Oxidative, photo-activated TiO₂ nanoparticles in the catalytic acetylation of primary alcohols

Abstract

A series of TiO₂ particles of varying particle sizes from nano to micro scales was treated with three different oxidants (O₂, TBHP, and aqueous H₂O₂) under irradiation conditions to form activated TiO₂ particles bearing surface peroxo Ti(O₂) species. The resultant, heterogeneous catalysts were tested for photo-catalytic acetylation of 2-phenylethanol by acetic anhydride in 8 different solvents. The best scenario involves the use of 32 nm grade of TiO₂ nanoparticles and aqueous H₂O₂ for pre-activation and the use of CH₂Cl₂ as the reaction solvent. The 2-phenethyl acetate product can be completely formed in 10 h and isolated in essential quantitative yield. It was also found that catalysts derived from TiO₂ nanoparticles are superior to those from ZrO₂, Y₂O₃ and WO₃ nanoparticles by using the oxidative, photo-activation protocol. The newly developed heterogeneous catalytic system can be smoothly applied to photocatalytic acetylation of several representative primary aliphatic and aromatic alcohols. The intermediacy of Ti–OH or Ti=O surface groups was proposed in the photo-catalytic acetylation conditions.

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The acylation of alcohols is important and is a commonly used transformation in organic synthesis.¹ Conventionally, these reactions are catalyzed well by Lewis acids² (e.g., AlCl₃, TiCl₄, La(O-i-Pr)₃ and CoCl₂) or Lewis bases³ (e.g., DMAP, phosphines and proazaphosphatrane). Trimethylsilyl (TMS) triflate⁴ and its metal salts derived from lithium,⁵magnesium,⁶bismuth,⁷indium,⁸tin,⁹scandium,¹⁰copper,¹¹titanium,¹²zinc,¹³vanadium,¹⁴ and molybdenum¹⁵ have been found to be effective in catalyzing the acylation of alcohols with anhydrides in homogeneous media. Herein, we describe a new catalytic and heterogeneous protocol for acetylation of alcohols by TiO₂ nanoparticles functionalized with active acetate surface groups.

It was demonstrated that infrared (IR) spectroscopy is a powerful method to study adsorbed species on TiO₂ surfaces.¹⁶ By UV-irradiation of TiO₂ powder in the presence of a hole scavenger in the gas phase, Szczepankiewicz et al.¹⁷ identified a new stretching band at 3716 cm⁻¹ by diffuse reflectance IR Fourier transform spectroscopy (DRIFTS). The absorption band was assigned as O–H stretching for TiOH on the particle surface formed by electron capture at acidic TiOOH centers.¹⁸ Following this observation, we sought to functionalize the surface of TiO₂ nanoparticles in the presence of a suitable oxidant under UV-irradiation conditions in order to generate putative Ti(IV)(O₂) surface groups. Further treatment of the resultant nanoparticles by acetic anhydride under UV irradiation conditions would lead to the corresponding Ti–OAc or Ti(OAc)₂ surface groups useful for subsequent nucleophilic acyl substitution by alcohols in catalytic fashion (vide infra).

Photo-activated TiO₂ nanoparticles (32 nm, 1 mol%) was first used to test the potential acetylation of 2-phenylethanol in the presence of 1.5 equiv. of Ac₂O. The reaction was somewhat complete in 48 h, leading to 2-phenethyl acetate in 88% yield. (entry 1, Table 1). Notably, the TiO₂ nanoparticles cannot catalyze the acetylation of 2-phenylethanol at all without prior photo-activation (0% yield, 48 h). The result indicates the crucial role of Ti(OH) or Ti(OH)₂ surface group in the catalytic reaction. Oxidative, photolytic activations of the TiO₂ nanoparticles with three different oxidants t-butyl hydroperoxide (TBHP), H₂O₂ and O₂ further increase the catalytic efficiency in the acetylation of 2-phenylethanol.¹⁹ The desired 2-phenethyl acetate can be isolated in 68% and 81% in 24 h when O₂ and TBHP were used as oxidants, respectively. The optimal choice of the oxidant for the activation of TiO₂ nanoparticles was aqueous H₂O₂. The resultant catalyst led to the complete consumption of 2-phenylethanol in 10 h and the corresponding 2-phenethyl acetate was obtained in > 99% yield (entry 4).

Table 1 Effects of oxidants on the acetylation of 2-phenylethanol catalyzed by photo-activated TiO₂ nanoparticles (32 nm)^a

Entry	Oxidant	t/h	Conversion (%)
a All reactions were carried out with 1 mol% of photo-activated TiO2 nano-catalysts and 1.5 equiv. of acetic anhydride in CH2Cl2. b Isolated yield.
1	none	48	88
2	O2	24	68
3	TBHP	24	81
4	H2O2	10	>99^b

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To gain insights into the effects of solvents on the catalytic efficiency of the activated TiO₂ nanoparticles, eight different solvents of varying polarity and coordination nature were examined. Among them, CH₂Cl₂ remains to be the best solvent of choice based on this newly developed catalytic protocol. The acetylations of 2-phenylethanol performed in non-polar, aromatic and aliphatic solvents like toluene and hexanes led to poor (26%) to moderate (45%) yields in 24 h under the optimal catalytic system (entries 2 and 3 in Table 2). Moderate conversions (45–48%) of the catalytic acetylation were attained by the use of ether type solvents of moderate coordination ability (e.g., ether and THF). In marked contrast, very poor performances (0–18% yields in 24 h) were observed when the catalytic acetylations were carried out in strong polar, coordinating solvents like acetone, EtOAc, and CH₃CN.

Table 2 Effects of solvents on the acetylation of 2-phenylethanol catalyzed by 32 nm TiO₂ nanoparticles with prior photo-activation in the presence of aqueous H₂O₂

Entry	Solvent	t/h	Conversion (%)
1	CH2Cl2	10	>99
2	Toluene	24	26
3	Hexanes	24	45
4	Ether	24	45
5	THF	24	48
6	Acetone	24	18
7	EtOAc	24	2
8	CH3CN	24	0

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In principle, the overall catalytic efficiency of the photo-activated TiO₂ with oxidative pre-treatment highly depends on the particle size and the overall surface density of the putative Ti(IV)(O₂) active sites on TiO₂. Functionalized TiO₂ catalysts derived from five different particle sizes were thus examined. Among them, the catalyst prepared from 32 nm grade of TiO₂ showed the best catalytic efficiency (entry 2, Table 3) for the test acetylation in CH₂Cl₂. A turnover number of 99 mol acetate per mol of 32 nm TiO₂ nanoparticles was found. Moderate conversions (69–74%) were observed by employing TiO₂ with sizes ranging from 300 nm to ≥50 μm. Conversely, functionalized TiO₂ catalyst derived from 9 nm grade tends to form aggregates during the acetylation,²⁰ thus leading to the worst catalytic profile (81% yield, 72 h). A couple of catalysts based on other metal oxide nanoparticles were also examined (entries 6 and 7, Table 3). It was found that moderate catalytic efficiency (68–77% yields, 24 h) was achieved by using Y₂O₃ and WO₃ nanoparticles (≤50–100 nm), respectively, when treated with aqueous H₂O₂ under irradiation.²¹ Besides, ZrO₂ was also found suitable for the new catalytic protocol. The acetylation proceeds in 87% in 24 h (entry 8).

Table 3 Effects of particle sizes on the acetylation of 2-phenylethanol catalyzed by photo-activated TiO₂ with pre-treatment of aqueous H₂O₂ and the other two metal oxide nanoparticles

Entry	Catalyst	t/h	Conversion (%)
a Specific surface area (SSA) about 131 ± 12 m^2 g^−1. b Anatase/rutile, 4/1, SSA about 45 ± 2 m^2 g^−1. c SSA about 6 m^2 g^−1. d SSA about 40 m^2 g^−1. e SSA about 5–20 m^2 g^−1. f SSA about 10 m^2 g^−1.
1	TiO2 (anatase, 9 nm)^a	72	81
2	TiO2 (32 nm)^b	10	>99
3	TiO2 (rutile, 300 nm)^c	24	74
4	TiO2 (rutile, 4,400 nm)	24	69
5	TiO2 (rutile, ≥ 50 mm)	24 (48)	71 (94)
6	Y2O3 (30–50 nm)^d	24	77
7	WO3 (≤100 nm)^e	24	68
8	ZrO2 (≤100 nm)^f	24	87

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Several representative primary aliphatic and aromatic alcohols were selected for the optimized catalytic acetylation protocol. The acetylation of benzyl and trans-cinnamyl alcohol proceeded smoothly in 18–26 h under the standard reaction conditions in CH₂Cl₂. The desired acetylated products were isolated in quantitative yields (entries 1 and 2 in Table 4). Salicylic acid can also be completely acetylated in 16 h, leading to aspirin in 88% isolated yield.

Table 4 Acetylation of three representative alcohols by using the optimal catalytic system

Entry	R–OH	t/h	Yield (%)
1		18	99
2		26	99
3		16	88

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Based on the presumption that Ti(IV)(O₂) peroxo surface groups are generated by the photo-activation of TiO₂ in aqueous H₂O₂, photoreduction or reductive photocleavage of Ti(O₂) under weakly acidic conditions (i.e. HOAc or Ac₂O) would generate the active catalyst bearing Ti(OH) or Ti(OH)₂ (Ti=O) surface groups (Scheme 1a). Acetylation of the surface groups by acetic anhydride would proceed with generation of acetic acid by-product, leading to Ti–OAc or Ti(OAc)₂ adducts as surface groups (Scheme 1b). Nucleophilic acyl substitution (addition followed by elimination) of the surface Ti–OAc or Ti(OAc)₂ groups by a given alcohol would provide the corresponding acetate product along with regeneration of Ti(OH) or Ti=O surface groups and acetic acid, thus completing the catalytic cycle.

Scheme 1 Proposed catalytic cycle on the acetylation of a given alcohol by photo-activated TiO₂ nanoparticles with oxidative pre-treatment of aqueous H₂O₂.

In conclusion, we have documented a new heterogeneous acetylation protocol for primary aliphatic and aromatic alcohols catalyzed by photo-activated TiO₂ nanoparticles with oxidative pretreatment of aqueous H₂O₂ under very mild reaction conditions. The activated TiO₂ nanoparticles and the remaining acetic anhydride/AcOH can be readily removed by sequential filtration and aqueous work up. Therefore, there is no need of chromatographic purification after completion of acetylation, auguring well for its practical application in industry.

Experimental

General

The method of Barbé was used to prepare TiO₂ nanoparticles.²² The particle size was found about 32 nm with a surface area of about 45 m² g⁻¹. Titanium dioxide nanoparticles (average particle size 34 nm, BET specific surface area 45 m² g⁻¹, 80% anatase and 20% rutile) can also be purchased from Nanophase Technologies Corporation (Romeoville, IL, USA). Y₂O₃ nanoparticle (30–50 nm, SSA 40 m² g⁻¹) and WO₃ (≤100 nm, SSA 5–20 m² g⁻¹) colloidal dispersion were purchased from SkySpring nanomaterials, Inc. ZrO₂ nanoparticle (100 nm, SSA 10 m² g⁻¹) colloidal dispersion was obtained from Alfa Aesar company. The UV-lightbox was purchased from “Topbio” company in Taiwan. UV lamp (15 W) at 254 nm fitted with a long-range UV filter is used a light source.

Representative experimental procedure for catalytic acetylation of a given alcohol

In a dry 25 mL quartz cell was placed 32 nm grade of TiO₂ nanoparticles (0.8 mg, 0.01 mmol, 1 mol%) and H₂O₂ (30 wt%, 10 mL) was added. The heterogeneous mixture was kept under UV irradiation (254 nm, 15 W × 6 tubes) at ambient temperature for 30 min and then concentrated. The resultant yellowish solid was then suspended in CH₂Cl₂ (3 mL) in a 5 mL quartz cell followed by addition of acetic anhydride (140 μL, 1.5 mmol) and 2-phenylethanol (120 μL, 1 mmol). The reaction mixture was stirred at ambient temperature under UV irradiation (254 nm, 15 W × 6 tubes) for 10 h. After completion of the reaction as monitored by TLC analysis, the reaction mixture was filtered and then quenched by saturated aqueous NaHCO₃ solution (5 mL). The organic layer was dried (MgSO₄), filtered, and evaporated to give 2-phenylethyl acetate in quantitative yield.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c0cy00005a

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