Download PDF
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 (online)

    Permissions and Reprints All articles of this category

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.

Key words

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

    References

  • 1a The Chemistry of the Nitro and Nitroso Groups   Feuer H. Wiley; New York: 1969. 
    Google Scholar
  • 1b Hanefeld W. In Organic Nitrogen Compounds I, C-Nitroso Compounds, Houben-Weyl   Vol. E16a, 4th ed.:  Klamann D. Thieme; Stuttgart: 1990.  Part 2. p.950-996  
    Google Scholar
  • 1c Askani R. Taber DF. In Comprehensive Organic Synthesis, Synthesis of Nitroso, Nitro and Related Compounds   Vol. 6:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.103 
    Google Scholar
  • 1d Kabalka GW. Varma RS. In Comprehensive Organic Synthesis, Reduction of Nitro and Nitroso Compounds   Vol. 8:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.363 
    Google Scholar
  • 2a Janzen EG. Blackburn BJ. J. Am. Chem. Soc.  1969,  91:  4481 
    Google Scholar
  • 2b Perkins MJ. Chem. Soc., Spec. Publ.  1970,  24:  97 
    Google Scholar
  • 3a Nakazono S. Karasawa S. Koga N. Iwamura H. Angew. Chem. Int. Ed.  1998,  37:  1550 ; Angew. Chem. 1998, 110, 1645
    CrossrefGoogle Scholar
  • 3b Mathevet F. Luneau D. J. Am. Chem. Soc.  2001,  123:  7465 
    CrossrefGoogle Scholar
  • 4 Lyapkalo IM. Ioffe SL. Strelenko YA. Tartakovsky VA. Russ. Chem. Bull.  1996,  45:  856 
    CrossrefGoogle Scholar
  • 5 Corey EJ. Gross AW. Tetrahedron Lett.  1984,  25:  491 
    CrossrefGoogle Scholar
  • 7 Bamberger E. Seligmann R. Chem. Ber.  1903,  36:  703 
    Google Scholar
  • 8a Zajac WW. Walters TR. Woods JM. Synthesis  1988,  808 
    CrossrefGoogle Scholar
  • 8b Zajac WW. Darcy MG. Subong AP. Buzby JH. Tetrahedron Lett.  1989,  30:  6495 
    CrossrefGoogle Scholar
  • 8c Zajac WW. Walters TR. Woods JM. J. Org. Chem.  1989,  54:  2468 
    CrossrefGoogle Scholar
  • 9a Holman RJ. Perkins MJ. J. Chem. Soc. C  1970,  2195 ; and references cited therein
    CrossrefGoogle Scholar
  • 9b Holman RJ. Perkins MJ. J. Chem. Soc. C  1971,  2324 
    CrossrefGoogle Scholar
  • 9c Greer ML. Sarker H. Mendicino ME. Blackstock SC. J. Am. Chem. Soc.  1995,  117:  10460 
    CrossrefGoogle Scholar
  • 10a Stowell JC. J. Org. Chem.  1971,  36:  3055 
    CrossrefGoogle Scholar
  • 10b Smith RJ. Pagni RM. J. Org. Chem.  1981,  46:  4307 
    CrossrefGoogle Scholar
  • 11 Synthesis of (CD3)3CN=O is described but no detailed procedure is given: Chiarelli R. Rassat A. Tetrahedron  1973,  29:  3639 
    CrossrefGoogle Scholar
  • 12 Emmons WD. J. Am. Chem. Soc.  1957,  79:  6522 
    CrossrefGoogle Scholar
  • 13 A laborious 3-step preparation of the product A on a large scale via the hydroxylamine 3a is described: Calder A. Forrester AR. Hepburn SP. Org. Synth. Coll. Vol. VI   Wiley; New York: 1972.  p.803 
    Google Scholar
  • 14a Alewood PF. Calder IC. Richardson RL. Synthesis  1981,  121 
    CrossrefGoogle Scholar
  • 14b Psiorz M. Zinner G. Synthesis  1984,  217 
    CrossrefGoogle Scholar
  • 14c White EH. Ribi M. Cho LK. Egger N. Dzadzic PM. Todd MJ. J. Org. Chem.  1984,  49:  4866 
    CrossrefGoogle Scholar
  • 14d Zhao C.-X. Peng Y.-Y. Qu Y.-L. J. Fluorine Chem.  1993,  61:  171 
    CrossrefGoogle Scholar
  • 15 A synthesis of the compound Ph(O)ONHCMe2CH2CMe3 (2c) is reported: Phanstiel O. Wang QX. Powell DH. Ospina MP. Leeson BA. J. Org. Chem.  1999,  64:  803 
    CrossrefGoogle Scholar
  • 17 Referred to pKa[HCO3-]aq and pKa[HPO4 2-]aq: Handbook of Chemistry and Physics   81st ed.:  Lide DR. 2000-2001.  p.8-44-8-45  
    Google Scholar
  • 18 Bunting JW. Stefanidis D. J. Am. Chem. Soc.  1990,  112:  779 
    CrossrefGoogle Scholar
  • 19 It was isolated at the following benzoyl cleavage step as a byproduct that was insoluble in water. The 1H NMR signals of the amide matches with those described in literature, see: Larsen J. Jorgensen KA. Christensen D. J. Chem. Soc., Perkin Trans. 1  1991,  1187 
    CrossrefGoogle Scholar
  • 22 Dicks PF. Glover SA. Goosen A. McCleland CW. Tetrahedron  1987,  43:  923 
    CrossrefGoogle Scholar
  • 25 Usuki T. Mita T. Lear MJ. Das P. Yoshimura F. Inoue M. Hirama M. Akiyama K. Tero-Kubota S. Angew. Chem. Int. Ed.  2004,  43:  5249 ; Angew. Chem. 2004, 116, 5361
    CrossrefGoogle Scholar
  • 26a Hayami S. Inoue K. Chem. Lett.  1999,  7:  545 
    CrossrefGoogle Scholar
  • 26b Itoh T. Matsuda K. Iwamura H. Angew. Chem. Int. Ed.  1999,  38:  1791 ; Angew. Chem. 1999, 111, 1886
    CrossrefGoogle Scholar
  • 28 Stowell JC. Lau CM. J. Org. Chem.  1986,  51:  3355 
    CrossrefGoogle Scholar
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.