A simple, mild and environmentally benign procedure for the cleavage of carbon–nitrogen double bonds using NaBrO₃ in the presence of [bmim]HSO₄

Abstract

A clean, mild and efficient deprotection of oximes, hydrazones, phenyl hydrazones, tosylhydrazones, Schiff's bases and azines to their corresponding carbonyl compounds has been developed using sodium bromate in the presence of acidic ionic liquid [bmim]HSO₄ at 60 °C. The experimental procedure is simple and the products are isolated in high yields. The ionic liquid [bmim]HSO₄ could be easily recovered and recycled.

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Introduction

Regeneration of carbonyl compounds from the corresponding oximes, hydrazones and phenyl hydrazones etc., which are the preferred derivatives for purification, is an important transformation in organic synthesis. A number of reagents have been reported for this transformation.¹ Regeneration of carbonyl compounds from the corresponding Schiff's bases and azines is not common. In view of the importance of this transformation, there is scope for unveiling new methodologies which are mild, benign, inexpensive and general in nature. Bromate anion (BrO₃⁻) is an important oxy-halo reagent which has proved versatile in effecting a variety of oxidation reactions. It has been used to affect the oxidation of functional groups such as thiols, sulfides and alcohols.² NaBrO₃ is normally used in aqueous media in presence of a co-reagent. Co-reagents that have been used with sodium bromate include HBr,³ Br₂,⁴ NaHSO₃,⁵ NH₄Cl,⁶ FeCl₃,⁷ Na₂S₂O₄,⁸ Mg(HSO₄)₂,⁹ cerium(IV)ammonium nitrate (CAN),¹⁰ RuCl₃·nH₂O,¹¹ H₂SO₄,¹² HClO₄ (ref. 13) and Lewis acids such as AlCl₃.¹⁴ The removal of excess sodium bromate from reaction mixture or co-reactant salts is difficult except HBr, Br₂ and ion exchange resin (IER).

Application of room temperature ionic liquids (ILs) is one of the rapidly growing areas of research as promising alternative green solvents in organic synthesis due to their non-volatility and reusability. In addition, the synthesis of task-specific ionic liquids (TSIL) has further extended the scope of application of ionic liquids in organic synthesis as they can act as a medium and catalyst simultaneously. Acidic ionic liquids have been successfully used in many organic reactions.¹⁵ Therefore, we decided to examine the application of sodium bromate with Brønsted acidic ionic liquid [bmim]HSO₄ as a co-catalyst and medium for regeneration of carbonyl group from >C=N– derivatives such as oximes, hydrazones, phenyl hydrazones, tosylhydrazone etc. to the corresponding carbonyl compounds.

Results and discussion

We report herein regeneration of carbonyl compounds from oximes, hydrazones, phenyl hydrazones, tosylhydrazones, Schiff's bases and azines. The regeneration could be achieved with sodium bromate in presence of [bmim]HSO₄ which acts as a co-reactant and reaction medium at 60 °C. A number of substrates have been examined.

Benzophenone oxime (1a) was chosen as the model substrate and reactions were carried out with sodium bromate (NaBrO₃) in [bmim]HSO₄, under various reaction conditions. The reaction of 1a with sodium bromate in 1 : 1 molar ratio in [bmim]HSO₄ (4 mL) was attempted at room temperature. The reaction was incomplete after 4 h but showed the formation of benzophenone by TLC. After workup and separation, 65% of benzophenone 2a was obtained (entry 1, Table 1). When the same reaction was attempted at 60 °C, it yielded 68% of 2a after 2.5 h (entry 2, Table 1). The reaction was then attempted using 1 : 3 molar ratio of 1a : NaBrO₃ at room temperature and at 60 °C. The reaction was incomplete at room temperature and yielded 70% of 2a after 60 min while it was sluggish at 60 °C and yielded 72% of 2a after 30 min (entries 3 and 4, Table 1). Subsequently we attempted the reaction of benzophenone oxime with sodium bromate and [bmim]HSO₄ in presence of water which could help the reaction by removing water soluble intermediates. Thus the reaction of 1a with NaBrO₃ (1 : 3 molar ratio) was attempted in [bmim]HSO₄ : H₂O (3 : 1, v/v) at 60 °C. The reaction was complete after 15 min and yielded 75% of 2a (entry 5, Table 1). The reaction was then repeated using 1 : 2 and 1 : 1 molar ratio of 1a : NaBrO₃ in [bmim]HSO₄ : H₂O (3 : 1, v/v) at 60 °C. Both the reactions were complete in 15 min and yielded 78% and 83% of 2a respectively (entries 6 and 7, Table 1). The reaction of 1a : NaBrO₃ (1 : 1 molar ratio) was then attempted using 1 : 1 and 1 : 3 (v/v) ratio of [bmim]HSO₄ : H₂O. The reaction gave inferior yields of 77% and 65% of 2a, respectively (entries 8 and 9, Table 1). Higher NaBrO₃ ratio w.r.t. substrate and lower [bmim]HSO₄ w.r.t. water lowered the reaction yield. Molar ratio of 1a with NaBrO₃ in 1 : 1 in presence of [bmim]HSO₄ : H₂O (3 : 1, v/v) gave the optimum yield of the product. Water helped the reaction by removing water soluble intermediates. The role of NaBrO₃ & [bmim]HSO₄ : H₂O ratios on the time and yield of 2a has been graphically illustrated in Fig. 1.

Table 1 Optimization for the oxidation of benzophenoneoxime (1a) with NaBrO₃ – [bmim]HSO₄ under different conditions

Entry	Substrate : NaBrO3	[bmim]HSO4 : H2O (v/v)	Temp. (°C)	Time (min)	Yield (%) benzophenone
1	1 : 1	4 : 0	RT	240	65
2	1 : 1	4 : 0	60	150	68
3	1 : 3	4 : 0	RT	60	70
4	1 : 3	4 : 0	60	30	72
5	1 : 3	3 : 1	60	15	75
6	1 : 2	3 : 1	60	15	78
7	1 : 1	3 : 1	60	15	83
8	1 : 1	1 : 1	60	20	77
9	1 : 1	1 : 3	60	30	65

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Fig. 1 Graphical representation of NaBrO₃ & [bmim]HSO₄ : H₂O ratios on reaction time and yield of 2a.

Thus the reaction of 1a with NaBrO₃ in 1 : 1 molar ratio in presence of [bmim]HSO₄ : H₂O (3 : 1, v/v) gave the optimum yield of the product. Subsequently, reactions of a variety of diaryl, arylalkyl and dialkyl ketoximes as well as, aromatic and aliphatic aldoximes were attempted with same optimized reaction conditions. All the reactions were complete in 10–25 min as monitored by TLC. It can be inferred from the data that there is no clear relationship between electron withdrawing or electron releasing groups and the reaction time and yield. In addition, it was observe that aldehydes did not undergo subsequent oxidation to carboxylic acids. Even hindered ketones like camphor and adamantanone could also be regenerated easily in high yields (eqn (1)) (Table 2).

Table 2 Reactions of ketoximes and aldoximes with sodium bromate in [bmim]HSO₄ : H₂O at 60 °C^a

Reactant	Product	Time (min)	Yield^b (%)	Mp °C
				Lit.^17	Obs.
a Reactions carried out using 1 : 1 equiv. of substrate : oxidant and 3 : 1 mL of IL : H2O at 60 °C.b Isolated yield.
		15	83	45	45
		15	95	144–147	142–145
		15	81	74–77	72–75
		10	90	142–145	141–144
		15	79	83.5	81–85
		20	82	101–103	102–103
		20	87	107–111	107–111
		15	80	49–52	48–50
		15	90	20–24	—
		25	80	76–80	76–78
		25	85	42	41–43
		25	80	94–97	94–97
		10	89	—	—
		15	97	45–47	46–47
		15	98	55–58	54–57
		15	76	103–105	103–105
		10	88	—	—
		10	90	—	—
		15	70	—	—
		15	68	—	—
		10	72	117–118	117–119
		15	82	43	43
		20	80	—	—
		10	80	—	—

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After screening reactions of a series of oximes, we decided to investigate the reactions of other carbonyl derivatives with NaBrO₃ and [bmim]HSO₄ under identical conditions. Therefore, a reaction of benzophenone hydrazone was attempted using with NaBrO₃ in (1 : 1) molar ratio in [bmim]HSO₄ : H₂O (3 : 1, v/v) at 60 °C. The reaction was observed to be complete after 20 min and yielded 84% of benzophenone after workup. Similarly, a reaction of benzophenone phenyl hydrazone was also investigated under identical reaction conditions. This reaction was also complete in 20 min and yielded 82% of benzophenone after workup. Subsequently, we also attempted the reaction of benzophenone tosylhydrazone. The reaction was complete in 20 min under identical conditions and yielded 89% of benzophenone. Thereafter, reactions of a variety of hydrazones, phenyl hydrazones and tosylhydrazones of aromatic and aliphatic ketones and aldehydes were carried out under identical conditions (eqn (2)). All the reactions were complete in 10–25 min and gave high yields of the corresponding ketones and aldehydes (Table 3). Even hindered adamantanone hydrazone, adamantanone phenylhydrazone and adamantanone tosylhydrazone could be readily deprotected to give the adamantanone in high yields.

Table 3 Reactions of hydrazones, phenyl hydrazones and tosyl hydrazones with sodium bromate (1 : 1) in [bmim]HSO₄ : H₂O (3 : 1) at 60 °C^a

Reactant	Product	Time (min)	Yield^b (%)	Mp °C
				Lit.^17	Obs.
a All reactions were carried out using 1 : 1 equiv. of substrate : oxidant in IL : H2O (3 : 1, v/v) at 60 °C.b Isolated yields.
		20	84	45	44
		15	98	144–147	145–147
		15	97	142–145	143–145
		15	78	84	82–84
		15	84	107–111	107–110
		15	87	49–52	48–51
		25	90	20	—
		10	88	55–58	55–58
		15	73	—	—
		15	80	—	—
		15	83	117–118	115–118
		15	75	43	43
		15	71	—	—
		20	82	45	44
		15	91	144–147	144–147
		15	76	105–108	105–108
		10	87	55–58	56–58
		15	71	—	—
		15	85	—	—
		15	68	117–118	115–117
		15	80	43	41–43
		10	71	—	—
		15	79	—	—
		15	86	45	45
		15	90	144–147	144–147
		10	82	49–52	51–52
		10	96	55–58	56–59
		10	83	—	—
		15	82	—	—
		15	90	117–118	117–118
		15	75	43	42–43
		15	60	—	—
		15	90	—	—

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We then investigated the reaction of N-salicylidene-p-toluidine (Schiff's base) with NaBrO₃ in presence of [bmim]HSO₄. The reaction was faster and complete in 10 min using 1 : 0.25 molar ratio of substrate : NaBrO₃ in [bmim]HSO₄ : H₂O (1 : 3, v/v) and gave corresponding o-salicylaldehyde (5a) in 89% of yield. NaBrO₃ was required in much lower amounts for deprotection of Schiff's bases compared to oximes, hydrazones, phenyl hydrazones and tosylhydrazones. Subsequently, reactions of a different Schiff's bases (–CH=N–) were attempted under these conditions. All the reactions were complete in 5–10 min as monitored by TLC using ethyl acetate : petroleum ether (20 : 80, v/v) as eluent. After work up, high yields of corresponding aldehydes (5a–5g, Table 4) were obtained (eqn (3)). Notably, [bmim]HSO₄ exhibits a dual character of being a medium as well as catalyst in presence of water.

Table 4 Reactions of Schiff's Bases to corresponding carbonyl compounds with sodium bromate in [bmim]HSO₄ : H₂O at 60 °C^a

Reactant	Product	Time (min)	Yield^b (%)	Mp °C
				Lit.^17	Obs.
a All reaction were carried out using 1 : 0.25 equiv. scale of substrate : oxidant in IL : H2O (1 : 3, v/v) at 60 °C.b Isolated yield of aldehydes.
		10	89	—	—
		8	91	55–58	55–58
		5	87	40–43	42–43
		3	92	103–105	103–105
		5	82	—	—
		7	84	—	—
		5	88	—	—
		7	86	55–58	55–58

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Reactions of azines, which are versatile intermediates in the construction of many heterocycles and in a variety of chemical reactions, were also attempted under identical conditions. All the reactions were fast and complete in 5–10 min using 1 : 1 molar ration of substrate : NaBrO₃ in [bmim]HSO₄ (3 : 1, v/v) at 60 °C. After workup, corresponding aldehydes were obtained in high yields (eqn (4)). The resulting data is summarized in Table 5.

Table 5 Reactions of azines to corresponding carbonyl compounds with sodium bromate in [bmim]HSO₄ : H₂O at 60 °C^a

Reactant	Product	Time (min)	Yield^b (%)	Mp °C
				Lit.^17	Obs.
a All reactions were carried out using 1 : 1 equiv. scale of substrate : oxidant in IL : H2O (3 : 1, v/v) at 60 °C.b Isolated yields.
		10	89	112–116	112–115
		10	91	55–58	57–58
		5	85	40–43	42–43
		5	90	103–105	102–105
		10	93	45–47	46–47
		5	83	57–60	57–60

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The use of oxidant in presence of [bmim]HSO₄ as reaction medium and co-catalyst led to deprotection of these compounds to the corresponding aldehydes without further oxidation to the corresponding acids.

Experimental

The products were identified by m.p., mixed m.p. (wherever applicable), IR and NMR spectra. Melting points were determined on Tropical m.p apparatus and are uncorrected. IR spectra were recorded in chloroform or as KBr pellets on Perkin-Elmer FT-IR SPECTRUM-2000. ¹H NMR spectra were recorded on a Hitachi FT-NMR model R-600 (60 MHz) with CDCl₃ as solvent and TMS as internal standard. All ketones and aldehydes were purchased from Spectrochem, Aldrich or Merck and used after purification. Oximes, hydrazones, phenyl hydrazones, tosylhydrazones, Schiff's bases and azines were prepared by reported procedure.^16a Ionic Liquids were prepared by reported procedure.^16b

Typical procedure for the reaction of oximes, hydrazones and azines to corresponding carbonyl compounds

In a typical procedure, a mixture of sodium bromate (1.04 mmol), oxime/hydrazone/phenylhydrazone/azine (1.04 mmol) and [bmim]HSO₄/H₂O (3 : 1 ratio), was placed in a 50 mL round-bottomed flask. The flask was connected to a reflux condenser and heated in an oil-bath maintained at 60 °C for the time specified in tables. The progress of the reaction was monitored by TLC using ethyl acetate : petroleum ether (20 : 80, v/v) as eluent. After completion of the reaction, the contents were allowed to cool to room temperature. A saturated solution of sodium thiosulphate (∼5 mL) was added into the reaction mixture in order to remove unreacted bromine. The mixture was poured into a beaker containing ice cold water (∼30 mL) and stirred well. The solid product was filtered under suction. The solid so obtained was recrystallized with ethanol to give the aldehydes/ketones in high yield. In case of liquid products, the mixture was poured into cold water (30 mL) and extracted with ether (3 × 10 mL). The combined ether extract was then dried over anhyd. sodium sulphate. The solvent was removed on a Buchi rotavapour and the product was dried under vacuum to yield aldehydes or ketones.

Typical procedure for the reaction of Schiff's bases to corresponding carbonyl compounds

In a typical procedure, a mixture of sodium bromate (0.25 mmol) and Schiff's base (1.04 mmol) in 2 mL of water were placed in a 50 mL round-bottomed flask. The flask was connected to a reflux condenser and heated in an oil-bath maintained at 60 °C. Then dropwise addition of [bmim]HSO₄ : H₂O (1 : 3, v/v) was done into the reaction mixture over the period of 5–10 min. The progress of the reaction was monitored by TLC using ethyl acetate : petroleum ether (20 : 80, v/v) as eluent. After completion of the reaction, the contents were allowed to cool to room temperature. The mixture was poured into a beaker containing ice cold water (∼30 mL) and stirred well. The solid product was filtered under suction. The solid so obtained was recrystallized with ethanol to give the aldehydes/ketones in high yield. In case of liquid products, the mixture was poured into cold water (30 mL) and extracted with diethyl ether (3 × 10 mL). The combined ether extract was dried over anhyd. sodium sulphate. The solvent was removed on a Buchi Rotavapour and the product was dried under vacuum to yield aldehydes or ketones.

Conclusion

We have reported a simple, efficient novel method for oxidation of oximes, hydrazones, phenyl hydrazones, tosyl hydrazones, Schiff's bases and azines using NaBrO₃ in presence of [bmim]HSO₄ for the synthesis of corresponding carbonyl compounds. All the reactions were rapid and gave high yields of products.

Acknowledgements

AL is thankful to University of Delhi, Delhi, India for the grant of UTA. RM thanks C.S.I.R., New Delhi, India for the grant of Junior Research Fellowship.

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