Synthesis 2006(9): 1423-1426  
DOI: 10.1055/s-2006-926442
PAPER
© Georg Thieme Verlag Stuttgart · New York

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

Ser Kiang Queka,b, Ilya M. Lyapkalo*a, Han Vinh Huynhb
a Institute of Chemical & Engineering Sciences Ltd., 1 Pesek Road, Jurong Island, 627833 Singapore
b Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543 Singapore
Fax: +6563166184; e-Mail: Ilya_Lyapkalo@ices.a-star.edu.sg;
Further Information

Publication History

Received 13 December 2005
Publication Date:
11 April 2006 (eFirst)

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.

    References

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6

USD 285.80 for 5 g (ALDRICH 2005-2006).

16

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 × CHm + CHp), 7.88-7.91 (m, 2 H, Ph, 2 × CHo). 13C NMR (100.65 MHz, DMSO-d 6): δ = 28.9 (CMe 3), 48.6 (CNH3 +), 127.0, 128.5 (CHm, CHo), 129.5 (CHp), 168.2 (CO2 -).

20

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.

21

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.

23

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.

27

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