Method for preparing tetra (dimethylamino) ethylene by one stepTechnical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing tetra (dimethylamino) ethylene by one step.
Background
Tetra (dimethylamino) ethylene (TDAE) is an organic reducing agent that can replace some of the practical use of flammable elemental metals (e.g., zinc dust) in organic reactions.
There are many reports about the reaction involved in TDAE, which is usually used for dehalogenating polyhalogenated compounds to prepare olefins, and can also be used as a reducing agent to participate in nickel-catalyzed or palladium-catalyzed reductive coupling reaction, and in addition, can also be used for carrying out addition reaction on aldehyde ketone or imine compounds by reacting with trifluoroiodomethane to obtain trifluoromethyl anions or benzyl anions.
At present, only one reported TDAE synthesis route exists (org. Lett.2017,19, 2150-2153.) and the high temperature reaction requiring two steps of time and the dangerous reaction involving lithium salt in one step make the preparation cost high, and limit the application of the TDAE synthesis route in the field of organic synthesis. In order to reduce the production cost, a new preparation method needs to be developed.
The current method for preparing TDAE requires the following three steps:
The first step: DMF was reacted with N, N-dimethylcarbamoyl chloride at 120℃for 3 days to give (dimethylaminomethylene) dimethyl ammonium chloride
And a second step of: the lithium dimethylamino is added to the product of the first step to obtain the tri (dimethylamino) methane
And a third step of: tris (dimethylamino) methane was reacted at 180℃for 5 days to give TDAE
。
Disclosure of Invention
The invention aims to: aiming at the defects and shortcomings in the prior art, the invention provides a method for preparing tetra (dimethylamino) ethylene by one step, and the method uses low-cost tetramethyl urea for deoxidization coupling, so that a target product can be obtained by only one step, the time cost, the material cost and the energy consumption of the reaction are reduced, and the high-temperature reaction of two step time and the dangerous reaction involving lithium salt in one step required by the prior method are avoided.
The technical scheme is as follows: in order to achieve the above object, the present invention provides a process for preparing tetra (dimethylamino) ethylene by one step, comprising the steps of:
Adding tetramethylurea and an organic solvent into a reaction container under inert gas atmosphere, adding titanium tetrachloride under low temperature, then stirring at room temperature, adding zinc powder, refluxing after the addition, recovering the room temperature after the reaction, quenching the reaction, filtering to remove salt, separating the obtained filtrate, extracting, washing an organic phase, drying, filtering, concentrating the filtrate to obtain a crude product, and then distilling under reduced pressure to collect fractions to obtain the tetra (dimethylamino) ethylene TDAE.
Wherein the molar ratio of the tetramethylurea to the titanium tetrachloride is 1:1-1:2, and the molar ratio of the titanium tetrachloride to the zinc powder is fixed to be 1:2.
Preferably, the molar ratio of the tetramethylurea to the titanium tetrachloride is 1:1.5.
Wherein the organic solvent is any one or more of tetrahydrofuran and methyl tertiary butyl ether.
Preferably, the organic solvent is tetrahydrofuran.
Wherein the low temperature condition is-30-0 ℃.
Preferably, the low temperature condition is-30-20 ℃. More preferably, the temperature is-30 ℃.
Wherein, the mixture is stirred for 0.5 to 1 hour at room temperature, and then zinc powder is added.
Wherein, the reflux reaction is carried out for 10-12h after the zinc powder is added.
Wherein, hydrochloric acid is added for quenching reaction, diatomite is used for filtering and desalting after stirring, the obtained filtrate is separated, ethyl acetate is used for extracting the water phase, the obtained organic phase is combined and washed by saturated sodium bicarbonate, anhydrous sodium sulfate is used for drying the organic phase, the filtration is carried out, the filtrate is concentrated to obtain a crude product, and then the 65 ℃ fraction is collected by reduced pressure distillation to obtain TDAE.
The reaction general formula of the method is shown as follows:
。
in the prior art, the target product is obtained by coupling the target product by removing dimethylamine from tris (dimethylaminomethane) at high temperature, and the method can bypass the use of tris (dimethylaminomethane), so that the high-temperature condition is avoided.
The beneficial effects are that: compared with the prior art, the invention has the following remarkable advantages:
the invention provides a brand new method for preparing tetra (dimethylamino) ethylene by one step, which effectively reduces the number of reaction steps and the cost, adopts cheap and easily obtained raw materials, has no harsh condition, has simple reaction treatment and good yield,
Is suitable for the process amplification process.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of tetra (dimethylamino) ethylene synthesized according to the present invention.
Detailed Description
The invention is further illustrated below with reference to examples.
The experimental methods described in the examples, unless otherwise specified, are all conventional; materials, reagents and the like used in the examples are commercially available unless otherwise specified.
Example 1
The four-necked flask was replaced with a stirrer for N2 times, then tetramethylurea (30 g) and tetrahydrofuran (500 mL) were added, cooled to-30℃and then titanium tetrachloride (73.48 g) was added, followed by stirring at room temperature for 0.5h, zinc powder (50.66 g) was added, and after the addition was completed, reflux reaction was carried out at 80℃for 12h. After completion of the reaction, the reaction was quenched by adding 1M hydrochloric acid (400 mL), stirring for 10min, then filtering with celite, separating the filtrate, extracting the aqueous phase twice more with ethyl acetate (500 mL), washing the combined organic phase with saturated sodium bicarbonate (300 mL), drying the organic phase with anhydrous sodium sulfate, filtering, concentrating the filtrate to obtain a crude product, and then distilling under reduced pressure to collect 65℃fraction to obtain TDAE (22.7 g,88% yield).1H NMR (400 MHz, C6D6 ) Delta 2.39 (s, 1H.) the nuclear magnetic pattern is shown in FIG. 1.
Example 2
The four-necked flask was stirred for three times with N2, then tetramethylurea (30 g) and tetrahydrofuran (500 mL) were added, cooled to 0℃and then titanium tetrachloride (73.48 g) was added, followed by stirring at room temperature for 0.5h, zinc powder (50.66 g) was added, and after the addition was completed, reflux reaction was carried out at 80℃for 12h. After completion of the reaction, the reaction was quenched by adding 1M hydrochloric acid (400 mL), stirring for 10min, then filtering with celite, separating the filtrate, extracting the aqueous phase twice more with ethyl acetate (500 mL), washing the combined organic phase with saturated sodium bicarbonate (300 mL), drying the organic phase with anhydrous sodium sulfate, filtering, concentrating the filtrate to obtain a crude product, and then distilling under reduced pressure to collect 65℃fraction to obtain TDAE (18.6 g,72% yield).
Example 3
The four-necked flask was stirred for three times with N2, then tetramethylurea (30 g) and methyl t-butyl ether (500 mL) were added, cooled to-30℃and then titanium tetrachloride (73.48 g) was added, followed by stirring at room temperature for 0.5h, zinc powder (50.66 g) was added, and after the addition was completed, the reaction was refluxed at 80℃for 12h. After completion of the reaction, the reaction was quenched by adding 1M hydrochloric acid (400 mL), stirring for 10min, then filtering with celite, separating the filtrate, extracting the aqueous phase twice more with ethyl acetate (500 mL), washing the combined organic phase with saturated sodium bicarbonate (300 mL), drying the organic phase with anhydrous sodium sulfate, filtering, concentrating the filtrate to obtain a crude product, and then distilling under reduced pressure to collect 65℃fraction to obtain TDAE (17.6 g,68% yield).
Example 4
The four-necked flask was stirred for three times with N2, then tetramethylurea (30 g) and tetrahydrofuran (500 mL) were added, cooled to-30deg.C, then titanium tetrachloride (58.78 g) was added, then stirred for 0.5h at room temperature, then zinc powder (40.53 g) was added, and after the addition was completed, the reaction was refluxed at 80℃for 12h. After completion of the reaction, the reaction was quenched by adding 1M hydrochloric acid (400 mL), stirring for 10min, then filtering with celite, separating the filtrate, extracting the aqueous phase twice more with ethyl acetate (500 mL), washing the combined organic phase with saturated sodium bicarbonate (300 mL), drying the organic phase with anhydrous sodium sulfate, filtering, concentrating the filtrate to obtain a crude product, and then distilling under reduced pressure to collect 65℃fraction to obtain TDAE (17.1 g,66% yield).
As can be seen from the above examples, the present invention can effectively reduce the number of reaction steps and reduce the cost by preparing tetra (dimethylamino) ethylene in one step. At the same time, the choice of solvent, the temperature at which titanium tetrachloride is added, and the amount of titanium tetrachloride and zinc powder (both of which must be consistent) all have significant effects on yield. Where example 1 is the preferred example, for example, the titanium tetrachloride addition temperature is-30 ℃, the yield cannot be significantly increased by continuing to decrease the temperature, while increasing to 0 ℃ significantly decreases the yield, and changing the solvent also results in a decrease in yield, but the yields of the various examples of the present invention still exceed the prior art methods.
Comparative example 1
The first step: the stirrer was added to a four-necked flask, the reflux condenser was connected, and N2 was replaced three times, followed by N, N-dimethylformamide (46 mL) and anhydrous DMF (77 mL) were added, and the mixture was heated to 120℃and reacted for 3 days. After completion of the reaction, the reaction mixture was returned to room temperature, and diethyl ether (300 mL) was added thereto for crystallization and filtration to give (dimethylaminomethylene) dimethyl ammonium chloride (60.3 g,88% yield).
And a second step of: a four-necked flask was stirred for three times to replace N2, then dehydrated ether (500 mL) and a 2M solution of dimethylamine in tetrahydrofuran (440 mL) were added, the temperature was lowered to-78℃and then a 2.5M solution of N-butyllithium in N-hexane (210 mL) was added, followed by stirring at room temperature for 30 minutes to obtain a solution of lithium dimethylamino turbidity. The turbid liquid was cooled to 0 ℃ again, and then (dimethylaminomethylene) dimethyl ammonium chloride (60.3 g) obtained in the first step was added thereto, followed by stirring at room temperature for 8 hours, and after completion of the reaction, the solvent was distilled off at normal pressure, and the obtained residue was distilled under reduced pressure to obtain tris (dimethylamino) methane (45.2 g,71% yield).
And a third step of: the stirrer was added to the four-necked flask, and the reflux condenser was connected to exchange N2 three times, followed by adding tris (dimethylamino) methane (45.2 g) obtained in the previous step, heating to 180℃and then reacting for 5 days. After the completion of the reaction, distillation under reduced pressure was performed, and the remaining raw material was distilled off at 30℃and then a 65℃fraction was collected to obtain tetrakis (dimethylamino) ethylene (19.4 g,62% yield).
As can be seen from the method of comparative example 1, the existing method uses tri (dimethylaminomethane) to remove dimethylamine at high temperature to obtain carbene for coupling to obtain the target product, and the high-temperature reaction requiring two steps of time and the one-step dangerous reaction involving lithium salt are long in route, high in cost and obviously inferior to the method of the invention in yield.