On the Oxidation of Different Iminic Bonds by Excess of 3-Chloroperbenzoic Acid

Abstract

In the present work the behavior of different substituted iminic bonds toward the oxidative action of 3-chloroperbenzoic acid is reported. The C=N bond was or was not oxidized to oxaziridines, amides, oximes, nitroso-, nitro-, and azodioxy compounds depending on the substituents at the iminic group and on the ­imine/MCPBA stoichiometric ratio.

Key words

imines - oxidation - oxaziridines - C-nitroso compound - oximes

Although the reduction[ ¹ ] and hydrolysis[ ² ] of imines has been largely studied, only a few publications report its behavior toward oxidizing agents. It has been reported that benzylidene alkylamines lead to the corresponding oxaziridines by stoichiometric oxidation with peracids,[ ³ ] urea hydrogen peroxide,[ ⁴ ] and cobalt-mediated molecular oxygen[ ⁵ ] (Scheme [1]).

Scheme 1 Synthetic methodology for oxaziridine generation

A number of thermally stable oxaziridines, obtained by oxidation of benzylidene alkylamines,[ ⁶ ] have been employed both as oxygenating and/or aminating agents of nucleophilic species[ ⁷ ] and as reagents in cycloaddition reactions with heterocumulenes,[ ⁸ ] alkenes,[ ⁹ ] alkynes,[ ¹⁰ ] and nitriles.[ ¹¹ ] Reports of reactions of imines with excess MCPBA are scarce. Previously, we have reported that the oxidation of benzylidene alkylamines 1–3 by 1.1 mmol of MCPBA in CH₂Cl₂ solution led to oxaziridines 1a–3a in good yields (>90%),[ ¹² ] while nitroso compounds 1b–3b rapidly dimerized to azodioxy compounds 1c–3c and were obtained employing 2.2 mmol of MCPBA (Scheme [2]). Furthermore compounds 2b, 3b, 2c, and 3c, having a hydrogen at the α position of R¹, undergo isomerization into oximes 2d and 3d by heating in toluene solution.

Moreover, the azodioxy dimer 3c was obtained in quantitative yield by reaction of 1.1 mmol MCPBA with the isolated oxaziridine 3a.

The same result was obtained on oxidizing the cyclic imine 3,4-dihydro-2H-pyrrole 4 with 1.1 mmol of MCPBA; the condensed oxaziridine 4a (yield 98%) was obtained in this case. Product 4a was subsequently oxidized into nitroso compound 4b that rapidly dimerized to azoxydimer 4c when a further 1.1 mmol of MCPBA were added. Furthermore, on heating 4c in toluene (80 °C), 4d was obtained (yield 80%, Scheme [3]).[ ¹² ]

Continuing our studies on the oxidation of imines with MCPBA we have discovered outcomes strongly dependent on the C=N bond substituents. Due to the lower ­basicity of the nitrogen in 5–7 with respect to compounds 1–4, the second oxygen transfer on oxaziridines 5a–7a, formed on initial oxidation, did not take place. Instead, N,N-diarylamides 8–10 were obtained both with 1.1 mmol or 2.2 mmol of peracid, after a carbon–nitrogen migration of the aryl group (Scheme [4]). Amides were also obtained in reactions of imines with sodium perborate[ ¹³ ] or with MCPBA and BF₃·OEt₂.[ ¹⁴ ]

Figure 1

A further decrease of basicity of the imine nitrogen as in oximes 11, isoxazolines 12, benzothiadiazines 13, and osazones 14 (Figure [1]), due to the presence of a heteroatom on the nitrogen atom, diminished the reactivity ­towards C=N oxidation, and starting materials were recovered even using 5.0 mmol of MCPBA. Instead the osazone 14 was oxidized on the amine nitrogen, leading to a mixture of different products.[ ¹⁵ ]

Scheme 2 Oxidative action of the MCPBA toward N-alkyl imines

Scheme 3 Oxidative action of MCPBA toward cyclic imines

Scheme 4 Oxidative action of MCPBA toward aryl imines

On the contrary, imines containing a heteroatom at the imine carbon showed high reactivity towards oxidation. Oxazolines 15 reacted with 1.1 mmol of peracid leading to the stable oxaziridines 15 after five hours. Further addition of 1.1 mmol of peracid to 15a led to an unstable N-oxide intermediate which converted into 15b in equilibrium with the dimeric compound 15c (yield 98%) and/or oxime 15d (R = H, Scheme [5]).[ ¹² ]

Other heterocycles with similar structure exhibit the same behavior. When 16 was treated with 2.2 mmol of peracid, 16b was formed, which converted into the azoxydimeric form 16c (yield 98%,[ ¹⁶ ] Scheme [6]). These results indicate that the oxygen bound to the iminic carbon atom increases reactivity toward oxidation reaction.

Imidazoline 17, which contains a nitrogen atom connected to the imine carbon was transformed (50%) into nitroso compound 17b and subsequently into azoxydimer 17c when treated with 1.1 mmol of MCPBA. It was not possible to isolate oxaziridine 17a and the intermediate form of the second oxidation because of their high reactivity. Instead, 17 led to 17c (yield 99%) when treated with 2.2 mmol of peracid (Scheme [7]).

Only a 50% conversion of 2H-1,2,4-benzothiadiazine derivatives 18 and 19,[ ¹⁷ ] structurally similar to the imidazolines, into nitroso compounds 18b–19b was observed on reacting with 1.1 mmol of MCPBA, with azoxydimers 18c and 19c being isolated as final products. On the other hand, when 2.2 mmol of peracid were employed the transformation to the azoxydimers was complete (99%, Scheme [8]).

Figure 2 Projection of compound 18e at 298 K

Scheme 5 Oxidative action of the MCPBA toward O-activated cyclic imines

Scheme 6 Oxidative action of the MCPBA toward O-activated cyclic imines

Scheme 7 Oxidative action of the MCPBA toward N-activated cyclic imines

Furthermore, nitro compound 18e (90% yield) was isolated on treatment of 18 with 5.5 mmol of MCPBA. The structure of 18e was characterized by X-ray crystallographic analysis (Figure [2]).[ ¹⁸ ]

In summary, in this work we have examined the influence of substituents on the behavior of imines towards ­MCPBA. Oxygen, nitrogen, or sulfur, attached to the nitrogen, render the substrates resistant to oxidation of the π-bond. On the contrary, a heteroatom or carbon substituent on the imine carbon make the imine double bond more reactive; oxaziridines, amides, oximes, nitroso-, nitro-, and azoxy compounds can be synthesized depending on the imine/MCPBA stoichiometric ratio.

Scheme 8 Oxidative action of the MCPBA toward S-activated cyclic imines

General Procedure

An excess of MCPBA (1.1 or 2.2 mmol) in CH₂Cl₂ (3 mL) was added to a solution of the requisite imine (1.0 mmol), dissolved in CH₂Cl₂ (5 mL), with stirring and cooling (0–5 °C). When reaction was complete (5–6 h), the excess of m-chloroperbenzoic acid, and the benzoic acid formed was removed by filtration. The filtrate was washed twice with a dilute solution of Na₂SO₃ (5%), then with a solution of Na₂CO₃ (5%), and finally with H₂O. After drying over anhyd MgSO₄, the mixture was concentrated in vacuo, and the crude product was purified by column chromatography (silica gel partly deactivated with Et₃N).

Acknowledgment

Thanks are due to the University of Salento and C.I.N.M.P.I.S. (Consorzio Interuniversitario Nazionale Metodologie e Processi Innovativi di Sintesi) for financial support. We would also like to thank Giuseppe Chita (Istituto di Cristallografia (IC-CNR), Via Amendola 122/o, 70125, Bari, Italy) for X-ray interpretation.

• References and Notes

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