* 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.
acetic acid; diethylamine; In 2-methyl-propan-1-ol; for 9h;Heating / reflux;
4-Aminobenzaldehyde oligomer (36.3 g, 0.3 mol) is suspended in 450 ml of isobutanol. 2-ethylhexyl cyanoacetate (59.1 g, 0.3 mol) and a catalyst consisting of diethylamine (0.375 ml) and of acetic acid (1.12 ml) are added thereto. The mixture is refluxed for 5 hours. A second addition of catalyst was performed and the reaction mixture refluxed for a further 4 hours. A light amount of insoluble material is filtered off while hot. After cooling the filtrate, it is concentrated to a volume of 300 ml and allowed to crystallize under cold conditions. After drying, 59.6 g (yield: 66%) of the expected derivative are obtained in the form of an orange-coloured solid.
2-ethylhexyl 3-(4-aminophenyl)-2-cyanoacrylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With acetic acid; In isopropyl alcohol;
a) Preparation of 2-ethylhexyl 3-(4-aminophenyl)-2-cyanoacrylate 36.3 g (0.3 mol) of p-aminobenzaldehyde are suspended in 450 ml of isopropanol. A mixture of 59.1 g (0.3 mol) of 2-ethylhexyl cyanoacetate and of catalyst (0.375 ml of diethylamine and 1.125 ml of acetic acid) is introduced therein. The mixture is refluxed for 5 hours. The same amount of catalyst is added again and refluxing is continued for a further 4 hours. The insoluble materials are removed by hot filtration and the mixture is concentrated to a volume of 300 ml and left to crystalize. After filtration and drying, 59.6 g (66% yield) of an orange-coloured powder are obtained, and are used without further purification for the following step.
2-ethylhexyl 3-(4-acetylaminophenyl)-2-cyanoacrylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
In isopropyl alcohol;
a) Preparation of 2-ethylhexyl 3-(4-acetylaminophenyl)-2-cyanoacrylate A mixture of 35 g (0.18 mol) of 2-ethylhexyl cyanoacetate and 30 g (0.18 mol) of 4-acetamidobenzaldehyde in 300 ml of isopropanol is refluxed for 3 hours. The reaction mixture is then allowed to cool and is crystallized. The crystals formed are separated out by filtration and are recrystallized from a minimum amount of isopropanol. After filtration and drying, 33.3 g (54% yield) of 2-ethylhexyl 3-(4-acetylaminophenyl)-2-cyanoacrylate are obtained in the form of a pale yellow powder. Melting point: 119 C. UW absorption (as a solution in ethanol): λmax=351 nm, εmax=30 960, EI %=904 Elemental analysis for C20H26N2O3 calculated: C 70.15; H 7.65; N 8.18; O 14.02 found: C 70.08; H 7.65; N 8.16; O 14.03
With toluene-4-sulfonic acid; In water; at 110℃; under 760.051 Torr; for 1h;Heating / reflux;
To a 1000 ml four neck flask fitted with mechanical agitator, thermometer, Dean and Stark apparatus and water condenser, add 237.5g (2.23 mol on pure substance) 80 wt.-% cyanoacetic acid in water, 44Og (3.38 mol) 2-ethylhexanol and 1.2g (6.3 mmol) p-toluenesulfonic acid monohydrate. Afterwards, the mixture is heated to reflux (1 100C) under atmospheric pressure for 1 hour and the water (both initial and formed) is azeotropically distilled out using a Dean and Stark apparatus returning the upper organic layer to the reactor. After 1 hour and at a temperature of 1300C gradually a vacuum of 400 mbar is applied using a water respirator. The azeotropic distillation is maintained for further 6 hours while gradually increasing the vacuum from 400 mbar to 30 mbar in order to maintain a temperature of 1300C until no further water is removed. After releasing the vacuum the reaction mixture is cooled to 900C. After the addition of about 100ml water (pre heated to 900C), the mixture is stirred at 85-900C for 10 minutes before separation of the phases. The upper organic layer is transferred to a 1000 ml four neck flask fitted with mechanical agitator, thermometer, packed column (ID=30mm, H=I 200mm, packing metal raschid rings D=7mm), water condenser and distillate flasks. Excess 2-Ethylhexanol is distilled out at 130- 1400C under a vacuum of 10-30 mbar. When complete increase the vacuum to 1.5 mbar and distilled out 2-ethylhexyl cyanoacetate at 130-1400C. 2-Ethylhexyl cyanoacetate is obtained as a colourless liquid. The reaction yield is 92% (based on cyanoacetic acid).
With ammonium acetate; acetic acid; In water; at 85 - 90℃; under 400 - 420 Torr; for 16h;
A 1000 mL four neck round bottom flask, equipped with a mechanical stirrer, a thermometer and a condenser, was charged with 2-ethylhexyl cyanoacetate (347 g, 1.76 gmol), benzophenone (200 g, 1.1 gmol) , recovered acetic acid (168.3 g containing 2% water, 2.75 gmol) and ammonium acetate (3 lg, 0.4 gmol). The stirred reaction mass was then heated to 85-90C. Azeotrope of acetic acid/water mixture was distilled off oyer a period of 16 h. under reduced pressure from 400-420 mm of Hg A till the Gas chromatographic analysis showed no further decrease in benzophenone concentration in reaction mass. The loss of acetic acid was continuously adjusted by adding the corresponding recovered acetic acid. The acetic acid was then recovered under reduced pressure (30-60 mm of Hg A). The HPLC analysis of reaction mass showed BPCA content of 0.19%. The crude reaction mixture was cooled and washed twice with 300 g portion of water and subsequently distilled to yield pale yellow colored viscous liquid (303 g, Yield 76.3%) which was found to be of 99.48% purity by Gas chromatographic analysis.
66.18 - 93.09%
With propionic acid;ammonium acetate; In n-heptane; at 110℃; under 760.051 Torr; for 5h;Product distribution / selectivity;
Into a 500ml four-neck round-bottom flask, equipped with a mechanical stirrer, a thermometer and a condenser is charged with 62.2 g (0.32mol) of 2-Ethylhexyl cyanoacetate (EHCA) and 81.Og (0.45 mol) of Benzophenone (BP) (molar ratio EHCA:BP = 0.71 : 1) and 27.7g (0.36 mol) of ammonium acetate and 81.0g (1.1 mol) of propionic acid and 81.0g of heptane. The mixture is heated under stirring. When the temperature reach H O0C, a mixture of propionic acid, water, heptane is distilled off over a period of 5 hours at normal pressure. Heptane phase is returned back to the flask. Then the reactant is cooled to 900C, and 100 ml of hot water is added to the reaction mixture. The mixture is kept at 85C for 10 minutes, and then transferred to a funnel for separation. To a flask equipped with a column 256.Og of crude 2-ethylhexyl 2-cyano-3,3- diphenylacrylate solution is added. Rectification is carried out at 1 mbar. 2-Ethylhexyl 2-cyano- <n="9"/>3,3-diphenylacrylate is distilled out at 2100C (vapor). After distillation, light yellow 2-ethylhexyl 2-cyano-3,3-diphenylacrylate is obtained. Reaction yields are as indicated in table 1 and assume recycle of unreacted benzophenone and 2-EHCA.The experiment is repeated by adjusting the amount of 2-EHCA in order to give the molar ratios as indicated in the table 1 below.
With propionic acid;ammonium acetate; In n-heptane; at 95 - 110℃; under 525.053 - 760.051 Torr; for 6h;Heating / reflux;Product distribution / selectivity;
A 2000ml reactor is charged with 3 U g of 2-ethylhexyl cyanoacetate, 70 g of ammoniumacetate, 404 g of benzophenones, 405 g of propionic acid and 405 g of n-heptane. The mixture is heated to about 950C under stirring at reduced pressure (about 700 mbar in order to maintain the reaction at reflux). When the temperature reached 950C a mixture of heptane, water and propionic acid is distilled off azeotropically over a period of 6h wherein the organic phase is recharged back in the reactor. During this time every hour 25 g of additional ammonium acetate is added stepwise (5 portions, 1 per hour). After the reaction is finished heptane and propionic acid are distilled off at reduced vacuum (up to 20 mbar while keeping the temperature below about 95C). When no more distillate is observed, 500g of water is added and the mixture is stirred for 10 min at 75C. After adding 340 g of n-heptane the organic phase is collected and the washing procedure is repeated. After evaporation of the solvent at reduced pressure (temperature is maintained below 95C) the crude product (comprising about 0.04 % of 2-cyano-3,3-diphenyl-2-propenamide) is collected followed by distillation using a wiped thin film evaporator. A second distillation yielded 388 g of light yellow octocrylene comprising about 0.38 % of 2-cyano-3,3-diphenyl- 2-propenamide (determined via HPLC). The reaction is repeated at normal pressure and a temperature of about HO0C (reflux temperature) resulting after purification in an amount of 0.7 % of 2-cyano-3,3- diphenyl- 2-propenamide
[N- (3-ANILINO-ALLYLIDENE)-ANILINE] (4.5 g, 0.02 mol) and cyanoacetic acid 2-ethylhexyl ester (4.2 g, 0.021 mol) are stirred in 10 ml of acetanhydride for 2 hours at [85-90XB0;C.] After removing the excess of acetanhydride in vacuo, the reaction batch is poured onto ice, and the resulting precipitate is filtered off and washed with copious amounts of water. After drying in vacuo at [60XB0;C,] the intermediate product is taken up in 10 ml of dry ethanol, and diethylamine (3.1 g, 0.042 mol) is added. The reaction mixture is stirred for 2 hours at 50- [55XB0;C.] The ethanol and the excess of amine are then distilled off in vacuo. The residue, in a mixture of toluene and acetone (9.5 : 0.5), is subjected to fractionated filtration over silica gel 60 from Merck and isolated. The pure product is dried under a high vacuum at [60XB0;C.] Yield : 4.5 g (73.5 % of theory).
[N- (3-ANILINO-ALLYLIDENE)-ANILINE] (4.5 g, 0.02 mol) and cyanoacetic acid 2-ethylhexyl ester [(4. 2] g, 0.021 mol) are stirred in 10 ml of acetanhydride for 2 hours at [85-90XB0;C.] After removing the excess of acetanhydride in vacuo, the reaction batch is poured onto ice, and the resulting precipitate is filtered off and washed with copious amounts of water. After drying in vacuo at [60XB0;C,] the intermediate product is taken up in 10 mi of dry ethanol, and piperazine (0.8 g, 0.01 mol) is added. After stirring for 2 hours at [50-55XB0;C,] the ethanol is distilled off in vacuo. Subsequent column chromatography over silica gel 60 from Merck using a mixture of toluene and acetone (9: 1) yields the pure product, which is [DRIED IN VACUO] at [60XB0;C.] Yield : 3.9 g (69 % of theory).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
