CN116212764B - Method for industrially synthesizing 2, 2-diphenyl ethanol by using continuous flow equipment - Google Patents

Abstract

The invention discloses a method for industrially synthesizing 2, 2-diphenyl ethanol by using continuous flow equipment, which comprises the following steps: s1, introducing a solution into the storage tank through an industrial diaphragm pump set, filling the solution into a pipeline, and discharging the gas in the storage tank; s2, introducing the solution into the reaction device through an industrial diaphragm pump set, and controlling the reaction temperature in the reaction device to perform three-stage reaction; s3, quenching the reaction by water to prepare the 2, 2-diphenyl ethanol. The invention has the innovation point that the continuous flow equipment is used in industry, a large amount of 2, 2-diphenyl ethanol can be synthesized, the risk coefficient of reaction amplification is reduced, the method has important significance for green environment protection, and a crude product with high purity (GC purity is 80% -90%) is obtained, so that the method has important significance.

Description

Method for industrially synthesizing 2,2-diphenylethanol using continuous flow equipment

Technical Field

The invention relates to the technical field of 2,2-diphenylethanol synthesis, in particular to a method for industrially synthesizing 2,2-diphenylethanol by utilizing continuous flow equipment.

Background technique

2,2-Diphenylethanol is an important intermediate for synthesizing many bioactive molecules, drugs, and other materials. For example, 2,2-Diphenylethanol is a key intermediate in the synthesis of proxylin and oxadiazole. In addition to blocking the influx of Ca2+, proxylin calcium antagonists also have phosphodiesterase and anti-sympathetic effects. Reducing myocardial contractility and relaxing vascular smooth muscle can increase coronary flow and reduce myocardial oxygen consumption. It plays an important role in the clinical treatment of cardiovascular and cerebrovascular diseases such as hypertension, angina pectoris, arrhythmia, cerebral vasospasm, and myocardial ischemia. Oxadiazole is mainly absorbed by the root system, inhibiting the cell division of the meristem of weeds, preventing the formation of young shoots and secondary roots, and killing weeds. In addition, it is also an important intermediate for some small molecule inhibitors. Therefore, the industrial synthesis of 2,2-diphenylethanol is of great significance.

At present, the main methods for synthesizing 2,2-diphenylethanol are boric acid oxidation, metal catalysis, and carbonyl reduction. The above synthesis methods require the use of catalysts, gases, or peroxides, etc. This method has great hazards, and the operation or post-processing is complicated, the risk factor is high, and it also has a certain destructive effect on the environment.

In order to solve the above problems, we propose a more practical method for industrially synthesizing 2,2-diphenylethanol using continuous flow equipment.

Summary of the invention

The object of the present invention is to provide a method for industrially synthesizing 2,2-diphenylethanol by utilizing a continuous flow device, thereby solving the existing problems.

To achieve the above-mentioned object, the present invention provides the following technical solution: a continuous flow device, comprising a storage tank, a mass flow meter, a damper and a back pressure valve arranged on the storage tank, and an industrial diaphragm pump group connected to the storage tank;

The industrial diaphragm pump group is connected to the reaction device;

The industrial diaphragm pump group includes an industrial diaphragm pump A, an industrial diaphragm pump B, an industrial diaphragm pump C and an industrial diaphragm pump D.

Preferably, the height of the storage tank is 1.5 meters higher than the industrial diaphragm pump.

The method for industrially synthesizing 2,2-diphenylethanol using a continuous flow device comprises the following steps:

S1. Introduce the solution into the storage tank through the industrial diaphragm pump group, fill the pipeline with the solution, and discharge the internal gas of the storage tank;

S2, introducing the solution into the interior of the reaction device through an industrial diaphragm pump group, and controlling the reaction temperature inside the reaction device to perform a three-stage reaction;

S3. The reaction is quenched with water to produce 2,2-diphenylethanol.

Preferably, the solution comprises styrene oxide solution, boron trifluoride ether solution and an organic lithium reagent;

Wherein, the solvent used in the styrene oxide solution is at least one of toluene, tetrahydrofuran and anhydrous ether;

The solvent used in the boron trifluoride ether solution must be toluene;

The organic lithium reagent is one of butyl lithium, sec-butyl lithium and tert-butyl lithium.

Preferably, the step S1 further comprises the following steps:

The bromobenzene solution and butyl lithium were pumped in simultaneously by industrial diaphragm pump A, and then 5 minutes later, the styrene oxide solution was pumped in by diaphragm pump C, and 10 minutes later, the boron trifluoride ether solution was pumped in by industrial diaphragm pump D.

Preferably, the flow rate of the industrial diaphragm pump A is 250g/min-330g/min, the flow rate of the industrial diaphragm pump B is 100g/min-200g/min, the flow rate of the industrial diaphragm pump C is 220g/min-280g/min, and the flow rate of the industrial diaphragm pump D is 260g/min-320g/min.

Preferably, in step S2, the reaction device controls the reaction temperature in three stages, wherein the temperature of the first stage is -70°C to -75°C, the temperature of the second stage is -60°C to -75°C, and the temperature of the third stage is -72°C to -78°C.

Preferably, in step S2, the retention time of the first section is 5 min-10 min, the retention time of the second section is 4 min-8 min, and the retention time of the third section is 6 min-9 min.

Compared with the prior art, the present invention has the following beneficial effects:

The present invention overcomes the shortcomings of the prior art, including the amount of catalyst used, the danger of peroxides, and the complicated operation, and is of great significance for developing new process methods.

Today, continuous flow technology is a hot topic in the chemical industry and is also the current and future development direction, reflecting the value of green chemistry. Because continuous flow technology has the following advantages

1) Continuous flow reaction has better heat and mass transfer effects;

2) Continuous flow chemistry has fast reaction speed and short reaction time;

3) There is no amplification effect in continuous flow reactions, thus avoiding the loss caused by the amplification effect;

4) Continuous flow reaction has the characteristics of simple operation and low risk factor.

The innovation of the present invention is that continuous flow equipment is used in industry to synthesize 2,2-diphenylethanol in large quantities, which reduces the risk factor of reaction amplification, is of great significance to green environmental protection, and obtains a high-purity crude product (GC purity is 80% to 90%), making the present invention of great significance.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a schematic diagram of the synthesis process of the present invention;

FIG. 2 is a schematic diagram of the device structure of the present invention.

Detailed ways

The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

The invention relies on nitrogen to balance the system pressure and uses an industrial diaphragm pump to realize continuous production through continuous feeding and discharging. The reaction is carried out in a sequential manner to undergo lithium halogen exchange between butyl lithium and phenyl bromide to obtain a phenyl lithium intermediate, which is further subjected to nucleophilic substitution with epoxy, and then undergoes ring opening under the action of boron trifluoride etherate, and finally the reaction is quenched by water, and then a target product is obtained through simple post-treatment.

Reaction process synthesis route:

Implementation Case 1:

As shown in Figures 1 and 2, a method for industrially synthesizing 2,2-diphenylethanol using a continuous flow device includes a storage tank, a mass flow meter, a damper and a back pressure valve configured on the storage tank, and an industrial diaphragm pump group connected to the storage tank, wherein the height of the storage tank is 1.5 meters higher than the industrial diaphragm pump;

The industrial diaphragm pump group is connected to the reaction device;

The industrial diaphragm pump group includes an industrial diaphragm pump A, an industrial diaphragm pump B, an industrial diaphragm pump C and an industrial diaphragm pump D.

The method for industrially synthesizing 2,2-diphenylethanol using a continuous flow device comprises the following steps:

S1. Introduce the solution into the storage tank through the industrial diaphragm pump group, fill the pipeline with the solution, and discharge the internal gas of the storage tank;

The solution includes styrene oxide solution, boron trifluoride ether solution and an organic lithium reagent;

Wherein, the solvent used in the styrene oxide solution is at least one of toluene, tetrahydrofuran and anhydrous ether;

The solvent used in the boron trifluoride ether solution must be toluene;

The organic lithium reagent is one of butyl lithium, sec-butyl lithium and tert-butyl lithium;

The bromobenzene solution and butyl lithium were pumped in simultaneously by industrial diaphragm pump A, and then styrene oxide solution was pumped in by diaphragm pump C after 5 minutes, and boron trifluoride ether solution was pumped in by industrial diaphragm pump D after 10 minutes;

The flow rate of the industrial diaphragm pump A is 250g/min-330g/min, the flow rate of the industrial diaphragm pump B is 100g/min-200g/min, the flow rate of the industrial diaphragm pump C is 220g/min-280g/min, and the flow rate of the industrial diaphragm pump D is 260g/min-320g/min;

S2, introducing the solution into the interior of the reaction device through an industrial diaphragm pump group, and controlling the reaction temperature inside the reaction device to perform a three-stage reaction;

The reaction device controls the reaction temperature in three stages, wherein the temperature of the first stage is -70°C to -75°C, the temperature of the second stage is -60°C to -75°C, and the temperature of the third stage is -72°C to -78°C;

The retention time of the first segment is 5min-10min, the retention time of the second segment is 4min-8min, and the retention time of the third segment is 6min-9min;

S3. The reaction is quenched with water to produce 2,2-diphenylethanol.

Specific implementation case 2:

As shown in Figure 1, each storage tank is protected with nitrogen, and then the tetrahydrofuran solution of bromobenzene is pumped into the storage tank with a diaphragm plunger pump, butyl lithium is pressed into the storage tank with nitrogen, the tetrahydrofuran solution of styrene oxide is pumped into the storage tank with a diaphragm plunger pump, and the toluene solution of boron trifluoride ether is pumped into the storage tank with a diaphragm plunger pump. The first reaction temperature is controlled at about -70 ^° C, the second reaction temperature is controlled at about -63 ^° C, and the third reaction temperature is -75 ^{° C.} C; exhaust and other operations were performed in advance to fill the pipeline with liquid, and then pump 1 and pump 2 were turned on at the same time to perform lithium halogen exchange in the reaction tube for 7 minutes, and the intermediate 2 obtained above and the THF solution of styrene oxide were subjected to nucleophilic substitution in the reaction tube for 5.5 minutes; finally, the intermediate 3 obtained in the second step was subjected to ring opening with the toluene solution of boron trifluoride ether in the reaction tube for 7 minutes; then the reactants were passed into (a 1/2 ice-water mixture) for quenching, and then the supernatant was taken and analyzed by GC, and the purity of the crude product was 86.1%;

¹ H NMR (400 MHz, CDCl ₃ ): δ=7.37-7.35 (m, 4H), 7.31-7.29 (m, 4H), 7.28-7.26 (m, 2H), 4.26-4.24 (m, 1H), 4.20 (t, J=6.6 Hz, 2H), 1.58 (t, J=6.2 Hz, 1H).

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims (4)

1. A method for synthesizing 2,2-diphenylethanol in industry by continuous flow equipment, characterized in that an industrial diaphragm pump is used to continuously feed and discharge materials to realize continuous production, the reaction is carried out by sequentially adding materials, undergoes lithium halogen exchange of an organic lithium reagent and phenyl bromide to obtain a phenyl lithium intermediate, further undergoes nucleophilic substitution with epoxy of styrene oxide solution, and then undergoes ring opening under the action of boron trifluoride etherate solution, and finally the reaction is quenched by water, and then a target product is obtained through simple aftertreatment. 2. The method for industrially synthesizing 2,2-diphenylethanol using a continuous flow device according to claim 1, characterized in that the continuous flow device comprises a storage tank, a mass flow meter, a damper and a back pressure valve configured on the storage tank, and an industrial diaphragm pump group connected to the storage tank; The industrial diaphragm pump group is connected to the reaction device; The industrial diaphragm pump group includes an industrial diaphragm pump A, an industrial diaphragm pump B, an industrial diaphragm pump C and an industrial diaphragm pump D. 3. The method for industrially synthesizing 2,2-diphenylethanol by continuous flow equipment according to claim 2, characterized in that the height of the storage tank is 1.5 meters higher than an industrial diaphragm pump. 4. The method for industrially synthesizing 2,2-diphenylethanol using a continuous flow device according to claim 1, characterized in that the solvent used in the styrene oxide solution is at least one of toluene, tetrahydrofuran and anhydrous ether; The solvent used in the boron trifluoride ether solution must be toluene; The organic lithium reagent is one of butyl lithium, sec-butyl lithium and tert-butyl lithium.