Silica Sulfuric Acid Catalyzed One-Pot Synthesis of α-Aminonitriles

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 silica sulfuric acid at room temperature. The silica sulfuric acid is reusable and could be ­applied in subsequent reactions with comparable activity.

aldehyde - amine - α-aminonitrile - silica sulfuric acid - one-pot synthesis

References

1 Shafran YM. Bakulev VA. Mokrushin VS. Russ. Chem. Rev.  1989,  58:  148 

2 Weinstock LM. Davis P. Handelsman B. Tull R. J. Org. Chem.  1967,  32:  2823 

3 Matier WL. Owens DA. Comer WT. Deitchman D. Ferguson HC. Seidehamel RJ. Young JR. J. Med. Chem.  1973,  16:  901 

4 Strecker A. Ann. Chem. Pharm.  1850,  75:  27 

5 Harusawa S. Hamada Y. Shioiri T. Tetrahedron Lett.  1979,  20:  4663 

6 Mai K. Patil G. Tetrahedron Lett.  1984,  25:  4583 

7 Iyer MS. Gigstad KM. Namdev ND. Lipton M. J. Am. Chem. Soc.  1996,  118:  4910 

8 Sigman MS. Jacobsen EN. J. Am. Chem. Soc.  1998,  120:  5315 

9 Takamura M. Hamashima Y. Usuda H. Kanai M. Shibasaki M. Angew. Chem. Int. Ed.  2000,  39:  1650 

10 Chakraborty TK. Reddy GV. Hussain KA. Tetrahedron Lett.  1991,  32:  7597 

11 Leblanc J. Gibson HW. Tetrahedron Lett.  1992,  33:  6295 

12 Hedari A. Fatemi P. Alizadeh AA. Tetrahedron Lett.  1998,  39:  3049 

13 Hajipour AR. Mirjalili BBF. Zarei A. Khazdooz L. Ruoho AE. Tetrahedron Lett.  2004,  45:  6607 

14 Zolfigol MA. Tetrahedron  2001,  57:  9509 

15 Zolfigol MA. Bamoniri A. Synlett  2002,  1621 

16 Zolfigol MA. Madrakian E. Ghaemi E. Molecules  2002,  7:  734 

17 Mirjalili BF. Zolfigol MA. Bamoniri A. Molecules  2002,  7:  751 

18 Zolfigol MA. Shirini F. Choghamarani AG. Mohammadpoor-Baltork I. Green Chem.  2002,  4:  562 

19 Salehi P. Dabiri M. Zolfigol MA. Fard MAB. Tetrahedron Lett.  2003,  44:  2889 

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Preparation of Silica Sulfuric Acid.
A 50-mL round-bottomed flask was charged with silica gel (15 g) and a magnetic stirrer. Chlorosulfonic acid (5.83 g, 50 mmol) was added dropwise at r.t. The HCl gas was conducted over an adsorbing solution. After the addition was complete, the resulting mixture was stirred until no HCl gas was evolved from the vessel. The product (silica sulfuric acid) of 19.0 g was obtained.

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Typical Reaction Procedure.
A mixture of benzaldehyde (1 mmol), aniline (1 mmol), trimethylsilyl cyanide (1.5 mmol) and silica sulfuric acid (95 mg, 0.25 mmol) in CH₂Cl₂ (2 mL) was stirred at r.t. for an appropriate time. After completion of the reaction, as indicated by TLC, the reaction mixture was filtered and washed with CH₂Cl₂. The combined organic layers were washed with brine, dried over anhyd Na₂SO₄, concentrated in vacuo and purified by column chromatography on silica gel to furnish 2-(N-anilino)-2-phenylacetonitrile (3a) in 88%; mp 72-73 °C. IR (KBr): ν = 3369, 2236, 1606, 1498 cm^-1. ¹H NMR (CDCl₃): δ = 7.69-7.58 (m, 2 H), 7.48-7.40 (m, 3 H), 7.29-7.25 (m, 2 H), 6.92 (d, J = 7.8 Hz, 1 H), 6.74 (d, J = 7.8 Hz, 2 H), 5.41 (d, J = 8.4 Hz, 1 H), 4.02 (d, J = 8.4 Hz, 1 H). HRMS: m/z calcd for C₁₄H₁₂N₂: 208.1000; found: 208.1004.
2-(N-Benzylamino)-2-(4-chlorophenyl)acetonitrile (3k): colorless oil. IR (KBr): ν = 3312, 2238, 1596, 1468 cm^-1. ¹H NMR (CDCl₃): δ = 7.49 (d, J = 8.4 Hz, 2 H), 7.39-7.28 (m, 7 H), 4.73 (s, 1 H), 3.99 (AB q, J = 12.8 Hz, 2 H). HRMS: m/z calcd for C₁₅H₁₃ClN₂: 256.0767; found: 256.0764.
2-(N-Benzylamino)-2-(4-methoxyphenyl)acetonitrile (3l): colorless oil. IR (KBr): ν = 3325, 3031, 2923, 2231, 1598, 1491 cm^-1. ¹H NMR (CDCl₃): δ = 7.44 (d, J = 8.8 Hz, 2 H), 7.41-7.29 (m, 5 H), 6.92 (d, J = 8.4 Hz, 2 H), 4.70 (s, 1 H), 4.00 (AB q, J = 12.8 Hz, 2 H), 3.82 (s, 3 H), 1.83 (s, 1 H). HRMS: m/z calcd for C₁₆H₁₆N₂O: 252.1263; found: 252.1259.
2-(N-4-Chloroanilino)-2-(4-chlorophenyl)acetonitrile (3m): mp 122-124 °C. IR (KBr): ν = 3307, 3064, 2237, 1595, 1491 cm^-1. ¹H NMR (CDCl₃): δ = 7.54 (d, J = 8.8 Hz, 2 H), 7.44 (d, J = 8.4 Hz, 2 H), 7.23 (d, J = 8.4 Hz, 2 H), 6.69 (d, J = 9.2 Hz, 2 H), 5.38 (d, J = 8.4 Hz, 1 H), 4.05 (d, J = 8.4 Hz, 1 H). HRMS: m/z calcd for C₁₄H₁₀Cl₂N₂: 276.0221; found: 276.0219.
2-(N-4-Chloroanilino)-2-(4-methoxyphenyl)acetonitrile (3o): mp 108-110 °C. IR (KBr): ν = 3328, 3032, 2237, 1596, 1493 cm^-1. ¹H NMR (CDCl₃): δ = 7.49 (d, J = 8.8 Hz, 2 H), 7.22 (d, J = 8.8 Hz, 2 H), 6.97 (d, J = 8.4 Hz, 2 H), 6.69 (d, J = 8.8 Hz, 2 H), 5.31 (d, J = 7.6 Hz, 1 H), 4.00 (d, J = 7.6 Hz, 1 H), 3.84 (s, 3 H). HRMS: m/z calcd for C₁₅H₁₃ClN₂O: 272.0716; found: 272.0717.