.81; H, 6.60.
9-(20-Hydroxynaphthyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octa-
hydroxanthene-1,8-dione (3f). White solid. M.p. 232–233 ꢀC. IR (KBr):
3324, 2959, 1687, 1652, 1617, 1490, 1363, 1200, 1135, 1012,
854 cmꢁ1 1 H NMR (400 MHz, CDCl3): d 11.01 (s, 1 H, OH, CH-20),
.
7.77–7.33 (m, 6 H, H-30, H-40, H-50, H-70, H-80, H-90, H-100), 5.25
(s, 1 H, CH-9), 2.60 (q, J= 16.0 Hz, 2 H, 2 H-4, 2 H-5), 2.38 (s, 4 H,
2CH-2, 2CH-7), 1.15 (s, 3 H, equatorial CH3), 1.06 (s, 3 H, equatorial
CH3), 0.98 (s, 3 H, axial CH3), 0.72 (s, 3 H, axial CH3). 13 C NMR
(100 MHz, CDCl3): d C-1, C-8; 199.10, C-11, C-13; 168.95, C-20; 155.4,
C-60; 131.11, C-50; 130.18, C-40, C-70; 128.24, C-90; 128.33, C-80;
126.26, C-100; 124.65, C-30; 122.27, C-10, C-12; 117.35, C-10; 116.4,
C-2, C-7; 50.36, C-9; 43.11, C-4, C-5; 41.24, C-3, C-6; 32.37, C-14,
C-16; 26.91, C-15, C-17; 26.31. EI-MS (m/z): 416 (M+). Anal. Calcd
for C27H28O4: C, 77.86; H, 6.78. Found: C, 77.79; H, 6.72.
9-(40-Hydroxyphenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
anthene-1,8-dione (3d). White solid. M.p. 249–251 ꢀC. IR (KBr):
3322, 2960, 1657, 1620, 1361 cmꢁ1 1 H NMR (400 MHz, CDCl3):
.
d 7.10–7.12 (d, J = 8.5 Hz, 2 H, H-20, H-60), 6.60 (d, J = 8.5 Hz, 2 H,
H-30, H-50), 5.72 (s, 1 H, OH, CH-40), 4.64 (s, 1 H, CH-9), 2.48
(s, 4 H, 2CH-2, 2CH-7), 2.20 (q, J = 16.2 Hz, 4 H, 2 H-4, 2 H-5), 1.09
(s, 6 H, equatorial 2CH3), 0.99 (s, 6 H, axial 2CH3). 13 C NMR
(100 MHz, CDCl3): d C ꢁ 1, C ꢁ 8; 195.28, C-11, C-13; 162.49, C-10;
140.17, C-40; 135.53, C-30, C-50; 128.21, C-20, C-6; 128.06, C-10,
C-12; 115.21, C-2, C-7; 50.63, C-9; 40.16, C-4, C-5; 32.45, C-3, C-6;
31.27, C-14, C-16; 29.13, C-15, C-17; 27.2. EI-MS (m/z): 366 (M+).
Anal. Calcd for C23H26O4: C, 75.38; H, 7.15. Found: C, 75.19; H 7.35.
9-(20-Thienyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
anthene-1,8-dione (3e). White solid. M.p. 163–164 ꢀC. IR (KBr): 2959,
2890, 1657, 1620, 1500, 1190 cmꢁ1
.
1 H NMR (400 MHz, CDCl3):
9-(Piperonyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
d 7.11 (d, J= 4.8 Hz, 1 H, H-30), 6.86 (d, J= 3.3 Hz, 1 H, H-50), 6.83–6.81
(m, 1 H, H-40), 5.01 (s, 1 H, CH-9), 2.45 (s, 4 H, 2CH-2, 2CH-7), 2.26
(s, 4 H, 2CH-4, 2CH-5), 1.09 (s, 6 H, equatorial 2CH3), 1.05 (s, 6 H, axial
anthene-1,8-dione (3 g). White solid. M.p. 243–245 ꢀC. IR (KBr): 3320,
2971, 1680, 1649, 1611, 1490, 1135, 1012, 850 cmꢁ1 1 H NMR
.
(400MHz, CDCl3): d 7.88 (s, 1 H, H-20), 7.81–7.85 (m, 2 H, H-50, H-60),
Appl. Organometal. Chem. (2012)
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M. Kidwai and A. Jain
5.76 (s, 2 H, C-70, CH2), 5.01 (s, 1 H, CH-9), 2.49 (q, J= 16.4 Hz, 4 H, 2
H-4, 2 H-5), 2.30(s, 4 H, 2CH-2, 2CH-7), 1.06 (s, 3 H, equatorial 2CH3),
0.98 (s, 3 H, axial 2CH3) 13 C NMR (100 MHz, CDCl3): d C-1, C-8;
198.41, C-11, C-13; 160.30, C-30; 149.01, C-40; 144.17, C-10; 135.53,
C-60; 128.21, C-20; 114.14, C-40; 113.20, C-10, C-12; 111.21, C-70;
101.12, C-2, C-7; 50.14, C-9; 41.01, C-4, C-5; 38.45, C-2, C-6; 32.27,
C-14, C-16; 28.12, C-15, C-17; 27.31. EI-MS (m/z): 393 (M+). Anal. Calcd
for C24H26O5: C, 73.08; H, 6.54 Found: C, 73.19; H, 6.72.
(400 MHz, CDCl3): d 7.01–7.03 (m, 1 H, H-40), 6.80–6.83(m, 2 H,
H-50, H-60), 6.48–6.51 (m, 1 H, H-30), 4.70 (s, 1 H, CH-9), 3.79
(s, 3 H, CH3 C-70), 2.34 (s, 4 H, 2CH-2, 2CH-7), 2.20 (q, J = 16.3 Hz,
4 H, 2 H-4, 2 H-5), 1.03 (s, 6 H, equatorial 2CH3), 0.98 (s, 6 H, axial
2CH3). 13 C NMR (100 MHz, CDCl3): d C-1, C-8; 197.11, C-40;
163.22, C-11, C-13; 160.00, C-10; 139.17, C-20, C-60; 135.23, C-30,
C-50; 114.14, C-10, C-12; 113.11, C-70; 55.10, C-2, C-7; 50.24, C-9;
41.34, C-4, C-5; 32.45, C-2, C-6; 32.27, C-14, C-16; 28.92, C-15,
C-17; 27.31. EI-MS (m/z): 379 (M+). Anal. Calcd for C24H28O4: C,
75.76; H, 7.42. Found: C, 75.45; H 7.30.
9-(40-Methylphenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahy-
droxanthene-1,8-dione (3j). White solid. M.p. 213–215 ꢀC. IR (KBr):
3028, 2978, 1680, 1660, 1622, 1493, 1365, 1201, 1135, 1000,
9-(40-Methoxyphenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
anthene- 1,8-dione (3 h). White solid. M.p. 204–205 ꢀC. IR (KBr):
3005, 2958, 2870, 1671, 1662, 1623, 1600, 1583 cmꢁ1 1 H NMR
.
850 cmꢁ1 1 H NMR (400 MHz, CDCl3): d 7.14 (d, J= 8.0 Hz, 2 H, H-20,
.
(400 MHz, CDCl3): d 7.08 (d, 2 H, H-20, H-60), 6.85 (d, 2 H, H-30,
H-50), 4.72 (s, 1 H, CH-9), 3.75 (s, 3 H, CH3, C-70), 2.32 (s, 4 H, 2CH-4,
2CH-5), 2.22 (q, J = 16.2 Hz, 4 H, 2 H-2, 2 H-7), 1.05 (s, 6 H,
equatorial 2CH3), 1.00 (s, 6 H, axial 2CH3). 13 C NMR (100 MHz,
CDCl3): d C-1, C-8; 198.41, C-40; 163.30, C-11, C-13; 160.01, C-10;
140.17, C-20, C-60; 135.53, C-30, C-5; 114.14, C-10, C-12; 113.20,
C-70; 55.13, C-2, C-7; 50.14, C-9; 41.01, C-4, C-5; 32.45, C-2, C-6;
32.27, C-14, C-16; 28.92, C-15, C-17; 27.31. EI-MS (m/z): 379 (M+).
Anal. Calcd for C24H28O4: C, 75.76; H, 7.42. Found: C, 75.49; H 7.35.
H-60), 7.01 (d, J= 8.0 Hz, 2 H, H-30, H-50), 4.72 (s, 1 H, CH-9), 2.44
(s, 4 H, 2CH-2, 2CH-7), 2.23 (s, 3 H, C-70 CH3), 2.19 (q, J= 16.3 Hz,
4 H, 2 H-4, 2 H-5), 1.09 (s, 6 H, equatorial 2CH3), 0.99 (s, 6 H, axial
2CH3). 13CNMR (100 MHz, CDCl3): d C-1,C-8; 195.14, C-11, C-13;
161.11, C-10; 141.10, C-40; 135.17, c-30, C-50; 128.57, C-20, C-60;
128.19, C-10, C-12; 115.57, C-2, C-7; 52.9, C-9; 50.37, C-4, C-5; 41.8,
C-3, C-6; 32.10, C-14, C-16; 29.25, C-15, C-17; 27.13, C-7’; 20.19.
EI-MS (m/z): 364 (M+). Anal. Calcd for C24H28O3: C, 79.09; H, 7.74.
Found: C, 79.56; H 7.52.
9-Ethyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydroxanthene-1,8-
dione (3 k). White solid. M.p. 147–149 ꢀC. IR (KBr): 2949, 1691,
9-(20-Methoxyphenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
1644, 1610, 1462, 1369, 1208, 1141, 1019, 840 cmꢁ1 1 H NMR
.
anthene-1,8-dione (3i). White solid. M.p. 257–258 ꢀC. IR (KBr):
(400 MHz, CDCl3): d 2.78–2.81 (m, 1 H, CH-9), 1.88-1.92 (m, 8 H,
3000, 2958, 2870, 1671, 1662, 1623, 1610, 1581 cmꢁ1
.
1 H NMR
C-2, C-4, C-5, C-7, 4CH2), 1.37 (m, 2 H, C-10, CH2), 1.10 (s, 6 H,
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Appl. Organometal. Chem. (2012)

Zn(proline)2 for the synthesis of xanthenediones in water
Scheme 1. Reaction between dimedone and aldehydes in the presence of Zn[(L)Proline]2 as a catalyst
equatorial 2CH3), 1.01 (s, 6 H, axial 2CH3), 0.91(m, 3 H, C-20 CH3).
13 C NMR (100 MHz, CDCl3): d C-1, C-8; 198.4, C-11, C-13; 153.1,
C-10, C-12; 112.5, C-2, C-7; 51.4, C-4, C-5; 38.50, C-3, C-6; 31.2,
C-14, C-16; 26.9, C-15, C-17; 25.6, C-10; 21.1, C-20; 13.1. EI-MS
(m/z): 301 (M+). Anal. Calcd for C19H26O3: C, 75.46; H, 8.67.
Found: C, 75.43; H, 8.91.
Table 2. Solvent system for model reactiona
Serial No.
Solvent system
Timeb
Yield (%)
1
2
3
4
5
6
7
8
9
Ethanol
Ethanol – Water
Water
0.5
0.5
0.5
2
85
95
94
85
78
60
60
50
80
Acetonitrile
THF
1
Toluene
DMF
1
1
DMSO
1
PEG-400
1.5
aReactions were performed with dimedone (0.02 mol), benzaldehyde
(0.01 mol) and Zn[(L)Proline]2 (2 mol%) as catalyst in the solvent
system (5 ml) by refluxing the mixture for x h.
bReaction progress monitored by TLC.
cIsolated yield.
C-11, C-13; 160.1, C-10, C-12; 113.5, C-2, C-7; 51.4, C-4, C-5; 44.1,
C-10; 32.1, C-2, C-6; 31.50, C-9; 30.2, C-14, C-16; 26.9, C-15, C-17;
25.6, C-20, C-30; 15.8. EI-MS (m/z): 316 (M+). Anal. Calcd for
C20H28O3: C, 75.91; H, 8.92. Found: C, 75.73; H, 8.80.
9-Isopropyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
anthene-1,8-dione (3 l). White solid. M.p. 155–157 ꢀC. IR (KBr): 2951,
1694, 1648, 1612, 1460, 1370, 1210, 1145, 1022, 844 cmꢁ1. 1 H NMR
(400 MHz, CDCl3): d 3.71 (d, J =3.0 Hz, 1 H, C-90, CH), 2.41–2.27
(m, 8 H, C-2, C-4, C-5, C-7, 4CH2), 1.81–1.77 (m, 1 H, C-10, CH), 1.13
(s, 6 H, equatorial, 2CH3), 1.11 (s, 6 H, axial 2CH3), 0.75 (d, J = 6.9Hz,
6 H, C-20, C-30, 2CH3). 13 C NMR (100 MHz, CDCl3): d C-1, C-8; 198.9,
Results and Discussion
In an initial endeavor, a blank reaction was carried out using 2
equiv. of dimedone and one equiv. of benzaldehyde. These were
refluxed in ethanol. After 20 h only 70% of the expected product
was obtained. The same reaction was then carried out using
Zn[(L)Proline]2 as catalyst in ethanol. Surprisingly, a significant
improvement was observed and the yield of product was dramat-
ically increased to 85% after refluxing the mixture for only 0.5 h.
After successfully optimizing the reaction conditions for the
synthesis of xanthenediones 3a, we then decided to carry out
the reaction using water as the sole solvent (because the catalyst
is water soluble). Water has clear advantages as a solvent
Table 1. Various catalysts for model reactions in watera
Serial No.
Catalyst
Timeb
Yieldc(%)
1
Zn(CH3COO)2
Zn(OTf)2
Zn (ClO4)2
Zn(NO3)2
ZnSO4
1
40
43
40
35
—
—
38
30
50
40
94
2
1
3
1
4
1.5
1.5
2
6
7
ZnCl2
8
L-Proline
Zn(Lys)2
1
9
2
10
11
12
Zn(Arg)2
Zn(His)2
2
2
Zn[(L)Proline]2
0.5
aReactions were performed with dimedone (0.02 mol), benzaldehyde
(0.01 mol) and various catalysts (2 mol%) in water by refluxing the
mixture for x h.
bReaction progress monitored by TLC.
cIsolated yield.
Figure 1. General structure of synthesized xanthenediones
Appl. Organometal. Chem. (2012)
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M. Kidwai and A. Jain
Table 3. Zn[(L)Proline]2-catalyzed synthesis of a library of xanthenedione derivativesa
Serial No.
Product
R
Yield (%)b
95
M.p. (ꢀC)[24,27]
1
3a
204–205
2
3
4
5
6
7
8
9
3b
3c
3d
3e
3f
97
95
96
92
89
80
91
93
287–288
222–224
249–251
163–164
232–233
243–245
204–205
257–259
3 g
3 h
3i
10
11
12
3j
3 k
3 l
92
63
67
213–215
147–149
155–157
aReactions were performed with the dimedone (0.02 mol), aldehydes (0.01 mol) and Zn[(L)Proline]2 (2 mol%) as a catalyst, solvent system (5 ml) by
refluxing the mixture for 0.5 h.
bIsolated yield.
because it is cheap, readily available and non-toxic. Moreover,
it has been argued that reactants that dislike water tend to
come closer (the hydrophobic effect) in order to realize the
reaction at a faster rate than in the absence of water.[50] Interest-
ingly, the two-component reaction when carried out in water
using Zn[(L)Proline]2 furnished 3a in a good isolated yield of
94% (Scheme 1).
The catalytic activities for the conversion of 1a to 3a in water
were also compared using various catalysts. Thus the model
reaction was initially tried with zinc acetate and proline individu-
ally, but results were not encouraging. Catalytic ability of other
Zn-(L)-amino acid complexes (2 mol % of catalyst, H2O) was then
investigated. The complexes were prepared and isolated as
described for Zn-proline. It was found that zinc acetate was not
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Appl. Organometal. Chem. (2012)

Zn(proline)2 for the synthesis of xanthenediones in water
able to catalyze the reaction efficiently, as the four-membered
ring formed by the acetate group on chelation with zinc was
not as stable as the five-membered ring formed by the proline
group. Moreover, only in Zn[(L)Proline]2, the amino acid
contains a secondary amine which ultimately enhances the
catalytic efficiency of Zn[(L)Proline]2. Other catalysts do not
contain any secondary amine. To explain the dominance of
Zn[(L)Proline]2 we tried the model reaction with other Zn salts.
It was found that other salts used were inferior to Zn[(L)Proline]2
and the results are reported in Table 1.
The main point of focus in this reaction is the solubility of
catalyst in the reaction mixture. Since the catalyst is highly water
soluble, when the reaction was carried out in water as a sole
solvent, the catalyst was soluble and catalyst is known to be
homogeneous with solvent but not with reactant. On the
other hand, whenever the reaction was carried out in ethanol,
Zn[(L)Proline]2 acted as a heterogeneous catalyst. Striving for bet-
ter results, the model reaction was carried out in water, ethanol,
and a water–ethanol system individually. We came to realize that
when the reaction was carried out in ethanol, it occurred but
with a slower mode. This particular observation explained the
fact of lesser selectivity and activity of heterogeneous catalyst
as compared to homogeneous catalyst. Also a range of organic
solvents were screened for model reaction. Polar solvents such
as ethanol and acetonitrile were much better than non-polar
solvents like THF in terms of better yield and shorter reaction
time, due to the enhanced solubility of reactants. The lower yields
were observed in the case of non-polar solvent due to the failure
of the substrate to access the catalyst. Thus we focused our
attention on the aqueous media. From all these observations
we concluded that reaction in water as a sole solvent would be
the preferable option as compared to the water–ethanol mixture
because of environmental considerations (Table 2).
Table 4. Catalyst recycling studiesa
Catalyst recycle
Yieldb (%)
1
2
3
4
5
94
91
88
85
85
aReactions were performed with dimedone (0.02 mol), benzaldehyde
(0.01 mol), and Zn[(L)Proline]2 (2 mol%) in water by refluxing the
mixture for 0.5 h.
bIsolated yield.
rings appears around 40.1 ppm. The carbonyl carbons appear in
the expected region around 195.3–200.9 ppm.
To further evaluate the scope of this Zn[(L)Proline]2 complex-
catalyzed process, reactions of dimedone with several aromatic
and aliphatic aldehydes containing electron-donating as well as
electron-withdrawing groups were carried out. In all the cases, very
good yields of products were obtained. Results are summarized in
Scheme 1 and Table 3.
Catalyst Recycling Ability
Recycling studies were carried out in order to evaluate the cata-
lytic activity of Zn[(L)Proline]2. Thus, in a model reaction dime-
done with benzaldehyde in water (5 ml) were thoroughly mixed
and refluxed for an appropriate time. The progress of the reaction
was monitored by TLC (Table 4). After completion of the reaction
the crude product was extracted with ethyl ether and the catalyst
was recovered by separation of aqueous and organic phases. The
catalyst was recovered by precipitating the aqueous layer by
simple addition of acetone.
The catalyst was then dried at 80 ꢀC for 2 h and used for the
next cycle, adopting the same procedure for all the recycling
studies. The results (Table 4) revealed that the catalyst exhibited
good catalytic activity up to three cycles without appreciable loss
of catalytic activity and no marginal difference in the yield of the
product which might be due to loss of catalyst during handling.
After that the catalyst was still showing good activity.
Primary elucidation of the structures for all isolated products
was done by NMR technique. The general structure of the pre-
pared xanthenediones is given in Fig. 1.
In 1 H NMR spectra of compound 3a, the four methyl groups
form two sets of axial and equatorial methyl groups and hence
appear differently, giving rise to two singlets each with six hydro-
gens at around 0.99 ppm and at 1.07 ppm, respectively. Due to the
possibility of free rotation and conformational considerations, the
four methyl groups do not become equivalent and appear as two
singlets at different chemical shifts in all the compounds showing
axial and equatorial positions. The two methylene protons at C-4
and C-5 positions are not equivalent owing to adjacent substituents
and ring conformation. The three adjacent rings are not planer with
respect to each other as C-9 carbon is not in the plane but is sp3
hybridized. Moreover, the angle C–11OC–13 is not 120ꢀ as oxygen
is also sp3 hybridized, owing to which rings experience strain.
Here C-4 and C-5 protons appeared as a quartet in the region
2.13–2.28 ppm (2 J =16.0 Hz), which could be due to the geminal
coupling of the methylene protons, giving a large coupling constant
and an apparent quartet for two 2CH2 protons. In the case of C-2 and
C-7 positions, methylene protons are not in the proximity of any
methyl protons (rotation of groups is in such a manner that there
is no proximal effect between adjacent protons), therefore it appear
as a singlet. The proton at the bridge between the two dimedone
rings appears normally in the region 4.6–4.8 ppm, and is not much
affected by its neighboring substituents.
Conclusions
This paper describes a convenient and an efficient process for the
synthesis of xanthenediones. The salient features of this protocol
are rapid synthesis, simple experimental procedure, mild reaction
conditions, greater selectivity, less cumbersome workup, envi-
ronmental friendliness by avoiding the use of volatile organic
compounds as reaction media, reusability of the catalyst,
improved yields, and cleaner reaction profile, which make it an
efficient, economic and ecofriendly process.
Acknowledgment
The author A. Jain is thankful to UGC, New Delhi, for a senior
research fellowship.
In 13 C NMR, carbon atoms of the two dimedone rings are
symmetrical and give rise to one signal for each set of equivalent
carbons. The carbon at the bridge between the two dimedone
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