Design of recyclable TEMPO derivatives bearing an ionic liquid moiety and N,N-bidentate group for highly efficient Cu(I)-catalyzed conversion of alcohols into aldehydes and imines

Abstract

Four different types of TEMPO derivatives incorporated with an ionic liquid moiety and N,N-bidentate coordination group (IL–TEMPO-N,N) were prepared. The CuBr/IL–TEMPO-N,N system showed high catalytic activity toward the synthesis of aldehydes and imines via the aerobic oxidation of alcohols in 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF₄). Both the Cu catalyst and IL–TEMPO-N,N co-catalyst in homogeneous catalytic systems could simultaneously be recovered from the products by extraction using Et₂O. The remaining catalyst system in the ionic liquid phase could be reused for several cycles without obvious loss of catalytic activity. Protocols for highly efficient and recyclable aerobic oxidation of alcohols to aldehydes and imines were established.

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Introduction

The selective oxidation of alcohols into their corresponding carbonyl compounds is one of the most important reactions in both the industrial synthesis of fine chemicals and laboratory research.^1–3 These transformations are traditionally performed with stoichiometric amounts of inorganic oxidants (e.g. CrO₃, KMnO₄, MnO₂, SeO₂, Br₂), which generate environmentally hazardous or toxic byproducts.⁴ Consequently, increasing efforts have been made to develop clean processes for the synthesis of carbonyl compounds. Many highly efficient catalysts such as Pd,⁵ Pt,⁶ Ru,⁷ Rh,⁸ Au,⁹ and Fe¹⁰ complexes have been developed for these conversions. From the practical and environmental points of view, there is a strong demand for the screening out efficient catalytic systems using inexpensive and environmentally benign metal catalysts and non-toxic air or O₂ as the sole terminal oxidant.¹¹ Since the fundamental studies by Semmelhack et al.,¹² the homogeneous Cu catalytic systems bearing various organic ligands in combination with 2,2,6,6-tetramethylpiperidinooxy (TEMPO) and its derivatives have been developed as a highly efficient method for the aerobic oxidation of alcohols using O₂ or air as the terminal oxidant.¹³ Despite the high activity achieved by these dual catalytic systems, the separation and recycling of the copper catalysts and TEMPO from the products remains a key issue. In recent decades, much attention has focused on the recyclability of heterogeneous¹⁴ or water-soluble Cu catalysts.¹⁵ Additionally, TEMPO derivatives could be immobilized on silicates,¹⁶ fluorous supports,¹⁷ soluble and insoluble polymers,¹⁸ magnetic nanoparticles,¹⁹ and ions/ionic liquids.²⁰ In the presence of a co-oxidant, these metal-free functionalized TEMPO catalysts provided a convenient tool for the oxidation of alcohols working as recyclable reservoirs. However, little research concerns how to achieve simultaneous recoverability of both TEMPO derivatives and Cu catalysts.²¹ Toy and co-authors developed a multipolymer system for the oxidation of alcohols to recover both TEMPO and Cu(II) catalyst at the same time.²² Rodionov et al. developed a functional surfactant architecture incorporating TEMPO moieties, Cu-binding sites and sulfonate groups.²³ Kitagawa et al. reported a novel porous coordination polymer (PCP) decorated with nitroxyl radicals could be an efficient and recyclable catalyst for the selective oxidation of a variety of alcohols to aldehydes or ketones.²⁴ Very recently, we have developed some well-defined water-soluble copper coordination complexes combined with TEMPO for the aerobic oxidation of alcohols to aldehydes and the ammoxidation of alcohols to nitriles in aqueous system.¹⁵ Gree, Ragauskas et al. reported TEMPO–CuCl²⁵ or acetamido–TEMPO/Cu(ClO₄)₂/DMAP (DMAP = 4-(dimethylamino)pyridine) in 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF₆)²⁶ catalyze the aerobic oxidation of primary and secondary alcohols. Although these water-soluble copper catalysts and ionic liquids showed a good cycle performance, the additional portion of TEMPO was required for next runs. TEMPO and its derivatives are rather expensive and, consequently, their separation and reuse after the aerobic oxidation reaction is highly desirable. In order to fulfil the recovery of TEMPO and copper catalyst simultaneously, we have designed a set of TEMPO derivatives (IL–TEMPO-N,N, 1a–1d) integrated with both ionic liquid moiety and N,N-bidentate coordination group (Scheme 1). In such multi-functional IL–TEMPO-N,N, the incorporating N,N-bidentate group may anchor copper ion to increase its catalytic activity while the attached TEMPO fragment is used as a co-catalyst, and the ionic liquid tag is crucial to the recyclability of the catalysts. In this context, we found that this resulting IL–TEMPO-N,N/CuBr homogeneous catalyst system showed remarkably high catalytic activity toward the synthesis of aldehyde and imine from a wide range of alcohols via the aerobic oxidation of alcohols in [bmim]BF₄. Moreover, both Cu catalyst and TEMPO co-catalyst can be readily reused at least six cycles.

Scheme 1 Synthesis of IL–TEMPO-N,N ligands 1a, 1b, 1c and 1d.

Results and discussion

The multi-functional TEMPO derivatives reported in this work were obtained through a simple two-step synthesis starting from 2-bromo-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine (3a), 5-bromo-2,2′-bipyridine (3b), 4-(1H-pyrazol-3-yl)pyridine (3c) and 2-(1H-pyrazol-3-yl)pyridine (3d), respectively. The synthesis routes of TEMPO radical derivatives bearing ion liquid and N,N-bidentate coordination groups (1a–1d) are depicted in Scheme 1. The first step involved the CuI-catalyzed cross-coupling reaction of 3a–3d with 1H-imidazole, 2-iodopyridine or 4-iodopyridine to give 2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(1H-imidazol-1-yl)pyridine (2a), 5-(1H-imidazol-1-yl)-2,2′-bipyridine (2b), 2-(3-(pyridin-4-yl)-1H-pyrazol-1-yl)pyridine (2c), 2-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)pyridine (2d). Four IL–TEMPO-N,N derivatives (1a–1d) were prepared by the reactions of 2a, 2b, 2c, 2d with 4-(2-iodineacetoxy)-2,2,6,6-tetramethylpiperidine-1-oxyl free radical in high yields. 1a–1d are stable toward air and moisture, and freely soluble in H₂O, MeOH, DMSO, CH₂Cl₂ and CHCl₃, but insoluble in toluene and Et₂O. Their IR spectra exhibit strong stretching vibrations at 1784 (1a), 1758 (1b), 1745 (1c) and 1753 (1d) cm⁻¹, which are attributable to the carboxyl group. The high-resolution positive-ion mass spectra of 1a–1d revealed that there exists one peak at m/z = 452.2528 (1a), 435.2257 (1b), 435.2285 (1c) and 435.2282 (1d), which can be assigned to the [IL–TEMPO-N,N]⁺ ion. These TEMPO species are isolated as paramagnetic solids. Phenylhydrazine can reduce them into the corresponding IL–TEMPOH-N,N derivatives,²⁰ⁱ which are identified by the in situ ¹H NMR spectroscopy in CDCl₃. ¹H NMR spectra of IL–TEMPOH-N,N show the doublets at δ = 1.14 (1a), 1.13 (1b), 1.11 (1c) and 1.22 (1d) ppm, which are assigned as the protons of the methyl group. The multiplets at δ = 1.67/1.93/5.08 (1a), 1.65/1.93/5.07 (1b), 1.64/1.93/5.07 (1c) and 1.87/2.07/5.13 (1d) ppm are assigned as the protons of the TEMPO ring. The singlet at 5.46 (1a), 5.54 (1b), 5.82 (1c) or 5.93 (1d) ppm is ascribed to the protons of the methylene group.

After these multi-functional IL–TEMPO-N,N derivatives (1a–1d) were obtained, 1a was chosen as a candidate to investigate its catalytic activity in combination with various copper salts using O₂ as a terminal oxidant in an ionic liquid [bmim][BF₄] (Table 1). At first, the oxidation reaction of p-tolylmethanol (4a) at 50 °C for 24 h produced 4-methylbenzaldehyde (5a) in 49% yield (Table 1, entry 1). The addition of K₂CO₃ (10 mol%) promoted the reaction to afford 5a in a higher yield (90%) (entry 2). To obtain optimized conditions for this reaction, we employed some other bases, such as Na₂CO₃, KOH, NaOH, Et₃N and DMAP (entries 3–7). Na₂CO₃ proved to be the best one to give the highest yield (entry 3). The blank experiments revealed that no product was isolated in the absence of the copper catalyst or co-catalyst 1a (entries 8 and 9). Under the same conditions, CuBr/TEMPO catalytic system exhibited low activity (entry 10), which indicated the coordination group on 1a played an important role in its catalytic reactivity. Notably, the catalyst and base loading could be reduced from 10 to 5 mol% without affecting the product yields (entries 3, 11 and 12). When the reaction temperature was lowered from 50 °C to 45 °C to 35 °C, the yield of 5a was slightly decreased from 99% to 97% to 93% (entires 12, 14 and 15). Various Cu catalysts were screened, and CuCl, CuI, Cu(OAc)₂ and Cu(NO₃)₂ exhibited slightly lower catalytic activity toward the oxidation of 4-methylbenzyl alcohol to 4-methylbenzaldehyde, as the desired product 5a was isolated in 42–86% yields (entries 16–19). To this end, the optimal reaction conditions were identified as follows: 5 mol% CuBr catalyst, 5 mol% Na₂CO₃ and 6 mol% 1a in [bmim][BF₄] at 50 °C for 24 h. With these conditions, the catalytic performances of 1b–1d were also investigated. As a result, 1b–1d all worked well. The high activity of CuBr/1a–1d can be most likely attributed to the combination of ionic liquid moiety and N,N-bidentate coordination group.

Table 1 Optimizing the reaction conditions for the synthesis of 4-methylbenzaldehyde from p-tolylmethanol

Entry^a	Cat. (mol%)	Ligand (mol%)	Base (mol%)	Yield^b (%)
a Reaction conditions: 4-methylbenzyl alcohol (1 mmol), [Cu], ligand, base, [bmim][BF4] (3 mL), O2 (1 atm), at 50 °C for 24 h.b GC yield.c 35 °C.d 45 °C.
1	CuBr (10)	1a (12)	—	49
2	CuBr (10)	1a (12)	K2CO3 (10)	90
3	CuBr (10)	1a (12)	Na2CO3 (10)	>99
4	CuBr (10)	1a (12)	DMAP (10)	96
5	CuBr (10)	1a (12)	KOH(10)	93
6	CuBr (10)	1a (12)	NaOH (10)	94
7	CuBr (10)	1a (12)	Et3N (10)	92
8	—	1a (12)	Na2CO3 (10)	Trace
9	CuBr (10)	—	Na2CO3 (10)	Trace
10	CuBr (10)	TEMPO (12)	Na2CO3 (10)	65
11	CuBr (5)	1a (6)	Na2CO3 (10)	>99
12	CuBr (5)	1a (6)	Na2CO3 (5)	>99
13	CuBr (3)	1a (3.6)	Na2CO3 (5)	43
14	CuBr (5)	1a (6)	Na2CO3 (5)	93^c
15	CuBr (5)	1a (6)	Na2CO3 (5)	97^d
16	CuCl (5)	1a (6)	Na2CO3 (5)	42
17	CuI (5)	1a (6)	Na2CO3 (5)	53
18	Cu(OAc)2 (5)	1a (6)	Na2CO3 (5)	86
19	Cu(NO3)2 (5)	1a (6)	Na2CO3 (5)	56
20	CuBr (5)	1b (6)	Na2CO3 (5)	95
21	CuBr (5)	1c (6)	Na2CO3 (5)	99
22	CuBr (5)	1d (6)	Na2CO3 (5)	70

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The scope of the aerobic oxidative reactions of alcohols was summarized in Table 2. Under the optimized conditions, a wide range of alcohols were smoothly oxidized into the corresponding aldehydes in good to excellent yields. As compared with bare benzyl alcohol, aromatic alcohols with substituted electron donating groups like –Me, –CMe₃, –OMe and –OCH₂O– exhibited a slightly increased conversion ratio (5a–5i, 92–99%). While the benzyl alcohols with electron-withdrawing substituents like –NO₂, –Cl, –Br and –CF₃ showed a decreased conversion ratio and required higher temperature (70 °C) to complete these transformations (5j–5m). The steric hindrance of benzyl alcohols also exerted impact on the catalytic activity of the transformation from benzylic alcohols to the corresponding benzaldehyde derivatives. The aromatic alcohols with a –Me or –OMe group substituted at different positions of phenyl ring showed different reaction rates in the order of ortho- < meta- < para-substituted (5b < 5c < 5a; 5d < 5e < 5f). (2,4,6-Trimethyl-phenyl)methanol was converted smoothly to the corresponding product in 88% yield (5t). The heteroatom-containing alcohols such as pyridin-3-ylmethanol, furan-2-ylmethanol and thiophen-2-ylmethanol underwent the aerobic oxidation reaction to produce the desired aldehydes (5n, 5o, 5p) in relatively high yields. Intriguingly, naphthalen-1-ylmethanol, 1,4-phenylenedimethanol and cinnamic alcohol could also be oxidized with satisfied yields under the standard reaction conditions (5q, 5r, 5s). We also examined the catalytic reactivity towards secondary alcohol. The oxidation of 1-phenylethan-1-ol under the similar reaction conditions gave the desired product acetophenone in 31% yield at 70 °C.

Table 2 The oxidation of alcohols to aldehydes catalyzed by CuBr/1a^a,b

a Reaction conditions: alcohol (2 mmol), CuBr (5 mol%), 1a (6 mol%), Na₂CO₃ (5 mol%), [bmim]BF₄ (3 mL), O₂ (1 atm), 50 °C, 24 h.b Isolated yield.c At 70 °C.d CuBr (20 mmol%), 1a (24 mmol%), Na₂CO₃(20 mmol%).

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In contrast to the unmodified TEMPO, the catalytic species can be also separated by simple extraction of products and reused without further purification. The oxidation reaction of p-tolylmethanol was performed with CuBr (5 mol%), 1a (6 mol%) and Na₂CO₃ (5 mol%) in [bmim]BF₄ to examine its reusability. After the first reaction run, the mixture was allowed to cool to room temperature for extraction with Et₂O. The upper layer containing product was removed by decantation. The lower layer left was dried to remove a small amount of water by vacuum and fresh substrates were then recharged for the next run. As showed in Fig. 1, the catalyst system still went smoothly and the conversion got decreased slightly during four cycles, from 98% to 85%. At the fifth or sixth reuse run, a relatively high yield (84%, 79%) was still obtained after 36 h. These results indicated that the use of this catalytic system might meet the goal of green chemistry. To further demonstrate that the catalytic system is efficient and practicable, a scale-up reaction was carried out under the optimal conditions. The oxidation reaction of p-tolylmethanol (1.22 g, 10 mmol) gave the product in 78% isolated yield.

Fig. 1 The reusability of the CuBr/1a catalytic system for the aerobic oxidation of p-tolylmethanol into 4-methylbenzaldehyde.

Table 3 lists a comparison of the results for the oxidation of phenylmethanol using different catalysts. Comparative runs with MPEG–Bipy/MPEG–TEMPO/CuBr₂ (85%), CuCl/TEMPO–IL (85%) and [Cu(μ-Cl)(Cl)(phen)]₂/TEMPO (83%) indicated that CuBr/1a exhibited higher catalytic activity (90%). At higher temperature, [Imim–PEG₁₀₀₀–TEMPO][CuCl₂] and Cu–NHC–TEMPO showed higher activity than that of CuBr/1a.

Table 3 Catalytic characteristics of conventional catalysts for the oxidation of phenylmethanol

Entry	Cat.	Cat. loading (mol%)	Addition	Solvent	Temp (°C)	Yield (%)	Ref.
1	[Imim–PEG1000–TEMPO][CuCl2]	5	—	—	60	96	21
2	Cu–NHC–TEMPO	10	—	C6H5Cl	80	96	20f
3	CuCl/TEMPO–IL	10	Molecular sieve 3A	[bmim][PF6]	80	85	20l
4	MPEG–Bipy/MPEG–TEMPO/CuBr2	5	t-BuOK	MeCN/H2O	80	85	22
5	Cu/TEMPO/amphiphile	2	DMAP	H2O	25	94	23
6	[Cu(μ-Cl)(Cl)(phen)]2/TEMPO	5	K3PO4	MeCN	R.T.	83	13a
7	Acetamido–TEMPO/Cu(ClO4)2	5	DMAP	[bmim][PF6]	R.T.	92	26
8	Acetamido–TEMPO/Cu(ClO4)2/DMAP	4	DABCO	DMSO	R.T.	98	13e
9	TEMPO/CuCl	5	—	[bmim][PF6]	65	98	25
10	[{Cu(NO3)}(μ-pzpypz)]2/TEMPO	5	K2CO3	H2O	30	95	15a
11	CuBr/1a	5	Na2CO3	[bmim][BF4]	50	90	This work

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To explore more applications of the CuBr/1a catalytic system in organic synthesis, we then studied the aerobic oxidative coupling of benzyl alcohols with amines (Table 4). We also investigated the efficiency of one-pot cascade reaction between benzyl alcohol and amine to prepare imine at 80 °C in the presence of 5 mol% of CuBr and 6 mol% of 1a. After completion of this reaction (24 h), the reactions went well to give the desired imines in good to excellent yields (60–92%). The cascade reactions of aniline with benzyl alcohol derivatives with electron-donating substituents on the phenyl ring could afford smoothly the corresponding imines in high yields (6b–g). Benzyl alcohols with –Cl, –NO₂ and –CF₃ could also proceed smoothly at higher temperature (100 °C), but in lower yields (6h–j). The heteroaromatic benzyl alcohols also went on in moderate yields (6l and 6m). With respect to the aniline-derived moiety of the amine, the presence or absence of an electron-donating group did not significantly affect the yields of imines. Over 85% isolated yields were obtained uniformly (6n–s). For naphthalen-1-ylmethanol or naphthalen-1-amine, the corresponding imines were attained in 67% and 60% isolated yield (6k and 6s).

Table 4 Synthesis of imines from alcohols and amines catalyzed by CuBr/1a^a,b

a Reaction conditions: alcohol (1 mmol), amine (1.2 mmol), CuBr (5 mol%), 1a (6 mol%), Na₂CO₃ (5 mol%), [bmim]BF₄ (3 mL), O₂ (1 atm), at 80 °C, for 24 h.b Isolated yield.c At 100 °C.

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Conclusions

In summary, we showed that both ionic liquid and N,N-bidentate coordination groups were used to support TEMPO nitroxyl radical simultaneously, yielding multi-functional TEMPO derivatives IL–TEMPO-N,N. The IL–TEMPO-N,N/CuBr was found to be a highly efficient catalyst system for the formation of aldehyde and imine from alcohols in [bmim]BF₄. Moreover, it could be recycled and reused without significant decay of catalytic activity after multiple runs. For this catalytic system, it would find a wider application in various reactions, which is ongoing in our laboratory.

Experimental

General

All reagents were used as purchased from commercial sources without further purification. 2-(3,5-Dimethyl-1H-pyrazol-1-yl)-6-(1H-imidazol-1-yl)pyridine,²⁷ 2-(3-(pyridin-4-yl)-1H-pyrazol-1-yl)pyridine,²⁸ and 2-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)pyridine²⁸ were prepared according to the published procedures. Column chromatography was performed on silica gel. ¹H NMR and ¹³C NMR spectra were recorded at ambient temperature on a Varian UNITY plus-400 spectrometer.

Synthesis of 5-(1H-imidazol-1-yl)-2,2′-bipyridine

A mixture of 5-bromo-2,2′-bipyridine (1.54 g, 6.6 mmol), 1H-imidazole (1.34 g, 19.7 mmol) and K₂CO₃ (1.81 g, 13.1 mmol) was added into a Schlenk tube equipped with a stirring bar. It was stirred at 190 °C for 18 h under a nitrogen atmosphere. After cooling to room temperature, the mixture was diluted in water and dichloromethane. The organic layer was separated, and the aqueous layer was extracted with dichloromethane for three times and washed three times with saturated aqueous Na₂CO₃ solution. The combined organic phases were dried over anhydrous Na₂SO₄ and filtrated. The solvent of the organic phase was removed under reduced pressure. Then, recrystallization of the orange residue from ethyl acetate (15 mL) afforded the white solid of 5-(1H-imidazol-1-yl)-2,2′-bipyridine (1.16 g, 80%). Mp 168.2–169.1 °C. HRMS calcd for C₁₃H₁₀N₄: 222.0905; found: 223.0979 [M + H]⁺. Anal. calcd for C₁₃H₁₀N₄: C, 70.26; H, 4.54; N, 25.21%. Found: C, 70.40; H, 4.73; N, 24.87%. ¹H NMR (400 MHz, DMSO-d₆): δ 9.06 (s, 1H), 8.69 (d, J = 3.8 Hz, 1H), 8.52–8.42 (m, 2H), 8.38 (d, J = 7.9 Hz, 1H), 8.25 (d, J = 8.5 Hz, 1H), 7.94 (dd, J = 15.5, 7.6 Hz, 2H), 7.52–7.39 (m, 1H), 7.19 (s, 1H). ¹³C NMR (101 MHz, DMSO-d₆): δ 154.3, 153.4, 149.4, 141.1, 137.5, 135.7, 133.6, 130.4, 128.7, 124.3, 121.1, 120.4, 117.9.

Synthesis of 2,2,6,6-tetramethylpiperidinooxy-4-yl 2-iodoacetate

This compound was prepared in a similar manner to chloroacetic acid 2,2,6,6-tetramethyl-1-oxy-piperidin-4-yl ester.²⁰ⁱ A mixture of 2-iodoacetic acid (0.78 g, 4.2 mmol), dicyclohexylcarbodiimide (0.95 g, 4.6 mmol), and 4-dimethyl-aminopyridine (0.05 g, 0.4 mmol) was added into an anhydrous CH₂Cl₂ solution (15 mL) of 4-hydroxy-2,2,6,6-tetramethylpiperdine-1-oxyl (0.72 g, 4.2 mmol). The resulting mixture were stirred at room temperature and checked by TLC. After the substrate was consumed, 50 mL H₂O was added. The mixture was extracted with CH₂Cl₂ for three times. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under vacuum to obtain a crude product, which was further purified by flash chromatography (petroleum ether–ethylacetate, v/v = 10 : 1) to afford the red solid of 2,2,6,6-tetramethylpiperidinooxy-4-yl 2-iodoacetate (0.85 g, 59%). HRMS calcd for C₁₁H₁₉INO₃: 340.0410; found: 341.0463 [M + H]⁺. Anal. calcd for C₁₁H₁₉INO₃: C, 38.84; H, 5.63; N, 4.12%. Found: C, 39.31; H, 5.65; N, 4.27%. ¹H NMR (400 MHz, CDCl₃): δ 4.98 (ddd, J = 15.5, 11.2, 4.2 Hz, 1H), 3.54 (s, 2H), 1.88–1.79 (m, 2H), 1.55 (t, J = 11.8 Hz, 2H), 1.13 (d, J = 12.5 Hz, 12H). IR (KBr disk, cm⁻¹): 3046 (w), 2965 (w), 1715 (s), 1466 (w), 1416 (w), 1311 (m), 1281 (s), 1178 (m), 1093 (s), 984 (m).

Synthesis of 3-(6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridin-2-yl)-1-(2-((1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy)-2-oxoethyl)-1H-imidazol-3-ium iodide (1a)

A solution of 2,2,6,6-tetramethylpiperidinooxy-4-yl 2-iodoacetate (0.66 g, 1.9 mmol) in anhydrous THF (10 mL) was treated with a solution of 2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(1H-imidazol-1-yl)pyridine (0.39 g, 1.6 mmol) in anhydrous THF (10 mL). The mixture was stirred at 50 °C for 12 h under N₂ atmosphere. During this time, a creamcolored solid precipitated in the flask. The suspension was cooled to room temperature, and the supernatant was decanted off. The resulting solid was washed with anhydrous THF and anhydrous ether for three times to afford the creamcolored solid of 1a (0.60 g, 81%). HRMS calcd for C₂₄H₃₂N₆O₃⁺: 452.2530; found: 452.2528. Anal. calcd for C₂₄H₃₂N₆O₃I: C, 49.75; H, 5.57; N, 14.50%. Found: C, 49.61; H, 5.57; N, 14.24%. ¹H NMR (400 MHz, CDCl₃): δ 10.83 (s, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.85 (d, J = 7.1 Hz, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.46 (s, 1H), 5.96 (s, 1H), 5.46 (s, 2H), 5.12–5.04 (m, 1H), 2.59 (s, 3H), 2.20 (s, 3H), 1.95–1.90 (m, 2H), 1.67 (t, J = 11.8 Hz, 2H), 1.14 (d, J = 23.2 Hz, 12H). IR (KBr disk, cm⁻¹): 3084 (w), 2976 (w), 1784 (s), 1612 (m), 1586 (m), 1484 (m), 1453 (s), 1384 (w), 1360 (m), 1280 (w), 1220 (s), 811 (m), 725 (w).

Synthesis of 3-([2,2′-bipyridin]-5-yl)-1-(2-((1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy)-2-oxoethyl)-1H-imidazol-3-ium iodide (1b)

Creamcolored solid of 1b was obtained by the similar approach to that used for the isolation of 1a, using 2,2,6,6-tetramethylpiperidinooxy-4-yl 2-iodoacetate (0.57 g, 1.7 mmol) and 5-(1H-imidazol-1-yl)-2,2′-bipyridin (0.31 g, 1.4 mmol) as starting materials. Yield: 0.45 g (74%). HRMS calcd for C₂₄H₂₉N₅O₃⁺: 435.2265; found: 435.2257. Anal. calcd for C₂₄H₂₉N₅O₃I: C, 51.25; H, 5.20; N, 12.45%. Found: C, 50.60; H, 5.29; N, 12.41%. ¹H NMR (400 MHz, CDCl₃): δ 10.20 (s, 1H), 8.84 (s, 1H), 8.59 (d, J = 4.1 Hz, 1H), 8.51 (d, J = 8.6 Hz, 1H), 8.30 (d, J = 7.8 Hz, 1H), 8.09 (d, J = 8.6 Hz, 1H), 7.73 (t, J = 7.4 Hz, 1H), 7.57 (s, 1H), 7.41 (s, 1H), 5.45 (s, 2H), 5.11–5.03 (m, 1H), 1.94–1.89 (m, 2H), 1.65 (t, J = 11.9 Hz, 2H), 1.13 (d, J = 21.5 Hz, 12H). IR (KBr disk, cm⁻¹): 2974 (s), 2936 (m), 2911 (m), 1758 (s), 1625 (w), 1563 (m), 1459 (s), 1360 (m), 1216 (s), 800 (m), 740 (m).

Synthesis of 1-(2-((1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy)-2-oxoethyl)-4-(1-(pyridin-2-yl)-1H-pyrazol-3-yl)pyridin-1-ium iodide (1c)

Creamcolored solid of 1c was obtained by the similar route to that used for the isolation of 1a, using 2,2,6,6-tetramethylpiperidinooxy-4-yl 2-iodoacetate (0.74 g, 2.2 mmol) and 2-(3-(pyridin-4-yl)-1H-pyrazol-1-yl)pyridine (0.40 g, 1.8 mmol) as starting materials. Yield: 0.75 g (74%). HRMS calcd for C₂₄H₂₉N₅O₃⁺: 435.2265; found: 435.2285. Anal. calcd for C₂₄H₂₉N₅O₃I: C, 51.25; H, 5.20; N, 12.45%. Found: C, 51.04; H, 5.33; N, 12.06%. ¹H NMR (400 MHz, CDCl₃): δ 8.91 (d, J = 6.4 Hz, 2H), 8.56 (d, J = 2.2 Hz, 1H), 8.33 (d, J = 4.1 Hz, 1H), 8.17 (d, J = 6.4 Hz, 2H), 7.94 (d, J = 8.2 Hz, 1H), 7.77 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 2.2 Hz, 2H), 5.82 (s, 2H), 5.14–5.00 (m, 1H), 1.96–1.90 (m, 2H), 1.64 (t, J = 11.9 Hz, 2H), 1.11 (d, J = 21.8 Hz, 12H). IR (KBr disk, cm⁻¹): 3075 (w), 2975 (m), 2940 (w), 1745 (s), 1641 (s), 1595 (m), 1468 (s), 1374 (m), 1214 (s), 964 (w), 795 (m), 720 (w).

Synthesis of 1-(2-((1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy)-2-oxoethyl)-4-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)pyridin-1-ium (1d)

Creamcolored solid of 1d was obtained by the similar method to that used for the isolation of 1a, using 2,2,6,6-tetramethylpiperidinooxy-4-yl 2-iodoacetate (0.55 g, 1.6 mmol) and 2-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)pyridine (0.30 g, 1.4 mmol) as starting materials. Yield: 0.53 g (70%). HRMS calcd for C₂₄H₂₉N₅O₃⁺: 435.2265; found: 435.2282. Anal. calcd for C₂₄H₂₉N₅O₃I: C, 51.25; H, 5.20; N, 12.45%. Found: C, 50.99; H, 5.32; N, 12.08%. ¹H NMR (400 MHz, CDCl₃): δ 9.10 (d, J = 6.0 Hz, 2H), 8.54 (d, J = 3.8 Hz, 1H), 8.41 (s, 1H), 8.27 (d, J = 6.3 Hz, 2H), 7.95 (d, J = 7.8 Hz, 1H), 7.67 (t, J = 7.2 Hz, 1H), 7.19 (d, J = 2.3 Hz, 2H), 5.93 (s, 2H), 5.14 (d, J = 10.5 Hz, 1H), 2.07 (d, J = 11.7 Hz, 2H), 1.87 (t, J = 11.2 Hz, 2H), 1.22 (d, J = 41.2 Hz, 12H). IR (KBr disk, cm⁻¹): 2972 (m), 2950 (w), 1753 (s), 1641 (s), 1525 (s), 1483 (m), 1373 (s), 1288 (w), 1211 (s), 952 (m), 775 (w).

Typical procedure for the formation of aldehydes from alcohols

A test tube equipped with a magnetic stirring bar was charged with CuBr (14.4 mg, 0.10 mmol, 5 mol%), 1a (70.6 mg, 0.12 mmol) and Na₂CO₃ (10.6 mg, 0.10 mmol). The reaction vessel was vacuumed and backfilled with oxygen for three times. Then 4-methylbenzyl alcohol (0.24 g, 2.0 mmol) and [bmim][BF₄] (3 mL) were added. The resulting solution was stirred under an oxygen balloon at 50 °C (or 70 °C for (4-nitrophenyl)methanol, (4-trifluorophenyl)methanol, (4-bromo-phenyl)methanol and (4-chlorophenyl)methanol) for 24 h. Then it was extracted three times with Et₂O (3 × 5 mL). The combined organic layer was washed with brine (20 mL), dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by flash column chromatography using petroleum ether and ethyl acetate as the eluent.

Typical procedure for the formation of imines from alcohols

A test tube equipped with a magnetic stirring bar was charged with CuBr (14.4 mg, 0.10 mmol), 1a (70.6 mg, 0.12 mmol) and Na₂CO₃ (10.6 mg, 0.10 mmol). The reaction vessel was vacuumed and backfilled with oxygen for three times. And then 4-methylbenzyl alcohol (0.24 g, 2.0 mmol), aniline (0.22 g, 2.4 mmol) and [bmim][BF₄] (3 mL) were added subsequently. The resulting solution was stirred under an oxygen balloon at 80 °C (or 100 °C for (4-nitrophenyl)methanol, (4-trifluorophenyl)methanol and (4-chlorophenyl)methanol) for 24 h. Then it was cooled to ambient temperature, and extracted three times with Et₂O (3 × 5 mL). The combined organic layer was washed with brine (20 mL), dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by flash column chromatography using petroleum ether and ethyl acetate as the eluent.

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 21373142 and 21471108 and 21531006), the State Key Laboratory of Organometallic Chemistry of Shanghai Institute of Organic Chemistry (2015kf-07), the “333” Project of Jiangsu Province, the Priority Academic Program Development of Jiangsu Higher Education Institutions, the “SooChow Scholar” Program of Soochow University.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: The ¹H and ¹³CNMR data of aldehyde and imine products, the ¹H and ¹³C NMR spectra of 4-(2-iodineacetoxy)-2,2,6,6-tetramethylpiperidine 1-oxyl, 1a–1d, 2b, aldehyde and imine products, and the positive-ion ESI mass spectra of 1a–1d. See DOI: 10.1039/c6ra10373a

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