New Highly Efficient Method for the Synthesis of tert-Alkyl Nitroso Compounds

Abstract

The syntheses of tert-alkyl nitroso compounds RCH₂CMe₂N=O from commercially available tert-alkyl amines RCH₂CMe₂NH₂ proceed cleanly via the intermediacy of the benzoyl derivatives RCH₂CMe₂NHOC(O)Ph and the corresponding hydroxylamines RCH₂CMe₂NHOH. Since the intermediates require no purification in the course of the transformations, the overall yields of the isolated crystalline nitroso dimers (75-80% for R = H, 75% for R = Me and 66% for R = Me₃C) are based on the corresponding amine precursors. In the latter case (R = Me₃C), significant steric demands and hydrophobicity of Me₃CCH₂CMe₂ group necessitate the application of more efficient reagents and conditions on the debenzoylation and oxidation steps. The syntheses are perfectly suitable for scale-up and were successfully performed on up to 500-mmol scale.

tert-alkyl amines - benzoyl peroxide - steric hindrance - selective oxidation - tert-alkyl nitroso compounds

References

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Salt S is insoluble in CHCl₃ but soluble in water and DMSO. ¹H NMR (400.23 MHz, DMSO-d ₆): δ = 1.20 (s, 9 H, CMe₃), 4.36 (br s, NH₃ ⁺, exchange peak with water), 7.31-7.41 (m, 3 H, Ph, 2 × CH_m + CH_p), 7.88-7.91 (m, 2 H, Ph, 2 × CH_o). ¹³C NMR (100.65 MHz, DMSO-d ₆): δ = 28.9 (CMe ₃), 48.6 (CNH₃ ⁺), 127.0, 128.5 (CH_m, CH_o), 129.5 (CH_p), 168.2 (CO₂ ^-).

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The use of yet more basic KOH led to the complete hydrolysis of (PhCO₂)₂ to PhCO₂K with the starting tert-butylamine (1a) remaining intact.

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Interestingly, K₂CO₃ was efficient enough to provide a complete conversion of the more hydrophobic amine 1c to the benzoyl derivative 2c. Apparently, a fine balance between hydrophilicity, basicity and aqueous solubility precluded the formation of the respective tert-alkyl­-ammonium benzoate under the reaction conditions.

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Dimerization time and hence the crystallization time dramatically increases with the increase of the steric demands of the tert-alkyl substituent: ca. 20-30 min for A, several hours in the refrigerator (+4 °C) for B, and at least a week in a deep freezer (-18 °C) for C. For the NMR study on the monomer-dimer equilibrium, see ref. 10a.

24

NMR monitoring of the blue liquid nitroso monomer C prior to the crystallization showed that it was sufficiently pure to be used as a reactant in subsequent transformations.

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The research on new type of metal-free nitrogen bases is currently in progress in our laboratory.

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