Manganese perchlorate-catalyzed greener synthesis of 12-aryl or 12-alkyl-8,9,10,12- tetrahydrobenzo[alpha]xanthen-11-one derivatives under ultrasonication

Article abstract of DOI:10.1080/00397911.2010.525677

A greener and more efficient protocol for the synthesis of 12-aryl or 12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives has been developed via one-pot, three-component reaction of aromatic aldehydes, 2-naphthol, and 1,3-cyclohexadione or 5,5

Full text of DOI:10.1080/00397911.2010.525677

Synthetic Communications1, 42: 447–453, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.525677
MANGANESE PERCHLORATE–CATALYZED GREENER
SYNTHESIS OF 12-ARYL OR 12-ALKYL-8,9,10,12-
TETRAHYDROBENZO[a]XANTHEN-11-ONE
DERIVATIVES UNDER ULTRASONICATION
Bhupinder Kaur,1 Anupama Parmar,2 and Harish Kumar1
1Department of Chemistry, Sant Longowal Institute of Engineering and
Technology, Longowal, India
2Postgraduate Department of Chemistry, M. M. Modi College, Patiala, India
GRAPHICAL ABSTRACT
Abstract
A greener and more efficient protocol for the synthesis of 12-aryl or
12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives has been developed via
one-pot, three-component reaction of aromatic aldehydes, 2-naphthol, and 1,3-cyclohexa-
dione or 5,5-dimethyl 1,3-cyclohexadione using manganese perchlorate hydrate as a cata-
lyst under ultrasonic irradiation. Good yield, shorter reaction time, simple workup
procedure, and milder reaction conditions make this protocol efficient and environmentally
benign.
Keywords Manganese perchlorate hydrate; multicomponent reaction; ultrasonic
irradiation; xanthenes
INTRODUCTION
Xanthenes constitute an important class of biologically active heterocycles pos-
sessing analgesic,[1] anti-inflammatory, antibacterial, and antiviral activities.[2–4]
These compounds are being utilized as antagonists for paralyzing action of zoxazo-
lamine[5] and in photodynamic therapy.[6] Xanthenes have also been employed as
dyes[7] and pH-sensitive fluorescent material for visualization of biomolecules[8]
and in laser technologies.[9] Many xanthene derivatives are potent nonpeptidic
inhibitors of recombinant human calpain I.[10] 12-Aryl or 12-alkyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one derivatives have been synthesized by the conden-
sation of aromatic aldehydes, 2-naphthol, and 1,3-cyclohexadione or 5,5-dimethyl
1,3-cyclohexadione. Many reagents have been reported in the literature for this
Received June 14, 2010.
Address correspondence to Harish Kumar, Department of Chemistry, Sant Longowal Institute of
Engineering and Technology, Longowal 148-106, India. E-mail: hk67@rediffmail.com
447

448
B. KAUR, A. PARMAR, AND H. KUMAR
condensation including ceric ammonium nitrate (CAN),[11] HBF4=SiO2,[12] HClO4=
SiO2,[13] dodecatungstophasphoric acid,[14] sulfamic acid,[15] cyanuric chloride,[16]
iodine,[17] and silica chloride.[18] Many of these processes suffer from one or
more limitations such as longer reaction time, occurrence of some side reactions,
use of hazardous solvents, drastic reaction conditions, poor yield, and tedious
workup procedure. For example, synthesis of 12-aryl or 12-alkyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one derivatives with some of the recently used cata-
[21]
lysts such as Sr(oTf)2[19], InCl3=P2O5,[20] or pTSA-[bmim]BF4 requires high tem-
perature and longer reaction time as compared to reaction with manganese
perchlorate. Comparison of reaction conditions of some important catalysts is given
in Table 1. Thus, there is a need to develop a general protocol for the rapid and
efficient synthesis of these types of xanthenes. Ultrasonication is a new trend in
organic chemistry, offering a versatile and facile pathway for large varieties of synth-
eses. A large number of reactions can be carried out under ultrasonication in good
yields, shorter reaction time, and milder conditions. Ultrasonication in combination
with heterogeneous catalysts had been used in the synthesis of a variety of organic
compounds. In continuation of our earlier efforts to develop a novel synthetic meth-
odology and the use of transition-metal perchlorates[22–24] as catalysts for the organic
synthesis, we report herein a facile, greener, one-pot, three-component synthesis of
12-aryl or 12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones from condensation
of aromatic aldehydes, 2-naphthol, and 1,3-dicarbonyl compounds (1,3-cyclohexadione
or 5,5-dimethyl 1,3-cyclohexadione) using hydrated manganese perchlorate as cata-
lyst under ultrasonic irradiations.
RESULTS AND DISCUSSION
The optimal condition for the synthesis of 12-aryl or 12-alkyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one was studied using benzaldehyde as a model
substrate. In
a typical experiment, mixtures of benzaldehyde (1.0 mmol),
5,5-dimethyl-1,3-cyclohexadione (1.2 mmol), and 2-naphthol (1.0 mmol) in ethanol
were placed either under ultrasonic irradiation (Scheme 1) or without ultrasonic
irradiation. To study the catalytic activity, hydrated manganese perchlorate was
added in varying amounts. It was found that 4 mol% catalyst was optimal to carry
out the reaction. Using more than 4 mol% of the catalyst did not affect the yield
Table 1. Synthesis of 12-aryl or 12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives in the
presence of various catalysts
Entry
Catalyst[ref.]
Temp. (ꢀC) Reaction time (h) Yield (%)
[22]
Sr(OTf)2
NH2SO3H[15]
1
2
3
4
5
6
7
80
120
120
80
5–7
70–89
79–84
63–85
84–96
82–92
83–93
75–88
1.5–2.16
0.30–0.75
2.5–3.5
[23]
InCl3=P2O5
pTSA in the presence of ionic liquid ([bmim]BF4)[24]
pTSA in the absence of ionic liquid ([bmim]BF4)[24]
Cyanuric chloride[16]
120
80
0.35–0.45
0.30–0.70
0.40–0.75
Hydrated Mn(ClO4)2
25

Mn(ClO4)2-CATALYZED SYNTHESIS OF XANTHENES
449
Scheme 1.
or time of the reaction. Further it was noted that under ultrasonic irradiation the
reaction completed in 40 min with 87% yield. Without ultrasonic irradiation, only
20% yield was formed in 120 min. The results of the model experiment have been
summarized in Table 2. To express the generality of the reaction, various aromatic
aldehydes were condensed with 1,3-dicarbonyl compound (1,3-cyclohexadione or
5,5-dimethyl-1,3-cyclohexadione) in the presence of 2-naphthol using manganese
perchloratate hydrate as catalyst under ultrasonic irradiation. After the completion
of reaction, the solid product was formed, which was recrystallized from ethanol.
The structures of the products 1a–t formed were established on comparison with
authentic samples prepared by other methods and from elemental analysis and spec-
troscopic analysis. The selected spectral and physical data are given in Table 3.
The methodology was also applied to heterocyclic aldehydes such as thiophene-2-
carbaldehyde, furfural, and N-formylpyrrolidine, but no reaction was observed in
these cases.
EXPERIMENTAL
Material and Apparatus
All melting points recorded are uncorrected, open capillary measurements,
using a sulfuric acid bath. Infrared (IR) spectra were recorded using KBr pellets
on a Perkin-Elmer spectrophotometer, and NMR spectra were on measured
AL-300 F (Bruker) Fourier transform (FT) NMR spectrophotometer using CDCl3
as internal standard. Sonication was performed in Elma, Transsonic T 310=H ultra-
sonic cleaner (with a frequency of 35 KHz) (Hans Schmidbauer GmbH & Co.,
Germany). The reactions were performed in open vessels.
Table 2. Effect of amount of catalyst with or without sonication for the synthesis of 12-aryl or
12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives at room temperature
With sonication
Without sonication
Yield (%) Time (min)
Entry
Mn(ClO4)2 (mol%)
Yield (%)
Time (min)
1
2
3
4
1
Nil
40
87
85
180
130
40
Nil
Nil
20
180
180
120
140
2.5
4
6
60
22

450
B. KAUR, A. PARMAR, AND H. KUMAR
Table 3. Manganese perchlorate–catalyzed synthesis of 12-aryl or 12-alkyl-8,9,10,12-tetrahydrobenzo-
[a]xanthen-11-one derivatives at room temperature
With ultrasonication
Without ultrasonication
Entry
R
R1 Time (min) Yield (%) Time (min) Yield (%)
Mp (lit. mp) (ꢀC)
1a
1b
1c
1d
1e
1f
C6H5
4-ClC6H4
CH3
CH3
CH3
CH3
CH3
CH3
40
45
55
70
75
65
50
65
45
40
50
55
65
60
65
55
70
65
70
65
87
88
82
80
78
85
82
88
75
78
85
83
76
85
75
78
75
84
80
86
120
150
160
165
150
130
140
150
130
130
145
150
170
180
155
160
180
165
175
180
20
25
35
40
35
38
42
43
48
30
5
148–151 (149–150)[14]
185–188 (187–188)[14]
147–150 (150–151)[14]
225–227 (223–225)[13]
167–170 (166–167)[16]
238–241 (240–241)[13]
176–179 (175–176)[14]
180–183 (179–180)[13]
173–175 (175–176)[16]
180–182 (181–182)[14]
205–207 (208–209)[14]
186–189 (189–190)[16]
204–207 (205–206)[14]
203–205 (205–206)[14]
205–207 (208–209)[14]
208–211 (209–210)[14]
235–237 (235–236)[13]
235–237 (234–235)[14]
246–249 (245–246)[14]
181–183 (181–182)[14]
4-OHC6H4
2-NO2C6H4
3-NO2C6H4
3-OHC6H4
1g
1h
1i
4- CH3C6H4 CH3
2-ClC6H4
4-NO2C6H4
3,4-Cl2C6H3
CH3
CH3
CH3
1j
1k
1l
4-OCH3C6H4 CH3
C6H5
H
H
H
H
H
H
H
H
H
25
28
35
24
26
35
28
35
30
1m
1n
1o
1p
1q
1r
1s
1t
4-ClC6H4
4- CH3C6H4
4-BrC6H4
3-ClC6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
4-OCH3C6H4
General Procedure for the Synthesis of 12-Aryl or
12-Alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one
A mixture of aromatic aldehyde (1 mmol), 2-naphthol (1 mmol), 1,3-dicarbonyl
compounds (1.2 mmol) (1,3-cyclohexadione or 5,5-dimethyl-1,3-cyclohexadione) and
manganese perchlorate hydrate (4 mol %) in ethanol was placed under ultrasonic
irradiation for the time mentioned in Table 3. The reaction was monitored by
thin-layer chromotography (TLC). After the completion of the reaction, the solid
product was filtered. The solid product was recrystallized from ethanol.
Selected Spectral and Physical Data of Products
9,9-Dimethyl-12-(3-nitrophenyl)-8,9,10,12-tetrahydrobenzo[a]xanthen-
11-one (1e). White solid, mp 166–167 ꢀC; IR (KBr) 3139, 2958, 2912, 1649, 1618,
1
1597, 1400, 1375, 1348, 1224, 1176, 1085, 812 cmꢁ1; H NMR (400 MHz, CDCl3):
d ¼ 0.94 (s, 3H), 1.12 (s, 3H), 2.23 and 2.31 (J ¼ 16.4 Hz, 2H), 2.59 (s, 2H), 5.80 (s,
1H), 7.32–7.39 (m, 3H), 7.34 (d, J ¼ 7.6 Hz, 1H), 7.77–7.80 (m, 3H), 7.85 (d,
J ¼ 8.4 Hz, 1H), 7.91 (d, J ¼ 8.0 Hz, 1H), 8.14 (d, J ¼ 8.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d ¼ 27.1, 29.3, 32.2, 34.7, 41.3, 50.7, 113.1, 116.0, 117.3, 121.6,
123.1, 123.2, 125.2, 127.4, 128.7, 129.1, 129.6, 130.9, 131.6, 134.8, 146.8, 147.8,
148.3, 164.6, 196.9; ESI-MS m=z ¼ 400 (M þ 1)þ. Anal. calcd for C25H21NO4: C,
75.17; H, 5.30; N, 3.51. Found: C, 75.32; H, 5.12; N, 3.70.

Mn(ClO4)2-CATALYZED SYNTHESIS OF XANTHENES
451
12-(3,4-Dichlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]xanthen-
11-one (1j). White solid, mp 181–182 ꢀC; IR (KBr) 3138, 2962, 1649, 1637, 1618,
1
1596, 1558, 1398, 1384, 1373, 1234, 1202, 1070, 819 cmꢁ1; H NMR (400 MHz,
CDCl3): d ¼ 0.98 (s, 3H), 1.12 (s, 3H), 2.24 and 2.30 (J ¼ 16.4 Hz, 2H), 2.58 (s,
2H), 5.70 (s, 1H), 7.19–7.24 (m, 1H), 7.30–7.48 (m, 5H), 7.78–7.85 (m, 2H), 7.86
(d, J ¼ 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d ¼ 27.2, 29.2, 32.3, 34.1, 41.3,
50.7, 113.3, 116.3, 117.1, 123.2, 125.1, 127.3, 128.0, 129.4, 130.1, 130.3, 131.0,
131.5, 132.2, 144.9, 147.7, 164.3, 196.8; ESI-MS m=z ¼ 423 (M þ 1)þ. Anal. calcd.
for C25H20Cl2O2: C, 70.93; H, 4.76. Found: C, 71.05; H, 4.68.
12-(4-Bromophenyl)-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one (1o). Col-
orless crystals, mp 208–209 ꢀC; IR (KBr): 2823, 647, 1595, 1473, 1375, 1224, 1190,
1
1175, 1130, 1066, 954, 812, 746 cmꢁ1; H NMR (400 MHz, CDCl3): 1.93–2.09 (m,
2H), 2.32–2.51 (m, 2H), 2.62–2.79 (m, 2H), 5.70 (s, 1H), 7.05 (t, J ¼ 8.0 Hz, 1H),
7.20 (d, J ¼ 8.0 Hz, 1H), 7.32–7.35 (m, 2H), 7.39 (t, J ¼ 7.6 Hz, 2H), 7.45 (t,
J ¼ 8.0 Hz, 1H), 7.78 (d, J ¼ 8.4 Hz, 1H), 7.80 (d, J ¼ 8.0 Hz, 1H), 7.89 (d, J ¼ 8.4 Hz,
Hz, 1H); Anal. calcd. for C23H17BrO2: C, 68.16; H, 4.23. Found: C, 68.32; H, 4.05.
12-(4-Methoxyphenyl)-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one (1t).
Colorless crystals, mp 181–182 ꢀC; IR (KBr): 2945, 2833, 1651, 1595, 1460, 1378,
1251, 1227, 1188, 1175, 1130, 1034, 952, 829, 748 cmꢁ1; 1H NMR (400 MHz, CDCl3):
1.91–2.08 (m, 2H), 2.31–2.48 (m, 2H), 2.57–2.76 (m, 2H), 3.69 (s, 3H), 5.69 (s, 1H),
6.71 (d, J ¼ 8.0 Hz, 2H), 7.23–7.45 (m, 5H), 7.77 (t, J ¼ 8.4 Hz, 2H), 7.96 (d,
J ¼ 8.4 Hz, 1H). Anal. calcd. for C24H20O3: C, 80.88; H, 5.66. Found: C, 81.02; H,
5.53.
CONCLUSION
We describe here a manganese perchlorate hydrate–catalyzed green protocol
for the synthesis of 12-aryl or 12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one
under ultrasonic irradiation in excellent yields. The present methodology gives sev-
eral advantages such as simple procedure, easy workup, clean reaction profile, use
of inexpensive catalyst, use of green solvents, and milder reaction conditions.
ACKNOWLEDGMENT
The authors are grateful to the head of the Department of Chemistry, Sant
Longowal Institute of Engineering and Technology, Longowal, for providing
laboratory facilities.
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