Synlett 2009(10): 1692-1693  
DOI: 10.1055/s-0029-1217223
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

Bromonitromethane: A Versatile Reagent in Organic Synthesis

Jun-min Zhang*
Industrial Institute of Fine Chemicals and Synthetic Drugs, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. of China.
e-Mail: zhang.junmin@yahoo.com.cn;

Dedicated to my dear research advisor Professor Ming Yan.


Further Information

Publication History

Publication Date:
02 June 2009 (online)

Biographical Sketches

Jun-min Zhang was born in 1980 in Pingdingshan, Henan Province, P. R. of China. He received his B.Sc. degree in chemistry at Luo­yang Normal University in 2004, and obtained his M.Sc. degree in organic chemistry from Suzhou University in 2007. Now he is working towards his Ph.D. degree at School of Pharmaceutical Sciences, Sun Yat-sen University, under the supervision of Professor Ming Yan. His current research interests focus on asymmetric organocatalysis.

Introduction

Bromonitromethane (BrCH2NO2) has received considerable attention as a one-carbon synthon for the synthesis of a variety of important organic intermediates. [¹] For examples, it was used in the synthesis of 2-nitrobenzofuran and 2-nitro-2,3-dihydrobenzofuran-3-ols, [²] nitrobenzo­thio-phenes, and nitrothiazoles, [³] polyfunctionalized nitrocyclopropanes. [4] It has also been utilized in the synthesis of 1-bromo-1-nitroalkan-2-ols [5] and aryl nitromethanes. In addition, it could be used as a bromine donor. [6]

Bromonitromethane is commercially available and can also be easily prepared according to the procedures reported by Fishwick et al. (Scheme  [¹] ). [³] A typical procedure is as following: freshly distilled nitromethane was stirred at 0 ˚C and bromine was dropped in 5 seconds. The resulted bromonitromethane could be used without further purification. [¹a]

Scheme 1

Abstracts

(A) 2-Nitrobenzo[b]furans 4 are prepared by reacting 2-hydroxybenz-aldehydes 1 and bromonitromethane 2 at low temperature. The intermediate 3 is then quantitatively dehydrated by heating in acetic anhydride to provide 4 in good yields. [²]

(B) Fishwick and co-workers described the preparation of 3-amino-2-­nitrobenzo[b]thiophene (a) starting from 2-sulfanylbenzonitrile and bromonitromethane. [³] Several 3-amino-2-nitrothiophenes were prepared starting from the sodium salt of disubstituted 3-sulfanyl-2-­propenenitriles and bromonitromethane. [³] The compounds b were obtained in the yields ranging from 30% to 70%. In another paper, thiophene c was synthesized by Gewald and Hain, starting from disubstituted β-chloroacrylonitrile, ­sodium sulfide and bromonitro­methane. [7] The formation of 5-phenyl-3-amino-2-nitroselenophene (d) was also observed.

(C) Recently, Kirsch and co-workers described a one-pot procedure to prepare new 2-aryl-5-nitrothiophenes efficiently from bromonitromethane and 3-chloro-3-aryl-propenals, [¹a] and to prepare substituted 3-amino-2-­nitrothiophenes and selenophenes from β-chloroacrylo­nitriles and bromonitromethane. [¹b]

(D) Shen and co-workers described a reaction of aldehydes and bromo­nitromethane in the presence of tri-n-butylarsine. The reaction provided substituted 1-bromo-1-nitroalkenes in good yields. [8]

(E) Concellón and co-workers described an efficient synthesis of 1-bromo-1-nitroalkan-2-ols. The reaction of bromonitromethane and a variety of aldehydes was catalyzed by NaI under mild conditions. While chiral N,N-dibenzyl alaninal was used, the corresponding (1S,2S,3S)-3-dibenzylamino-1-bromo-1-nitrobutan-2-ol was obtained with excellent stereoselectivity. [5] In addition they also reported a ­samarium-promoted synthesis of (E)-nitroalkenes from 1-bromo-1-­nitroalkan-2-ols in good yields. [9]

(F) Alcaide and co-workers reported a coupling reaction of azetidine-2,3-diones (α-oxo-β-lactams) and bromonitromethane in aqueous media and in the presence of catalytic amounts of sodium azide. The stereoselectivity of the process was generally good and reasonable anti/syn ratios were achieved by substrate control. Based on the reaction, a simple and efficient synthesis of the potentially bioactive 3-substituted 3-hydroxy-β-lactam moiety has been developed. 2-Azetidinone-­tethered 1-halo-1-nitroalkan-2-ols are highly useful building blocks. For example, they can be converted into spiro and fused bicyclic-β-lactams. [¹0]

(G) Nitrocyclopropane has been successfully prepared by the reaction of bromonitromethane, potassium carbonate and electrophilic alkenes bearing electron-withdrawing groups both in the α- and β-positions. The method provided good yields and moderate to good diastereo­selectivity for linear alkenes. The exo-products were exclusively formed for N-alkylmale­imides. [4b]

(H) Ley and co-workers reported the first organocatalytic enantioselective nitrocyclopropanation of 2-cyclohexen-1-one and bromonitro-methane with good yields and enantioselectivities. 5-(Pyrrolidin-2-yl)-1H-tetrazole was used as the efficient catalyst. [¹¹ ] Recently, the same group developed a general organocatalytic synthesis of chiral nitrocyclopropanes from bromonitromethane and a variety of cyclic and acyclic enones. [¹²] Wang and co-workers reported the same reaction catalyzed by chiral primary amines. Good yields and excellent enantio­selectivities were achieved. [¹³] Very recently, Yan and co-workers reported an efficient synthesis of chiral 4-bromo-4-nitroketones via the asymmetric conjugate addition of bromonitromethane to alkyl vinyl ketones. [¹4]

(I) Córdova and co-workers described a novel organocatalytic nitro­cyclopropanation of α,β-unsaturated aldehydes with bromo­nitromethane. 1-Nitro-2-formylcyclopropanes were obtained in good yields and with excellent enantioselectivities. [¹5] Recently, Yan and co-workers used MeOH-AcONa instead of CHCl3-Et3N resulting in better yields for a variety for substrates. [¹6]

    References

  • 1a Rodríguez Dominguez JC. Thomae D. Seck P. Kirsch G. Synlett  2008,  286 
  • 1b Thomae D. Rodríguez Dominguez JC. Kirsch G. Seck P. Tetrahedron  2008,  64:  3232 
  • 2a Ohishi Y. Doi Y. Nakanishi T. Chem. Pharm. Bull.  1984,  32:  4260 
  • 2b Tromelin A. Demerseman P. Royer R. Synthesis  1985,  1074 
  • 3 Fishwick BR. Rowles DK. Stifling CJM. J. Chem. Soc., Perkin Trans. 1  1986,  1171 
  • 4a Braish TF. Castaldi M. Chan S. Fox DE. Keltonic T. McGarry J. Hawkins JM. Norris T. Rose PR. Sieser JE. Sitter BJ. Watson HJr. Synlett  1996,  1100 
  • 4b Ballini R. Fiorini D. Palmieri A. Synlett  2003,  1704 
  • 5 Concellón JM. Rodríguez-Solla H. Concellón C. García-Granda S. Díaz MR. Org. Lett.  2006,  8:  5979 
  • 6 Sherrill ML. J. Am. Chem. Soc.  1924,  46:  2753 
  • 7 Gewald K. Hain U. Monatsh. Chem.  1992,  123:  455 
  • 8 Shen Y. Yang B. Synth. Commun.  1993,  23: 
  • 9 Concellón JM. Bernad PL. Rodríguez-Solla H. Concellón C. J. Org. Chem.  2007,  72:  5421 
  • 10 Alcaide B. Almendros P. Luna A. Torres MR. Org. Biomol. Chem.  2008,  6:  1635 
  • 11 Hansen HM. Longbottom DA. Ley SV. Chem. Commun.  2006,  4838 
  • 12 Wascholowski V. Hansen HM. Longbottom DA. Ley SV. Synthesis  2008,  1269 
  • 13 Lv J. Zhan J. Wang Y. Chem. Eur. J.  2009,  15:  972 
  • 14 Dong L.-t. Lu R.-j. Du Q.-s. Zhang J.-m. Liu S.-p. Xuan Y.-n. Yan M. Tetrahedron  2009,  65:  4124 
  • 15 Vesely J. Zhao GL. Bartoszewicz A. Córdova A. Tetrahedron Lett.  2008,  49:  4209 
  • 16a (a) Zhang J.-m. Hu Z.-p. Zhao S.-q. Yan M. Tetrahedron  2009,  65:  802 
  • 16b (b) Zhang J.-m. Hu Z.-p. Dong L.-t. Xuan Y.-n. Lou C.-l. Yan M. Tetrahedron: Asymmetry  2009,  20:  355 

    References

  • 1a Rodríguez Dominguez JC. Thomae D. Seck P. Kirsch G. Synlett  2008,  286 
  • 1b Thomae D. Rodríguez Dominguez JC. Kirsch G. Seck P. Tetrahedron  2008,  64:  3232 
  • 2a Ohishi Y. Doi Y. Nakanishi T. Chem. Pharm. Bull.  1984,  32:  4260 
  • 2b Tromelin A. Demerseman P. Royer R. Synthesis  1985,  1074 
  • 3 Fishwick BR. Rowles DK. Stifling CJM. J. Chem. Soc., Perkin Trans. 1  1986,  1171 
  • 4a Braish TF. Castaldi M. Chan S. Fox DE. Keltonic T. McGarry J. Hawkins JM. Norris T. Rose PR. Sieser JE. Sitter BJ. Watson HJr. Synlett  1996,  1100 
  • 4b Ballini R. Fiorini D. Palmieri A. Synlett  2003,  1704 
  • 5 Concellón JM. Rodríguez-Solla H. Concellón C. García-Granda S. Díaz MR. Org. Lett.  2006,  8:  5979 
  • 6 Sherrill ML. J. Am. Chem. Soc.  1924,  46:  2753 
  • 7 Gewald K. Hain U. Monatsh. Chem.  1992,  123:  455 
  • 8 Shen Y. Yang B. Synth. Commun.  1993,  23: 
  • 9 Concellón JM. Bernad PL. Rodríguez-Solla H. Concellón C. J. Org. Chem.  2007,  72:  5421 
  • 10 Alcaide B. Almendros P. Luna A. Torres MR. Org. Biomol. Chem.  2008,  6:  1635 
  • 11 Hansen HM. Longbottom DA. Ley SV. Chem. Commun.  2006,  4838 
  • 12 Wascholowski V. Hansen HM. Longbottom DA. Ley SV. Synthesis  2008,  1269 
  • 13 Lv J. Zhan J. Wang Y. Chem. Eur. J.  2009,  15:  972 
  • 14 Dong L.-t. Lu R.-j. Du Q.-s. Zhang J.-m. Liu S.-p. Xuan Y.-n. Yan M. Tetrahedron  2009,  65:  4124 
  • 15 Vesely J. Zhao GL. Bartoszewicz A. Córdova A. Tetrahedron Lett.  2008,  49:  4209 
  • 16a (a) Zhang J.-m. Hu Z.-p. Zhao S.-q. Yan M. Tetrahedron  2009,  65:  802 
  • 16b (b) Zhang J.-m. Hu Z.-p. Dong L.-t. Xuan Y.-n. Lou C.-l. Yan M. Tetrahedron: Asymmetry  2009,  20:  355 

Scheme 1