Selective oxidation of primary benzylic alcohols to aldehydes using NaNO 3 under ball milling

Abstract

A facile method for oxidation of primary benzylic alcohols to the corresponding aldehydes is reported using NaNO₃/P₂O₅ under high-speed ball-milling conditions. This approach is clean, efficient, and exhibits broad functional group compatibility.

Keywords

alcohols aldehydes ball milling oxidation

Introduction

The selective oxidation of alcohols to the corresponding aldehydes/ketones plays a central role in the synthetic chemist’s toolkit and has received increasing attention in recent years.^1,2 Many reagents have been developed for oxidation of benzylic alcohols to the corresponding carbonyl compounds, such as chromium reagents,^3,4 manganese oxidizing reagents,^5–8 2,2,6,6-tetramethylpiperidyl-1-oxy (TEMPO)-related reagents,^9–11 and nitrite- and nitrate-related reagents.^12–16 However, these reactions usually suffer from disadvantages, including the application of heavy-metal-based reagents, harsh reaction conditions, long reaction times, and toxic solvents. With ever-increasing environmental concerns, the development of a general and efficient synthetic protocol for the oxidation of benzylic alcohols is still highly desirable.

Mechanochemical organic methodologies have recently attracted significant attention as a powerful tool for organic chemists.^17–25 Mechanochemistry is generally performed under solvent-free conditions, and as the reagent concentrations are high, this often leads to accelerated reactions and alterations in product selectivity, typically in favor of the discovery of new chemical transformations. In addition, the technique also covers multiple aspects of green chemistry, which can avoid bulk solvents and reduce environmental pollution.²⁶

In our previous work in the area of mechanochemical synthesis, the combination of Bi(NO₃)₃·5H₂O and MgSO₄ was successfully employed for the nitration of aromatic compounds.²⁷ Recently, we reported that the combination of Fe(NO₃)₃·9H₂O and P₂O₅ could convert deactivated arenes into the corresponding nitrated arenes in excellent yields under high-speed ball-milling (HSBM) conditions.²⁸ We proposed that the N₂O₄/NO₂, which was produced in situ from the reaction of nitrates and the auxiliary, should play a major role in these mechanochemical nitrations. Since N₂O₄/NO₂ species are also well-known as oxidants,^29–31 we set out to explore the oxidative nature of the combination of nitrates and auxiliary. In this paper, a combination of NaNO₃ and P₂O₅ is employed as a simple, stable, and inexpensive oxidant for the oxidation of primary benzylic alcohols to aldehydes under HSBM conditions.

Results and discussion

Initially, 4-methylbenzyl alcohol (1a) was chosen as the model substrate and the molar ratio of 1a/nitrate salt/P₂O₅ was fixed at 1:3:1 to optimize the reaction conditions (Table 1, entries 1–5). The reactions were conducted in a standard 2.5-mL screw-capped milling beaker and milled with one stainless steel ball of 6.0-mm diameter in a high-energy vibrational MM400 mixer mill at a frequency of 28 Hz for 2 h at room temperature. A variety of different nitrate salts were tested for oxidation of the alcohol to an aldehyde under HSBM conditions (Table 1, entries 1–5). Several nitrate salts including Cu(NO₃)₂·9H₂O, Al(NO₃)₃·9H₂O, Cr(NO₃)₃, and Fe(NO₃)₃·9H₂O were ineffective in producing the corresponding aldehyde (Table 1, entries 1–4). Encouragingly, 1a underwent smooth oxidation to afford a 57% yield of the desired 4-methylbenzaldehyde (2a), together with 23% of over-oxidized product 3a and 4% of nitrate ester 5a, when NaNO₃ was used (Table 1, entry 5). The control experiments revealed that both the nitrate salt and P₂O₅ were indispensable for the current oxidation reaction, since no conversion of 1a was observed in the absence of P₂O₅ and only a trace amount of 2a was afforded in the absence of NaNO₃ (Table 1, entries 6 and 7).

Table 1.

Optimization of the reaction conditions.^a


Entry	Nitrate	Molar ratio^b	Reaction time (h)	Conversion (%)	Yield (%)^c
Entry	Nitrate	Molar ratio^b	Reaction time (h)	Conversion (%)	2a	3a	4a	5a	Unknown
1	Cr(NO₃)₃	1:3:1	2	96	36	8	N.D.	2	50
2	Cu(NO₃)₂·9H₂O	1:3:1	2	95	48	1	N.D.	4	42
3	Al(NO₃)₃·9H₂O	1:3:1	2	94	43	3	N.D.	1	47
4	Fe(NO₃)₃·9H₂O	1:3:1	2	95	13	1	N.D.	1	80
5	NaNO₃	1:3:1	2	97	57	23	N.D.	4	13
6	NaNO₃	1:3:0	2	0	N.D.	N.D.	N.D.	N.D.	N.D.
7	NaNO₃	1:0:1	2	96	Trace	7	N.D.	N.D.	89
8	NaNO₃	1:3:0.75	2	96	68	7	N.D.	3	18
9	NaNO₃	1:3:0.5	2	97	86	5	1	3	N.D.
10	NaNO₃	1:3:0.25	2	80	60	N.D.	18	2	N.D.
11	NaNO₃	1:3:0.125	2	27	20	N.D.	6	1	N.D.
12	NaNO₃	1:5:0.5	2	96	86	5	3	2	N.D.
13	NaNO₃	1:4:0.5	2	96	86	6	2	2	N.D.
14	NaNO₃	1:2:0.5	2	91	80	4	2	2	N.D.
15	NaNO₃	1:1:0.5	2	77	71	2	2	2	N.D.
16	NaNO₃	1:3:0.5	1	82	76	3	N.D.	2	N.D.
17	NaNO₃	1:3:0.5	0.5	47	44	N.D.	N.D.	2	N.D.

N.D.: not detected.

The side products are known compounds and were determined by ¹H NMR (see ESI for details).

Reaction conditions: 1a (0.05 mmol), reaction frequency (28 Hz), 2 h.

Molar ratio of 1a/nitrate/P₂O₅.

Yields were determined by ¹H NMR analysis of the crude reaction mixture using dibromomethane as an internal standard.

We noticed that the nitrate/P₂O₅ molar ratio had a strong influence on the outcome of the reactions during our exploration of these HSBM reactions.^28,32 To obtain the best yield of the product, the HSBM reaction conditions were further optimized by adjusting the molar ratio of NaNO₃ and P₂O₅ in relation to 1a (Table 1, entries 8–15). First, in order to find a relatively good molar ratio of P₂O₅, the molar ratio of 1a/NaNO₃ was fixed as 1:3 and milled with different quantities of P₂O₅ (Table 1, entries 8–11). When performing the reaction using 0.75 equiv. of P₂O₅, a 68% yield of 2a was achieved (Table 1, entry 8). On further decreasing the quantity of P₂O₅ to 0.5 equiv., the yield of 2a sharply increased to 86% (Table 1, entry 9). However, further decreasing the quantity of P₂O₅ to 0.25 equiv. and 0.125 equiv. resulted in decreased conversions of 1a to 80% and 27%, leading to significant decreases of the yields of 2a to 60% and 20%, respectively, implying that the best molar ratio of 1a/P₂O₅ was 1:0.5 for this HSBM reaction (Table 1, entries 10 and 11). Next, by keeping the molar ratio of 1a/P₂O₅ as 1:0.5, the amount of NaNO₃ was studied. On increasing of the quantity of NaNO₃ to 4 equiv. and 5 equiv., the product yield plateaued at 86% (Table 1, entries 12 and 13), while decreasing the quantity of NaNO₃ to 2 equiv. and 1 equiv. led to lower yields of 80% and 71%, respectively (Table 1, entries 14 and 15), implying that the best molar ratio of 1a/NaNO₃ was 1:3. In light of these results, a molar ratio of alcohol/NaNO₃/P₂O₅ of 1:3:0.5 was selected for the HSBM reactions in further studies. When the ratio of alcohol/NaNO₃/P₂O₅ was set as 1:3:0.5, shortening the reaction times to 1 and 0.5 h resulted in sharp decreases in the conversion of benzyl alcohol, leading to 76% and 44% yields of aldehyde 2a, respectively (Table 1, entries 16 and 17).

The conversion of 1a into the corresponding aldehyde in the presence of NaNO₃/P₂O₅ was also carried out under conventional refluxing conditions in different organic solvents (Table 2). On refluxing in tetrahydrofuran, the reaction was not complete, even after 8 h and consequently gave a poor yield (Table 2, entry 1). Other solvents like acetonitrile, ethyl acetate, and dichloromethane gave even lower yields of product 2a (Table 2, entries 2–4). These results indicate that ball milling gives better results in comparison to conventional heating for this application.

Table 2.

Oxidation of 1a by NaNO₃/P₂O₅ under heating in a solvent.^a

Entry	Solvent	Conversion (%)	Yield (%)^b
1	Tetrahydrofuran	37	30
2	Acetonitrile	34	25
3	Ethyl acetate	16	8
4	Dichloromethane	10	trace

Reaction conditions: 1a (0.3 mmol). Molar ratio (1a/NaNO₃/P₂O₅): 1:3:0.5. Solvent 4 mL, reflux, 8 h.

Yields were determined by ¹H NMR analysis of the crude reaction mixture using dibromomethane as an internal standard.

With optimized reaction conditions in hand, we next explored the scope of our oxidation system on a series of benzylic primary alcohols. Benzyl alcohol (1b) and 4-phenylbenzyl alcohol (1c) afforded the desired aldehydes 2b and 2c in high yields (Table 3, entries 1 and 2). The primary benzylic alcohols 1d–k with electron-withdrawing groups on the phenyl ring were smoothly oxidized to give the corresponding aldehydes 2d–k in good to excellent yields (78%–100%) (Table 3, entries 3–10). It should be noted that all of these substrates afforded the corresponding aldehydes, accompanied with traces of over-oxidized products 3. These results are similar to those of Tokunaga using tert-butyl nitrite as the oxidizing agent in solution chemistry; however, the reaction yields obtained in our work are much higher.¹⁶ For primary benzylic alcohols 1l–o, bearing electron-donating groups gave somewhat lower yields than those with electron-withdrawing groups (55%–74% vs 78%–100%) (Table 3, entries 11–14). These results imply that the presence of electron-donating groups leads to reduced reactivity during the oxidation.

Table 3.

Oxidation of different primary aromatic alcohols to the corresponding aldehydes.^a


Entry	Substrate		Conversion (%)	Yield (%)^b
Entry	Substrate		Conversion (%)	2	3
1		1b	98	83	13
2		1c	99	89	6
3		1d	100	92	5
4		1e	94	89	3
5		1f	100	98	2
6		1g	100	100	N.D.
7		1h	78	78	N.D.
8		1i	100	100	N.D.
9		1j	100	98	N.D.
10		1k	92	87	5
11		1l	89	74	9
12		1m	72	63	N.D.
13		1n	89	70	11
14		1o	73	55	6
15		1p	74 82^c	74 82^c	N.D.

N.D.: not detected.

Reaction conditions: primary aromatic alcohol 1 (0.05 mmol), reaction frequency (28 Hz), 2 h. Molar ratio (primary aromatic alcohol/NaNO₃/P₂O₅): 1:3:0.5.

Yields were determined by ¹H NMR analysis of the crude reaction mixture using dibromomethane as an internal standard.

Reaction was run for 4 h.

Many hydrolyzable and oxidatively sensitive functional groups such as amido, ester, and formyl are tolerated under these ball-milling conditions, indicating that our NaNO₃/P₂O₅ system is an effective combination for obtaining aldehydes, and can be used widely for the oxidation of various substituted benzylic primary alcohols. In addition, 2-naphthalenemethanol (1p) was converted into 2-naphthaldehyde (2p) in 74% yield (Table 3, entry 15). Extending the reaction time to 4 h increased the yield to 82% and shows that this protocol is also applicable to the oxidation of fused-ring aromatic primary alcohols.

We also examined the properties of NaNO₃/P₂O₅ as an oxidant reagent for secondary benzylic alcohols. In contrast to the behavior of primary benzylic alcohols, 6a–c mainly gave the corresponding nitrate esters 7 and ethers 8 (Table 4, entries 1–3). A similar pattern was observed in the oxidation of benzylic alcohols and ethers using nitric acid in dichloromethane reported by Strazzolini and Runcio.¹⁵ It can be assumed that compared with primary benzylic alcohols 1, the presence of an α-substituted group in the secondary benzylic alcohols 6 facilitates the formation of the intermediate cations during the reaction, depressing the yields of carbonyl products owing to the competitive esterification and etherification to afford esters 7 and ethers 8.

Table 4.

Oxidation of different secondary aromatic benzylic alcohols.^a


Entry	Substrate		Conversion (%)	Yield (%)^b
Entry	Substrate		Conversion (%)	7	8
1		6a	92	12	80
2		6b	57	15	25
3		6c	75	27	48

Reaction conditions: secondary aromatic alcohol 6 (0.05 mmol), reaction frequency (28 Hz), 2 h. Molar ratio (secondary aromatic alcohol/NaNO₃/P₂O₅): 1:3:0.5.

Yields were determined by ¹H NMR analysis of the crude reaction mixture using dibromomethane as an internal standard.

Mechanistically, a nitrate ester could be a candidate intermediate toward the formation of aromatic aldehydes.^33,34 Since small amount of nitrate ester 5 was detected in our experiment, we performed the same ball-milling reaction in Table 3 by replacing primary aromatic alcohol 1 with 5b to explore if the aromatic aldehyde is formed from nitrate ester in the present work. The results revealed that 87% of 5b were remained unchanged, while 10% of 4-nitrobenzyl nitrate and 3% of 2-nitrobenzyl nitrate ester were obtained, respectively. No corresponding benzyl aldehyde 2b was formed (Supplemental Figure S2, ESI), indicating that the nitrate ester could not be an intermediate in our benzylic oxidation as proposed in some instances.

Considering that NaNO₃/P₂O₅ system works effectively for the oxidation of primary benzylic alcohols, we therefore turned our attention to primary non-benzylic alcohols. Interestingly, while the oxidation of primary benzylic alcohols proceeded well, 2-(4-methylphenyl)ethanol (9) was found to be inert toward the present reaction conditions (Scheme 1). This result agrees with Nishiguchi’s work using metallic nitrates supported on silica gel as oxidants.¹² In addition, we also observed a brown gas during the experiments, just as Nishiguchi reported, when we opened the mill beaker straight after the reaction. This result suggests nitrogen dioxide, which is a radical, is formed under the HSBM condition.

Scheme 1.

Oxidation of 2-(4-methylphenyl) ethanol.

Since excellent oxidation of the benzylic primary hydroxy group was observed, while an aliphatic primary alcohol was inert under this NaNO₃/P₂O₅ system, we decided to evaluate the selectivity of the reagent. The selective oxidation of diols containing both a primary benzylic and an aliphatic hydroxy group was studied as shown in Scheme 2. The diol 10 gave 70% conversion and underwent chemoselective oxidation of the primary benzylic hydroxy group to give 11, without oxidation of the aliphatic hydroxy group, in 55% yield, together with a 15% yield of unknown side products. This result showed the practicality and efficiency of the NaNO₃/P₂O₅ system as a chemoselective oxidant for primary benzylic alcohols.

Scheme 2.

Chemoselective oxidation of diol 10.

Currently, we do not understand the precise mechanism of this reaction. Nishiguchi and Strazzolini have presumed a radical mechanism for the oxidation of alcohols.^12,15 Thus, we propose a radical pathway for our oxidation of benzylic alcohols since our results are comparable with those of Strazzolini and Nishiguchi (Scheme 3). First, NaNO₃ would react with P₂O₅ to generate nitric acid, which could be decomposed to generate N₂O₄/NO₂ under the mechanical force, as described in our previous work.^27,28 Next, the in situ-produced N₂O₄/NO₂ should be responsible for the oxidation, most probably, following the radical-type mechanism reported by Nishiguchi and Strazzolini.^12,15

Scheme 3.

A proposed mechanism for the oxidation of primary benzylic alcohols.

Conclusion

In conclusion, we have reported a methodology for the selective oxidation of primary benzylic alcohols to the corresponding aldehydes using a combination of NaNO₃ and P₂O₅ under HSBM conditions. Chemoselective oxidation of a diol containing both a primary benzylic and a primary aliphatic hydroxy group was also performed. This procedure offers several advantages, including good to excellent yields of aldehydes, compatibility with a broad range of functional groups, the use of simple and inexpensive oxidants, and solvent-free reaction conditions. These features make the present method a useful alternative to current methods for the oxidation of benzylic alcohols.

Experimental

General

All chemicals and reagents were purchased from Meryer (Shanghai, China), Alfa Aesar (Ward Hill, MA, USA), or Energy Chemical (Shanghai, China), and were used as received. The reactions were conducted in a stainless steel milling beaker (2.5 mL) using a stainless steel milling ball in an MM400 mixer ball mill (Retsch GmbH, Germany). Column chromatography was performed using 100–200 mesh silica gel purchased from Qingdao Haiyang Chemical Co. Ltd. (China). Appropriate solvent systems for chromatography were selected according to thin-layer chromatography (TLC) analysis using UV light (254 and 365 nm) to visualize the reaction components. Melting points (m.p.) were obtained on a digital melting point apparatus and are uncorrected. Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker AV 400 spectrometer (Billerica, MA, USA) at 400 MHz (¹H NMR) and at 101 MHz (¹³C NMR). The peak patterns are designated as follows: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; dt, doublet of triplets; m, multiplet. Coupling constants, J, are reported in Hz. The product was dissolved in the appropriate deuterium reagent (CDCl₃ or dimethyl sulfoxide (DMSO)) and tetramethylsilane (TMS) or the solvent peak was used as a standard. An APEX II (Bruker Inc.) mass spectrometer was used for high-resolution mass spectrometry (HRMS) analysis.

General procedure for the synthesis of compounds 2 and 11

For all the experiments, a mixture of alcohol (1) (0.05 mmol), NaNO₃ (0.15 mmol), and P₂O₅ (0.025 mmol) was added to a stainless steel milling beaker (2.5 mL), along with a stainless steel milling ball (ø = 6 mm). The beaker was sealed and placed in the mixer mill. The mechanochemical reaction was performed at 28 Hz for 2 h at room temperature. Subsequently, the reaction mixture was extracted with dichloromethane (8 × 2 mL). The organic extracts from 12 such reactions were combined, and the mixture was filtered. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography on silica gel to afford aldehyde 2.

4-Methylbenzaldehyde (2a):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 86% yield (62.01 mg); colorless liquid (lit.³⁵); ¹H NMR (400 MHz, CDCl₃): δ 9.97 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 2.44 (s, 3H); ¹³C NMR (101 MHz, CDCl₃): δ 192.1, 145.6, 134.2, 129.9, 129.8, 21.9; HRMS (ESI): m/z [M + H]⁺ calcd for C₈H₈O: 121.0648; found: 121.0641.

Benzaldehyde (2b):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 83% yield (52.85 mg); colorless liquid (lit.³⁶); ¹H NMR (400 MHz, CDCl₃): δ 10.03 (s, 1H), 7.89 (d, J = 7.4 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.6 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃): δ 192.5, 136.4, 134.5, 129.8, 129.0; HRMS (ESI): m/z [M + H]⁺ calcd for C₇H₆O: 107.0491; found: 107.0495.

4-Biphenylcarboxaldehyde (2c):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 89% yield (97.31 mg); light yellow solid; m.p. 55–57 °C (lit.³⁷ 55 °C); ¹H NMR (400 MHz, CDCl₃): δ 10.06 (s, 1H), 7.96 (d, J = 8.2 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.64 (d, J = 7.3 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.42 (t, J = 7.4 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃): δ 192.0, 147.3, 139.8, 135.2, 130.3, 129.1, 128.5, 127.7, 127.4; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₃H₁₀O: 205.0624; found: 205.0629.

4-Fluorobenzaldehyde (2d):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 92% yield (68.51 mg); colorless liquid (lit.³⁸); ¹H NMR (400 MHz, CDCl₃): δ 9.97 (s, 1H), 7.92 (dd, J = 8.7, 5.5 Hz, 2H), 7.22 (t, J = 8.5 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃): δ 190.6 (s), 166.6 (d, J = 256.8 Hz), 133.0 (d, J = 2.7 Hz), 132.3 (d, J = 9.7 Hz), 116.4 (d, J = 22.3 Hz); ¹⁹F NMR (376 MHz, CDCl₃): δ −102.34; HRMS (ESI): m/z [M + H]⁺ calcd for C₇H₅FO: 125.0397; found: 125.0394.

4-Chlorobenzaldehyde (2e):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 89% yield (75.06 mg); light yellow solid; m.p. 44–45 °C (lit.³⁹ 44–46 °C); ¹H NMR (400 MHz, CDCl₃): δ 9.99 (s, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃): δ 190.9, 141.0, 134.8, 131.6, 131.0, 129.5, 129.0; HRMS (ESI): m/z [M + Na]⁺ calcd for C₇H₅ClO: 162.9921; found: 162.9924.

4-Bromobenzaldehyde (2f):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 98% yield (108.79 mg); light yellow solid; m.p. 56–58 °C (lit.³⁹ 57–59 °C); ¹H NMR (400 MHz, CDCl₃): δ 9.98 (s, 1H), 7.72 (dd, J = 25.5, 8.5 Hz, 4H); ¹³C NMR (101 MHz, CDCl₃): δ 191.1, 135.1, 132.5, 131.0, 129.8; HRMS (ESI): m/z [M + Na]⁺ calcd for C₇H₅BrO: 206.9416; found: 206.9419.

2,4-Dibromobenzaldehyde (2g):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 100% yield (158.35 mg); white crystalline solid; m.p. 81–84 °C (lit.⁴⁰ 84–85 °C); ¹H NMR (400 MHz, CDCl₃): δ 10.30 (s, 1H), 7.85 (s, 1H), 7.78 (d, J = 8.3 Hz, 1H), 7.59 (d, J = 8.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃): δ 190.8, 136.4, 132.4, 131.5, 130.8, 129.9, 127.5; HRMS (ESI): m/z [M + Na]⁺ calcd for C₇H₄Br₂O: 284.8521; found: 284.8526.

4-Formylbenzoic acid (2h):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 10:1) in 78% yield (70.26 mg); yellow crystalline solid; m.p. 246–247 °C (lit.⁴¹ 245–246 °C); ¹H NMR (400 MHz, DMSO): δ 13.41 (s, 1H), 10.10 (s, 1H), 8.12 (d, J = 7.6 Hz, 2H), 8.01 (d, J = 7.7 Hz, 2H); ¹³C NMR (101 MHz, DMSO-d6): δ 192.8, 166.4, 138.7, 135.4, 129.7, 129.3; HRMS (ESI): m/z [M − H]⁻ calcd for C₈H₆O₃: 149.0244; found: 149.0249.

1,4-Benzenedicarboxaldehyde (2i):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 10:1) in 100% yield (80.48 mg); white solid; m.p. 114–115 °C (lit.⁴² 114–115 °C); ¹H NMR (400 MHz, CDCl₃): δ 10.14 (s, 2H), 8.05 (s, 4H); ¹³C NMR (101 MHz, CDCl₃): δ 191.5, 140.1, 130.2; HRMS (ESI): m/z [M + Na]⁺ calcd for C₈H₆O₂: 157.0260; found: 157.0265.

2-Nitrobenzaldehyde (2j):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 20:1) in 98% yield (88.86 mg); yellow crystalline solid; m.p. 42–43 °C (lit.⁴³ 43 °C); ¹H NMR (400 MHz, CDCl₃): δ 10.44 (s, 1H), 8.13 (d, J = 7.9 Hz, 1H), 7.97 (d, J = 7.6 Hz, 1H), 7.75-7.82 (m, 2H); ¹³C NMR (101 MHz, CDCl₃): δ 188.1, 149.6, 134.1, 133.7, 131.4, 129.7, 124.5; HRMS (ESI): m/z [M + H]⁺ calcd for C₇H₅NO₃: 152.0342; found: 152.0347.

4-Nitrobenzaldehyde (2k):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 20:1) in 87% yield (78.88 mg); yellow crystalline solid; m.p. 105–106 °C (lit.⁴³ 105 °C); ¹H NMR (400 MHz, CDCl₃): δ 10.16 (s, 1H), 8.40 (d, J = 8.6 Hz, 2H), 8.08 (d, J = 8.7 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃): δ 190.3, 151.2, 140.1, 130.5, 124.4; HRMS (ESI): m/z [M + Na]⁺ calcd for C₇H₅NO₃: 174.0162; found: 174.0168.

4-Methoxybenzaldehyde (2l):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 25:1) in 74% yield (60.45 mg); colorless liquid (lit.³⁵); ¹H NMR (400 MHz, CDCl₃): δ 9.89 (s, 1H), 7.84 (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.6 Hz, 2H), 3.89 (s, 3H); ¹³C NMR (101 MHz, CDCl₃): δ 190.9, 164.6, 132.0, 130.0, 114.4, 55.6; HRMS (ESI): m/z [M + H]⁺ calcd for C₈H₈O₂: 137.0597; found: 137.0602.

3-Methoxybenzaldehyde (2m):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 25:1) in 63% yield (51.46 mg); colorless liquid (lit.⁴⁴); ¹H NMR (400 MHz, CDCl₃): δ 9.98 (s, 1H), 7.48–7.44 (m, 2H), 7.40 (d, J = 2.0 Hz, 1H), 7.19 (dt, J = 6.8, 2.5 Hz, 1H), 3.87 (s, 3H); ¹³C NMR (101 MHz, CDCl₃): δ 192.2, 160.2, 137.8, 130.1, 123.6, 121.6, 112.0, 55.5; HRMS (ESI): m/z [M + Na]⁺ calcd for C₈H₈O₂: 159.0417; found: 159.0421.

4-Acetoxybenzaldehyde (2n):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 70% yield (68.95 mg); colorless liquid (lit.⁴⁵); ¹H NMR (400 MHz, CDCl₃): δ 9.99 (s, 1H), 7.92 (d, J = 8.6 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 2.34 (s, 3H); ¹³C NMR (101 MHz, CDCl₃): δ 191.0, 168.8, 155.4, 134.0, 131.3, 122.4, 21.2; HRMS (ESI): m/z [M + Na]⁺ calcd for C₉H₈O₃: 187.0366; found: 187.0369.

4-Acetamidobenzaldehyde (2o):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 30:1) in 55% yield (53.85 mg); yellow crystalline solid; m.p. 151–153 °C (lit.⁴⁶ 149–151 °C); ¹H NMR (400 MHz, CDCl₃): δ 9.93 (s, 1H), 7.86 (d, J = 8.6 Hz, 2H), 7.69 (d, J = 8.3 Hz, 1H), 7.37 (s, 1H), 2.24 (s, 3H); ¹³C NMR (101 MHz, CDCl₃): δ 191.0, 168.6, 143.5, 132.4, 131.2, 119.3, 24.8; HRMS (ESI): m/z [M + Na]⁺ calcd for C₉H₉NO₂: 186.0525; found: 186.0518.

2-Naphthalenecarboxaldehyde (2p):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 25:1) in 74% yield (69.34 mg); yellow solid; m.p. 54–55 °C (lit.⁴⁷ 56–59 °C); ¹H NMR (400 MHz, CDCl₃): δ 10.17 (s, 1H), 8.36 (s, 1H), 8.03–7.91 (m, 4H), 7.67–7.59 (m, 2H); ¹³C NMR (101 MHz, CDCl₃): δ 192.4, 138.1, 138.0, 136.5, 134.6, 132.7, 129.6, 129.2, 129.2, 128.1, 127.1, 122.8; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₁H₈O: 179.0467; found: 179.0462.

4-(2-Hydroxyethyl)benzaldehyde (11):

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 10:1) in 55% yield (49.56 mg); colorless oil (lit.⁴⁸); ¹H NMR (400 MHz, CDCl₃): δ 9.99 (s, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 7.9 Hz, 2H), 3.93 (t, J = 6.5 Hz, 2H), 2.96 (t, J = 6.4 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃): δ 192.0, 146.2, 135.0, 130.1, 129.7, 63.1, 39.3; HRMS (ESI): m/z [M + Na]⁺ calcd for C₉H₁₀O₂: 173.0573; found: 173.0578.

Supplemental Material

sj-docx-1-chl-10.1177_17475198221101983 – Supplemental material for Selective oxidation of primary benzylic alcohols to aldehydes using NaNO3 under ball milling

Supplemental material, sj-docx-1-chl-10.1177_17475198221101983 for Selective oxidation of primary benzylic alcohols to aldehydes using NaNO3 under ball milling by Jing-Fei Wang, Li-Yu Lu, Pu Zhang, Yu-Jun Qin and Zhi-Xin Guo in Journal of Chemical Research

Footnotes

Acknowledgements

The authors are thankful to the Renmin University of China for providing necessary facilities.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Pu Zhang

Supplemental material

Supplemental material for this article is available online.

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