Green bromine: in situ generated catalyst for the selective oxidation of alcohols using H₂O₂ as a benign oxidant

Abstract

The selective oxidation of benzylic/secondary alcohols to the corresponding aldehydes/ketones with a catalytic amount of bromide–bromate (10 mol%) couple and H₂O₂ as a benign oxidant has been developed. The oxidation reactions were achieved through acid (15 mol%) activation of 5 : 1 mole ratios of a bromide–bromate couple for the in situ generation of the Br₂/BrOH species. The In situ generation of the Br₂/BrOH species is also supported by UV-Visible spectrophotometric studies. High selectivity and yields of aldehydes/ketones were obtained without the use of any transition metal catalyst under aqueous conditions.

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The oxidation of alcohols to carbonyl compounds is an important functional group transformation in synthetic chemistry. The conventional oxidation of alcohols predominantly involves transition metal catalysts which work as oxygen carriers. However, most of these catalysts require specific conditions like high temperatures, an inert reaction atmosphere, and occasionally co-catalysts. Furthermore the disposal of the unrecovered catalyst is also a matter of concern with respect to both the environment and the cost. Therefore the development of alternate reagents/catalysts to precious metal catalysts which can mediate the selective oxidation of alcohols is desirable. The halogen species (Cl, Br, and I) are frequently used for the oxidation of alcohols.¹ Although, bromine is hazardous to handle, ship and use, it is still being used in industry as well as in academia due to its ready availability. Numerous methods have been reported for the oxidation of alcohols with varying amounts (2–40 mol%) of bromine or bromine based catalysts.² Further, in some reported procedures, undesired oxidation products were observed.²

Conventional reagents employed for the oxidation of alcohols include permanganates,³ dichromates,⁴cerium salts,⁵nitric oxide,⁶ and other transition metal catalysts.⁷ During the last decade, a large number of metal catalysed oxidations have been disclosed and most of these oxidations were performed with complexes of precious metals.⁸ On the other hand, molecular O₂ and H₂O₂ are cleaner oxidizing reagents.^9,10 However, these reagents are not amenable to oxidise all the functional groups selectively. The hazardous effects associated with elemental bromine, the limited availability and high price of precious metals necessitate the continuous search for more economical and environmental friendly reagents/catalysts for such transformations. One such cost-effective oxidizing reagent is chlorine-gas/hypochlorite but its direct use in organic synthesis is limited due to the possibility of non-selective oxidation. Besides its direct use, chlorine/hypochlorite plays an important role in the preparation of other oxidizing agents.¹¹ Additionally, there are useful halogen or halide derivatives such as oxy-halo compounds of bromine and iodine,¹² and N-halosuccinimides¹³ are reported for the oxidation of alcohols. By choosing the right oxidizing reagent it is possible to control the oxidizing power and, consequently, the selectivity.

Assessment of results for halogen based oxidation of alcohols to aldehydes is presented in Table 1. As can be seen from the data of Table 1, most of the reported methods require stoichiometric or more than stoichiometric amounts of halogen containing reagents for oxidations along with other catalysts. In continuation of our efforts towards green and sustainable processes,¹⁴ we report in the present manuscript a selective oxidation of benzylic/secondary alcohols to corresponding carbonyl compounds using a bromide–bromate couple (10 mol%) with reference to alcohol under aqueous medium at room temperature (Scheme 1).

Scheme 1 Oxidation of alcohols.

Table 1 Comparative halide based oxidation of benzylalcohol to benzaldehyde

Entry	Reagents	Reagent ratio (eqv.)^a	Isolated yield (%)	Ref.
a Reagents used w.r.t. one eqv. of benzyl alcohol. b Yield based on GC conversion. IER = Ion exchange resin, MPHT = N-methylpyrrollidine-2-one hydro-tribromide, TEMPO = (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl, DBDMH= 1, 3-dibromo-5, 5 dimethyl hydantoin.
1	NaBrO3/IER	6.6	95	16
2	Br2/PhIO2/NaNO2	0.02/0.01/0.01	94	17
3	HBr/NaNO2	0.10/0.02	90	2n
4	NBS	1	53.7^b	14g
5	NaIO4/H^+	1/1	79	18
6	N2H4·H2/I2	1/2	3.7	19
7	KIO4/Et4NBr	1/0.25	98	20
8	MPHT/H2O2	0.1/2	93	21
9	Br2/TEMPO/NaNO2	0.4/0.1/0.4	95	22
10	DBDMH/TEMPO/NaNO2	40/0.1/0.4	88	23
11	NaBr-NaBrO3/H^+	0.05–0.4/0.15	84	14c
12	HBr/H2O2	0.1/1.2	78	14d
13	NaBr-NaBrO3/H^+/H2O2	0.084–0.016/0.15/1.2	90	Present

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We initiated the oxidation of benzylic/secondary alcohols using the in situ generation of catalytic Br₂ (10 mol%) as a bromine source and H₂O₂ as a benign oxidant (eqn (1)–(3)). In this study, the bromide–bromate and acid generates brominein situ (eqn (1)), under aqueous conditions, bromine disproportionates to HBr and BrOH (eqn (2)).^2m,15BrOH is revealed to be a mild and selective oxidizing agent for a number of organic substrates.

5Br⁻ + BrO₃⁻ + 6H⁺→3Br₂ + 3H₂O (1)

Br₂ + H₂O→BrOH + HBr (2)

2HBr + H₂O₂→Br₂ + 2H₂O (3)

In order to prove the formation of the BrOH species from the present system, we recorded the UV-absorption spectra of a mixture of bromide–bromate acid under aqueous medium in the absence (Fig. 1A) and presence (Fig. 1B) of an organic substrate according to the composition of equations 1–3. The absorption spectra were recorded at different concentrations (250, 300, 350 and 500 ppm) of bromide. As evidenced from the plot of the absorbance (Fig. 1A), it clearly shows the absorption bands at 220 nm, 266 nm and 390 nm correspond to HBr, BrOH and Br₂ respectively.^24,25 When the same spectra was recorded in the presence of an organic substrate (Fig. 1B) the same peaks at 220 nm and 266 nm correspond to HBr and BrOH were observed respectively. Initially the BrOH is observed clearly, as oxidation proceeds, HBr will be generated simultaneously with decrease of BrOH (Fig. 1B). In presence of H₂O₂, HBr oxidises to BrOH to continue the catalytic oxidation cycle as shown in Scheme 2.

Fig. 1 UV-Absorption spectra of BrOH (A) in absence and (B) in presence of organic substrate.

Scheme 2 Proposed mechanism for the oxidation of alcohols.

Under the present reagent conditions (Table 1, entry 13), benzaldehyde was isolated in 90% yield (Table 2, entry 1). p-Methyl benzyl alcohol provided a 94% yield with 100% selectivity (Table 2, entry 2). Benzylic alcohols with electron withdrawing nitro groups at positions (p/m/o) were selectively oxidized to the corresponding aldehyde in 95%, 93% and 75% isolated yields respectively (Table 2, entries 3–5). Similarly halogen (Br and Cl) substituted benzylic alcohols at different positions produced the corresponding aldehydes in good to excellent yields (88–95%) (Table 2, entries 6–9). The present protocol was extended towards the oxidation of secondary alcohols to the corresponding carbonyl compounds and the results are compiled in Table 3. As can be seen from the data of Table 3, various secondary alcohols such as cyclic, aryl and aryl-alkyl proceeded smoothly to provide the corresponding ketones in good yields (80–95%). To confirm the role of bromate, we carried out a controlled experiment without bromate on the oxidation of benzyl alcohol under similar reaction conditions to Table 1 with only 10 mol% of sodium bromide. We observed only 65% benzaldehyde formation during a period of 24 h against a 90% yield (Table 2, entry 1) in the presence of 1.6 mol% bromate. This study indicates that not only is a catalytic amount of bromate required for the efficient oxidation of alcohols, but it also significantly reduces the reaction time.

Table 2 Oxidation of benzylic alcohols to aldehydes^a

a Conditions: 1 eqv. alcohol, 5 : 1 NaBr–NaBrO3 (10 mol%), H^+ (15 mol%) and 1.2 eqv. H2O2 in aq. Dioxane at r.t. b Isolated yields after column chromatography.
Entry	Substrate	Product	Time (h)	Aldehyde^b^[Ref]
1			14	90^14c,d
2			15	94^14c,d
3			18	95^14c,d
4			18	93^14c,d
5			18	75^14c,d
6			16	95^14c,d
7			16	92^14c,d
8			16	88^14c,d
9			15	95^14c,d

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Table 3 Oxidation of secondary alcohols to ketones^a

Entry	2°Alcohol	Ketone	Time (h)	Yield(%)^b	[Ref]
a Conditions: 1 eqv. alcohol, 5 : 1 NaBr-NaBrO3 (10 mol%), H^+ (15 mol%) and 1.2 eqv. H2O2 in aq. Dioxane at r.t. b Isolated yields after separation by column chromatography.
1			8	80	14c
2			9	88	14c
3			7	87	14c
4			8	93	14c
5			6	95	14c
6			8	91	14c

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After the oxidation of alcohols to their corresponding carbonyl compounds, the bromide atoms end up in the aqueous effluent as HBr.²⁶ The aqueous effluent containing HBr could be treated with H₂O₂ (eqn (3)) to regenerate the species (Br₂/BrOH) for the effective oxidation of alcohols. In this manner the catalytic bromine generated in situ from the bromide–bromate couple accelerates the selective oxidation of alcohols to carbonyl compounds and makes the process environmentally friendly by dispensing in the use of precious/heavy metals.

To prove the recyclability of the reagent, an oxidation reaction was carried out at a 5.0 g (46.3 mmol) scale with benzyl alcohol as a substrate with 10 mol% of total bromide (5 : 1 NaBr : NaBrO₃), 15 mol% acid (H₂SO₄) and 1.2 eqv. of 30% aqueous H₂O₂ under similar reaction conditions for a period of 16 h. The effluent obtained after the extraction of organic part was reused as the bromide source, to which a further calculated amount of substrate (5 g) and H₂O₂ (1.2 eqv. 30%) were added and the reaction was stirred for another 16 h. The same procedure was followed for three such consecutive runs and their conversion and turnover number (TON) are summarized in Table 4.

Table 4 Reusability of the bromide present in effluent^a

Cycles	Yield (%)^b	TON
a Reactions were carried out at a 5 g (46.3 mmol) scale of benzyl alcohol under similar reaction conditions. b Based on GC area%. [TON = (mmol. substrate/mmol. cat) conv.]
fresh	88	880
recycle 1	83	830
recycle 2	80	800
recycle 3	76	760
recycle 4	73	730

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In conclusion, we have described an efficient and selective method for the oxidation of benzylic/secondary alcohols to corresponding carbonyl compounds with catalytic bromine generated in situ as a halogen source and H₂O₂ as a cleaner and terminal oxidant under aqueous medium at room temperature without any transition metal catalyst. The bromide ion which ends up in the aqueous effluent is recyclable and can reused for the same oxidation process.

Acknowledgements

We thank Mr. Hitesh, Mr. V. Agrawal, Mr. H. Brahmbhatt and Mr. A.K. Das of this institute for supporting NMR, IR, GC-MS and LC-MS analyses respectively. G. J. and R. D. are thankful to CSIR, New Delhi, India for the award of SRF.

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26. General Procedure for the oxidation of benzylic/ secondary alcohols ( benzyl alcohol as a representative substrate, Table 2 Entry 1): To a solution of benzyl alcohol (0.5 g, 4.625 mmol) in dioxane (2 mL) was added sodium bromide (0.040 g, 0.39 mmol) and sodium bromate (0.0117 g, 0.07 mmol) in water (1 mL). To the above mixture was added 15 mol% (0.04 g, 0.693 mmol) conc. H₂SO₄ (in 1 mL water) under stirring at room temperature during a period of 20 min followed by the slow addition of 1.2 eqv. of aqueous 30% H₂O₂ over a period of 2 h. The reaction mixture was stirred for a period of 12 h. The reaction was monitored by TLC. After the completion of the reaction, the product was extracted with ethyl acetate (5 mLx3). The combined organic extracts were washed with 5% sodium thiosulphate solution, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The crude product was purified by column chromatography over silica gel (100–200 mesh size) and 90% (0.442 g) of benzaldehyde was obtained. The spectral data (NMR, IR, Mass etc.) were well matched with the literature data.^14c,dSimilarly spectral data (NMR, IR, Mass etc.) of other products reported in Tables 2 and 3 were well matched with the reported data.

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