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DOI: 10.1055/s-2005-872654
Silica Sulfuric Acid Catalyzed One-Pot Synthesis of α-Aminonitriles
Publication History
Publication Date:
05 August 2005 (online)
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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.
Key words
aldehyde - amine - α-aminonitrile - silica sulfuric acid - one-pot synthesis
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References
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.
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.