Sulfamic Acid Catalyzed Direct Condensation of Aldehydes, Amines, and TMSCN to α-Aminonitriles at Ambient Temperature

Abstract

A simple and efficient method has been developed for the synthesis of α-aminonitriles by a one-pot three-component ­condensation of aldehydes, amines, and trimethylsilyl cyanide in the presence of a catalytic amount of sulfamic acid at room temperature.

Key words

aldehyde - amine - α-aminonitrile - sulfamic acid - three-component reaction

References and Notes

• 1 Shafran YM. Bakulev VA. Mokrushin VS. Russ. Chem. Rev.  1989,  58:  148 
• 2a Probst KC. Jung G. Amino Acids  2006,  30:  243 
• 2b Dyker G. Angew. Chem., Int. Ed. Engl.  1997,  36:  1700 
• 3a Meyer N. Werner F. Opatz T. Synthesis  2005,  945 
• 3b Herrero S. Garcia-Lopez MT. Herranz R. J. Org. Chem.  2003,  68:  4582 
• 3c McLaughlin M. Mohareb RM. Rapoport H. J. Org. Chem.  2003,  68:  50 
• 3d Malassene R. Sanchez-Bajo L. Toupet L. Hurvois JP. Moinet C. Synlett  2002,  1500 
• 3e Abele E. Lukevics E. Heterocycles  2002,  57:  361 
• 4a Bernstein MP. Bauschlicher CW. Sandford SA. Adv. Space Res.  2004,  33:  40 
• 4b Maurel M.-C. Decout J.-L. Tetrahedron  1999,  55:  3141 
• 4c Sutherland JD. Whitfield JN. Tetrahedron  1997,  53:  11493 
• 5a Groger H. Chem. Rev.  2003,  103:  2795 
• 5b Enders D. Shilvock JP. Chem. Soc. Rev.  2000,  29:  359 
• 6a Mori Y. Kimura M. Seki M. Synthesis  2003,  2311 
• 6b Matsumoto K. Kim JC. Hayashi N. Jenner G. Tetrahedron Lett.  2002,  43:  9167 
• 6c Kobayashi S. Busujima T. Nagayama S. Chem. Commun.  1998,  981 
• 7 Spino C. Angew. Chem. Int. Ed.  2004,  43:  1764 
• 8 Kobayashi S. Ishitani H. Ueno M. Synlett  1997,  115 
• 9a Das B. Ramu R. Ravikanth B. Reddy KR. Synthesis  2006,  1419 
• 9b Royer L. De SK. Gibbs RA. Tetrahedron Lett.  2005,  46:  4595 
• 9c De SK. Gibbs RA. Synth. Commun.  2005,  35:  961 
• 9d Yadav JS. Reddy BVS. Eeshwaraiah B. Srinivas A. Tetrahedron  2004,  60:  1767 
• 9e Ranu BC. Dey SS. Hajra A. Tetrahedron  2002,  58:  2529 
• 9f Heydari A. Fatemi P. Alizadeh AA. Tetrahedron Lett.  1998,  39:  3049 
• 9g Mai K. Patil G. Tetrahedron Lett.  1984,  25:  4583 
• 10a Paraskar AS. Sudalai A. Tetrahedron Lett.  2006,  47:  5759 
• 10b Fetterly BM. Jana NK. Verkade JG. Tetrahedron  2006,  62:  440 
• 11a Hoashi Y. Okino T. Takemoto Y. Angew. Chem. Int. Ed.  2005,  44:  4032 
• 11b Tsogoeva SB. Hateley MJ. Yalalov DA. Meindl K. Weckbecker C. Huthmacher K. Bioorg. Med. Chem.  2005,  13:  5680 
• 11c Shibasaki M. Yoshikawa N. Chem. Rev.  2002,  102:  2187 
• 11d Groger H. Chem. Eur. J.  2001,  7:  5247 
• 12a Kano T. Sasaki K. Konishi T. Mii H. Maruoka K. Tetrahedron Lett.  2006,  47:  4615 
• 12b Suzuki Y. Baker A. Muramatsu K. Sato M. Tetrahedron  2006,  62:  4227 
• 13a Martinez R. Ramon DJ. Yus M. Tetrahedron Lett.  2005,  46:  8471 
• 13b Leblanc JP. Gibson HW. Tetrahedron Lett.  1992,  33:  6295 
• 13c Chakraborty TK. Reddy GV. Hussain KA. Tetrahedron Lett.  1991,  32:  7597 
• 14a Matsumoto K. Kim JC. Iida H. Hamana H. Kumamoto K. Kotsuki H. Jenner G. Helv. Chim. Acta  2005,  88:  1734 
• 14b Jenner G. Ben Salem R. Kim JC. Matsumoto K. Tetrahedron Lett.  2003,  44:  447 
• 14c Matsumoto K. Kim JC. Hayashi N. Jenner G. Tetrahedron Lett.  2002,  43:  9167 
• 15 Yadav JS. Reddy BVS. Eshwaraiah B. Srinivas M. Vishnumurthy P. New J. Chem.  2003,  27:  462 
• 16a Li Z. Ren X. Wei P. Wan H. Shi Y. Ouyang P. Green Chem.  2006,  8:  433 
• 16b Li Z. Ren X. Shi Y. Ouyang P. Synth. Commun.  2007,  37 ; in press
• 17a Li Z. Sun Y. Ren X. Li W. Shi Y. Ouyang P. Synth. Commun.  2007,  37 ; in press
• 17b Li Z. Sun Y. Ren X. Shi Y. Ouyang P. Heterocycles  2007,  71 ; in press
• 18a Rajitha B. Kumar BS. Geddy YT. Reddy PN. Sreenivasulu N. Tetrahedron Lett.  2005,  46:  8691 
• 18b Wang B. Gu YL. Luo C. Yang T. Yang LM. Suo JS. Tetrahedron Lett.  2004,  45:  3369 
• 18c Singh PR. Singh DU. Samant SD. Synlett  2004,  1909 
• 19a Philip D. Eapen A. Aruldhas G. J. Solid State Chem.  1995,  116:  217 
• 19b Canageratna M. Ott ME. Leopold KR. Chem. Phys. Lett.  1997,  281:  63 

20

Cost of sulfamic acid: 31.5 $/kg; less than one-tenth of the unit price of the least expensive catalyst Lewis acid in ref. 9, see http://www.sigmaaldrich.com/catalog/search/ (accessed 12/2006).

21

General Experimental Procedure.
A mixture of aldehyde (2.0 mmol), amine (2.0 mmol) and sulfamic acid (20 mg) in MeCN (5.0 mL) was stirred at r.t. for 20 min and then trimethylsilyl cyanide (1.6 mL, 2.4 mmol) was added. The resulting reaction mixture was stirred at r.t. for the appropriate time. After completion of the reaction (TLC, hexane-EtOAc = 1:5), sulfamic acid was filtered off, the filtrate was extracted with EtOAc (3 × 10 mL), the combined organic phase was washed with H₂O (20 mL) and sat. aq NH₄Cl (20 mL), dried over anhyd MgSO₄ and concentrated in vacuo to give the crude product, which was purified by silica gel column chromatography (hexane-EtOAc = 1: 3) to afford the pure 3a-v, all of which were thoroughly characterized.
Spectral Data of Representative Compounds.
2-(o-Toluidino)-2-phenylacetonitrile (3b): pale yellow solid; mp 71-72 [lit.^9e 72-73] °C. IR (KBr): 3365, 2237 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.20 (s, 3 H), 3.38 (br d, J = 8.1 Hz,1 H, NH), 5.45 (d, J = 8.1 Hz, 1 H), 6.80 (t, J = 7.9 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 1 H), 7.20 (d, J = 7.9 Hz, 1 H), 7.40-7.50 (m, 3 H), 7.50 (d, J = 8.0 Hz, 2 H). ESI-HRMS: m/z calcd for C₁₅H₁₅N₂ ⁺ [M + H]⁺: 223.1235; found: 223.1231.
2-Phenyl-2-(pyrrolidin-1-yl)acetonitrile (3l): colorless oil. IR (neat): 2223 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.75 (m, 4 H), 2.71-2.58 (m, 4 H), 5.03 (s, 1 H), 7.43-7.31 (m, 3 H), 7.53-7.49 (m, 2 H). ESI-HRMS: m/z calcd for C₁₂H₁₅N₂ ⁺ [M+H]⁺: 187.1235; found: 187.1237.
2-(Benzylamino)-2-(3-methoxyphenyl)acetonitrile (3r): colorless oil. IR (neat): 3323, 2243 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.84 (br s, 1 H), 3.77 (s, 3 H), 3.94 (q, J = 13.0 Hz, 2 H), 4.66 (s, 1 H), 6.86 (dd, J = 2.5, 9.4 Hz, 1 H), 7.23 (m, 2H), 7.83-7.29 (m, 6 H). ESI-HRMS: m/z calcd for C₁₆H₁₇N₂O⁺ [M + H]⁺: 253.1341; found: 253.1338.
2-(Benzylamino)-3-methylbutanenitrile (3v): colorless oil. IR (neat): 3347, 2228 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.07 (d, J = 6.7 Hz, 3 H), 1.08 (d, J = 6.8 Hz, 3 H), 1.55 (br s, 1 H), 1.98 (m, 1 H), 3.25 (d, J = 6.0 Hz, 1 H), 3.79 (d, J = 13.0 Hz, 1 H), 4.06 (d, J = 13.0 Hz, 1 H), 7.36-7.23 (m, 5 H). ESI-HRMS: m/z calcd for C₁₂H₁₇N₂ ⁺ [M + H]⁺: 189.1392; found: 189.1390.