Epoxides as a new feedstock for the synthesis of xanthene derivatives by using highly efficient, reusable tungstated zirconia heterogeneous catalyst

Article abstract of DOI:10.1016/j.catcom.2017.01.001

This paper reports the synthesis of tungstated zirconia (WO_x/ZrO₂) by sol-gel technique and its characterization with XRD, FT-IR, Raman, TGA, N₂ adsorption–desorption isotherms, NH₃-TPD, SEM, and TEM analysis. T

Full text of DOI:10.1016/j.catcom.2017.01.001

Accepted Manuscript
Epoxides as a new feedstock for the synthesis of xanthene
derivatives by using highly efficient, reusable tungstated zirconia
heterogeneous catalyst
Venkata Subba Rao Ganga, Manoj K. Choudhary, Rajkumar Tak,
Prathibha Kumari, Sayed H.R. Abdi, Rukhsana I. Kureshy, Noor-
ul H. Khan
PII:
DOI:
Reference:
S1566-7367(17)30001-8
doi: 10.1016/j.catcom.2017.01.001
CATCOM 4900
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
4 September 2016
24 November 2016
2 January 2017
Please cite this article as: Venkata Subba Rao Ganga, Manoj K. Choudhary, Rajkumar Tak,
Prathibha Kumari, Sayed H.R. Abdi, Rukhsana I. Kureshy, Noor-ul H. Khan , Epoxides
as a new feedstock for the synthesis of xanthene derivatives by using highly efficient,
reusable tungstated zirconia heterogeneous catalyst. The address for the corresponding
author was captured as affiliation for all authors. Please check if appropriate.
Catcom(2017), doi: 10.1016/j.catcom.2017.01.001
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ACCEPTED MANUSCRIPT
Epoxides as a new feedstock for the synthesis of xanthene derivatives by using highly efficient,
reusable tungstated zirconia heterogeneous catalyst
Venkata Subba Rao Gangaa,b, Manoj K. Choudharya,b, Rajkumar Taka,b, Prathibha Kumaria,b,
Sayed H. R. Abdia,b, * , Rukhsana I. Kureshya,b , Noor-ul H. Khana,b
aInorganic Materials and Catalysis Division, CSIR-Central Salt and Marine Chemicals
Research Institute (CSIR-CSMCRI), Bhavnagar- 364 002, Gujarat, India.
bAcademy of Scientific and Innovative Research, CSIR-Central Salt and Marine Chemicals
Research Institute (CSIR-CSMCRI), G. B. Marg, Bhavnagar- 364002, Gujarat, India.

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Abstract
This paper reports the synthesis of tungstated zirconia (WOx/ZrO2) by sol-gel technique and
its characterization with XRD, FT-IR, Raman, TGA, N2 adsorption–desorption isotherms,
NH3-TPD, SEM, and TEM analysis. The catalyst was used for a new one-pot synthesis of
biologically active xanthene derivatives (Yield up to 94%) by using readily available epoxides
and 2-naphthol/sesamol. The catalytic performance of WOx/ZrO2 was found to be better as
compared with other catalysts viz., H3[P(W3O10)4].xH2O, HPA-zirconia, HPA-MCM-41,
Amberlist-15, sulphated silica and sulphated zirconia particularly in terms of recyclability. This
method is convenient, rapid, clean, reusable (6 cycles) and high yielding reaction for the
synthesis of xanthene derivatives.
Keywords. Epoxides; Heterogeneous catalysis; Xanthene derivatives; Recyclability; 2-
Naphthol.
*Corresponding author: Tel.: +91 278 2567760, Fax: +91 278 2567562 / 2566970. Email
address: shrabdi@csmcri.org (S. H. R Abdi).
1. Introduction
Xanthenes and benzoxanthenes are biologically important drug intermediates for the synthesis
of compounds having antibacterial [1], anti-inflammatory [2] and antiviral [3] activities (Fig
S1). The other useful applications of these heterocycles are in the area of photo-dynamic
therapy [4-5], dyes [6-9], fluorescent materials for visualization of biomolecules [10] and in
laser technologies [11]. Moreover, several polycyclic compounds containing xanthene skeleton
have been isolated from natural sources for their prospective bio-activity [12-13]. When we

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looked into the synthesis of 14-H-dibenzo [a,j] xanthenes, we found that most protocols use 2-
naphthol as substrate in combination with 2-naphthol-1-methanol [14]/formamide [15]/carbon
monoxide [16]/aldehydes [17-19] by using an alkali or an acidic catalyst like p-toluenesulfonic
acid [20], sulfamic acid [21], AcOH/H2SO4 [22], iodine [23], K5CoW12O40·3H2O [24],
cyanuric chloride [25], LiBr [26], HClO4·SiO2 [27], KAl(SO4)2·12H2O [28], silica sulfuric acid
[29], Yb(OTf)3 [30], and tungstophosphoric acid-zirconia composites [31]. In the present
report we would like to introduce a simple yet powerful and general method for the preparation
of this class of compound by using readily available epoxides and 2-naphthol/sesamol in the
presence of tungstated zirconia as a solid acid catalyst. The genesis of using epoxide as a
substrate is the understanding that epoxides, depending upon structure, can be rearranged to
aldehydes or ketones in the presence of a Lewis acid catalyst. This property comes handy
particularly where availability of a preformed aldehydes is difficult and expensive than
generating them in situ via easily accessible epoxides.
2. Experimental
2.1 General remarks
Synthesis of tungstated zirconia (WOx/ZrO2) catalyst
The tungstated zirconia catalyst was prepared by the sol-gel technique, wherein 30 wt% of
Zr(OPr)4 (35 g) was hydrolyzed by the addition of aqueous NH3 (~6 mL) under constant
stirring (pH = ~10) over 30 minutes. The sol thus obtained was further stirred for 3 h at room
temperature. An aqueous solution of ammonium metatungstate (16 wt%) (2 g AMT) was added
drop-wise to the above formed gel (pH remained same), and the resulting slurry was vigorously
o
stirred for 10 h at room temperature, filtered, dried at 110 C for 12 h, crushed, sieved (150
o
mesh) and finally calcined in a muffle furnace at 700 C for 4 h. The resulting sample was
designated as WOx/ZrO2.
2.2 Synthesis of Xanthenes

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In a typical procedure (Scheme S1), a mixture of 2-naphthol (2 mmol), an appropriate epoxide
(1 mmol) and the catalyst WOx/ZrO2 (100 mg) were stirred in dry ethyl acetate (2 mL) at
room temperature for a desired period. After the completion of the reaction, the catalyst was
filtered and washed thoroughly with ethyl acetate. The filtrate was evaporated to dryness under
reduced pressure and the residue was crystallized from hexane. The products thus obtained
were characterized by 1H and 13C NMR spectroscopy.
3. Results and discussions
Powder X-ray diffraction (PXRD) pattern showed that as synthesized catalyst is
crystalline in nature with predominately tetragonal ZrO2 peaks at 2θ = 30.3, 35.4, 50.2, 60.3,
62.7 (Fig. 1).
5000
Reused catalyst
Tungstated Zirconia
4000
3000
2000
1000
0
10
20
30
40
50
60
70
80
2
Fig 1. PXRD pattern of WOx/ZrO2 and reused WOx/ZrO2.
The isotherms (Fig. 2) obtained for WOx/ZrO2 corresponds to type IV hysteresis loop in the
Brunauer, Deming, Deming, and Teller (BDDT) classification. The H3 hysteresis loop with
sharp decline in the desorption curve indicates the mesoporous nature of the material.

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Tungstated Zirconia
50
40
30
20
10
(2a)
0.0
0.2
0.4
0.6
0.8
1.0
Relative Pressure (p/po)
0.0005
0.0004
0.0003
0.0002
0.0001
0.0000
Tungstated zirconia
(2b)
0
20
40
60
80
100
Pore Diameter (nm)
Fig 2. (2a) Nitrogen adsorption-desorption isotherms at 77 K and (2b) BJH-pore size
distribution curves of WOx/ZrO2.
SEM images of fresh (S5a) and reused (S5b) WOx/ZrO2 show no change in its
elliptical morphology. TEM image (3a) of TungZr shows tungstates as dark dots on the
surface of ZrO2 particles possibly due to its migration from inside of zirconia tetragonal
framework at calcination temperature. The EDX mapping image of WOx/ZrO2 in Fig. (3b)
exhibited the presence of W, O and Zr elements, which further proved successful loading of
tungstate on Zirconia.
(3b)

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(3a)
50 nm
Fig 3. TEM (3a) and EDX (3b) image of WOx/ZrO2.
The acid site concentration of WOx/ZrO2 was determined by NH3-TPD (Fig. 4). NH3
is a strong non-site-specific base (pKb ∼ 5) that adsorbed on the Brønsted and Lewis acid sites.
The catalysts has total acid site concentration of 0.21 mmol/g. NH3 desorption occurred at
relatively weak and moderate acid sites in the temperature regions, <250 and 250-500
respectively.
Fig 4. NH3-TPD data of WOx/ZrO2.
3.1. Catalytic Activity for the synthesis of xanthenes
The catalytic activity of WOx/ZrO2 (200 mg) was evaluated in the synthesis of 14H-
dibenzo[a,j]xanthenes by using styrene oxide (1 equivalent) and 2-naphthol (2 equivalent) as

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model substrates in ethyl acetate at room temperature under stirring for 6 h. The catalyst was
removed by filtration, solvent was evaporated under reduced pressure and the crude product
was recrystallized from hexane to get the product in 92% isolated yield (Table 1, entry 1). The
product was characterized by various spectrochemical analysis and single crystal X-ray
analysis (Fig. S6). In order to optimize the reaction condition first we varied the amount of
catalyst by keeping other reaction parameters constant (entries 2-5). An increase in catalyst
loading to 300 mg (entry 2) had no significant effect on the outcome of the results. However,
on decreasing the catalyst amount till 100 mg (entries3-4) had a positive effect on the reaction
outcome (Yield 94%). A further decrease in the catalyst loading caused significant reduction in
the product yield (89%, entry 5). Therefore, a catalyst loading of 100 mg (entry 4) was taken
as optimum and used for optimization of reaction temperature (entries 6-7) that revealed that
increasing the reaction temperature has caused a decrease in product yield. Therefore, room
temperature at a catalyst loading of 100 mg were taken as optimum (entry 6) for finding
suitable reaction medium (entries 8-12). It is to be noted that most aprotic solvents used in this
reaction, be it non-polar solvents like toluene (entry 8) or polar solvents like methylene
chloride, and THF, it had little effect on the reaction outcome (entries 9-10. However, protic
solvent like methanol (entry 11) and highly polar DMF (entry 12) caused decrease in the
product yield substantially, possibly due to the masking of catalytically active acidic sites by
the solvent molecules.
Table 1 Optimisation of reaction conditionsa
Entry
Catalyst loading (mg)
Temperature
Solvent
Yield (%)b

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1
200
300
150
100
50
RT
RT
RT
RT
RT
40
Ethyl acetate
Ethyl acetate
Ethyl acetate
Ethyl acetate
Ethyl acetate
Ethyl acetate
Ethyl acetate
Toluene
92
92
94
94
89
92
89
92
93
93
82
80
2
3
4
5
6
100
100
100
100
100
100
100
7
60
8
RT
RT
RT
RT
RT
9
CH2Cl2
10
11
12
THF
Methanol
DMF
aReaction conditions: All the reactions were carried out by using styrene oxide = 1 mmol, 2-
naphthol = 2 mmol, time 6 h with WOx/ZrO2 in 2 mL of dry solvent. bIsolated yields after
column chromatography.
Finally, the reaction parameters used in the entry 4 (Table 1) was taken as optimum for
extending the substrate scope of this reaction and the data are given in Table S1 (entries 1-9).
It can be seen from the results that this method is general in nature and is able to accommodate
a wide range of epoxides e.g., aryl and alkyl and substituted 2-naphthol (entries1-3) providing
the product in more or less similar isolated yields. Besides this, replacing 2-naphthols with
sesamol also gave desired products with respective epoxides in excellent yields (entries 8-9).
In order to compare the catalytic performance of WOx/ZrO2 with other well-known solid acid
catalysts viz., H3[P(W3O10)4].XH2O, HPA-zirconia, HPA-MCM-41, Amberlist-15, sulphated
silica and sulphated zirconia we carried out the reaction of styrene oxide with 2-naphthol under
identical conditions (as per entry 1; Table S1) and the results are presented in Fig. S7. It can be
seen from the data that sulphated zirconia has shown closest performance vis-à-vis WOx/ZrO2,
but clearly better than other solid acids studied (Fig. S7). However, it is to be noted that during
catalyst recycle studies in the case of sulphated zirconia, the performance of the catalyst

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dropped significantly due to the leaching. On the other hand the catalyst WOx/ZrO2 showed no
sign of deactivation even after six reuse. .
3.1.2 Catalyst recyclability
In order to demonstrate recyclability of the catalyst WOx/ZrO2 we used 2-naphthol and
styrene oxide as substrates under the optimized reaction condition (Table 1, entry 4). After the
reaction was over the catalyst was filtered out and washed with ethyl acetate (3 times). The
recovered catalyst was used for the next cycle. We have successfully repeated this for 6 times
with no apparent loss in the reactivity of the catalyst (Fig. S8). This shows that the catalyst
WOx/ZrO2 is robust under our reaction conditions. The recovered catalyst showed
characteristics peaks in XRD and IR (see Fig 1 and Fig S2a) as observed in fresh catalyst.
3.1.3 Reaction mechanism
The condensation of 2-naphthol with an aldehydes in the presence of a catalyst is well studied
and follow the path as depicted in Scheme S2 [32]. Accordingly, phenylacetaldehyde (A) on
condensation with 2-naphthol (1) form an intermediate B, which in the presence of an acid
catalyst generates a carbocation (C). The carbocation thus generated reacts with another
molecule of 2-naphthol to form an intermediate methanebisnaphthols (D), which on
dehydration produces the product xanthene (3a). According to us this mechanism is still
operative; the only difference is that we are in situ generating phenylacetaldehyde (A) by the
rearrangement of styrene oxide (2) as shown in scheme S3. We have confirmed the formation
of phenylacetaldehyde (B) on GC by allowing the styrene oxide to react with WOx/ZrO2
under our reaction condition in the absence of 2-naphthol. Such a rearrangement is reported in
the literature [33-34].
4. Conclusions

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In conclusion, we have successfully developed an alternative method for preparing a variety of
14-substituted-14H-dibenzo [a,j]xanthene derivatives by the reactions of various epoxides with
2-naphthol/sesamol in the presence of a catalytic amount of tungstated zirconia as against
conventionally used aldehydes as starting materials. Here, we have successfully demonstrated
that tungstated zirconia is also able to perform isomerization of epoxides to aldehyde/ketone
while catalysing the condensation with phenols to yield the desired product in high yield at
room temperature in short reaction time. Thus developed methodology expanded the substrate
scope to those aldehydes, which are difficult to produce directly in a cost effective manner.
Acknowledgements
CSIR-CSMCRI registration no is 059/2016. The authors acknowledge DST (SR/S1/OC-
56/2009), New Delhi for the financial support. G. V. S. Rao is thankful to the Academy of
Scientific and Innovative Research (AcSIR) for a Ph.D. enrolment. G. V. S. Rao acknowledges
CSIR, New Delhi, for the award of Senior Research Fellowship and Analytical Discipline and
Centralized Instruments Facility (AD&CIF) of CSMCRI.
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Graphical abstract

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Highlights:
 Design, synthesis and characterization of Tungstated zirconia.
 Epoxides as a new feedstock for the synthesis of xanthene derivatives.
 14-aryl-14-H-dibenzo[a,j]xanthenes and its derivatives were synthesised.
 Tungstated zirconia catalyst was found to be stable over several recycle run.
 A plausible mechanism for the synthesis of xanthenes is presented.