CN117800865A - Synthesis method of N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide - Google Patents
Synthesis method of N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide Download PDFInfo
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- -1 hexyl oxyethyl malonamide Chemical compound 0.000 title claims abstract description 29
- 238000001308 synthesis method Methods 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 26
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 25
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 24
- HXXNTEDKEYTYPD-UHFFFAOYSA-N 2-ethoxyethyl 4-methylbenzenesulfonate Chemical compound CCOCCOS(=O)(=O)C1=CC=C(C)C=C1 HXXNTEDKEYTYPD-UHFFFAOYSA-N 0.000 claims abstract description 20
- UPGSWASWQBLSKZ-UHFFFAOYSA-N 2-hexoxyethanol Chemical class CCCCCCOCCO UPGSWASWQBLSKZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims abstract description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 49
- 238000003756 stirring Methods 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- 238000005406 washing Methods 0.000 claims description 20
- 239000003960 organic solvent Substances 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 230000002194 synthesizing effect Effects 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- SEGJNMCIMOLEDM-UHFFFAOYSA-N n-methyloctan-1-amine Chemical compound CCCCCCCCNC SEGJNMCIMOLEDM-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 239000007821 HATU Substances 0.000 claims description 7
- 238000006482 condensation reaction Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 6
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- 238000010791 quenching Methods 0.000 claims description 3
- 230000000171 quenching effect Effects 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 abstract description 27
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 5
- WRIRWRKPLXCTFD-UHFFFAOYSA-N malonamide Chemical compound NC(=O)CC(N)=O WRIRWRKPLXCTFD-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001412 amines Chemical class 0.000 abstract description 2
- UBGCCBQQNSSDHM-UHFFFAOYSA-N n,n'-dimethyl-n,n'-dioctylpropanediamide Chemical compound CCCCCCCCN(C)C(=O)CC(=O)N(C)CCCCCCCC UBGCCBQQNSSDHM-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002243 precursor Substances 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 239000000047 product Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 238000000605 extraction Methods 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- MQXAJNXSULJYCY-UHFFFAOYSA-N dihexyl propanedioate Chemical compound CCCCCCOC(=O)CC(=O)OCCCCCC MQXAJNXSULJYCY-UHFFFAOYSA-N 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthetic method of N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide, which comprises the steps of firstly, preparing an intermediate DMDOMA by condensing malonic acid and amine serving as precursors; nucleophilic substitution of 2- (hexyloxy) ethane-1-ol with p-toluenesulfonyl chloride (PTSC) to obtain ethoxyethyl 4-methylbenzenesulfonate; finally, the malonamide intermediate N, N '-dimethyl N, N' -dioctylmalonamide (DMDOMA) is reacted with ethoxyethyl 4-methylbenzenesulfonate to obtain N, N '-dimethyl-N, N' -dioctylhexyloxyethyl malonamide (DMDOHEMA). Compared with the prior art, the method has the advantages of high yield, simple steps, high reagent safety, advantages in industrial large-scale synthesis and the like.
Description
Technical Field
The invention relates to the field of organic synthesis of malonamide extractant, in particular to a method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide.
Background
DMDOHEMA has very good irradiation resistance and hydrolysis resistance, and because of ultra-strong hydrophobicity, DMDOHEMA is used as an extractant to inhibit the generation of a third phase.
Few reports on DMDOHEMA synthesis are currently made, patil et al have reported on a synthetic method of DMDOHEMA by first refluxing dihexyl malonate and methyl octylamine in a solvent to obtain a malonamide intermediate N, N '-dimethyl N, N' -dioctylmalonamide (DMDOMA); then, tosyl chloride (PTSC) is reacted with 2- (hexyloxy) ethane-1-alcohol to obtain 4-methylbenzenesulfonic acid ethoxyethyl ester; and finally, coupling the DMDOMA with an ether chain to obtain the DMDOHEMA. The above method for synthesizing DMDOHEMA is relatively complex, has low overall yield, and is basically difficult to be applied to industrial production.
In conclusion, the synthesis method with high yield, simple steps and high reagent safety is developed, and the method has important significance for laying a foundation for industrial scale.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a synthesis method of N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide, which has the advantages of high yield, simple steps and high reagent safety.
The aim of the invention can be achieved by the following technical scheme:
a method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide, which comprises the following steps:
a1: synthesis of DMDOMA: mixing malonic acid, N-methyl octylamine and Triethylamine (TEA), adding a first organic solvent, stirring, adding a condensing agent, stirring for condensation reaction, extracting, washing, drying and distilling to obtain DMDOMA;
a2: synthesis of ethoxyethyl 4-methylbenzenesulfonate: placing a second organic solvent in ice bath, stirring, adding 2- (hexyloxy) ethane-1-alcohol, triethylamine and p-toluenesulfonyl chloride (PTSC), removing the ice bath, performing nucleophilic substitution reaction, extracting, washing, drying, distilling and purifying to obtain 4-methylbenzenesulfonic acid ethoxyethyl ester;
a3: synthesis of DMDOHEMA: and (3) placing the third organic solvent in ice bath, adding catalyst, DMDOMA and 4-methyl benzene sulfonate ethoxyethyl ester, removing the ice bath, raising the temperature to a certain temperature for reflux reaction, cooling, adding water for quenching, extracting, washing, drying, distilling and purifying to obtain DMDOHEMA.
Further, in the step A1, the molar ratio of malonic acid, N-methyloctamine, TEA and condensing agent is 1:2: (2.1-3): (2.1-3).
Further, in the step A1, the first organic solvent is N, N-Dimethylformamide (DMF), and the molar volume ratio of the malonic acid to the first organic solvent is 0.05 to 10mol/L, preferably 0.1 to 1mol/L.
Further, in step A1, the condensing agent comprises 2- (7-azabenzotriazol) -N, N, N ', N' -tetramethyluronium Hexafluorophosphate (HATU), O-benzotriazol-tetramethyluronium Hexafluorophosphate (HBTU), 6-chlorobenzotriazol-1, 3-tetramethyluronium Hexafluorophosphate (HCTU), preferably HATU.
Further, in the step A1, the condensation reaction temperature is 0 to 25 ℃, preferably room temperature.
Further, in the step A1, the condensation reaction time is 1 to 3 hours.
Further, in step A1, the extracting agent used in the extraction is ethyl acetate.
Further, in the step A1, the washing process is to adopt saturated sodium chloride, saturated sodium bicarbonate, 0.5-3 mol/L hydrochloric acid solution and saturated sodium chloride to wash for 1-3 times in sequence.
Further, in step A1, the organic phase obtained by extraction and washing is dried with anhydrous sodium sulfate.
Further, in step A1, the distillation is reduced pressure distillation for the purpose of removing the solvent.
Further, in step A2, the molar ratio of 2- (hexyloxy) ethane-1-ol and PTSC is 1: (1.4-2).
Further, in the step A2, the molar volume ratio of the 2- (hexyloxy) ethane-1-ol to TEA is 0.05 to 10mol/L, preferably 0.5 to 2mol/L.
Further, in step A2, the second organic solvent comprises Dichloromethane (DCM), and the molar volume ratio of the 2- (hexyloxy) ethane-1-ol to the second organic solvent is 0.05-10 mol/L, preferably 0.1-1 mol/L.
Further, in the step A2, the temperature of the ice bath is-4 to 4 ℃.
Further, in step A2, the temperature of the nucleophilic substitution reaction is room temperature.
Further, in the step A2, the nucleophilic substitution reaction time is 1 to 4 hours.
Further, in step A2, the extracting agent used in the extraction is ethyl acetate extraction.
Further, in the step A2, the washing process is to use saturated sodium bicarbonate, saturated sodium chloride and 0.5-3 mol/L hydrochloric acid solution for washing 1-3 times.
Further, in step A2, the organic phase obtained by extraction and washing is dried with anhydrous sodium sulfate.
Further, in step A2, the distillation is reduced pressure distillation for the purpose of removing the solvent.
Further, in step A2, the purification process uses column chromatography to purify the distilled product, wherein the eluting solvent is a mixture of ethyl acetate and petroleum ether.
Further, the volume ratio of the ethyl acetate to the petroleum ether is 1: (5-15).
Further, in the step A3, the molar ratio of the catalyst to the DMDOMA to the ethoxyethyl 4-methylbenzenesulfonate is (1-1.5): 1: (1-1.5).
Further, in the step A3, the catalyst is sodium hydride (NaH), the third organic solvent includes DMF, tetrahydrofuran (THF) or a mixture of both, and the molar volume ratio of the DMDOMA to the third organic solvent is 0.05 to 10mol/L, preferably 0.1 to 1mol/L.
Further, in the step A3, the ethoxyethyl 4-methylbenzenesulfonate is required to be dissolved in a third organic solvent and then added dropwise to the reaction system.
Further, in the step A3, the temperature of the reflux reaction is 60 to 90 ℃.
Further, in the step A3, the temperature of the ice bath is-4 to 4 ℃.
Further, in step A3, the cooled temperature is room temperature.
Further, in the step A3, the mass-to-water volume ratio of the DMDOMA in the water adding quenching process is 10-100 g/L.
Further, in step A3, the extracting agent used in the extraction is ethyl acetate extraction.
Further, in the step A3, the washing process is to use saturated sodium bicarbonate and saturated sodium chloride for washing 1-3 times respectively.
Further, in step A3, the organic phase obtained by extraction and washing is dried with anhydrous sodium sulfate.
Further, in step A3, the distillation is reduced pressure distillation for the purpose of removing the solvent.
Further, in step A3, the purification process uses silica gel column chromatography to purify the distilled product, wherein the eluting solvent is a mixture of ethyl acetate and petroleum ether.
Further, the volume ratio of the ethyl acetate to the petroleum ether is (1-5): 10.
further, the mesh number of the silica gel is 100-200 mesh.
Compared with the prior art, the invention has the following advantages:
(1) Firstly, preparing an intermediate DMDOMA by condensing malonic acid and amine serving as precursors; nucleophilic substitution of 2- (hexyloxy) ethane-1-alcohol with PTSC to obtain 4-methyl benzene sulfonate ethoxyethyl ester, and finally DMDOMA reacts with 4-methyl benzene sulfonate ethoxyethyl ester to obtain DMDOHEMA. The synthesis process is simpler, and has advantages in industrial large-scale synthesis.
(2) The synthesis process of the invention has high production safety, and the used reagent has no high corrosion and high toxicity.
(3) The method utilizes HATU, HBTU or HCTU as a condensing agent to synthesize the intermediate DMDOMA, has mild reaction conditions and extremely high yield (> 92%), does not need column chromatography separation, shortens the yield and efficiency of the overall synthesis, is beneficial to realizing large-scale synthesis, and saves equipment cost and labor cost in the industrialized process.
Drawings
FIG. 1 is a synthetic scheme for DMDOHEMA shown in example 1;
FIG. 2 is a schematic diagram of DMDOHEMA shown in example 1;
FIG. 3 is a schematic diagram of DMDOMA as shown in example 1 1 H-NMR spectrum;
FIG. 4 is a drawing of ethoxyethyl 4-methylbenzenesulfonate of example 1 1 H-NMR spectrum;
FIG. 5 is a diagram of DMDOHEMA as shown in example 1 1 H-NMR spectrum;
fig. 6 is a mass spectrum of DMDOHEMA shown in example 1.
Detailed Description
The invention will now be described in detail with reference to the drawings and specific examples. The present embodiment is implemented on the premise of the technical scheme of the present invention, and a detailed implementation manner and a specific operation process are given, but the protection scope of the present invention is not limited to the following examples. All other embodiments, based on the examples given, which a person of ordinary skill in the art would obtain without undue burden, are within the scope of protection of the present application.
Unless specifically indicated otherwise, the reagents, methods, apparatus and devices employed in the present invention are those conventional in the art.
In the examples below, the CAS numbers for the reactants and solvents were respectively: malonic acid (CAS: 141-82-2), N-methyloctamine (CAS: 2439-54-5), triethylamine (TEA, CAS: 121-44-8), N, N-dimethylformamide (DMF, CAS: 68-12-2), 2- (7-azabenzotriazol) -N, N, N ', N' -tetramethylurea hexafluorophosphate (HATU, CAS: 148893-10-1), O-benzotriazol-tetramethylurea hexafluorophosphate (HBTU, CAS: 94790-37-1), 6-chlorobenzotriazol-1, 3-tetramethylurea hexafluorophosphate (HCTU, CAS: 330645-87-9), dichloromethane (DCM, 75-09-2), 2- (hexyloxy) ethane-1-ol (CAS: 112-25-4), p-toluenesulfonyl chloride (PTSC, CAS: 98-59-9), tetrahydrofuran (THF, 109-99-9), 6-69-7 (NaH, 6-69-7), ethyl acetate (CAS: 76400-32-141), petroleum ether (CAS: 76400-32-8), petroleum ether (CAS).
Example 1
A method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide, see fig. 1, comprising the steps of:
a1: synthesis of DMDOMA: placing 5.20g of malonic acid, 14.33g N-methyl octylamine and 12.4g of TEA into a 500mL round bottom flask, adding 250mL of DMF, stirring, adding 45.72g of HATU, stirring for 1.5h for condensation reaction, extracting the product after the reaction by using ethyl acetate, washing the product by using saturated sodium chloride, saturated sodium bicarbonate, hydrochloric acid solution (1 mol/L) and saturated sodium chloride for 2 times in sequence, drying the organic phase by using anhydrous sodium sulfate, and distilling under reduced pressure to remove the solvent to obtain DMDOMA, wherein the yield is more than 92%;
a2: synthesis of ethoxyethyl 4-methylbenzenesulfonate: a500 mL round bottom flask was placed in a stirring magnet, 250mL DCM was added to the flask, the flask was placed in an ice bath (0 ℃ C.), 4.51g of 2- (hexyloxy) ethan-1-ol was weighed into the flask, followed by 30mL TEA, and after stirring for 2 minutes 9.53g PTSC was added dropwise. The ice bath was removed and nucleophilic substitution reaction was performed at room temperature for 2 hours. Extraction with ethyl acetate, washing with saturated sodium bicarbonate, saturated sodium chloride and hydrochloric acid solution respectively for 2 times, drying with anhydrous sodium sulfate, distilling under reduced pressure, purifying the product by column chromatography, eluting with ethyl acetate as solvent: petroleum ether (V: v=1:10) to obtain ethoxyethyl 4-methylbenzenesulfonate.
A3: synthesis of DMDOHEMA: a500 mL round bottom flask was taken, placed in a stirring magnet, 100mL DMF and 50mL THF were added to the flask, and placed in an ice bath (temperature 0 ℃). 0.48g of NaH (60%) was weighed in, followed by dropwise addition of 3.55g of DMDOMA and stirring for 10 minutes. 2.44g of ethoxyethyl 4-methylbenzenesulfonate was dissolved in 50mL of DMF and added dropwise to the reaction system. The round bottom flask was removed from the ice bath and reacted at 70℃under reflux for 24 hours. After the reaction was completed, cooled to room temperature, quenched with 50mL of water, extracted with ethyl acetate, washed 2 times with saturated sodium bicarbonate and saturated sodium chloride solution, dried over anhydrous sodium sulfate, distilled under reduced pressure, and the obtained product was purified by silica gel column chromatography, and the eluent was ethyl acetate: petroleum ether (V: V=3:10), silica gel mesh number 100-200 mesh, obtain product DMDOHEMA, yield 81%, actual diagram see figure 2.
Performing nuclear magnetic resonance analysis on the DMDOMA obtained in the step A1 to obtain 1 H-NMR spectrum, as shown in FIG. 3, with peak positions corresponding to DMDOMA, [ 1 H NMR(400MHz,CDCl3):δ0.9(t,6H),1.24(br,s,20H),1.5-1.6(m,4H)2.8-2.9,3.0-3.1(m,6H),3.37(t,4H)3.51-3.54(m,2H),3.7(m,4H)]
Performing nuclear magnetic resonance analysis on the ethoxy ethyl 4-methylbenzenesulfonate obtained in the step A2 to obtain 1 The H-NMR spectrum is shown in FIG. 4, and the peak position corresponds to the substance.
[ 1 H NMR(400MHz,CDCl3)δ0.88-0.91(m,3H),1.25-1.31(m,6H),1.48-1.52(m,2H),2.46(s,3H),3.37-3.40(t,J＝6.7Hz,2H),3.61-3.63(m,2H)4.16-4.19(m,2H),7.74-7.36(d,J＝8.2Hz,2H),7.81-7.83(d,J＝8.2Hz,2H)]
Performing nuclear magnetic resonance analysis on the DMDOHEMA obtained in the step A3 to obtain 1 The H-NMR spectrum, as shown in FIG. 5, demonstrates that the product structure is DMDOHEMA and that there are no peaks.
The peak position is: [ 1 H NMR(400MHz,CDCl3),δ:0.85(t,9H,J＝7Hz,CH3),1.2–1.3(m,26H,CH2),1.53-1.57(m,8H,CH2),2.75-3.14(m,6H,CH3),3.2-3.7(m,8H,CH2),4.1(m,1H,CH)]
And C, carrying out mass spectrometry on the DMDOHEMA obtained in the step A3 to obtain a mass spectrum, wherein the mass spectrum is consistent with the mass of the DMDOHEMA, and the DMDOHEMA is proved to be the product as shown in figure 6.
Example 2
A method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide, which comprises the following steps:
a1: synthesis of DMDOMA: placing 5.20g of malonic acid, 14.33g N-methyl octylamine and 12.4g of TEA into a 500mL round bottom flask, adding 250mL of DMF, stirring, adding 45.48g of HBTU, stirring for 1.5h for condensation reaction, extracting the product after the reaction by using ethyl acetate, washing the product by using saturated sodium chloride, saturated sodium bicarbonate, hydrochloric acid solution (1 mol/L) and saturated sodium chloride for 2 times in sequence, drying the organic phase by using anhydrous sodium sulfate, and distilling under reduced pressure to remove the solvent to obtain DMDOMA, wherein the yield is more than 92%;
a2: synthesis of ethoxyethyl 4-methylbenzenesulfonate: a500 mL round bottom flask was taken, placed in a stirring magnet, 250mL DCM was added to the flask, placed in an ice bath (0 ℃ C.), 4.51g of 2- (hexyloxy) ethan-1-ol was weighed into the flask, followed by 30mL of triethylamine, and after stirring for 2 minutes 9.53g of PTSC were added dropwise. The ice bath was removed and nucleophilic substitution reaction was performed at room temperature for 2 hours. Extraction with ethyl acetate, washing with saturated sodium bicarbonate, saturated sodium chloride and hydrochloric acid solution respectively for 2 times, drying with anhydrous sodium sulfate, distilling under reduced pressure, purifying the product by column chromatography, eluting with ethyl acetate as solvent: petroleum ether (V: v=1:10) to obtain ethoxyethyl 4-methylbenzenesulfonate.
A3: synthesis of DMDOHEMA: a500 mL round bottom flask was taken, placed in a stirring magnet, 100mL DMF and 50mL THF were added to the flask, and placed in an ice bath (temperature 0 ℃). 0.48g of NaH (60%) was weighed in, followed by dropwise addition of 3.55g of DMDOMA and stirring for 10 minutes. 2.44g of ethoxyethyl 4-methylbenzenesulfonate was dissolved in 50mL of DMF and added dropwise to the reaction system. The round bottom flask was removed from the ice bath and reacted at 70℃under reflux for 24 hours. After the reaction was completed, cooled to room temperature, quenched with 50mL of water, extracted with ethyl acetate, washed 2 times with saturated sodium bicarbonate and saturated sodium chloride solution, dried over anhydrous sodium sulfate, distilled under reduced pressure, and the obtained product was purified by silica gel column chromatography, and the eluent was ethyl acetate: petroleum ether (V: V=3:10), silica gel mesh number is 100-200 mesh, and the product DMDOHEMA is obtained with the yield of 80%.
Example 3
A method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide, which comprises the following steps:
a1: synthesis of DMDOMA: placing 5.20g of malonic acid, 14.33g N-methyl octylamine and 12.4g of TEA into a 500mL round bottom flask, adding 250mL of DMF, stirring, adding 49.64g of HCTU, stirring for 1.5h for condensation reaction, extracting the product with ethyl acetate after the reaction is finished, washing the product with saturated sodium chloride, saturated sodium bicarbonate, hydrochloric acid solution (1 mol/L) and saturated sodium chloride for 2 times in sequence, drying the organic phase with anhydrous sodium sulfate, and distilling under reduced pressure to remove the solvent to obtain DMDOMA, wherein the yield is more than 90%;
a2: synthesis of ethoxyethyl 4-methylbenzenesulfonate: a500 mL round bottom flask was taken, placed in a stirring magnet, 250mL DCM was added to the flask, placed in an ice bath (0 ℃ C.), 4.51g of 2- (hexyloxy) ethan-1-ol was weighed into the flask, followed by 30mL of triethylamine, and after stirring for 2 minutes 9.53g of PTSC were added dropwise. The ice bath was removed and nucleophilic substitution reaction was performed at room temperature for 2 hours. Extraction with ethyl acetate, washing with saturated sodium bicarbonate, saturated sodium chloride and hydrochloric acid solution respectively for 2 times, drying with anhydrous sodium sulfate, distilling under reduced pressure, purifying the product by column chromatography, eluting with ethyl acetate as solvent: petroleum ether (V: v=1:10) to obtain ethoxyethyl 4-methylbenzenesulfonate.
A3: synthesis of DMDOHEMA: a500 mL round bottom flask was taken, placed in a stirring magnet, 100mL DMF and 50mL THF were added to the flask, and placed in an ice bath (temperature 0 ℃). 0.48g of NaH (60%) was weighed in, followed by dropwise addition of 3.55g of DMDOMA and stirring for 10 minutes. 2.44g of ethoxyethyl 4-methylbenzenesulfonate was dissolved in 50mL of DMF and added dropwise to the reaction system. The round bottom flask was removed from the ice bath and reacted at 70℃under reflux for 24 hours. After the reaction was completed, cooled to room temperature, quenched with 50mL of water, extracted with ethyl acetate, washed 2 times with saturated sodium bicarbonate and saturated sodium chloride solution, dried over anhydrous sodium sulfate, distilled under reduced pressure, and the obtained product was purified by silica gel column chromatography, and the eluent was ethyl acetate: petroleum ether (V: V=3:10), silica gel mesh number is 100-200 mesh, and the product DMDOHEMA is obtained with the yield of 79%.
As can be seen from the above examples, the synthesis of DMDOMA, an intermediate product, using HATU, HBTU or HCTU as condensing agent, is gentle in reaction conditions, extremely high in yield, and free of column chromatography. Is beneficial to the realization of large-scale synthesis and saves equipment cost and labor cost in the industrialized process.
While the invention has been described in detail in the foregoing general description, embodiments and experiments, it will be apparent to those skilled in the art that modifications and improvements can be made thereto. Accordingly, such modifications or improvements may be made without departing from the spirit of the invention and are intended to be within the scope of the invention as claimed.
Claims (10)
1. A method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide, which is characterized by comprising the following steps:
a1: synthesis of DMDOMA: mixing malonic acid and N-methyl octylamine, mixing TEA, adding a first organic solvent, stirring, adding a condensing agent, stirring for condensation reaction, extracting, washing, drying and distilling to obtain DMDOMA;
a2: synthesis of ethoxyethyl 4-methylbenzenesulfonate: placing a second organic solvent under ice bath, stirring, adding 2- (hexyloxy) ethane-1-alcohol, triethylamine and PTSC, removing the ice bath, performing nucleophilic substitution reaction, extracting, washing, drying, distilling and purifying to obtain 4-methylbenzenesulfonic acid ethoxyethyl ester;
a3: synthesis of DMDOHEMA: and (3) placing the third organic solvent in ice bath, adding catalyst, DMDOMA and 4-methyl benzene sulfonate ethoxyethyl ester, removing the ice bath, raising the temperature to a certain temperature for reflux reaction, cooling, adding water for quenching, extracting, washing, drying, distilling and purifying to obtain DMDOHEMA.
2. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide according to claim 1, wherein in step A1, the molar ratio of malonic acid, N-methyl octylamine, TEA and condensing agent is 1:2: (2.1-3): (2.1-3).
3. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide according to claim 1, wherein in the step A1, the first organic solvent is DMF, DCM, and the molar volume ratio of the malonic acid to the first organic solvent is 0.05-10 mol/L.
4. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide according to claim 1, wherein in step A1, said condensing agent comprises HATU, HBTU, HCTU.
5. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyloxyethyl malonamide according to claim 1, wherein in step A2, the molar ratio of the 2- (hexyloxy) ethane-1-ol to the PTSC is 1: (1.4-2).
6. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyloxyethyl malonamide according to claim 1, wherein in the step A2, the molar volume ratio of the 2- (hexyloxy) ethane-1-ol to TEA is 1-3mol/L.
7. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyloxyethyl malonamide according to claim 1, wherein in step A2, the second organic solvent comprises DCM, and the molar volume ratio of the 2- (hexyloxy) ethane-1-ol to the second organic solvent is 0.05 to 10mol/L.
8. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide according to claim 1, wherein in step A3, the molar ratio of the catalyst, DMDOMA, 4-methyl benzenesulfonic acid ethoxyethyl ester is (1-1.5): 1: (1-1.5).
9. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide according to claim 1, wherein in step A3, the catalyst is NaH, the third organic solvent comprises DMF, THF or a mixture of both, and the molar volume ratio of DMDOMA to the third organic solvent is 0.05-10 mol/L.
10. The method for synthesizing N, N '-dimethyl-N, N' -dioctyl hexyl oxyethyl malonamide according to claim 1, wherein in step A3, the temperature of the reflux reaction is 60-90 ℃.
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