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Structure of Oleoyl Chloride
CAS No.: 112-77-6
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CAS No. : | 112-77-6 |
Formula : | C18H33ClO |
M.W : | 300.91 |
SMILES Code : | CCCCCCCC/C=C\CCCCCCCC(Cl)=O |
MDL No. : | MFCD00134332 |
InChI Key : | MLQBTMWHIOYKKC-KTKRTIGZSA-N |
Pubchem ID : | 5364783 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In dichloromethane; water; | EXAMPLE 1 1,3,5-Triazine-1,3,5(2H, 4H, 6H)triethanol Monooleate 1,3,5-Tris(2-hydroxyethyl)perhydro-s-tria-zine (21.6 g, 0.1 mole) and potassium carbonate (35 g) are combined in a mixture of 50 ml of water and 150 ml of methylene chloride at 0 C. Oleic acid chloride (30 g, 0.1 mole) in 50 ml of methylene chloride is added at a rate such that the reaction mixture is retained at a temperature below about 10 C. After complete addition, the mixture is stirred at 0 C. for 15 hours and then at about 25 C. for an additional 16 hours. The organic layer is separated, dried over magnesium sulfate and concentrated to a yellow oil. Analysis by infrared spectroscopy and nuclear magnetic resonance spectroscopy identify the product as 1,3,5-triazine-1,3,5-(2H, 4H, 6H)triethanol monooleate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at -5 - 20℃;Inert atmosphere; Large scale; | 3-dimethylamino-1,2-propanediol 500 g,1600 g of diisopropylethylamine and 15 L of tetrahydrofuran are added to the reaction vessel.Cool down to minus 5°CThe gas in the replacement axe is nitrogen,A solution of 2800 g of oleic acid chloride in tetrahydrofuran was slowly added dropwise.Keep the temperature in the reactor not higher than 10°C,Then slowly warm up to room temperature,Continue to react for 2-3 hours,Concentrate under reduced pressure,Add Ethyl Acetate and Cold Water,Liquid separation,The organic phase is washed with saturated saline solution.Liquid separation,The organic phase is dried over anhydrous magnesium sulfate,filter.The organic phase is concentrated and dried under reduced pressure to obtain1,2-Dioleoyl-3-diamino-propane2580 g, yield 95percent. |
72% | With pyridine;dmap; In dichloromethane; at 0 - 20℃; for 6h; | An alternative synthesis is as follows: to a solution of 3-(dimethylamino)-l,2- propandiol (0.2 mL, 1.68 mmol), pyridine (0.55 mL, 6.72 mmol) and DMAP (20 mg, 0.17 mmol), in CH2CI2 (10 mL) at 00C was added dropwise oleoyl chloride (1.38 mL, 4.2 mmol). The reaction mixture was allowed to warm up slowly to room temperature. After stirring for 6 hours at room temperature, the reaction mixture was diluted with CH2Cl2 (50 mL), washed sequentially with 5percent aqueous sodium bicarbonate (15 mL), water (15 mL), and saturated aqueous NaCl (15 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. Purification by column chromatography (SiO2, elution with 0.2percent MeOH in CHCl3) furnished compound II (0.782 g, 72percent) as oily liquid. NMR spectra coordinates are as follows: 1H NMR (CDCl3): delta 5.47-5.32 (m, 4H), 5.28-5.18 (m, IH), 4.40 (dd, J= 11.8, 3.0 Hz, IH)5 4.13 (dd, J= 12.0, 6.8 Hz, IH)5 2.56-2.42 (m, 2H)5 2.35 (dt, J= 7.6, 2.8 Hz, 4H), 2.30 (s, 6H), 2.12-1.97 (m, 8H), 1.71- 1.58 (m, 4H), 1.44-1.23 (m, 40H), 0.92 (t, J= 7.0 Hz, 6H).Another crop of of (+/-)-N,N-Dimethyl-N-[2,3-bis(9-(2)-octadecanoyloxy)- propyl] amine (II) was prepared and had the following 1H NMR characteristics: (400 |
With pyridine; In chloroform; at 4℃;Product distribution / selectivity; | In the herein reproduced experiment of Feigner et al., all experimental conditions have been chosen to stay in close accordance with US5,264,618 (Feigner et al.), Example 5, column 27, lines 15 to 47. 31.5 g of oleoylchloride (FLUKA 0733IAH) dissolved in 125 ml chloroform was added dropwise at 4°C under cooling over a period of 11/2 hour to 5.0 g of 3-(dimethylamino)-1 ,2-propanediol, dissolved in 37.5 ml chloroform and 25 ml of pyridine. The yellow solution was stirred overnight. Then 125 ml of cold water and 125 ml diethylether was added. The organic phase was washed twice with 100 ml of 0.5N HCL and also twice with 100 ml 0.5N sodium bicarbonate solution. 39 g anhydrous sodium sulfate was added and the so obtained suspension was filtrated and washed with 100 ml chloroform. The filtrate was then concentrated under reduced pressure at 40°C. 40.1 g of a brown liquid (SM-0318-A) having a (2R,S)-DODAP content of 24.3percent w/w measured by HPLC resulted. A further drying under reduced pressure at 60°C resulted in a reduction of weight to 31.2 g.31.0 g of this material was purified by silicic acid column chromatography as follows:Silica gel: 129 g (the amount of silica gel was calculated relative to the amount (2R,S)-DODAP) Merck 60 F 63-200umColumn: diameter 4 cm, height 60 cmFlow: about 8 ml/minAs mobile phase first 1 ,500 ml methylene chloride (fractions 1-27), then 1 ,000 ml methylene chloride/methanol 95:5 (fractions 28-47) and finally 1 ,000 ml methanol was used. Fractions were collected and combined according to their TLC analysis. So fractions 4-33 were concentrated together under reduced pressure. 10.8 g of a brown oil (SM-0318-B) having a (2R,S)-DODAP content of 65.6percent w/w measured by HPLC resulted. And fractions 34-42 resulted in 12.6 g of a brown oil (SM 0318-D) having a (2R,S)-DODAP content of 54.2percent w/w measured by HPLC.10.4 g Methylene chloride was added to 9.6 g of the compound obtained out of the fractions 4-33 (SM-0318-B) in a high pressure glass tube. The glass tube was then closed and the brownish solution was heated over night at 50°C to form an emulsion. Then the tube was opened and residual methylene chloride was removed by evaporation. 8.0 g of a yellow wax (SM-0318-E) having a (2R,S)-DOTAP chloride content of 65.0percent w/w and 1.3percent w/w (2R,S)-DODAP both measured by HPLC resulted.14.0 g acetonitrile was added to this wax (SM-0318-E). The so obtained emulsion was transferred with 80 ml acetonitrile (to obtain a ratio solid to solvent of about 1 :12) into a flask and cooled down to 20°C. Nocrystallisation could be observed. At 20°C a solidified honey like yellow- brownish material resulted which even when only slightly warming it up tended to become a sticky viscous brownish material.ConclusionThe data demonstrate that 1 ,2-dioleoyl-3-propyltrimethylammonium chloride ((2R,S)-DOTAP chloride) prepared according to the above procedure, which is in accordance with US 5,264,618 (Feigner et al), Example 5, column 27, lines 15 to 47 cannot be obtained in a crystalline form.See also Figures 6 and 7 illustrating (2R,S)-DOTAP chloride emulsion (SM- 0318-E) in acetonitrile when cooling down and (2R,S)-DOTAP chloride emulsion (S -0318-E) in acetonitrile after having been cooled it down to - 20°C, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36.14 g | In tetrahydrofuran; for 3h; | 56.4 g (0.2 mol) of oleic acid, 17.85 g (0.15 mol) of thionyl chloride was added, After mixing for 3 hours at 70 C, 20 ml of a tetrahydrofuran solution containing 15.4 g (0 lmo 1) alpha-<strong>[98-55-5]terpineol</strong> was added, Continue to react for 3 hours, The reaction solution was adjusted to pH 6-7 with NaOH solution. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with saturated brine and dried over Na2S04 overnight. The solvent was evaporated and the column chromatography For 200 to 300 mesh), B petroleum ether and ethyl acetate (15: 1) as eluent, The eluent was distilled off to give 36.14 g of a slightly yellow liquid in a yield of 84%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1) Proline alcohol (47.6 mmol, 4.8 g) was sequentially added to the reactor. 40mL of acetone, 20mL water, Sodium hydroxide (95.2 mmol, 10 g), Cool down to 0 C, Oleoyl chloride(shown by Formula II-c) (47.6 mmol, 13.45 g) was added dropwise. After 5 hours of reaction, the mixture was extracted with dichloromethane, Washed, Rotary evaporation gave a white solid. 2) The above white solid (17.4 mmol, 6.4 g), Soluble in 50mL of dichloromethane, Add triethylamine (52.2 mmol, 5.28 g), Phosphorus oxychloride (8.7 mmol, 1.33 g) was added dropwise thereto. After 12 hours of reaction, Add 5mL of water, Reflux for 4 hours, Washed in 6 mol/L hydrochloric acid solution and water, dry, Rotating to give a white solid, Recrystallization of ethanol gave bis(N-oleoyl decylamino)-phosphoric acid (shown by Formula I-c). |