Synlett 2007(9): 1475-1476  
DOI: 10.1055/s-2007-980375
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Ammonium Acetate

Madan Gopal Barthakur*
Medicinal Chemistry Division, Regional Research Laboratory (CSIR), Jorhat 785006, Assam, India
e-Mail: mgb_chem@rediffmail.com;

Further Information

Publication History

Publication Date:
23 May 2007 (online)

Biographical Sketches

Madan Gopal Barthakur was born in Jagiroad, Assam, India. He obtained his B.Sc. in Chemistry (1999) and M.Sc. in Organic Chemistry (2001) from the Gauhati University, Assam. He is currently pursuing his Ph.D. under the supervision of Dr. Romesh Chandra Boruah in the Medicinal Chemistry Division of Regional Research Laboratory (CSIR), Jorhat, India. His research involves the study of steroidal A-ring modification and synthesis of steroidal hetero­cycles.

Introduction

Ammonium acetate (NH4OAc) is an easily biodegradable chemical, which displays its versatility in almost all arrays of chemical science. It is a white crystalline solid with a melting range of 110-114 °C and is generally stored at low temperature under vacuum because it is hygroscopic and decomposes at elevated temperatures. Pure ammonium acetate can be prepared by saturating glacial acetic acid with dry ammonia. [1] Qualities like cheap and wide commercial availability, safe and easy handling, fair solubility in water and organic solvents and, above all, its non-toxic and eco-friendly nature make ammonium acetate a popular reagent and effective alternative to gaseous ­ammonia.

From the budding stage of chemistry it has been used in textile and rubber industries, agro and food technology, for analytical purposes as buffer, [2] and in many organic ­reactions (Knoevenagel condensation, [3a] Hantzsch pyridine synthesis, [3b] Krohnke pyridine synthesis, [3c] reactions involving NH4OAc/HOAc combination [3d] ).

In 1957, Hasselstrom et al. reported an amazing synthesis of amino acids by β-radiation of NH4OAc. [4] In some cases ammonium acetate shows excellent catalytic activity. [5] Literature reveals that it has been extensively used in the synthesis of N-heterocyclic compounds (pyridines, [6-8] ­pyridopyrimidines, [9] aziridines, [10] imidazoles, [11] benz­oxazines [12] ), many of which exhibit ­pharmacological activity or act as drug precursors. Moreover, it finds application in modern techniques of analytical chemistry [13a] and molecular biology (purification and ­precipitation of DNA, [13b] protein crystallization [13c] ). Recently, a valuable regioselective synthesis of synthetically important α-iodo acetates from alkenes, NH4OAc, and I2 was reported. [14a]

Ammonium acetate is an efficient reagent in low- and high-boiling organic solvents at room temperature [14b] as well as under reflux conditions. [6-9] Its high efficacy as ­reagent in water, [7a] ionic liquids, [7b] microwave-promoted solvent-less synthesis, [12] and supercritical water [15] gives it a unique position in the present scenario of green ­chemistry.

Abstracts

(A) Raston and Cave [6a] reported a practical synthesis of Krohnke-type pyridines, both symmetrical and unsymmetrical 2,6-bisaryl-substituted, in high yield (75%) by cyclocondensation of a preformed 1,5-diketo compound with NH4OAc in acetic acid. Krohnke pyridines and related terpyridines [6b] are building blocks in supramolecular chemistry and used as therapeutic agents.

(B) 1,4-Dihydropyridines (1,4-DHP’s) and Hantzsch esters are calcium-channel blockers and drugs against cardiovascular diseases. [7] In a green approach 1,4-DHP derivatives were prepared by a multicomponent reaction of an aromatic aldehyde, a cyclic or ­acyclic 1,3-dicarbonyl compound, Meldrum’s acid and NH4OAc in ionic liquid. [7b]

(C) Bagley and co-workers [8] provided a route to polysubstituted ­pyridines with total regiocontrol via a one-pot reaction of an alkynone, a 1,3-diketo compound, and NH4OAc without using acid catalysts and applied this strategy in the total synthesis of the acid-sensitive target dimethyl sulfomycinamate, which is a member of the sulfomycin family of thiopeptide antibiotics.

(D) A 1,3-diazabicyclo[3,1,0]hex-3-ene system was obtained in high yield and excellent diastereocontrol via a three-component one-pot synthesis involving phenacyl chloride, aldehyde, and NH4OAc. The method provides an easy route to bridgehead aziridines, which are potential drug precursors. [10]

(E) Ammonium acetate has been utilized to prepare medicinally important enantiopure substituted imidazoles through a cyclocondensation reaction of 1,2-aminoalcohol with an aldehyde, a 1,2-dicarbonyl compound, and NH4OAc. A study using different ammonia sources in this method established that NH4OAc is superior to other sources like aqueous NH3 and NH4Cl in its efficiency and in the stereoselectivity of the reaction. [11a]

(F) A reinvestigation reaction of NH4OAc with acetyl derivatives of Baylis-Hillman adducts in dry methanol at room temperature resulted in the formation of 2° and 3° allylamines (in the case of acrylonitrile and acrylates, respectively) instead of 1° allylamines. This method provides a route to 2° and 3° allylamines and points out the role of ammonium acetate in product selectivity. [14a]

(G) Ammonium acetate is employed to prepare synthetically ­important α-iodo acetates in a regioselective synthesis via the ­reaction of cyclic or acyclic alkenes with NH4OAc and I2 in acetic acid. [14b]

    References

  • 1 Morley HF. Muir MMP. Watt’s Dictionary of Chemistry   Longmans, Green & Co.; London: 1899.  9: 
  • 2 Schollenberger CJ. J. Am. Chem. Soc.  1932,  54:  2568 
  • 3a Weiss M. J. Am. Chem. Soc.  1952,  74:  5193 
  • 3b Stork G. McElvain SM. J. Am. Chem. Soc.  1946,  68:  1053 
  • 3c Zecher W. Krohnke F. Angew. Chem., Int. Ed. Engl.  1963,  2:  380 
  • 3d Svetlic J. Turecek F. Hanus V. J. Chem. Soc., Perkin Trans. 1.  1987,  563 
  • 4 Hasselstrom T. Henry MC. Murr B. Science  1957,  125:  350 
  • 5 Tanemura K. Suzuki T. Nishida Y. Satsumabayashi K. Horagushi T. Chem. Commun.  2004,  470 
  • 6a Cave WV. Raston CL. Chem. Commun.  2000,  2199 
  • 6b Hasson J. Migianu E. Beley M. Kirsch G. Synthesis  2004,  267 
  • 7a Xia JJ. Wang GW. Synthesis  2005,  2379 
  • 7b Fan XS. Li YZ. Zhang XY. Qu GR. Wang JJ. Hu XY. Heteroat. Chem.  2006,  17:  382 
  • 8 Xiong X. Bagley MC. Chapaneri K. Tetrahedron Lett.  2004,  45:  6121 
  • 9 Zhao L. Liang F. Bi X. Sun S. Liu Q. J. Org. Chem.  2006,  71:  1094 
  • 10 Risitano F. Grassi G. Foti F. Moraci S. Synlett  2005,  1633 
  • 11a Matsuoka Y. Ishida Y. Sasaki D. Saigo K. Tetrahedron  2006,  62:  8199 
  • 11b Deng X. Mani NS. Org. Lett.  2006,  8:  269 
  • 12 Yadav LDS. Rai VK. Tetrahedron Lett.  2006,  47:  395 
  • 13a Iavarone AT. Udekwu OA. Williams ER. Anal. Chem.  2004,  76:  3944 
  • 13b Saporito-Irwin SM. Geist RT. Gutmann DH. Biotechniques  1997,  23:  424 
  • 13c Shilton BH. Li Y. Tessier D. Thomas DY. Cygler M. Protein Sci.  1996,  5:  395 
  • 14a Sing V. Pathak R. Kanojia S. Batra S. Synlett  2005,  2465 
  • 14b Myint YY. Pasha MA. Synth. Commun.  2004,  34:  4477 
  • 15 Tajima K. Uchida M. Minami K. Osada M. Sue K. Toshiyuki N. Hattori H. Arai K. Environ. Sci. Technol.  2005,  39:  9721 

    References

  • 1 Morley HF. Muir MMP. Watt’s Dictionary of Chemistry   Longmans, Green & Co.; London: 1899.  9: 
  • 2 Schollenberger CJ. J. Am. Chem. Soc.  1932,  54:  2568 
  • 3a Weiss M. J. Am. Chem. Soc.  1952,  74:  5193 
  • 3b Stork G. McElvain SM. J. Am. Chem. Soc.  1946,  68:  1053 
  • 3c Zecher W. Krohnke F. Angew. Chem., Int. Ed. Engl.  1963,  2:  380 
  • 3d Svetlic J. Turecek F. Hanus V. J. Chem. Soc., Perkin Trans. 1.  1987,  563 
  • 4 Hasselstrom T. Henry MC. Murr B. Science  1957,  125:  350 
  • 5 Tanemura K. Suzuki T. Nishida Y. Satsumabayashi K. Horagushi T. Chem. Commun.  2004,  470 
  • 6a Cave WV. Raston CL. Chem. Commun.  2000,  2199 
  • 6b Hasson J. Migianu E. Beley M. Kirsch G. Synthesis  2004,  267 
  • 7a Xia JJ. Wang GW. Synthesis  2005,  2379 
  • 7b Fan XS. Li YZ. Zhang XY. Qu GR. Wang JJ. Hu XY. Heteroat. Chem.  2006,  17:  382 
  • 8 Xiong X. Bagley MC. Chapaneri K. Tetrahedron Lett.  2004,  45:  6121 
  • 9 Zhao L. Liang F. Bi X. Sun S. Liu Q. J. Org. Chem.  2006,  71:  1094 
  • 10 Risitano F. Grassi G. Foti F. Moraci S. Synlett  2005,  1633 
  • 11a Matsuoka Y. Ishida Y. Sasaki D. Saigo K. Tetrahedron  2006,  62:  8199 
  • 11b Deng X. Mani NS. Org. Lett.  2006,  8:  269 
  • 12 Yadav LDS. Rai VK. Tetrahedron Lett.  2006,  47:  395 
  • 13a Iavarone AT. Udekwu OA. Williams ER. Anal. Chem.  2004,  76:  3944 
  • 13b Saporito-Irwin SM. Geist RT. Gutmann DH. Biotechniques  1997,  23:  424 
  • 13c Shilton BH. Li Y. Tessier D. Thomas DY. Cygler M. Protein Sci.  1996,  5:  395 
  • 14a Sing V. Pathak R. Kanojia S. Batra S. Synlett  2005,  2465 
  • 14b Myint YY. Pasha MA. Synth. Commun.  2004,  34:  4477 
  • 15 Tajima K. Uchida M. Minami K. Osada M. Sue K. Toshiyuki N. Hattori H. Arai K. Environ. Sci. Technol.  2005,  39:  9721