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With thionyl chloride for 3h; Heating; |
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With thionyl chloride for 1.5h; Heating; |
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With thionyl chloride for 1.5h; Heating / reflux; |
3.A
n-Pentadecanoic acid (24.3 g, 0.1 mol) was refluxed with 45 mL of thionyl chloride for 90 minutes. The thionyl chloride in excess was evaporated under reduced pressure, 20 mL of hexane was added and then evaporated under reduced pressure to remove the traces of any remaining thionyl chloride. Anhydrous aluminum chloride (13.5 g, 0.1 mol) was added to the crude pentadecanoyl chloride under stirring and external cooling. The mixture became homogeneous in about 10 minutes. Then 12 mL (0.15 mmol) of mesityl oxide was added dropwise, and the reaction mixture was stirred at room temperature for 12 h. The resulting dark viscous mass was hydrolyzed by carefully adding 50 mL of ice-cold 5% hydrochloric acid and 50 mL of diethyl ether, with external cooling (ice bath). The ethereal layer was separated and extracted another time with 20 mL of diluted hydrochloric acid, then discarded. The combined aqueous solutions. were extracted with 20 mL of diethyl ether, separated and treated with 15 mL of hexafluorophosphoric acid, when the crude pyrylium hexafluorophosphate (10, n=13) separated as a brown oil. After extraction with chloroform, separation, drying on anhydrous sodium sulfate and evaporation of the solvent, 25.9 g of crude compound were obtained. It was recrystallized twice from ethanol to afford 11.2 g (yield 25%) of pure pyrylium hexafluorophosphate (10, n=13). Characterization: m.p. 85° (determined by differential scanning calorimetry) 1H-NMR (CDCl3), δ, ppm: 7.70 (s, 1H: H-3, pyrylium), 7.61 (s, 1H: H-5, pyrylium), 3.06 (t, J=7.9 Hz, 2H: Cα-, 2.86 (s, 3H: CH3 γ-pyrylium), 2.69 (s, 3H: CH3 α-pyrylium), 1.81 (q, J=7.6 Hz, 2H: Cα-CH, 1.40 (q, J=7.6 Hz, 2H: Cα-CH2CH, 1.25 (m, 20H: 10 CH2 from fatty chain), 0.87 (t, J=6.7 Hz, 3H: CH3 from fatty chain); 13C-NMR (CDCl3), δ, ppm: 180.9 (C-6, pyrylium), 177.7 (C-4, pyrylium), 174.7 (C-2, pyrylium), 123.8 (C-3, pyrylium), 122.5 (C-5, pyrylium), 34.7 (Cα-H2-), 31.8, 29.64, 29.62, 29.60, 29.57, 29.51, 29.32, 29.30, 29.0 (2C), 27.01 (all from fatty chain), 23.5 (CH3 α-pyrylium), 22.6 (fatty chain), 21.1 (CH3 γ-pyrylium), 14.0 (CH3 from fatty chain). |
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With thionyl chloride; N,N-dimethyl-formamide at 20℃; |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h; Inert atmosphere; |
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With oxalyl dichloride In dichloromethane at 20℃; for 2h; Inert atmosphere; |
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With oxalyl dichloride In dichloromethane at 0℃; for 1h; Inert atmosphere; |
1.4.1
To a solution of acid R'COOH (484 mg, 2 mmol) in dichloromethane (10 ml) placed at 0° C. under inert atmosphere of nitrogen are added three drops of dry dimethylformamide (DMF) and oxalyl chloride (1.04 ml, 12 mmol). The mixture is stirred at 0° C. for 1 h. The dichloromethane and the excess oxalyl chloride are evaporated at 70° C. under reduced pressure. The acid chloride R'COCl thus obtained is dissolved in 5 ml dichloromethane. |
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With thionyl chloride for 0.5h; Reflux; |
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With thionyl chloride at 20℃; Inert atmosphere; |
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With thionyl chloride for 1h; Reflux; |
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h; Inert atmosphere; |
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With oxalyl dichloride In dichloromethane at 20℃; |
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With thionyl chloride In toluene for 4h; Reflux; |
The recovery standard pentadecanoic acid cholesteryl ester(hereafter referred to as 15:0-CE) was prepared accordingto Lusby et al. [20] with slight modifications. Pentadecanoicacid (121 mg, 0.5 mmol) was placed in a 50-ml flaskand dissolved in 10 ml of toluene. About 120 μl thionylchloride was added, and the solution was refluxed for 4 hto obtain the acid chloride. Afterwards, the remaining thionylchloride and parts of the toluene were removed underreduced pressure. To the residue (about 2 ml), 153 mgcholesterol (0.4 mmol) dissolved in 10 ml toluene wasadded, and the solution was stirred overnight at room temperature.The solvent was removed on a rotary evaporator,and the residue was re-dissolved in 4 ml n-hexane. Thissolution was purified by SPE. For this purpose, 15 g ofsilica gel deactivated with 20 % water (w/w) was giveninto a glass column (i.d. 2.5 cm) and pre-conditionedwith n-hexane. After 50 ml of n-hexane (fraction 1), three50-ml fractions (fractions 2-4) were collected with n-hexane/ethyl acetate (99:1, v/v) as eluent. Fractions 3 and 4yielded 154.3 and 64.8 mg of 15:0-CE. The purity inboth fractions was >99 % according to GC/MS and NMRspectroscopy analysis. |
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With thionyl chloride at 70℃; for 4h; |
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With oxalyl dichloride |
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With oxalyl dichloride |
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With thionyl chloride In tetrachloromethane for 2h; Reflux; |
General Procedures for Synthesis of AcidChlorides
General procedure: For the preparation of chlorides higher than 10 Catoms the corresponding acid was refluxed for 2 h withthionyl chloride in CCl4.38 The solvent and the excess ofthionyl chloride were removed with the aid of the waterpump vacuum. |
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With thionyl chloride In N,N-dimethyl-formamide Reflux; |
General procedure: A solution of suitable carboxylic acids 1a-k (1.0 mmol) and DMF(0.05 ml) in thionyl chloride (1.2 mmol) were refluxed for 3.5 h. Aftercooling at room temperature the mixture was concentrated to afford theacid chlorides 2a-k. A solution of acid chlorides 2a-k (1.0 mmol) in drydistilled acetone (20 ml) was added drop wise to a suspension of potassiumthiocyanate (1.0 mmol) in dry acetone and refluxed for 1.5 hr at50 °C to afford the corresponding isothiocyanates. After cooling onroom temperature, a solution of 3-aminobenzenesulfonamide 3(1.0 mmol) in dry acetone was added in it and the reaction mixture wasrefluxed for 9 h. After completion checked by TLC (n-Hexane: Ethylacetate 1: 1) the reaction mixture was poured onto crushed ice and theresulting precipitates were collected via simple filtration, washed, driedand recrystallized from ethanol to obtain the 1-aroyl/acyl-3-(3-aminosulfonylphenyl)thioureas 4a-k in excellent yields (Scheme 1). |
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With thionyl chloride In 1,2-dichloro-ethane; N,N-dimethyl-formamide at 20℃; for 3h; |
6; 13 Example 6: Synthesis of 1,5-anhydro-D-glucitol-2,3,4,6-O-tetrapentadecanoate
Pentadecanoic acid (3 g, 12.4 mmol)The 1,2-dichloroethane (30 ml)And N, N-dimethylformamide (953 μl, 12.4 mmol) and dispersed.Add thionyl chloride (4.5 ml, 61.9 mmol),It reacted at room temperature for 3 hours. After completion of the reaction, concentrate under reduced pressure,Liquid pentadecanoyl chloride was obtained. This was used as it is in the next reaction. |
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With oxalyl dichloride In dichloromethane at 20℃; for 2h; Inert atmosphere; |
2.2. Synthesis of NATs
General procedure: NATs were synthesized by the reaction of acid chlorides with taurine. For this, long-chain fatty acids were converted to the corresponding acid chlorides by treating with 4 mol equivalents of oxalylchloride at room temperature for 2 h under nitrogen atmosphere[Kamlekar et al., 2010]. After completion of the reaction, the excessoxalyl chloride was removed under a stream of dry nitrogen gas. NATs were synthesized by the drop-wise addition of about 1 mol equivalent of the acid chloride in dichloromethane to a solution of 1.2 mol equivalent of taurine in 1 M NaOH (to maintain pH 9-10.5) underconstant stirring at room temperature. After addition of all the reagents, the reaction was allowed to continue for two hours (Scheme 1). The crude NATs obtained as slurry was dissolved in ethanol by refluxing. The solution was filtered and the filtrate was stored in freezer (ca. 4 °C) overnight. This led to precipitation of the NATs and then later recovered by filtration. The obtained NATs were further purified bycolumn chromatography on silica gel with ethyl acetate/methanol/ammonium hydroxide (80/18/2) mixture as elution solvent. The overall yield for different NATs ranged around ∼70 %. The final productswere characterized by FT-IR, 1H and 13C NMR spectroscopy as well as by LC-MS. |
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