Synlett 2007(8): 1326-1327  
DOI: 10.1055/s-2007-980340
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Hydroxylamine Hydrochloride

Moyurima Borthakur*
Medicinal Chemistry Division, Regional Research Laboratory, ­Jorhat 785006, Assam, India
e-Mail: moyurima27@rediffmail.com;

Further Information

Publication History

Publication Date:
08 May 2007 (online)

Biographical Sketches

Moyurima Borthakur was born in Shillong, Meghalaya, India, and is a permanent resident of Jorhat, Assam, India. She received her B.Sc. in chemistry from Dibrugarh University (2001), Assam, India and her M.Sc. in organic chemistry from Gauhati University (2003), Assam, India. Presently she is working towards her Ph.D. at the ­Regional Research Laboratory, Assam, under the supervision of Dr. Romesh Chandra Boruah, Head of the Medicinal Chemistry Division. Her research interests lie in the field of synthesis of steroidal heterocycles using novel methodologies.

Introduction

Hydroxylamine hydrochloride is a hygroscopic white crystalline powder (mp 151-152 °C). Explosion of the reagent may occur if it is heated above 115 °C. Hydroxyl­amine hydrochloride is harmful if inhaled or swallowed and it is irritating to eyes, skin, and respiratory tract. [1] The reagent decomposes slowly on contact with moisture and should not be stored above 65 °C. Hydroxylamine as a free base is available in the form of large white flakes or needles; however, due to its instability, commercially available hydroxylamine hydrochloride is used as a stable source of hydroxylamine. [2] This versatile reagent can be prepared by treatment of sulfur dioxide with a cold ­solution of potassium nitrate and potassium acetate under controlled reaction conditions below 0 °C.

For over a century, hydroxylamine hydrochloride has found wide application in organic synthesis including electrophilic substitution reactions, [1] oximation, [3] the ­synthesis of pyrazoles, [4] nitriles, [5] isoxazoles, [6] pyridines, [7] nitrones, [8] etc. It is also used as reducing agent [9] and its importance in areas like bioorganic and medicinal chemistry is also vivid. For example, this reagent greatly facilitates the synthesis of a new class of glycosylated β-amino ­acids, which exhibit good activity against human anti-­malarial parasite Plasmodium falciparum.10

Abstracts

(1) A novel one-pot synthesis of pyrazoles has been accomplished by the reaction of β-formyl enamides with hydroxylamine hydrochloride catalysed by potassium dihydrogenphosphate in acidic medium. [4] The reaction has been successfully extended to steroidal, aliphatic, cyclic, and aromatic β-formyl enamides.

(2) A one-pot transformation of aliphatic and aromatic aldehydes to the corresponding nitriles can be easily performed by the reaction of an aldehyde with a slight excess of hydroxylamine hydrochloride in refluxing acetonitrile and in the presence of 0.5 equivalent of sodium iodide as catalyst. [5]

(3) 3,5-Disubstituted isoxazoles are obtained in good yields by a convenient one-pot, three-step procedure utilizing a regioselective copper(I)-catalysed cycloaddition reaction between in situ generated nitrile oxides and terminal acetylenes. [6a] This corresponding ­nitrile oxide can be obtained by reacting hydroxylamine hydrochloride in the presence of NaOH and TsN(Cl)Na·3H2O with the unsaturated aldehyde.

(4) A one-pot synthesis of enantiopure five-membered cyclic nitrones has been accomplished via condensation of hydroxylamine with readily available lactols and subsequent esterification with methanesulfonylchloride. These cyclic nitrones have been employed for the preparation of pyrrolizidines. [8]

(5) Glycosylated β-amino acids afforded glycosyl β-aminohydroxamates in fair yields on reaction with NH2OH·HCl in the presence of DIC/DCC. These compounds were screened against human ­malarial parasite. [10]

(6) Reaction of hydroxylamine hydrochloride with aryltrifluoro­methyl-β-diketones affords 5-hydroxy-5-trifluoromethyl-Δ2-isoxazoles which, upon dehydration, yield 5-trifluoromethyl-isoxazoles. [11]

(7) A short synthesis of pyrrolo-2-aminoimidazoles such as oroidin and its derivatives via N-acyl-1,2-dihydropyridine intermediate [12] is reported. The key step of the strategy is a one-pot oxidative ­bromine-mediated addition of protected guanidine to N-acyl-1,2-dihydropyridine in the presence of NH2OH.

(8) Synthesis of 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines has been reported starting from 2-acetyl quinoxaline via dehydrogenative cyclisation with hydroxylamine hydrochloride in acidic medium. [13]

    References

  • 1 Encyclopedia of Reagents for Organic Synthesis   Vol. 4:  Paquette LA. John Wiley & Sons; Chichester: 1995.  p.2760-2764  
  • 2 Handbook of Inorganic Compounds   Perry DL. Phillips SL. CRC Press; Boca Raton: 1995.  p.196 
  • 3 Wu M. Chen R. Huang Y. Synthesis  2004,  2441 
  • 4 Saikia A. Barthakur MG. Borthakur M. Saikia CJ. Bora U. Boruah RC. Tetrahedron Lett.  2006,  47:  43 
  • 5 Ballini R. Fiorini D. Palmieri A. Synlett  2003,  1841 
  • 6a Hansen TV. Wu P. Fokin VV. J. Org. Chem.  2005,  70:  7761 
  • 6b Gupta R. Pathak D. Jindal DP. Eur. J. Med. Chem.  1999,  34:  659 
  • 7 Jun J. Shin HS. Kim SH. J. Chem. Soc., Perkin Trans. 1  1993,  71:  1815 
  • 8 Cicchi S. Marradi M. Vogel P. Goti A. J. Org. Chem.  2006,  71:  1614 
  • 9 Gangadhar A. Rao TC. Subbarao R. Lakshminarayana G. J. Am. Oil Chem. Soc.  1989,  66:  1507;   Chem. Abstr. 1990, 112, 22677j
  • 10 Mishra RC. Tripathi R. Katiyar D. Tewari N. Singh D. Tripathi RP. Bioorg. Med. Chem.  2003,  11:  5363 
  • 11 Kumar V. Aggarwal R. Singh SP. J. Fluorine Chem.  2006,  127:  880 
  • 12 Gregoire CS. Travert N. Zaparucha A. Mourabit A. Org. Lett.  2006,  8:  2961 
  • 13 Sarodnick G. Heydenreich M. Linker T. Kleinpeter E. Tetrahedron  2003,  59:  6311 

    References

  • 1 Encyclopedia of Reagents for Organic Synthesis   Vol. 4:  Paquette LA. John Wiley & Sons; Chichester: 1995.  p.2760-2764  
  • 2 Handbook of Inorganic Compounds   Perry DL. Phillips SL. CRC Press; Boca Raton: 1995.  p.196 
  • 3 Wu M. Chen R. Huang Y. Synthesis  2004,  2441 
  • 4 Saikia A. Barthakur MG. Borthakur M. Saikia CJ. Bora U. Boruah RC. Tetrahedron Lett.  2006,  47:  43 
  • 5 Ballini R. Fiorini D. Palmieri A. Synlett  2003,  1841 
  • 6a Hansen TV. Wu P. Fokin VV. J. Org. Chem.  2005,  70:  7761 
  • 6b Gupta R. Pathak D. Jindal DP. Eur. J. Med. Chem.  1999,  34:  659 
  • 7 Jun J. Shin HS. Kim SH. J. Chem. Soc., Perkin Trans. 1  1993,  71:  1815 
  • 8 Cicchi S. Marradi M. Vogel P. Goti A. J. Org. Chem.  2006,  71:  1614 
  • 9 Gangadhar A. Rao TC. Subbarao R. Lakshminarayana G. J. Am. Oil Chem. Soc.  1989,  66:  1507;   Chem. Abstr. 1990, 112, 22677j
  • 10 Mishra RC. Tripathi R. Katiyar D. Tewari N. Singh D. Tripathi RP. Bioorg. Med. Chem.  2003,  11:  5363 
  • 11 Kumar V. Aggarwal R. Singh SP. J. Fluorine Chem.  2006,  127:  880 
  • 12 Gregoire CS. Travert N. Zaparucha A. Mourabit A. Org. Lett.  2006,  8:  2961 
  • 13 Sarodnick G. Heydenreich M. Linker T. Kleinpeter E. Tetrahedron  2003,  59:  6311