English

• 1.   Introduction

  It is well known that carbonyls are a class of essential functional groups as well as important structural units that were found in numerous biologically active compounds, the direct oxidation through alcohols has been extensively explored^[1~3] and the typical of transition metals such as trioxide^[4~8] or manganese^[9~11] have been generally utilized as catalysts, however, the catalyst system suffers from some drawbacks, for instance, the high cost and potential environmental toxicity of transition metals. Subsequently, the use of inexpensive, abundant and non-toxic metal^[12] as catalyst has been widely explored. In 1984, Semmelhack and co-workers^[13~17] reported a copper and TEMPO as co-catalyst system catalyzed oxidation of primary alcohols. In 2002, Knochel^{[18, 19]} and Gree^[20] reported a copper and TEMPO catalyzed oxidation of alcohol by using contain fluorine double phase and ionic liquid under oxygen condition (Scheme 1). However, this protocol utilizes molecular oxygen as oxidant and contains fluorine phase and ionic liquid, which can greatly limit its practical applications.^{[21, 22]} In recent years, Stahl et al.^[23~26] devised a new protocol which utilized nitrogen ligand of Cu and TEMPO system (Scheme 1). Although significant improvements such as higher efficiency and milder reaction conditions have been achieved by introducing the method, limitations still exist, for instance, the use of an unfavorable organic solvent, a nitrogen ligand and stoichiometric amount of base has greatly limited its practical applications. Herein, we wish to report our recent results in the facile, base-free catalytic oxidation of benzyl alcohols by common low-cost copper catalyst and TEMPO, where water was used as a green solvent (Scheme 1). This represents a novel example of catalytic oxidation of benzyl alcohols to corresponding aromatic aldehydes.

  Scheme 1

  

  Scheme 1.  Copper-catalysed aerobic oxidation of primary alcohols

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  2.   Results and discussion

  Initially, we used 4-methoxybenzyl alcohol (1a) as the starting materials for metal-catalyzed oxidation, and a systematic condition optimization was undertaken. The results are summarized in Table 1. To our delight, the desired 4-methoxybenzaldehyde (2a) was obtained in 85% yield when oxine-copper (10 mol%) was chosen as a catalyst and the reaction was conducted in water in the presence of sodium carbonate (Na₂CO₃) and TEMPO at 60 ℃ for 24 h under air (Entry 1, Table 1). Further screening by altering temperature was carried out and affording 2a in 87% yield under the same conditions (Entry 2). To our delight, the desired product 2a was obtained in 94% yield when the reaction was conducted under the same conditions in the absence of base (Entry 3). In contrast, other Cu^Ⅰ and Cu^Ⅱ salts were found to be less active catalysts for the reaction (Entries 4~8). In order to further improve the efficiency for the conversion of 4-methoxybenzyl alcohol, we then tested the reaction with an changed amount of oxinecopper, but the results were found to be worse (Entries 9, 10). Finally, decreasing the amount of TEMPO resulted in a decreased yield of 2a (69%, Entry 11).

  Table 1

  

  Table 1.  Optimization of reaction conditions^a

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  Entry	Catalyst	Cocatalyst	Solvent	Temp./℃	Yield/%
  1b	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	60	85
  2b	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	87
  3	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	94
  4	Copper(Ⅱ) triflate	TEMPO	H2O	25	92
  5	Cupric acetylacetonate	TEMPO	H2O	25	86
  6	CuBr2	TEMPO	H2O	25	90
  7	CuI	TEMPO	H2O	25	79
  8	CuSO4	TEMPO	H2O	25	93
  9c	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	69
  10d	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	87
  11e	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	69
  a 4-Methoxybenzyl alcohol (0.3 mmol), cat. (10 mol%), TEMPO (0.5 equiv.), H2O (2 mL), 24 h. b Na2CO3 (50 mol%). c Cat. (5 mol%). d Cat. (20 mol%). e TEMPO (0.25 equiv.). f All yields are for isolated products.

  Having established the optimized reaction conditions for the synthesis of 2a, we then focused on the extension of the substrate scopes for the reactions and the results are summarized in Table 2. It was revealed that benzyl alcohol containing either electron-donating or electron-withdrawing groups on their aromatic rings could be smoothly transformed into the desired products. Gratifyingly, methyl and methoxy substituent at different positions (orth-, meta- or para-) of the benzene ring did not affect the efficiency and the corresponding aldehydes (2b~2d) were all obtained in good to excellent yields (Entries 2~4, Table 2). Using 4-mehylbenzyl alcohol as the substrate, the desired product 2e could be acquired in 85% yield (Entry 5). Specifically, halo substituents (Br and Cl) on the para-position of benzyl alcohol did not affect the efficiency and the corresponding products (2f~2g) were obtained in high yields (Entries 6, 7). To our surprise, even though the strong electron-withdrawing nitro-group was used, the expected product 2h was isolated in 93% yield (Entry 8). The reactions involving (3-phenoxyphenyl) methanol also afforded the desired product 2i in 90% yield (Entry 9).

  Table 2

  

  Table 2.  Scope of bis(8-quinolinolato)copper(Ⅱ)/TEMPO-catalyzed aerobic oxidation of benzyl alcohols to aromatic aldehydes^a

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  Entry	Alcohol	Aldehyde	Yield/%
  1			94
  2			93
  3			89
  4			91
  5			85
  6			92
  7			90
  8			93
  9			90
  a Catalytic conditions: benzyl alcohol (0.3 mmol), bis(8-quinolinolato) copper(Ⅱ) (10 mol%), TEMPO (0.5 equiv.), H2O (2 mL), 25 ℃, 24 h.

  As for the possible mechanism, based on the pioneer works, ^{[27, 28]} we proposed the possible catalytic cycle as shown in Scheme 2. Firstly, the Cu^Ⅱ-hydroxide species A could be generated by direct oxidation of L_nCu^Ⅰ by O₂, which comes from air. In the presence of TEMPO, the LnCu^Ⅱ-OH could be obtained. Adding the benzyl alcohol, the intermediate B could be acquired via removing water. Finally, B could react with the TEMPO radical with release of TEMPOH and cuprous species to afford the desired aldehydes.^[29]

  Scheme 2

  

  Scheme 2.  The possible catalytic cycle

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  3.   Conclusion

  In summary, we have successfully developed a novel, effective and direct oxidation of benzyl alcohol catalyzed by bis(8-quinolinolato) copper(Ⅱ) in the presence of TEMPO as an oxidant in water without using any base at 25 ℃ for 24 h under air. The present copper catalysis system is suitable for the oxidation reactions between a wide range of benzyl alcohol, benzyl alcohol containing either electron-donating or electron-withdrawing groups on their aromatic rings could be smoothly transformed into the desired products. The use of inexpensive, abundant and non-toxic copper as catalyst and water as a green solvent, as well as the base-free conditions make this method much attractive and promising for industrial applications. Further studies of relevant reaction mechanisms and the exploration of further applications of this methodology are underway in our laboratory.

  4.   Experimental

  4.1   Materials and methods

  ¹H NMR (400 MHz) spectral and ¹³C NMR (100 MHz) data were recorded on a Varian 400 M spectrometers using CDCl₃ as solvent. ¹H NMR spectra was recorded with tetramethylsilane as internal reference; ¹³C NMR spectra was recorded with CDCl₃ (δ 77.00) as internal reference. MS were performed by the State-authorized Analytical Center in Southwest Petroleum University. All manipulations were carried out under air atmosphere. Benzyl alcohols were purchased from Acros Organics and used without further purification. TEMPO and copper catalysts were purchased from Adamas corporation. Column chromatography was generally performed on silica gel (300~400 mesh) and reactions were monitored by thin layer chromatography (TLC) using UV light to visualize the course of the reactions.

  4.2   General procedure for the oxidation reaction for benzyl alcohol

  To a Schlenk tube equipped with a magnetic stir bar, benzyl alcohol (0.5 mmol), bis(8-quinolinolato) copper(Ⅱ) (0.05 mmol), TEMPO (0.25 mmol) and water (2 mL) were added under air condition. The resulting reaction mixture was kept stirring at 25 ℃ for 24 h. At the end of the reaction, the reaction mixture was poured into a saturated aqueous NaCl solution (20 mL) and extracted with ethyl acetate (15 mL×3). The organic phases were combined, and the volatile components were evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using ethyl acetate and petroleum ether mixtures to afford the desired product in high purity.

  4.3   Characterization data of the representative products

  4-Methoxybenzaldehyde:^{[30, 31]} m.p. 182 ℃; boiling point 275 ℃. Solubility: soluble in methanol, ethanol, ether, insoluble in hot water. ¹H NMR (600 MHz, CDCl₃) δ: 9.85 (s, 1H), 7.81 (d, J＝8.8 Hz, 2H), 6.97 (d, J＝8.6 Hz, 2H), 3.85 (s, 3H); ¹³C NMR (151 MHz, CDCl₃) δ: 190.8, 164.6, 131.9, 129.9, 114.3, 55.6.

  4-Methylbenzaldehyde:^[30] Colorless liquid with soft floral and almond aromas; m.p. －6 ℃; b.p. 106 ℃. Solubility: miscible with ethanol, ether and acetone, slightly soluble in water. ¹H NMR (600 MHz, CDCl₃) δ: 9.91 (s, 1H), 7.72 (d, J＝8.0 Hz, 2H), 7.27 (d, J＝7.7 Hz, 2H), 2.37 (s, 3H); ¹³C NMR (151 MHz, CDCl₃) δ: 191.8, 145.5, 134.2, 129.8, 129.7, 21.8.

  4-Chlorobenzaldehyde:^{[30, 31]} Colorless flake crystals; m.p. 46 ℃; b.p. 213~214 ℃. Solubility: soluble in benzene, toluene and other solvents, insoluble in water. ¹H NMR (600 MHz, Chloroform-d) δ: 9.98 (s, 1H), 7.82 (d, J＝8.4 Hz, 2H), 7.51 (d, J＝8.4 Hz, 2H); ¹³C NMR (151 MHz, CDCl₃) δ: 190.9, 140.9, 134.7, 130.9, 129.4.

  4-Bromobenzaldehyde:^[31] Colorless or yellowish leaf crystal with pungent smell; m.p. 67 ℃; b.p. 67~68 ℃. Solubility: soluble in ethanol and benzene, insoluble in water.¹H NMR (400 MHz, CDCl₃) δ: 10.00 (s, 1H), 7.80~7.75 (m, 2H), 7.74~7.69 (m, 2H); ¹³C NMR (151 MHz, CDCl₃) δ: 191.0, 135.1, 132.4, 131.0, 129.7.

  Supporting Information  Copies of ¹H NMR and ¹³C NMR spectra for representative products. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

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• 

  Scheme 1  Copper-catalysed aerobic oxidation of primary alcohols

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  Scheme 2  The possible catalytic cycle

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  Table 1.  Optimization of reaction conditions^a

  Entry	Catalyst	Cocatalyst	Solvent	Temp./℃	Yield/%
  1b	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	60	85
  2b	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	87
  3	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	94
  4	Copper(Ⅱ) triflate	TEMPO	H2O	25	92
  5	Cupric acetylacetonate	TEMPO	H2O	25	86
  6	CuBr2	TEMPO	H2O	25	90
  7	CuI	TEMPO	H2O	25	79
  8	CuSO4	TEMPO	H2O	25	93
  9c	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	69
  10d	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	87
  11e	Bis(8-quinolinolato) copper(Ⅱ)	TEMPO	H2O	25	69
  a 4-Methoxybenzyl alcohol (0.3 mmol), cat. (10 mol%), TEMPO (0.5 equiv.), H2O (2 mL), 24 h. b Na2CO3 (50 mol%). c Cat. (5 mol%). d Cat. (20 mol%). e TEMPO (0.25 equiv.). f All yields are for isolated products.

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  Table 2.  Scope of bis(8-quinolinolato)copper(Ⅱ)/TEMPO-catalyzed aerobic oxidation of benzyl alcohols to aromatic aldehydes^a

  Entry	Alcohol	Aldehyde	Yield/%
  1			94
  2			93
  3			89
  4			91
  5			85
  6			92
  7			90
  8			93
  9			90
  a Catalytic conditions: benzyl alcohol (0.3 mmol), bis(8-quinolinolato) copper(Ⅱ) (10 mol%), TEMPO (0.5 equiv.), H2O (2 mL), 25 ℃, 24 h.

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