Development of a NewHeterogeneous Lewis Acid Catalyst for Chemoselective Tetrahydropyranylation of Different Hydroxyl Compounds

Amino functionalized triazine supported on silica-gel was prepared and characterized. is new triazine derivative was applied as a coordinating agent for aluminum chloride. is novel Lewis acid supported on heterogeneous surface was used as an effective catalyst for protection of alcohols and phenols in the presence of 3,4-dihydro-2H-pyran. is catalyst can be reused without any signi�cant loss of activity, and it protects alcohols in the presence of phenols.


Introduction
Contemporary organic synthesis faces the challenge of developing new, efficient, atom, economical, and ecofriendly processes that enable the preparation of diverse structures in a rapid and cost-effective manner.According to the principles of Green Chemistry, catalytic reagents (as selective as possible) are superior to stoichiometric reagents.In general, catalysts reduce the amount of reagents required and restrict the waste generated in a reaction.ey reduce energy requirements and decrease the number of separation steps due to increased selectivity [1][2][3].
�tilization of heterogeneous catalyst ful�lls some of the Green Chemistry criteria [4,5].Of these, enhanced stability, higher selectivity, easier handling, simple workup procedures, nontoxicity, noncorrosiveness, mildness of the reaction conditions, ease of recovery, and reuse of the catalyst and the most important is that it can protects the water-sensitive Lewis acids from hydrolysis by atmospheric moisture until it is suspended in an appropriate solvent, where it can be used in a chemical reaction [5].
e protection of hydroxyl group in alcohols and phenols is a common and versatile event in multistep organic synthesis.Several methods such as acetylation [6,7], trimethylsilylation [8,9], methoxymethylation [10], and tetrahydropyranylation have been developed for masking hydroxyl groups.Amongst them, tetrahydropyranylation is the most frequently used method because of its low cost, ease of preparation, and ease of removing protecting groups as well as the remarkable stability of tetrahydropyranyl ethers under a variety of conditions such as Grignard reagents, alkyl lithiums, oxidative reagents, and acylating reagents [11,12].A variety of catalysts that have been reported for this conversion include the use of LiOTf [13], Pyridinium p-toluenesulfonate [14], silicasulphuric acid [15], SiO 2 -AlCl 3 [16], polystyrene-AlCl 3 [17], CeCl 3 ⋅7H 2 O/NaI [18], copper nitrate/acetic acid [19], heteropolyacids [20], and 1-alkyl-3methylimidazolium tetrachloroindate under microwave irradiation [21].Although these methods are suitable, many of them are associated with several drawbacks, which include long reaction time, high cost, harsh and acidic conditions, poor selectivity, formation of polymeric by-products of the dihydropyran, and isomerization.Furthermore, some of these catalysts may affect other existing functional of molecules, and some are not recyclable and require tedious workup of the reaction mixture.

Experimental
2.1.Materials and Solvents.e reagents and solvents were purchased from Merck, Fluka and Aldrich Chemical companies.e samples were analyzed by FT-IR spectroscopy (PerkinElmer Spectrum Version 65), and the aluminum content of the catalysts was estimated by atomic absorption spectrometer (AAS) (Perkin-Elmer, Analyst 300).Scanning electron microscope (SEM); studies were recorded on AIS-2100, Korea microscope equipped with an energy dispersive X-ray analyzer (EDX).

Preparation of Aminated Triazine Supported on Silica-Gel (AT-Silica
). 1.2 g Silica gel (particle size 20-63 m, 70-230 mesh pore size 100 Å) and 10 mL dry tetrahydrofuran (THF) in a 25 round bottom �ask were cooled in an ice bath.To this mixture triethylamine (TEA, 0.5 mL, 3.7 mmol) was added and stirred for 10 min.en cyanuric chloride (1.2 g, 6.5 mmol) was added and the mixture was stirred for 1 h in an ice bath and 2 h at room temperature.e solid was �ltered, washed with dry THF, and dried at 60 ∘ C for 2 h to give 1.9 g of cyanuric chloride graed on silica-gel (CCsilica).In the second step 1.5 g of CC-silica in 10 mL dry THF was reacted with 1.5 mL ethylenediamine (EDA) in the round bottom �ask.e reaction mixture was stirred in an ice bath for 1 h and heated to room temperature, and then TEA (1 mL) was added and stirred overnight.Finally, it was re�uxed for 45 min, and the solid was �ltered to give 1.9 g aminated-triazine supported on silica-gel (AT-silica).

Coordination of AlCl
3 on to AT-Silica.e new catalyst was prepared by re�uxing the mixture of 1.2 g (8.9 mmoL) of anhydrous AlCl 3 , carbon tetrachloride (3 mL), and ATsilica (1.0 g) for 17 h.e solid was �ltered and washed with carbon tetrachloride three times, and then it was dried under vacuum for 3 h at 60 ∘ C to give Al 3+ supported on AT-silica (Al/AT-silica).e aluminum content of Al/AT-silica was determined by atomic absorption method and was found to be 3.27 mmol Al 3+ per gram of the catalyst.

Tetrahydropyranylation Reaction. Alcohol or phenol
(1 mmol) was added to a mixture of 3,4-dihydro-2H-pyran (1.2 mmol) and Al/AT-silica (0.03 g) in dichloromethane (CH 2 Cl 2 , 0.5 mL).e mixture was stirred at 40 ∘ C. e progress of the reaction was monitored by gas chromatography (GC) and thin layer chromatography (TLC).Aer completion of the reaction, the mixture was �ltered, and the residue was washed with dichloromethane.e �ltrate was concentrated on a rotary evaporator under reduced pressure to give the product.Further puri�cation was achieved by

Results and Discussion
Silica-gel surfaces were modi�ed with an aliphatic amine (EDA) via a two-step chemical reaction.Cyanuric chloride was chemically bound with surface hydroxyl groups of silicagel followed by reaction with EDA (Scheme 1).is new triazine derivate was applied as a coordination agent for AlCl 3 in carbon tetrachloride.e structure of this catalyst was con�rmed by FT-IR spectroscopy.e spectrum of silica-gel shows absorptions bands around 1103 cm −1 (Si-O) and 3450 cm −1 (SiO-H) (Figure 1(a)).Aer reaction of silica-gel with cyanuric chloride, new peaks at 1721 cm −1 , 1477 cm −1 , and 1590 cm −1 (C-Cl, C=N stretching of triazine ring) as well as existing bonds at 1103 to 1105 cm −1 appeared (Figure 1(b)).e FT-IR spectrum of AT-silica (Figure 1(c)) displays a broad absorption (with two-week peaks) around 3300-3400 cm −1 (stretching N-H) and two peaks at 1495 and 1588 cm −1 (broad, C=N stretching and N-H vibration).Figure 2 shows the SEM images of (a) AT-silica and (b) the immobilized aluminum on AT-silica (Al/AT-silica).Clear changes in the morphologies of the catalyst aer introduction of metals were observed by SEM.
Comparisons of EDX analysis of AT-silica with Al/ATsilica con�rmed addition of aluminum to the catalyst, which suggested the formation of metal complexes with the anchored ligand (Figure 3).e catalytic activity of this new heterogeneous Lewis acid evaluated for the tetrahydropyranylation reaction of alcohols and phenols (Scheme 2).
Since the solvents play an important role for the catalytic activity of the Al/AT-silica catalyst, a variety of solvents such as toluene, -hexane, acetone, dioxane, tetrahydrofuran, and dichloromethane were used for tetrahydropyranylation of benzyl alcohol as a model substrate (Table 1).e results show that dichloromethane as solvent give better result for tetrahydropyranylation of alcohols.e amounts of catalyst, molar ratio of DHP to alcohol, reaction time, and temperature were also varied in order to monitor the progress of reaction.e various test reactions demonstrated that the best results for tetrahydropyranylation of 1 mmoL benzyl alcohol were 0.03 g of the catalyst, 1.2 mmoL of DHP in the presence of CH 2 Cl 2 as a solvent at 40 ∘ C. e results of the protection reactions of a diverse range of alcohols and phenols are collected in Table 2. Al/AT-silica can promote tetrahydropyranylation of primary, secondary, and benzylic alcohols, as well as phenols, in good to excellent yields.Primary benzylic alcohols with electron-donating and electron-withdrawing groups were tetrahydropyranylated in this catalyst, and the corresponding tetrahydropyranyl ethers were obtained in almost quantitative yields (Table 2, entries 1-7).e ability of Al/AT-silica was also investigated in the tetrahydropyranylation of phenol under the same reaction conditions described for alcohols, and the corresponding THP-ethers were obtained in high yields (Table 2, entry 8).e nitro derivatives of phenols (Table 2, entry 10-11) produced the corresponding protected product in lower yield.e possible reason ascribed to this observation could be the electron-withdrawing effect of the nitro group.Tetrahydropyranylation of linear and saturated primary and secondary alcohols were also achieved in the presence of this catalyst in high yields.
e stability and reusability are the main advantages of this novel heterogeneous catalyst.e Al/AT-silica catalyst could be stored and used under open air conditions.Furthermore, the catalyst was quantitatively recovered by simple �ltration and washing and proved to be reusable up to 4 times without appreciable loss of catalytic activity and selectivity (Figure 4).
In order to examine the chemoselectivity of the present method, equimolar mixtures of phenol and primary alcohols such as benzyl alcohol and hexanol were allowed to react with DHP in the presence of Al/AT-silica.Scheme 3 shows the conversion of alcohols or phenol to their corresponding THP-ether in compare with its starting hydroxy compounds.is scheme demonstrates that Al/AT-silica can discriminate between alcohols and phenol from each other in   tetrahydropyranylation reaction; a transformation that is difficult to accomplish via conventional methods.

Conclusion
In this study, a novel heterogeneous catalyst (Al/ATsilica) containing amino-functionalized triazine supported on silica-gel was synthesized via reaction of cyanuric chloride with silica-gel followed by treatment with ethylenediamine and coordination of aluminum chloride.is new triazine derivate was applied as a highly efficient catalyst for the tetrahydropyranylation of alcohols and phenols in the presence of DHP.In addition, this catalyst shows chemoselectivity for protection of alcohol in the mixture of alcohol and phenol.e main advantages of this catalytic system are easy catalyst preparation, mild reaction conditions, catalyst stability, easy work-up procedure, and low cost of the catalyst.In addition, it can be recycled and reused several times without loss of activity.

S 3 :
Chemoselective tetrahydropyranylation of alcohols in the presence of phenols catalyzed by Al/AT-silica.

F 3 :F 4 :
EDX analysis of (a) AT-silica and (b) Al/AT-silica.Reusability of Al/AT-silica for protection of benzyl alcohol.