Titanium aminophosphates as efficient, economical, and recyclable catalysts for the synthesis of xanthenediones

Article abstract of DOI:10.1080/00397911.2016.1220578

Titanium aminophospates have been used as catalysts in the synthesis of xanthenediones at room temperature. Among the three catalysts tested, titanium n-propyl aminophosphate (TNPAP) was found to be more efficient catalyst for the synthesis of xanthenedio

Full text of DOI:10.1080/00397911.2016.1220578

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Titanium Aminophosphates as Efficient, Economic
and Recyclable Catalysts for the Synthesis of
Xanthenediones
A. Rajini, C. Suman, A. Ajay kumar, S. Suresh & N. Venkatathri
To cite this article: A. Rajini, C. Suman, A. Ajay kumar, S. Suresh & N. Venkatathri (2016):
Titanium Aminophosphates as Efficient, Economic and Recyclable Catalysts for the Synthesis of
Xanthenediones, Synthetic Communications, DOI: 10.1080/00397911.2016.1220578
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1220578
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Date: 18 August 2016, At: 02:54

Titanium aminophosphates as efficient, economic and recyclable catalysts for the
synthesis of xanthenediones
1
1
1
1
1
A. Rajini , C. Suman , A. Ajay kumar , S. Suresh , N. Venkatathri
1
Department of Chemistry, National Institute of Technology, Warangal, Telangana, India
Corresponding author to N. Venkatathri, E-mail : venkatathrin@yahoo.com
Abstract
The titanium aminophospates have been used as catalysts in the synthesis of
xanthenediones at room temperature. Among the three catalysts tested, titanium n-propyl
aminophosphate (TNPAP) was found to be more efficient catalyst towards the synthesis
of xanthenediones. The solvents screening studies for this catalytic reaction reveals us,
MeOH: H O was found to be suitable solvent system, yielding higher amounts (89 %) of
2
products. The TNPAP catalyst was found to be reusable for five successive cycles. The
optimized reaction conditions are, benzaldehyde (1.0 mmol), dimedone (2.0 mmol,),
solvent (Methanol: water (5.0 mL)), temperature (RT) and TNPAP dosage (100 mg). A
plausible mechanism for the catalytic reactions has been proposed.
GRAPHICAL ABSTRACT
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KEYWORDS: titanium; aminophosphates; xanthenediones
INTRODUCTION
A large variety of xanthenediones have been used as anti-malarial, anti-inflammatory,
antiasthmatic, antibacterial, antihypertensive due to their interesting biochemical
significance. Xanthenediones form structural units in many of the natural products [1].
Xanthenediones and its derivatives have received much importance in various
applications including fragrances, pharmaceuticals, food additives, cosmetics and tunable
dye lasers [2,3]. Benzoxanthenes are important biological heterocycles possessing
therapeutic properties such as anti-viral [4], anti-inflammatory [5], anti-bacterial [6] and
antimalarial activities. They act as antagonists for drug resistant leukemia and also for
paralyzing the action of zoxazolamine [7]. A number of catalysts such as NaHSO .SiO
4
2
[
8], amberlyst-15 [9], PPA-SiO [10], DBSA [11], p-TSA [12], silica sulfuric acid [13],
2
Al(HSO ) [14], TCCA [15] and alumina sulphuric acid [16] have been employed for
4
3
synthesizing xanthenedione derivatives [17]. Most of the reported synthetic methods
have limitations such as strong acidic media, high temperatures, inert atmosphere,
stoichiometric amounts of reaction promoters, moisture sensitiveness of the catalysts and
difficulty in the separation of the products. Thus, there is ample scope for the
development of new synthetic protocols to assemble such scaffolds.
Phosphate based materials are important in several industrial acid catalysed reactions
[
18]. In recent years inorganic phosphorous containing materials have received much
attention on account of their ability to selectively uptake specific ions, resistance to
2

oxidation, high thermal and chemical stability. In addition, the presence of phosphate in
materials seems to enhance catalytic properties, stabilize surface area, crystal phase,
improve surface acidity and make the material porous [19]. Research on phosphate based
materials with open frameworks is currently in progress due to their applications in
catalysis and gas separation [20]. Study of phosphates of transition metals has received
great attention in recent years. Phosphate frameworks stabilize reduced oxidation states,
3
-
due to its high charge (PO ) and hence favour the formation of anionic frameworks with
4
a high degree of chemical, mechanical and thermal stability.
Aminophosphates are having the organic functionality in aminophosphate framework
enhances hydrophobicity and shows high activity in base catalyzed reactions [21].
Incorporation of transition metals such as titanium or vanadium or palladium in
aminophosphates leads to novel materials with redox properties. In particular, titanium
4
+
cation Ti in framework positions is found to exhibit good activity in shape selective
redox reactions. This manuscript deals with the synthesis of biologically active
heterocyclic compounds like xanthenediones at room temperature using titanium
aminophosphates. Owing to the presence of titanium that has Lewis acid , redox site,
Lewis and Bronsted acidity nitrogen donor alkyl groups in titanium aminophosphates, the
materials are expected to have catalytic applications.
RESULTS AND DISCUSSION
The catalytic applications of titanium aminophosphates deals with one pot multi
component synthesis of xanthenediones over titanium aminophosphates (Scheme 1).
3

To explore the efficacy of the titanium aminophosphate catalysts and to establish the
optimum conditions required, the reaction was investigated at room temperature by
varying solvents, aromatic aldehydes and catalyst dosage. Among TNPAP, TNOAP and
TNDDAP catalysts used for the synthesis of xanthenediones, TNPAP is found to exhibit
higher catalytic activity with respect to short reaction time and yield of the product (Table
1
).
In order to examine the influence of various solvents, model reaction of benzaldehyde
and dimedone was carried out in different solvents using TNPAP as catalyst (Table 2).
Solvents acetonitrile, chloroform, water, tetrahydrofuran did not favour the formation of
product even after stirring the reaction mixture for 4 h. This may be due to solubility
difference as the reaction mixture becomes triphasic with the organic substrate, solvent
and catalyst. In the presence of solvents dimethyl formamide (DMF) and dimethyl
sulfoxide (DMSO) the reaction requires more time due to their nature of adsorption on
the active sites of catalyst surface and reported that these solvents may retard the
condensation of the intermediates [25]. Methanol: water mixture was found to be most
suitable solvent for the reaction. The results reveal that methanol and water solubilize the
organic substrates and bring the reactants onto the surface of the catalyst, thus reducing
phase separation and enhancing the yield [12]. The merit of the co-solvent is attributed to
the good solubility of the organic reactants and the inorganic base.
The effect of amount of catalyst on the model reaction has been studied by varying the
amount of TNPAP catalyst in the range 10 – 100 mg to determine the optimum amount of
4

catalyst and the obtained results are shown in Table 3. It was found that 100 mg is able to
catalyze the reaction efficiently. The results indicate that the yield increases with the
increase in amount of catalyst. With increase in dosage of TNPAP catalyst from 10 to
1
00 mg, the products yields were increased from 40% to 90% with the reaction times as
detailed in the Table 3. Hence, the catalyst amount of 100 mg has been chosen as
optimum amount to carry out the reaction.
After establishing the optimum reaction conditions, the protocol was extended to
different substituted aromatic aldehydes. The results of the % yield of products are shown
in Table 4. The nature of the substituent’s on the aromatic aldehydes shows some effects
on the yields and reaction times. The p-bromo and p-nitro benzaldehydes was reacted
faster and produced the corresponding products at higher yields in short reaction times.
The p-hydroxy, p-methoxy and p-methyl benzaldehydes need long reaction times to get
good yields. It was observed that all the aromatic aldehydes have reacted in short reaction
times. It was found that p-fluoro benzaldehyde and p-fluoro benzaldehyde is more
reactive than p-chloro and p-methyl benzaldehydes. This may be attributed to the smaller
size of fluorine atom, which allows the reactant molecules to gain closer proximity to the
active centres of the titanium species compared to the larger chlorine and methyl groups.
However, the differences in the reactivity of various substituted aldehydes are dependent
on the synergetic effect of molecular parameters such as mesomeric (+M), inductive (+I/-
I) and steric effect of substituents.
5

The reaction of benzaldehyde and dimedone to give xanthenediones was chosen
as a model reaction to test the reusability of TNPAP catalyst (Table 5). After completion
of the reaction, methanol was added to dissolve the product. The catalyst was filtered off,
washed with ether and dried under vacuum and reused for the reaction under same
reaction conditions.
A plausible mechanism for the synthesis of xanthenediones over TNPAP catalyst is
depicted in Fig. 1. The mechanism follows a Knoevenagel condensation, Michael
addition and cyclodehydration reactions. The aldehyde (I) forms an oxygen bonded
complex through titanium of TNPAP. The first molecule of dimedone (II) undergoes
Knoevenagel condensation reaction with the aldehyde to form an intermediate (III). The
intermediate (III) thus formed successfully looses water molecule to give Knoevenagel
product (IV) which inturn undergoes Michael addition with second molecule of
dimedone. Then Michael adduct (V) underwent hemiketal formation, followed by
dehydration gave xanthenedione (VI).
CONCLUSION
The titanium aminophospates were investigated in the synthesis of xanthenediones at
room temperature. TNPAP acts as an efficient catalyst towards the synthesis of
xanthenediones. Methanol: water was found to be suitable solvent system for the
reaction, yielding higher amounts (89 %) of products. The TNPAP catalyst were found
to be reusable for five successive cycles. The optimized reaction conditions are,
benzaldehyde (1.0 mmol), dimedone (2.0 mmol,), solvent (Methanol: water (5.0 mL)),
6

temperature (RT) and TNPAP dosage (100 mg). A plausible mechanism for the
catalytic reaction has been proposed.
EXPERIMENTAL
Titanium n-propyl aminophosphate (TNPAP), Titanium n-octyalaminophosphate
(TNOAP) and Titanium n-dodecylaminophosphate (TNDDAP) are synthesized and
1
characterized by various procedures reported elsewhere [22-24]. The H Nuclear
magnetic resonance (NMR) spectroscopy was performed at room temperature on a DSX-
3
00 Avance-III 400(L) NMR spectrometer with a spinning rate of 10-12 KHz operating
at 75.47 MHz using a 5 mm dual probe. Titanium aminophosphates TNPAP, TNOAP
and TNDDAP synthesized in our studies were tested for their catalytic activity in the
synthesis of xanthenediones. A mixture of aromatic aldehyde (1.0 mmol), dimedone (2.0
mmol) and methanol: water (1:1) (5.0 mL) was taken in a round bottom flask. 50 mg of
catalyst was added to the reaction mixture and contents were stirred at room temperature.
1
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The products formed were authenticated by their melting points, H NMR, C NMR and
MASS spectra.
ACKNOWLEDGEMENT
The authors are thankful to the MHRD, New Delhi for a fellowship.
REFERENCES
[
1]
2]
Wang, H. K.; Morris-Natschke, S. L.; Lee, K. H. Med. Res. Rev. 1997, 17, 367.
[
Rakavishnikov, A.V.; Smith, M. P.; Birrell, G. B.; Keana, J. F. W.; Griffith, O. H.
Tetrahedron Lett. 1998, 39, 6637.
7

[
3]
Fairlamb, A. H. Tetrahedron 2003, 59, 2289.
4] Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes, K. E. B.; Thomas, G. J.
Chem. Abstr. 1997, 126, 212377; PCT Int. Appl. WO 9706178, 1997.
5] Poupelin, J. P.; Saint-Rut, G.; Foussard-Blanpin, O.; Narcisse, G.; Uchida-
Ernouf, G.; Lacroix, R. Eur. J. Med. Chem. 1978, 13, 67.
6] El Ashry, E. S. H.; Awada, L. F.; Ibrahim, E. S. I.; Bdeewy, O. K.; Arkivoc
006, 2, 178.
7] Nguyen, H. T.; Lallemand, M. C.; Boutefnouchet, S.; Michel, S.; Tillequin, F. J.
Nat. Prod. 2009, 72, 527.
8] Das, B.; Thirupathi, P.; Reddy, K. R.; Ravikanth, B.; Nagarapu, L. Cat.
Commun. 2007, 8, 535.
9] Das, B.; Thirupathi, P.; Mahender, I.; Reddy, V. S.; Rao, Y. K. J. Mol. Catal. A:
Chem. 2006, 247, 233.
10] Kantevari, S.; Vuppalapati, S. V. N.; Biradar, D. O.; Nagarapu, L. J. Mol. Catal.
A: Chem. 2007, 269, 53.
Chibale, K.; Visser, M. R.; Van Schalkwyk, D.; Smith, P. J.; Saravanamuthu, A.;
[
[
[
2
[
[
[
[
[
[
11]
12]
Jin, T. S.; Zhang, J. S.; Guo, T. T.; Wang, A. Q.; Li, T. S. Synlett. 2004, 5, 866.
Venkatesan, K.; Pujari, S. S.; Lahoti, R. J.; Srinivasan, K. V. Ultrason.
Sonochem. 2008, 15, 548.
[
[
13]
14]
Seyyedhamzeh, M.; Mirzaei, P.; Bazgir, A. Dyes. Pigments. 2008, 76, 836.
Srinivasa, A.; Varma, P. P.; Hulikal, V.; Mahadevan, K. M. Monatsh. Chem.
2
008, 139, 111.
8

[
15]
Bigdeli, M. A.; Nemati, F.; Hossein Mahdavinia, G.; Doostmohammadi, H.
Chin. Chem. Lett. 2009, 20, 1275.
[
[
16] Pramanik, A.; Bhar, S. Catal. Commun. 2012, 20, 17.
17] Jing-Ju, M.; Chun, W.; Qiu-Hua, W.; Ran-Xiao, T.; Hai-Yan, Liu.; Qing, L.
Heteroatom Chemistry. 2008, 19, 609.
[
18]
67.
Samantaray, S. K.; Mishra, T.; Parida, K. M. J. Mol. Catal. A: Chem. 2000, 156,
2
[
[
19]
20]
Samantaray, S. K.; Parida, K. M. J. Mol. Catal. A: Chem. 2001, 176, 151.
Cheetham, A. K.; Ferey, G.; Loiseau, T. Angew. Chem. Int. Ed. Engl. 1999, 38,
3
268.
21]
0, 219.
22]
Advances. 2016, 6, 507.
23] Rajini, A.; Nookaraju, M.; Suman, C.; Ajay Kumar, A.; Venkatathri, N. RSC
Advances. 2015, 5, 106509.
24]
7713.
25]
[
Berlini, C.; Guidotti, M.; Moretti, G.; Psaro, R.; Ravasio, N. Catal. Today. 2000,
Rajini, A.; Ajay Kumar, A.; Suman, C.; Suresh, S.; Venkatathri, N. RSC
6
[
[
[
Rajini, A.; Ajay Kumar, A.; Suman, C.; Venkatathri, N. RSC Advances, 2015, 5,
Karthikeyan, G.; Pandurangan, A. J. Mol. Catal. A: Chem. 2009, 311, 36.
8
[
9

Table 1. Synthesis of xanthenediones using titanium aminophosphate catalysts
Reaction conditions: benzaldehyde = 1.0 mmol, dimedone = 2.0 mmol, methanol: water
=
5.0 mL, catalyst dosage = 100 mg.
S.No Catalyst Solvent/Temp. (C) Time (h)
Yield (%) TOF (x
TON
-
3 -1
1
0 s )
1
2
3
.
.
.
TNPAP
MeOH:H O / RT
0.5
1.0
0.8
89
74
80
1.55
1.29
2.47
5.6
4.6
8.9
2
TNOAP
TNDDAP
MeOH:H O / RT
2
MeOH:H O / RT
2
1
0

Table 2. Synthesis of xanthenediones using different solvents in the presence of TNPAP
catalyst
Reaction conditions: Benzaldehyde = 1.0 mmol, Dimedone = 2.0 mmol, Solvent = 5.0
mL, Temperature = RT, TNPAP dosage = 100 mg, NR = No reaction.
-3
-1
-1
S.No Solvent
Time (h) Yield (%)
TOF (x 10 s ) TON (h )
1
2
3
4
5
6
7
8
.
.
.
.
.
.
.
.
Methanol
2.0
4.0
75
0.3
-
1.2
-
Chloroform
No reaction
Tetrahydrofuran 5.0
Ethanol 2.3
Methanol: Water 0.5
No reaction
-
-
70
0.3
1.6
-
1.0
5.6
-
89
Water
DMF
-
No reaction
2.3
3.0
72
74
0.3
0.2
1.0
0.8
DMSO
1
1

Table 3. Effect of TNPAP catalyst dosage on the synthesis of xanthenediones
Reaction conditions: Benzaldehyde = 1.0 mmol, Dimedone = 2.0 mmol,
Methanol: Water = 5.0 mL, Temperature = RT.
-
-
S.No
Amount of catalyst
mg)
Time (h)
Yield (%) TOF (x 10 TON (x h
3
-1
1
(
s )
)
1
2
3
4
5
.
.
.
.
.
10
30
50
70
100
1.5
1.0
0.7
0.6
0.5
40
55
70
80
90
0.2
0.5
0.9
1.2
1.6
0.8
1.7
3.1
4.2
5.6
1
2

Table 4. Synthesis of xanthenediones from various aromatic aldehydes by employing
TNPAP
Reaction conditions: Benzaldehyde = 1.0 mmol, Dimedone = 2.0 mmol,
Methanol: Water = 5.0 mL, Temperature = RT, TNPAP dosage = 100 mg.
-
S.No
Reactant
Product
Time (h)
Yield
TOF (x TON (h
-3
-1
1
(%)
10 s )
)
1
2
.
.
0.5
0.7
89
1.6
5.6
2.8
70
7.9
3
4
5
.
.
.
0.5
0.5
0.6
74
72
75
1.1
1.2
1.0
3.8
4.3
3.5
1
3

6
7
8
.
.
.
1.0
0.6
1.0
69
74
60
0.6
1.0
0.5
2.1
3.7
1.7
1
4

Table 5. Reusability of TNPAP catalyst towards the synthesis of xanthenediones
Reaction conditions: Benzaldehyde = 1.0 mmol, Dimedone = 2.0 mmol,
Methanol: Water = 5.0 mL, Temperature = RT, TNPAP dosage = 100 mg.
S.No
Catalyst
Fresh
Time (h)
0.5
Yield (%)
1
2
3
4
5
.
.
.
.
.
89
88
87
86
85
Recycle 1
Recycle 2
Recycle 3
Recycle 4
0.5
0.5
0.5
0.5
1
5

Scheme 1. Synthesis of xanthenediones over titanium aminophosphates.
1
6

Figure 1. A plausible mechanism for the synthesis of xanthenediones over TNPAP
catalyst.
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7