An Efficient and Fast Procedure for the Preparation of 2-Nitrophenylamines under Microwave Conditions

Abstract

2-Nitrophenylamines were prepared in good yields from 2-chloronitrobenzen (or 2-fluoronitrobenzene) and amines in the presence of anhydrous potassium fluoride under microwave irradiation and solvent free conditions.

Key words

aminations - amines - microwave irradiation - nucleophilic aromatic substitution

References

• 1a Anon UK. Expert Opinion on Therapeutic Patents  2002,  12:  601 
• 1b Clande P. Carine E. Stephane R. Gerald B. Jean-Claudde GB. Gerard H. J. Chem. Soc., Dalton Trans.  2000,  3999 
• 2a Lantz RL. Obellianne P. Bull. Soc. Chim. Fr.  1956,  311 
• 2b John HG. J. Chem. Soc., Perkin Trans. 1  1988,  1331 
• 3a Wolfe JP. Tomori H. Sadighi JP. Yin J. Buchwald SL. J. Org. Chem.  2000,  65:  1158 
• 3b Emoto T. Kubosaki N. Yamagiwa T. Kamilawa T. Tetrahedron Lett.  2000,  41:  355 
• 4 Kulagowski JJ. Rees CW. Synthesis  1980,  215 
• 5 Zhu YF. Lin GQ. Chen YQ. Synthesis  1990,  430 
• 6a Abramovich RA. Org. Prep. Proced. Int.  1991,  23:  683 
• 6b Bose DS. Jayalakshmi B. J. Org. Chem.  1999,  64:  1713 
• 7 Loupy A. Petit A. Hamelin J. Texier-Boullet F. Jacquault P. Mathe D. Synthesis  1998,  1213 
• 8a Salmoria GV. Dall’Ogllo E. Zucco C. Tetrahedron Lett.  1998,  39:  2471 
• 8b Cherng YJ. Tetrahedron  2002,  58:  887 
• 8c Cherng YJ. Tetrahedron  2002,  58:  1125 
• 8d Cherng YJ. Tetrahedron  2002,  58:  4931 
• 9a Kidwai M. Sapra P. Dave B. Synth. Commun.  2000,  30:  4479 
• 9b Chaouchi M. Loupy A. Marque S. Petit A. Eur. J. Org. Chem.  2002,  1278 
• 10 Grigor’ev AD. Dmitrieva NM. EI’tsov AV. Ivanov AS. Panarina AE. Sokolova NB. Russ. J. Gen. Chem.  1997,  67:  981 
• 11a Perreux L. Loupy A. Tetrahedron  2001,  57:  9199 
• 11b Lidstrom P. Tierney J. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 

12

General Procedure: The preparation of N-(4′-methoxy-phenyl)-2-nitrophenylamine (3a) is representative for all synthesis.
p-Methoxy phenylamine (1.1 mmol), anhyd KF (1.1 mmol) and K₂CO₃ (1.1 mmol) were well powdered with a mortar and pestle. 2-Chloronitrobenzene (or 2-fluoronitrobenzene) (1.1 mmol) was then added to the mixture and mixed well in a glass vial. After irradiation under microwave (90 W), the mixture was treated with water and CH₂Cl₂. The organic layer was washed with 10% HCl and brine. The CH₂Cl₂ solution was dried over anhyd Na₂SO₄, evaporated and crystallized from petroleum ether (bp 60-90 °C) to give orange crystals [mp 83-86 °C (lit. ref. [4] : mp 89 °C)]. ¹H NMR (CDCl₃, 300MHz): δ = 3.85 (s, 3 H, OCH₃₎, 6.72-8.19 (8 H, aromatic H), 9.41 (s, br, 1 H, NH). MS (EI) m/z = 244 [M⁺], 229 [M⁺ - 15].