Analytical grade reagents were purchased from Sigma-Aldrich, Fluka, and Merck (Darmstadt, Germany). The solvents were purchased from Penta Chemicals (Prague, Czech Republic). Reactions were monitored by thin-layer chromatography (TLC) using pre-coated silica gel 60 F254 TLC alumina sheet. Column chromatography was performed with silica gel 0.063e0.200 mm. Melting points (m. p.) were determined on a micro heating stage PHMK 05 (VEB Kombinat Nagema, Radebeul, Germany) and are uncorrected. All compounds were fully characterized by NMR spectra and HRMS. NMR spectra were recorded on a Varian VNMR S500 (operating at 500 MHz for 1H and 125 MHz for 13C; Varian Co., Palo Alto, CA, USA). The chemical shifts (d) are given in ppm, relative to tetramethylsilane (TMS) as internal standard. Coupling constants (J) are reported in Hz. Splitting patterns are designated as s, singlet; d, doublet; t, triplet; and m, multiplet. Mass spectra were recorded using a combination of liquid chromatography and mass spectrometry: high-resolution mass spectra (HRMS) and sample purities were obtained by high-performance liquid chromatography (HPLC) with UV and mass spectrometric (MS) detection gradient method. The system used in this study was a Dionex Ultimate 3000 UHPLC: RS Pump, RS Column Compartment, RS Autosampler, Diode Array Detector, controlled by Chromeleon (version 7.2.9 build 11323) software (Thermo Fisher Scientific, Germering, Germany) with Q Exactive Plus Orbitrap mass spectrometer with Thermo Xcalibur (version 3.1.66.10.) software (Thermo Fisher Scientific, Bremen, Germany). Detection was performed by mass spectrometer in positive mode. Settings of the heated electrospray source were: Spray voltage 3.5 kV, Capillary temperature: 262 °C, Sheath gas: 55 arbitrary units, Auxiliary gas: 15 arbitrary units, Spare gas: 3 arbitrary units, Probe heater temperature: 250 °C, Max spray current: 100 mA, S-lens RF Level: 50. C18 column (Kinetex EVO C18, 3 × 150 mm, 2.6 µm, Phenomenex, Torrance, CA, USA) was used in this study. Mobile phase A was ultrapure water of ASTM I type (resistivity 18.2 MΩ.cm at 25 °C) prepared by Barnstead Smart2Pure 3 UV/UF apparatus (Thermo Fisher Scientific, Bremen, Germany) with 0.1% (v/v) formic acid (HPLC-MS grade, Sigma Aldrich, Steinheim, Germany); mobile phase B was acetonitrile (MS grade, Honeywell-Sigma Aldrich) with 0.1% (v/v) of formic acid. The flow was constant at 0.4 mL/min. The method started with 1 min of isocratic flow of 5% B, and then the gradient of B rose to 100% B in 3 min and remained constant at 100% B for 1 min. The composition then went back to 5% B and equilibrated for 5 min. Total runtime of the method was 10 min. The column was heated to 27 °C. Samples were dissolved in methanol (LC-MS grade, Fluka-Sigma Aldrich) at a concentration 1 mg/mL and sample injection was 1 µL. Purity was determined from UV spectra measured at wavelength 254 nm. HRMS was determined by total ion current spectra from the mass spectrometer collected at resolution of 140,000 in a range 105–1000 m/z. Clog P was calculated with the MarvinSketch (version 14.9.8.0) software.
2.1.3. NMR and HRMS Analysis
N,N-Bis(2-hydroxyethyl)-N-decylamine (3a). Yellow oil, (2.40 g, 65%); 1H-NMR (chloroform-d) δ 3.63 (t, J = 5.4 Hz, 4H), 2.68 (t, J = 5.4 Hz, 4H), 2.57–2.50 (m, 2H), 1.51–1.44 (m, 2H), 1.35–1.21 (m, 14H), 0.89 (t, J = 6.8 Hz, 3H); 13C-NMR (chloroform-d) δ 59.67, 56.05, 54.79, 31.88, 29.61, 29.55, 29.30, 27.36, 27.17, 22.67, 14.10; HRMS: m/z 246.2424 [M + H]+ (calculated m/z 246.2428 for [C14H32NO2]).
N,N-Bis(2-hydroxyethyl)-N-dodecylamine (3b). Yellow oil, (3.75 g, 91%); 1H-NMR (chloroform-d) δ 3.63 (t, J = 5.4 Hz, 4H), 2.68 (t, J = 5.4 Hz, 4H), 2.58–2.51 (m, 2H), 1.52–1.44 (m, 2H), 1.32–1.22 (m, 18H), 0.89 (t, J = 7.1, 1.7 Hz, 3H); 13C-NMR (chloroform-d) δ 59.46, 56.08, 54.80, 31.87, 29.62, 29.59, 29.52, 29.30, 27.33, 26.80, 22.64, 14.07; HRMS: m/z 274.2736 [M + H]+ (calculated m/z 274.2741 for [C16H36NO2]).
N,N-Bis(2-hydroxyethyl)-N-tetradecylamine (3c). Yellow oil, (3.07 g, 67%); 1H-NMR (chloroform-d) δ 3.62 (t, J = 5.4 Hz, 4H), 2.66 (t, J = 5.4 Hz, 4H), 2.55–2.49 (m, 2H), 1.49–1.43 (m, 2H), 1.32–1.22 (m, 22H), 0.88 (t, J = 6.9 Hz, 3H); 13C-NMR (chloroform-d) δ 59.65, 56.05, 54.79, 31.90, 29.67, 29.65, 29.63, 29.62, 29.57, 29.56, 29.34, 27.37, 27.08, 22.67, 14.09; HRMS: m/z 302.3054 [M + H]+ (calculated m/z 302.3054 for [C18H40NO2]).
N,N-Bis(2-hydroxyethyl)-N-hexadecylamine (3d). Yellow oil, (3.82 g, 77%); 1H-NMR (chloroform-d) δ 3.62 (t, J = 5.4 Hz, 4H), 2.66 (t, J = 5.4 Hz, 4H), 2.56–2.49 (m, 2H), 1.51–1.43 (m, 2H), 1.29–1.25 (m, 26H), 0.89 (t, J = 6.9 Hz, 3H); 13C-NMR (chloroform-d) δ 59.65, 56.05, 54.79, 31.91, 29.68, 29.66, 29.64, 29.62, 29.56, 29.34, 27.37, 27.09, 22.67, 14.09; HRMS: m/z 330.3361 [M + H]+ (calculated m/z 330.3367 for [C20H44NO2]).
N,N-Bis(2-hydroxyethyl)-N-octadecylamine (3e). Yellow solid, m. p. 48.1–49.7 °C (5.17 g, 96%); 1H-NMR (chloroform-d) δ 3.62 (t, J = 5.4 Hz, 4H), 2.66 (t, J = 5.4 Hz, 4H), 2.55–2.49 (m, 2H), 1.49–1.43 (m, 2H), 1.29–1.24 (m, 30H), 0.88 (t, J = 6.9 Hz, 3H); 13C-NMR (chloroform-d) δ 61.10, 59.62, 56.04, 54.78, 50.94, 31.90, 29.67, 29.64, 29.61, 29.56, 29.33, 27.37, 27.00, 22.66, 14.09; HRMS: m/z 358.3675 [M + H]+ (calculated m/z 358.3680 for [C22H48NO2]).
N-benzyl-N,N-bis(2-hydroxyethyl)decan-1-aminium chloride (5a). White solid, m. p. 114.0–114.6 °C (4.09 g, 78%); 1H-NMR (chloroform-d) δ 7.63–7.57 (m, 2H), 7.47–7.39 (m, 3H), 5.73 (t, J = 5.4 Hz, 2H), 4.86 (s, 2H), 4.29–4.10 (m, 4H), 3.71–3.52 (m, 4H), 3.39–3.32 (m, 2H), 1.89–1.80 (m, 2H), 1.38–1.14 (m, 14H), 0.87 (t, J = 6.9 Hz, 3H); 13C-NMR (chloroform-d) δ 133.18, 130.61, 129.25, 127.27, 64.39, 60.20, 59.60, 55.83, 31.78, 29.37, 29.36, 29.18, 29.13, 26.22, 22.69, 22.59, 14.05; HRMS: m/z 336.2888 [M]+ (calculated m/z 336.2897 for [C21H38NO2]+).
N-benzyl-N,N-bis(2-hydroxyethyl)dodecan-1-aminium chloride (5b). White solid, m. p. 118.7–119.0 °C (4.68 g, 41%); 1H-NMR (chloroform-d) δ 7.62–7.57 (m, 2H), 7.47–7.39 (m, 3H), 5.30 (t, J = 5.4 Hz, 2H), 4.86 (s, 2H), 4.27–4.14 (m, 4H), 3.71–3.53 (m, 4H), 3.38–3.31 (m, 2H), 1.89–1.80 (m, 2H), 1.36–1.19 (m, 18H), 0.88 (t, J = 6.9 Hz, 3H); 13C-NMR (chloroform-d) δ 133.17, 130.61, 129.26, 127.27, 64.39, 60.21, 59.61, 55.83, 31.84, 29.55, 29.42, 29.39, 29.27, 29.15, 26.23, 22.69, 22.62, 14.06; HRMS: m/z 364.3207 [M]+ (calculated m/z 364.3210 for [C23H42NO2]+).
N-benzyl-N,N-bis(2-hydroxyethyl)tetradecan-1-aminium chloride (5c). White solid, m. p. 120.6–120.9 °C (3.92 g, 65%); 1H-NMR (methanol-d4) δ 7.68–7.62 (m, 2H), 7.60–7.49 (m, 3H), 4.79 (s, 2H), 4.09 (t, J = 5.1 Hz, 4H), 3.51 (t, J = 7.4, 5.0 Hz, 4H), 3.38–3.31 (m, 2H), 1.98–1.88 (m, 2H), 1.45–1.28 (m, 22H), 0.90 (t, J = 6.9 Hz, 3H); 13C-NMR (methanol-d4) δ 134.34, 131.79, 130.36, 129.11, 65.40, 61.34, 61.08, 56.71, 33.06, 30.79, 30.77, 30.75, 30.71, 30.61, 30.53, 30.46, 30.18, 27.34, 23.72, 23.49, 14.44; HRMS: m/z 392.3515 [M]+ (calculated m/z 392.3523 for [C25H46NO2]+).
N-benzyl-N,N-bis(2-hydroxyethyl)hexadecan-1-aminium chloride (5d). White solid, m. p. 121.6–121.9 °C (4.39 g, 68%); 1H-NMR (chloroform-d) δ 7.63–7.57 (m, 2H), 7.48–7.40 (m, 3H), 5.73 (t, J = 5.4 Hz, 2H), 4.86 (s, 2H), 4.28–4.14 (m, 4H), 3.69–3.55 (m, 4H), 3.39–3.32 (m, 2H), 1.90–1.80 (m, 2H), 1.32–1.23 (m, 26H), 0.87 (t, J = 6.9 Hz, 3H); 13C-NMR (chloroform-d) δ 133.22, 130.67, 129.31, 127.31, 64.43, 60.25, 59.65, 55.89, 31.92, 29.70, 29.66, 29.61, 29.48, 29.45, 29.36, 29.21, 26.28, 22.75, 22.68, 14.11; HRMS: m/z 420.3828 [M]+ (calculated m/z 420.3836 for [C27H50NO2]+).
N-benzyl-N,N-bis(2-hydroxyethyl)octadecan-1-aminium chloride (5e). White solid, m. p. 124.2–124.7 °C (3.59 g, 52%); 1H-NMR (chloroform-d) δ 7.62–7.57 (m, 2H), 7.49–7.39 (m, 3H), 5.72 (t, J = 5.4 Hz, 2H), 4.87 (s, 2H), 4.22 (t, J = 10.8, 6.3, 5.6 Hz, 4H), 3.62 (t, J = 39.6, 14.4, 6.5, 3.3 Hz, 4H), 3.38–3.31 (m, 2H), 1.90–1.81 (m, 2H), 1.38–1.15 (m, 30H), 0.88 (t, J = 6.8 Hz, 3H); 13C-NMR (chloroform-d) δ 133.19, 130.63, 129.28, 127.28, 64.40, 60.22, 59.61, 55.87, 31.88, 29.68, 29.64, 29.62, 29.59, 29.46, 29.42, 29.32, 29.18, 26.24, 22.71, 22.65, 14.08; HRMS: m/z 448.4153 [M]+ (calculated m/z 448.4149 for [C29H54NO2]+).