One-Pot Synthesis of Cationic Amphiphiles from n-Alcohols and Allyl Alcohols

Abstract

A novel, efficient one-pot method has been developed to synthesize amphiphiles such as N-alkylated/N-allylated triethyl­amines and pyridinium salts for the first time from n-alcohols and naturally occurring terpenes (allyl alcohols) in good yields. These amphiphiles have got industrial application as surfactants, DNA carriers, and other biological applications. The DNA delivery efficacy and cytotoxicity of N-alkylated and N-allylated triethylamine and pyridinium salts were studied.

Key words

one-pot synthesis - n-alcohols - allyl alcohols - amphiphiles - DNA delivering agents - surfactants - cytotoxic agents - trialkylamine salts - pyridinium salts

References and Notes

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39

Representative Procedure for the Preparation of N , N , N -Triethyltridecan-1-aminium Chloride (2a) A solution of 1a (5.0 g, 25.0 mmol) in CH₂Cl₂ (10 mL) and Et₃N (10 mL) was added dropwise to a stirred solution of POCl₃ (7.6 g, 50.0 mmol) in dichloromethane (10 mL) at 0 ˚C. After stirring the solution for 1 h, a solution of N,N-diethylethanolamine (4.4 g, 37.5 mmol) in Et₃N (10 mL) was added. The whole reaction mixture was stirred for 1 h at 0 ˚C followed by 2 h at r.t. Water (5 mL) was added dropwise to the reaction mixture and stirred for additional 30 min. Then, 10 mL of 10% solution of citric acid and MeOH-H₂O (1:1) was added to the reaction mixture and extracted into CHCl₃ (3 × 100 mL). The combined organic layer was washed with MeOH-H₂O (1:1) and dried over anhyd Na₂SO₄. The solvent was evaporated under reduced pressure, and the crude product was chromatographed on silica gel as stationary phase and CHCl₃-MeOH-H₂O (91.5:8:0.5) as mobile phase to afford the compound 2a (4.26 g, 60%). ^¹H NMR (300 MHz, CDCl₃): δ = 3.60-3.03 (m, 8 H), 1.43 (m, 2 H), 1.18-1.04 (m, 29 H), 0.70 (t, J = 6.2 Hz, 3 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 57.6, 53.6 (3 C), 32.2, 30.0 (6 C), 29.8, 29.7, 29.5, 26.8, 26.1, 23.0, 22.2, 14.4. ESI-MS:
m/z = 284.4.

40

Representative Procedure for the Preparation of 1-Nonylpyridinium Chloride (2f) A solution of 1f (5 g, 26.9 mmol) in CH₂Cl₂ (10 mL) and pyridine (10 mL) was added dropwise to the stirred solution of POCl₃ (8.25 g, 53.7 mmol) in CH₂Cl₂ (10 mL) at 0 ˚C. After stirring for 1 h, a solution of N,N-diethylethanolamine (4.7 g, 40.3 mmol) in pyridine (10 mL) was then added at 0 ˚C. The whole reaction mixture was stirred for 1 h at 0 ˚C followed by 2 h at r.t. Water (5 mL) was added dropwise to the reaction mixture and stirred for additional 30 min. Then, 10 mL of 10% solution of citric acid and MeOH-H₂O (1:1) was added in the reaction mixture and extracted into CHCl₃ (2 × 100 mL). The combined organic layer was washed with MeOH-H₂O (1:1) and dried over anhyd Na₂SO₄. The solvent was evaporated under reduced pressure, and the crude product was chromatographed on silica gel as stationary phase and CHCl₃-MeOH-H₂O (89.5:10:0.5) as mobile phase to afford the compound 2f (3.67 g, 55%). ^¹H NMR (200 MHz, CD₃OD): δ = 9.04 (d, J = 5.8 Hz, 2 H), 8.61 (t, J = 7.7 Hz, 1 H), 8.13 (t, J = 6.9 Hz, 2 H), 4.66 (t, J = 7.6 Hz, 2 H), 2.03 (t, J = 6.9 Hz, 2 H), 1.38-1.28 (m, 18 H), 0.89 (t, J = 6.7 Hz, 3 H). ^¹³C NMR (50 MHz, CD₃OD): δ = 145.9, 145.0 (2 C), 128.6 (2 C), 62.2, 32.1, 31.5, 29.7 (2 C), 29.6, 29.5, 29.1, 26.2, 22.7, 13.5. ESI-MS: m/z = 248.3.