General Procedure for the Synthesis of N-Alkyl-Pyridinium Bromides (1, 2, 3, 4 and 5)
Supplementary Information
General procedure for the synthesis of N-alkyl-pyridinium bromides (1, 2, 3, 4 and 5)
The alkyl bromide (0.01 mol) was heated under reflux conditions in pyridine (100 mL, 1.24 mol) for 2-3 hours. The excess pyridine was removed under reduced pressure to yield the crude material. The crude products that were oils (1, 2 and 3) were dissolved in a minimal volume of water and washed three times with hexane. The water was removed under reduced pressure and the resulting oil dissolved in CHCl3 and dried over anhydrous magnesium sulfate. After filtration the CHCl3 was removed under reduced pressure to give the pure compounds, where 3 became solid. The crude products that were solid (4 and 5) were dissolved in minimal amounts of CHCl3 and dripped into stirring ethyl acetate. The precipitate formed was isolated by filtration to yield pure white powders of the N-alkylpyridinium bromides. These compounds were crystallised by slow evaporation of a saturated water solution or from heated acetone.
Proton labelling scheme
N-Octylpyridinium bromide, (1)
Clear oil, 2.67 g, (98%), 1H NMR: δ 0.80 (ω-CH3, 3H, t, J = 7.0 Hz), 1.27 ((CH2)5, 10H, m), 2.01 (β-CH2, 2H, qt, J = 7.5 Hz), 4.96 (α-CH2, 2H, t, J = 7.5 Hz), 8.14 (b-py, 2H, t, J = 7.0 Hz), 8.51 (c-py, 1H, t, J = 8.0 Hz), 9.53 (a-py, 2H, d, J = 5.5 Hz); 13C NMR: δ 14.0, 22.5, 26.0, 28.9, 28.9, 31.6, 32.0, 62.0, 128.5, 145.1, 145.2; IR (neat film), ν (cm-1): 3045 (C-H py), 2914 (υas CH2), 2849 (υs CH2), 1631 (C-N+-C), 1468 (C=N), 1211 (C-C), 777 (py ring), 718 (py ring), 683 (py ring), 665 (py ring); Anal. Calcd. (%) for C13H22BrN: C; 57.4, H; 8.2, N; 5.2, Found: C; 57.0, H; 8.2, N; 5.1.
N-Decylpyridinium bromide, (2)
Clear solid, 2.74 g, (91%), M.P. 22.0 – 23.0 oC; 1H NMR: δ 0.86 (ω-CH3, 3H, t, J = 7.0 Hz), 1.32 ((CH2)7, 14H, m), 2.03 (β-CH2, 2H, qt, J = 7.5 Hz), 5.01 (α-CH2, 2H, t, J = 7.5 Hz), 8.13 (b-py, 2H, t, J = 7.0 Hz), 8.51 (c-py, 1H, t, J = 8.0 Hz), 9.48 (a-py, 2H, d, J = 5.5 Hz); 13C NMR: δ 14.1, 22.7, 26.1, 29.1, 29.3, 29.4, 29.5, 31.8, 32.1, 62.3, 128.4, 145.1, 145.2; IR (neat film), ν (cm-1): 3045 (C-H py), 2918 (υas CH2), 2852 (υs CH2), 1636 (C-N+-C), 1468 (C=N), 1211 (C-C), 777 (py ring), 718 (py ring), 686 (py ring), 665 (py ring); Anal. Calcd. (%) for C15H26BrN: C; 60.0, H; 8.7, N; 4.7, Found: C; 59.9, H; 8.9, N; 4.4.
N-Dodecylpyridinium bromide, (3)
White solid, 3.12 g, (96%), M.P. 76.5 – 78.0 oC; 1H NMR: δ 0.85 (ω-CH3, 3H, t, J = 7.0 Hz), 1.32 ((CH2)9, 18H, m), 2.02 (β-CH2, 2H, qt, J = 7.5 Hz), 4.99 (α-CH2, 2H, t, J = 7.5 Hz), 8.14 (b-py, 2H, t, J = 6.0 Hz), 8.51 (c-py, 1H, t, J = 8.0 Hz), 9.46 (a-py, 2H, d, J = 5.5 Hz), 13C NMR: δ 14.1, 22.7, 26.1, 29.1, 29.3, 29.4, 29.5, 29.6, 29.6, 31.9, 32.0, 62.3, 128.5, 145.1, 145.2; IR (neat film), ν (cm-1): 3047 (C-H py), 2921 (υas CH2), 2853 (υs CH2), 1637 (C-N+-C), 1470 (C=N), 1211 (C-C), 777 (py ring), 718 (py ring), 686 (py ring), 665 (py ring); Anal. Calcd. (%) for C17H30BrN: C; 62.2, H; 9.2, N; 4.3, Found: C; 62.0, H; 9.3, N; 4.1.
N-Tetradecylpyridinium bromide, (4)
White solid, 3.57 g, (100%), M.P. 60.5 – 63.0 oC;1H NMR: δ 0.86 (ω-CH3, 3H, t, J = 7.0 Hz), 1.30 ((CH211, 22H, m), 2.03 (β-CH2, 2H, qt, J = 7.5 Hz), 5.00 (α-CH2, 2H, t, J = 7.5 Hz), 8.13 (b-py, 2H, t, J = 6.5 Hz), 8.49 (c-py, 1H, t, J = 7.8 Hz), 9.44 (a-py, 2H, d, J = 5.5 Hz), 13C NMR: δ 14.2, 22.7, 26.1, 29.1, 29.4, 29.5, 29.6, 29.7, 29.7, 29.7, 29.7, 32.0, 32.0, 62.3, 128.4, 145.1, 145.2; IR (neat film), ν (cm-1): 3045 (C-H py), 2912 (υas CH2), 2847 (υs CH2), 1636 (C-N+-C), 1471 (C=N), 1211 (C-C), 777 (py ring), 717 (py ring), 687 (py ring), 667 (py ring), Anal. Calcd. (%) for C19H34BrN: C; 64.0, H; 9.6, N; 3.9, Found: C; 63.3, H; 9.6, N; 3.6.
N-Hexadecylpyridinium bromide, (5)
White solid, 3.77 g, (98%), M.P. 68.5 – 72.0 oC;1H NMR: δ 0.85 (ω-CH3, 3H, t, J = 7.0 Hz), 1.29 ((CH2)13, 26H, m), 2.02 (β-CH2, 2H, qt, J = 7.5 Hz), 5.00 (α-CH2, 2H, t, J = 7.5 Hz), 8.13 (b-py, 2H, t, J = 7.0 Hz), 8.51 (c-py, 1H, t, J = 7.8 Hz), 9.46 (a-py, 2H, d, J = 5.5 Hz); 13C NMR: δ 14.2, 22.7, 26.1, 29.1, 29.4, 29.5, 29.6, 29.7, 29.7, 29.7, 29.7, 29.7, 29.7, 31.9, 32.0, 62.3, 128.4, 145.1, 145.2; IR (neat film), ν (cm-1): 3046 (C-H py), 2912 (υas CH2), 2847 (υs CH2), 1640 (C-N+-C), 1471 (C=N), 1210 (C-C), 777 (py ring), 717 (py ring), 686 (py ring), 665 (py ring); IR (neat film), ν (cm-1): 3046 (C-H py), 2912 (υas CH2), 2847 (υs CH2), 1640 (C-N+-C), 1471 (C=N), 1210 (C-C), 777 (py ring), 717 (py ring), 686 (py ring), 665 (py ring), Anal. Calcd. (%) for C21H38BrN: C; 65.6, H; 10.0, N; 3.6, Found: C; 65.6, H; 9.9, N; 3.6.
General procedure for the synthesis of N-alkyl-4-hydroxymethylpyridinium bromides (6, 7, 8, 9 and 10)
The N-alkyl-4-hydroxymethylpyridinium bromides were synthesised from 4-hydroxylmethylpyridine (0.97 g, 0.01 mol) and a two-fold excess of the alkyl bromide (0.02 mol). The mixture was heated under reflux in acetonitrile for 2.5 hours. The solvent was removed under reduced pressure and the crude material dissolved in a minimal amount of water. This solution was washed three times with hexane and the water removed under reduced pressure. The resulting crude material was then dissolved in CHCl3 and dried with anhydrous magnesium sulfate. After filtration, the CHCl3 was removed under reduced pressure yielding the pure materials that were solid at room temperature except 6, which was an oil.
Proton labelling scheme
N-Octyl-4-hydroxymethylpyridinium bromide, (6)
Clear oil, 2.90 g, (96%), 1H NMR: δ 0.82 (ω-CH3, 3H, t, J = 7.0 Hz), 1.27 ((CH2)x, 10H, m), 1.98 (β-CH2, 2H, qt, J = 7.5 Hz), 4.77 (α-CH2, 2H, t, J = 7.5 Hz), 4.91 (c-CH2, 2H, s), 8.08 (b-py, 2H, d, J = 7.0 Hz), 9.07 (a-py, 1H, d, J = 7.0 Hz); 13C NMR: δ 14.0, 22.5, 26.1, 29.0, 31.6, 31.8, 31.9, 61.4, 61.8, 125.4, 143.8, 163.7; IR (neat film), ν (cm-1): 3358 (-OH), 3028 (C-H py), 2915 (υas CH2), 2851 (υs CH2), 1632 (C-N+-C), 1457 (C=N), 1158 (C-C), 777 (py ring), 719 (py ring), 685 (py ring), 662 (py ring); Anal. Calcd. (%) for C14H24BrNO: C; 55.6, H; 8.0, N; 4.6, Found: C; 55.5, H; 7.9, N; 4.6.
N-Decyl-4-hydroxymethylpyridinium bromide, (7)
White crystalline solid, 3.25 g, (98%), M.P. 54.0 – 55.5 oC;1H NMR: δ 0.86 (ω-CH3, 3H, t, J = 7.0 Hz), 1.30 ((CH2)x, 14H, m), 1.99 (β-CH2, 2H, qt, J = 7.5 Hz), 4.76 (α-CH2, 2H, t, J = 7.5 Hz), 4.93 (c-CH2, 2H, s), 8.09 (b-py, 2H, d, J = 7.0 Hz), 9.03 (a-py, 1H, d, J = 7.0 Hz); 13C NMR: δ 14.2, 22.7, 26.2, 29.1, 29.3, 29.4, 29.5, 29.6, 29.6, 31.0, 31.8, 31.9, 61.6, 61.9, 125.5, 143.7; IR (neat film), ν (cm-1): 3360 (-OH), 3032 (C-H py), 2925 (υas CH2), 2853 (υs CH2), 1637 (C-N+-C), 1458 (C=N), 1164 (C-C), 777 (py ring), 718 (py ring), 686 (py ring), 663 (py ring). Anal. Calcd. (%) for C16H28BrNO: C; 58.2, H; 8.5, N; 4.2, Found: C; 58.2, H; 8.5, N; 4.3.
N-Dodecyl-4-hydroxymethylpyridinium bromide, (8)
White crystalline solid, 3.51 g, (98%), M.P. 69.0 – 71.0 oC;1H NMR: δ 0.86 (ω-CH3, 3H, t, J = 7.0 Hz), 1.30 ((CH2)x, 18H, m), 1.99 (β-CH2, 2H, qt, J = 7.5 Hz), 4.76 (α-CH2, 2H, t, J = 7.5 Hz), 4.92 (c-CH2, 2H, s), 8.09 (b-py, 2H, d, J = 7.0 Hz), 9.03 (a-py, 1H, d, J = 7.0 Hz). 13C NMR: δ 14.2, 22.7, 26.2, 29.1, 29.4, 29.4, 29.5, 29.6, 29.6, 31.0, 31.8, 31.9, 61.6, 61.9, 125.5, 143.7, 164.0; IR (neat film), ν (cm-1): 3037 (C-H py), 2918 (υas CH2), 2851 (υs CH2), 1638 (C-N+-C), 1467 (C=N), 1225 (C-C), 761 (py ring), 719 (py ring), 704 (py ring); Anal. Calcd. (%) for C18H32BrNO: C; 60.3, H; 9.0, N; 3.9, Found: C; 60.0, H; 8.8, N; 4.1.
N-Tetradecyl-4-hydroxymethylpyridinium bromide, (9)
White crystalline solid, 3.81 g, (99%), M.P. 80.0 – 81.0 oC;1H NMR: δ 0.86 (ω-CH3, 3H, t, J = 7.0 Hz), 1.23 ((CH2)x, 22H, m), 1.99 (β-CH2, 2H, qt, J = 7.5 Hz), 4.77 (α-CH2, 2H, t, J = 7.5 Hz), 4.92 (c-CH2, 2H, s), 8.09 (b-py, 2H, d, J = 7.0 Hz), 9.05 (a-py, 1H, d, J = 7.0 Hz); 13C NMR δ 14.2, 22.7, 26.2, 29.1, 29.4, 29.4, 29.6, 29.7, 29.7, 31.0, 31.8, 31.9, 61.6, 61.9, 125.5, 143.7, 164.0; IR (neat film), ν (cm-1): 3037 (C-H py), 2918 (υas CH2), 2851 (υs CH2), 1638 (C-N+-C), 1467 (C=N), 1225 (C-C), 761 (py ring), 719 (py ring), 704 (py ring); Anal. Calcd. (%) for C20H36BrNO: C; 62.2, H; 9.4, N; 3.6, Found: C; 62.4, H; 9.6, N; 3.6.
N-Hexadecyl-4-hydroxymethylpyridinium bromide, (10)
White crystalline solid, 4.10 g, (99%), M.P. 86.0 – 88.0 oC;1H NMR: δ 0.86 (ω-CH3, 3H, t, J = 7.0 Hz), 1.28 ((CH2)x, 26H, m), 1.98 (β-CH2, 2H, qt, J = 7.5 Hz), 4.76 (α-CH2, 2H, t, J = 7.5 Hz), 4.92 (c-CH2, 2H, s), 8.09 (b-py, 2H, d, J = 7.0 Hz), 9.03 (a-py, 1H, d, J = 7.0 Hz); 13C NMR δ 14.3, 22.9, 26.4, 29.3, 29.6, 29.6, 29.8, 29.9, 29.9, 29.9, 32.0, 32.1, 32.1, 61.7, 62.1, 125.6, 143.9, 164.1; IR (neat film), ν (cm-1): 3037 (C-H py), 2915 (υas CH2), 2853 (υs CH2), 1638 (C-N+-C), 1472 (C=N), 1258 (C-C), 753 (py ring), 723 (py ring), 706 (py ring); Anal. Calcd. (%) for C22H40BrNO: C; 63.8, H; 9.7, N; 3.4, Found: C; 63.8, H; 10.0, N; 3.4.
General procedure for the synthesis of N-alkyl-N-N-N-trimethylammonium bromides (11 and 12)
The appropriate alkyl bromide (0.01 mol) was added to an aqueous solution of trimethylamine (26% w/v water, 20.1 mL, 0.12 mol) with a minimal amount of acetonitrile to dissolve the alkyl bromide. This was stirred at 60 oC overnight under positive pressure (using N2) to prevent the escape of trimethylamine from solution. After this time, the acetonitrile, water and excess trimethylamine was removed under reduced pressure. For the first 20 minutes, this was done at 0.8 atm at 40 oC with the vacuum running through a water solution and a liquid nitrogen trap to collect the excess trimethylamine. After this time, the vacuum was strengthened the temperature was increased to 80 oC to remove the water and acetonitrile using CH2Cl2 as an azeotrope. The resulting oils were dissolved in water and washed with ethyl acetate. The water was then removed under reduced pressure using CH2Cl2 as an azeotrope. The remaining water could be removed by redissolving the product in CHCl3 and drying with anhydrous magnesium sulfate. The CHCl3 was removed under reduced pressure to yield the pure products.
Proton labelling scheme
N-Octyl-N,N,N-trimethylammonium bromide, (11)
Clear oil, 2.03 g, (81%), 1H NMR: δ 0.83 (ω-CH3, 3H, t, J = 7.0 Hz), 1.36 ((CH2)5, 10H, m), 1.76 (β-C2, 2H, qt, J = 7.5 Hz), 3.48 (a-CH3, 6H, s), 3.61 (α-CH2, 2H, J = 7.5 Hz); 13C NMR: δ 14.1, 22.7, 23.3, 26.2, 29.5, 29.6, 31.9, 53.4, 53.4, 53.4, 66.9; IR (neat film), ν (cm-1): 3018 (N+-R), 2961 (υas CH2), 2861 (υs CH2), 1631 (C-N+-C), 1472 (C=N); Anal. Calcd. (%) for C11H26BrN: C; 52.4, H; 10.4, N; 5.6, Found: C; 51.6; H; 10.4, N; 5.4.
N-Decyl-N,N,N-trimethylammonium bromide, (12)
Clear oil, 2.54 g, (91%), 1H NMR: δ 0.82 (ω-CH3, 3H, t, J = 7.0 Hz), 1.34 ((CH2)7, 14H, m), 1.75 (β-C2, 2H, qt, J = 7.5 Hz), 3.48 (a-CH3, 6H, s), 3.61 (α-CH2, 2H, J = 7.5 Hz); 13C NMR: δ 14.1, 22.7, 23.3, 26.2, 29.3, 29.4, 29.5, 29.6, 31.9, 53.4, 53.4, 53.4, 66.9; IR (neat film), ν (cm-1): 3016 (N+-R), 2961 (υas CH2), 2863 (υs CH2), 1629 (C-N+-C), 1472 (C=N); Anal. Calcd. (%) for C13H30BrN: C; 55.7, H; 10.8, N; 5.0, Found: C; 55.8, H; 10.9, N; 4.9.
General procedure for the synthesis of N-alkyl-N-(2-hydroxyethyl)-N,N-dimethylammonium bromides (16, 17, 18, 19 and 20)
The appropriate alkyl bromide (0.04 mol) and dimethylethanolamine (0.89 g, 0.01 mol) were dissolved in ~20 mL 3:1 v/v CHCl3 : CH3OH and reacted under reflux conditions for 3 to 4 hours. The resulting solution was removed from the heat and concentrated under reduced pressure. The crude materials of those compounds with longer alkyl chains (17, 18, 19 and 20) were dissolved in a small amount of CHCl3 and precipitated by addition to ethyl acetate. The resulting solid material was filtered and recrystallised from acetone and dry methanol and filtered to give the pure compounds. The shorter chain derivatives (15 and 16) had the solvent removed under reduced pressure and were redissolved in water. This solution was washed with ethyl acetate and the aqueous layer concentrated under reduced pressure using CH2Cl2 as an azeotrope. The remaining oil was then dissolved in CHCl3 which was dried over anhydrous magnesium sulfate and the CHCl3 removed under reduced pressure to afford the pure oils.
Proton labelling scheme
N-Octyl-N-(2-hydroxyethyl)-N,N-dimethylammonium bromide, (16)
Clear oil, 2.70 g, (96%), 1H NMR: δ 0.86 (ω-CH3, 3H, t, J = 7.0 Hz), 1.27 ((CH2)5, 10H, m), 1.74 (β-CH2, 2H, qt, J = 7.0 Hz), 3.35 (a-CH3, 6H, s), 3.53 (α-CH2, 2H, m), 3.74 (b-CH2, 2H, m), 4.12 (c-CH2, 2H, bs), 5.01 (-OH, 1H, bs); 13C NMR: δ 13.8, 22.3, 22.6, 25.7, 25.8, 26.4, 31.1, 52.0, 55.7, 55.7, 65.5, 65.8; IR (neat film), ν (cm-1): 3332 (O-H stretch), 3014 (N+-R), 2955 (υas CH2), 2856 (υs CH2), 1631 (C-N+-C), 1467 (C=N), 1420 (C-O), 1087 (C-C); Anal. Calcd. (%) for C12H28BrNO : C; 51.1, H; 10.0, N; 5.0, Found: C; 50.8, H; 9.8, N; 4.9.
N-Decyl-N-(2-hydroxyethyl)-N,N-dimethylammoniumbromide, (17)
White solid, 3.00 g, (97%), M.P. 167.0 – 168.0 oC;1H NMR: δ 0.87 (ω-CH3, 3H, t, J = 7.0 Hz), 1.27 ((CH2)7, 14H, m), 1.75 (β-CH2, 2H, qt, J = 7.5 Hz), 3.37 (a-CH3, 6H, s), 3.53 (α-CH2, 2H, m), 3.75 (b-CH2, 2H, m), 4.14 (c-CH2, 2H, bs), 5.01 (-OH, 1H, s); 13C NMR: δ 14.2, 22.7, 22.9, 26.3, 29.2, 29.3, 29.4, 29.5, 31.9, 52.2, 56.0, 56.0, 65.8, 66.3; IR (neat film), ν (cm-1): 3356 (O-H stretch), 3014 (N+-R), 2924 (υas CH2), 2854 (υs CH2), 1637 (C-N+-C), 1466 (C=N), 1420 (C-O), 1087 (C-C); Anal. Calcd. (%) for C14H32BrNO: C; 54.2, H; 10.4, N; 4.5, Found: C; 54.2, H; 10.2, N; 4.5.
N-Dodecyl-N-(2-hydroxyethyl)-N,N-dimethylammonium bromide, (18)
White solid, 3.37 g, (100%), M.P. 192.0 – 196.0 oC; 1H NMR: δ 0.88 (ω-CH3, 3H, t, J = 7.0 Hz ), 1.29 ((CH2)9, 18H, m), 1.75 (β-CH2, 2H, qt, J = 7.5 Hz), 3.37 (a-CH3, 6H, s), 3.53 (α-CH2, 2H, m), 3.76 (b-CH2, 2H, m), 4.15 (c-CH2, 2H, bs), 5.00 (-OH, 1H, s); 13C NMR: δ 14.2, 22.7, 23.0, 26.3, 29.2, 29.4, 29.4, 29.5, 29.6, 32.0, 52.3, 56.0, 56.0, 65.8, 66.4; IR (neat film), ν (cm-1): 3346 (O-H stretch), 3018 (N+-R), 2917 (υas CH2), 2850 (υs CH2), 1636 (C-N+-C), 1470 (C=N), 1414 (C-O), 1086 (C-C); Anal. Calcd. (%) for C16H36BrNO: C; 56.8, H; 10.7, N; 4.1, Found: C; 56.6, H; 10.5, N; 4.1.
N-Tetradecyl-N-(2-hydroxyethyl)-N,N-dimethylammoniumbromide, (19)
White solid, 3.65 g, (100%), M.P. 204.0 – 206.5 oC;1H NMR: δ 0.87 (ω-CH3, 3H, t, J = 7.0 Hz), 1.27 ((CH2)11, 22H, m), 1.74 (β-CH2, 2H, qt, J = 7.5 Hz), 3.36 (a-CH3, 6H s), 3.53 (α-CH2, 2H, m), 3.75 (b-CH2, 2H, m), 4.13 (c-CH2, 2H, bs), 5.00 (-OH, 1H, s); 13C NMR: δ 14.4, 22.9, 23.1, 26.5, 29.5, 29.6, 29.6, 29.7, 29.8, 29.9, 29.9, 31.2, 32.2, 52.4, 56.1, 56.2, 66.0, 66.5; IR (neat film), ν (cm-1): 3349 (O-H stretch), 3019 (N+-R), 2915 (υas CH2), 2850 CH2), 1636 (C-N+-C), 1470 (C=N), 1414 (C-O), 1089 (C-C); Anal. Calcd. (%) for C18H40BrNO: C; 59.0, H; 11.0, N; 3.8, Found: C; 59.1, H; 10.9, N; 3.9.
N-Hexadecyl-N-(2-hydroxyethyl)-N,N-dimethylammonium bromide, (20)
White solid, 3.90 g, (99%), M.P. 218.0 – 224.0 oC; 1H NMR: δ 0.88 (ω-CH3, 3H, t, J = 7.0 Hz), 1.31 ((CH2)13, 26H, m), 1.76 (β-CH2, 2H, qt, J = 7.5 Hz), 3.37 (a-CH3, 6H, s), 3.53 (α-CH2, 2H, m), 3.75 (b-CH2, 2H, m), 4.17 (c-CH2, 2H, bs), 5.01 (-OH, 1H, s); 13C NMR: δ 14.2, 22.8, 23.0, 26.3, 29.2, 29.4, 29.5, 29.5, 29.6, 29.6, 29.7, 29.7, 29.8, 31.2, 32.2, 52.4, 56.2, 66.0, 66.5; IR (neat film), ν (cm-1): 3345 (O-H stretch), 3019 (N+-R), 2915 (υas CH2), 2849 (υs CH2), 1636 (C-N+-C), 1471 (C=N), 1414 (C-O), 1089 (C-C); Anal. Calcd. (%) for C20H44BrNO: C; 60.9, H; 11.2, N; 3.6, Found: C; 60.2, H; 11.3, N; 3.6.