CN116514851A - Preparation process of lithium diisopropylamide - Google Patents

Abstract

The application relates to the technical field of chemical intermediate preparation, and particularly discloses a preparation process of lithium diisopropylamide, which comprises the steps of cleaning and drying a reaction kettle, replacing gas in the reaction kettle by inert gas, and keeping the inert gas introduced after the replacement is completed; premixing styrene and tetrahydrofuran to obtain a mixed solvent for standby; sequentially adding metal lithium, diisopropylamine and tetrahydrofuran into a reaction kettle, and stirring and cooling to obtain a mixed system; maintaining the temperature of the mixed system, dropwise adding the mixed solvent while stirring, continuously stirring and mixing after the dropwise adding is finished, and finally pressing into a bottle for sedimentation; the preparation method has the advantages of simple preparation process, mild preparation conditions, low energy consumption, high yield and good stability of the obtained lithium diisopropylamide, and is suitable for industrial production.

Description

A kind of preparation technology of lithium diisopropylamide

technical field

The application relates to the technical field of preparation of chemical intermediates, more specifically, it relates to a preparation process of lithium diisopropylamide.

Background technique

Lithium Diisopropylamide (Lithium Diisopropylamide), referred to as LDA, is a large steric hindrance, non-nucleophilic organic strong base commonly used in the organic chemical synthesis process. As an organic strong base, LDA has a pKa=36 in tetrahydrofuran, and is widely used in unit reactions such as enolization of aldehydes and ketone alfa-positions, deprotonation to form carbanions, and halogen-lithium exchange.

The most classic synthesis method of lithium diisopropylamide is to slowly add butyllithium n-hexane solution dropwise to diisopropylamine tetrahydrofuran solution at low temperature to obtain it. Butyllithium is very easy to spontaneously ignite, and has a high potential safety hazard. In addition, during the process of dropping butyllithium, the reaction releases a large amount of heat, so it needs to be kept at a low temperature. The general reaction temperature is minus 78 degrees to minus 25 degrees, and the reaction conditions are harsh. High energy consumption. In addition, during the preparation of LDA, the reaction of butyllithium and diisopropylamine produces an equimolar amount of flammable gas n-butane. Furthermore, commercially available LDA is its solution, and the solvent is usually a polar aprotic solvent, such as THF or diethyl ether. However, LDA has poor stability in solvents and can decompose rapidly at room temperature. Therefore, in practical applications, especially when used in small doses (less than 50 mmol), it often needs to be prepared immediately before use, and the convenience of use is poor. Based on this, the present application provides a preparation process of lithium diisopropylamide.

Contents of the invention

In order to obtain lithium diisopropylamide with high stability and improve the feasibility of the preparation process, the present application provides a preparation process for lithium diisopropylamide.

The application provides a preparation process for lithium diisopropylamide, adopting the following technical scheme:

A preparation process for lithium diisopropylamide, comprising the following steps:

After cleaning and drying the reaction kettle, replace the gas in the reaction kettle with an inert gas, and keep the inert gas flowing after the replacement is completed;

Pre-mixing styrene and tetrahydrofuran to obtain a mixed solvent for subsequent use;

Add metal lithium, diisopropylamine and tetrahydrofuran to the reaction kettle in sequence, stir and cool down to obtain a mixed system;

Keep the cooling temperature of the mixed system, add the mixed solvent dropwise while stirring, continue to stir and mix after the dropwise addition, and finally press into the bottle to settle.

Preferably, the inert gas is argon.

Preferably, the number of inert gas replacements is 3-4 times.

By adopting the above-mentioned technical scheme, this application selects metal lithium and diisopropylamine as reaction raw materials. Compared with the butyllithium raw materials of traditional technology, it has high safety, mild reaction conditions and low energy consumption. By continuously passing argon gas during the reaction process, The stable progress of the reaction can be guaranteed; the preparation process of the present application is simple, the obtained lithium diisopropylamide has a high yield and good stability, and is suitable for industrial production.

Preferably, the mass volume ratio of styrene and tetrahydrofuran in the mixed solvent is (1-1.5) g:1 ml.

Preferably, the mass volume ratio of lithium metal, diisopropylamine and tetrahydrofuran is (1.4-1.8)g:(12-15)g:(32-34)ml.

Preferably, the mass volume ratio of lithium metal, diisopropylamine and tetrahydrofuran is 1.5g:12.65g:32.5ml.

Preferably, the stirring speed of the metal lithium, diisopropylamine and tetrahydrofuran is 100-200 r/min, and the cooling temperature is below 0°C.

Preferably, the cooling temperature is -4°C.

Preferably, the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent is 6-7:1.

By adopting the above technical scheme, controlling the amount of raw materials in the reaction process, the reaction temperature and other parameters can greatly improve the yield of lithium diisopropylamide while ensuring the smooth progress of the reaction, and increase the yield of lithium diisopropylamide. stability.

In summary, the application has the following beneficial effects:

This application selects metal lithium and diisopropylamine as the reaction raw materials. Compared with the butyllithium raw materials of the traditional process, it has higher safety, mild reaction conditions, and low energy consumption. By continuously passing argon gas during the reaction process, the stable progress of the reaction can be guaranteed. ; The preparation process of this application is simple, and the obtained lithium diisopropylamide has high yield and good stability, and is suitable for industrial production.

By controlling the amount of raw materials in the reaction process, the reaction temperature and other parameters, the application can greatly improve the yield of lithium diisopropylamide while ensuring the smooth progress of the reaction, and improve the stability of lithium diisopropylamide .

Detailed ways

The present application will be further explained below in conjunction with specific embodiments.

Embodiments 1-9 provide a preparation process of lithium diisopropylamide.

Example 1

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor is cleaned and dried, the gas in the reactor is replaced with argon, and the replacement is performed 3 times, and the argon is maintained;

According to the mass volume ratio of 1g:1ml, premix styrene and tetrahydrofuran evenly to obtain a mixed solvent for later use;

Add metal lithium, diisopropylamine and tetrahydrofuran sequentially to the reaction kettle kept argon, control the mass volume ratio of metal lithium, diisopropylamine and tetrahydrofuran to be 1.4g:12g:32ml, stir at a speed of 100r/min, stir and cool down to -2°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent to 6:1, keep the cooling temperature of the mixed system, add the mixed solvent dropwise while stirring, keep stirring and mixing for 0.5h after the dropwise addition, and finally press into the bottle After medium sedimentation, the concentration is prepared to be 2.0mol/L.

Example 2

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor was cleaned and dried, the gas in the reactor was replaced with argon gas, and the gas in the reactor was replaced 4 times, and the argon gas was maintained;

According to the mass volume ratio of 1.2g:1ml, styrene and tetrahydrofuran were premixed evenly to obtain a mixed solvent for later use;

Add metal lithium, diisopropylamine and tetrahydrofuran sequentially to the reaction kettle kept argon, control the mass volume ratio of metal lithium, diisopropylamine and tetrahydrofuran to be 1.5g:13g:33ml, stir at a speed of 120r/min, stir and cool down to -5°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent to 6.2:1, keep the cooling temperature of the mixed system, and add the mixed solvent dropwise while stirring. After medium sedimentation, the concentration is prepared to be 2.0mol/L.

Example 3

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor was cleaned and dried, the gas in the reactor was replaced with argon gas, and the gas in the reactor was replaced 4 times, and the argon gas was maintained;

According to the mass volume ratio of 1.3g:1ml, styrene and tetrahydrofuran were premixed uniformly to obtain a mixed solvent for later use;

Add lithium metal, diisopropylamine and tetrahydrofuran successively to the reaction kettle that keeps flowing argon, control the mass volume ratio of lithium metal, diisopropylamine and tetrahydrofuran to be 1.5g:12.65g:32.5ml, and the stirring speed is 150r/min, Stir and cool down to -4°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent to 6.5:1, keep the cooling temperature of the mixed system, add the mixed solvent dropwise while stirring, keep stirring and mixing for 1 hour after the dropwise addition is completed, and finally press into the bottle After sedimentation, prepare the concentration to be 2.0mol/L.

Example 4

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor is cleaned and dried, the gas in the reactor is replaced with argon, and the replacement is performed 3 times, and the argon is maintained;

According to the mass volume ratio of 1.4g:1ml, premix styrene and tetrahydrofuran evenly to obtain a mixed solvent for later use;

Add metal lithium, diisopropylamine and tetrahydrofuran sequentially to the reaction kettle kept argon, control the mass volume ratio of metal lithium, diisopropylamine and tetrahydrofuran to be 1.6g:14g:34ml, stir at a speed of 180r/min, stir and cool down to -10°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent to 6.8:1, keep the cooling temperature of the mixed system, and add the mixed solvent dropwise while stirring. After medium sedimentation, the concentration is prepared to be 2.0mol/L.

Example 5

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor was cleaned and dried, the gas in the reactor was replaced with argon gas, and the gas in the reactor was replaced 4 times, and the argon gas was maintained;

According to the mass volume ratio of 1.5g:1ml, premix styrene and tetrahydrofuran evenly to obtain a mixed solvent for later use;

Add lithium metal, diisopropylamine and tetrahydrofuran sequentially to the reaction kettle kept argon, control the mass volume ratio of lithium metal, diisopropylamine and tetrahydrofuran to be 1.7g:15g:34ml, stir at a speed of 200r/min, stir and cool down to -10°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to the mixed furan in the mixed solvent to 7:1, keep the cooling temperature of the mixed system, and add the mixed solvent dropwise while stirring. After medium sedimentation, the concentration is prepared to be 2.0mol/L.

Example 6

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor was cleaned and dried, the gas in the reactor was replaced with argon gas, and the gas in the reactor was replaced 4 times, and the argon gas was maintained;

According to the mass volume ratio of 1.3g:1ml, styrene and tetrahydrofuran were premixed uniformly to obtain a mixed solvent for later use;

Add lithium metal, diisopropylamine and tetrahydrofuran successively to the reaction kettle that keeps flowing argon, control the mass volume ratio of lithium metal, diisopropylamine and tetrahydrofuran to be 1.5g:12.65g:32.5ml, and the stirring speed is 150r/min, Stir and cool down to -2°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent to 6.5:1, keep the cooling temperature of the mixed system, add the mixed solvent dropwise while stirring, keep stirring and mixing for 1 hour after the dropwise addition is completed, and finally press into the bottle After sedimentation, prepare the concentration to be 2.0mol/L.

Example 7

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor was cleaned and dried, the gas in the reactor was replaced with argon gas, and the gas in the reactor was replaced 4 times, and the argon gas was maintained;

According to the mass volume ratio of 1.3g:1ml, styrene and tetrahydrofuran were premixed uniformly to obtain a mixed solvent for later use;

Add lithium metal, diisopropylamine and tetrahydrofuran successively to the reaction kettle that keeps flowing argon, control the mass volume ratio of lithium metal, diisopropylamine and tetrahydrofuran to be 1.5g:12.65g:32.5ml, and the stirring speed is 150r/min, Stir and cool down to -10°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent to 6.5:1, keep the cooling temperature of the mixed system, add the mixed solvent dropwise while stirring, keep stirring and mixing for 1 hour after the dropwise addition is completed, and finally press into the bottle After sedimentation, prepare the concentration to be 2.0mol/L.

Example 8

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor was cleaned and dried, the gas in the reactor was replaced with argon gas, and the gas in the reactor was replaced 4 times, and the argon gas was maintained;

According to the mass volume ratio of 1.3g:1ml, styrene and tetrahydrofuran were premixed uniformly to obtain a mixed solvent for later use;

Add lithium metal, diisopropylamine and tetrahydrofuran successively to the reaction kettle that keeps flowing argon, control the mass volume ratio of lithium metal, diisopropylamine and tetrahydrofuran to be 1.5g:12.65g:32.5ml, and the stirring speed is 150r/min, Stir and cool down to -4°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent to 6:1, keep the cooling temperature of the mixed system, add the mixed solvent dropwise while stirring, keep the rotation speed after the dropwise addition, continue stirring and mixing for 1 hour, and finally press into the bottle After sedimentation, prepare the concentration to be 2.0mol/L.

Example 9

A kind of preparation technology of lithium diisopropylamide proposed by the application comprises the following steps:

After the reactor was cleaned and dried, the gas in the reactor was replaced with argon gas, and the gas in the reactor was replaced 4 times, and the argon gas was maintained;

According to the mass volume ratio of 1.3g:1ml, styrene and tetrahydrofuran were premixed uniformly to obtain a mixed solvent for later use;

Add lithium metal, diisopropylamine and tetrahydrofuran successively to the reaction kettle that keeps flowing argon, control the mass volume ratio of lithium metal, diisopropylamine and tetrahydrofuran to be 1.5g:12.65g:32.5ml, and the stirring speed is 150r/min, Stir and cool down to -4°C to obtain a mixed system;

Control the volume ratio of tetrahydrofuran in the mixed system to mixed furan in the mixed solvent to 7:1, keep the cooling temperature of the mixed system, add the mixed solvent dropwise while stirring, keep the rotation speed after the dropwise addition, continue stirring and mixing for 1 hour, and finally press into the bottle After sedimentation, prepare the concentration to be 2.0mol/L.

The yield of lithium diisopropylamide prepared in Examples 1-9 of the present application is as follows in Table 1;

Table 1:

Example 1 2 3 4 5 6 7 8 9 Yield/% 98.0 98.3 99.4 98.5 98.2 98.6 99.4 98.7 98.3

From the data shown in Table 1, it can be seen that the yield of lithium diisopropylamide prepared in Examples 1-9 of the present application can reach more than 98%, and the preparation conditions are mild, which can be applied to large-scale industrial production.

The stability of the lithium diisopropylamide solution prepared in Examples 1-9 is detected, and the lithium diisopropylamide solution after the sealed filling is placed for 12 months, and the lithium diisopropylamide solution is placed on the 1st, 3rd, and 6th days respectively. , 9 and 12 months, the concentration and activity of lithium diisopropylamide lithium in the lithium diisopropylamide solution were tested, and the test results showed that the lithium diisopropylamide solution could still maintain the 12th month after preparation. Good activity, and the concentration of lithium diisopropylamide in the lithium diisopropylamide solution is still between 1.9-2.0mol/L, showing that the lithium diisopropylamide solution prepared according to the application has good stability, Can be stored for a long time.

This specific embodiment is only an explanation of this application, and it is not a limitation of this application. Those skilled in the art can make modifications to this embodiment without creative contribution according to needs after reading this specification, but as long as the rights of this application All claims are protected by patent law.

Claims (9)

1. a preparation technique for lithium diisopropylamide, is characterized in that, comprises the following steps: After cleaning and drying the reaction kettle, replace the gas in the reaction kettle with an inert gas, and keep the inert gas flowing after the replacement is completed; Pre-mixing styrene and tetrahydrofuran to obtain a mixed solvent for subsequent use; Add metal lithium, diisopropylamine and tetrahydrofuran to the reaction kettle in sequence, stir and cool down to obtain a mixed system; Keep the cooling temperature of the mixed system, add the mixed solvent dropwise while stirring, continue to stir and mix after the dropwise addition, and finally press into the bottle to settle. 2. the preparation technology of a kind of lithium diisopropylamide according to claim 1, is characterized in that, described inert gas is argon. 3. the preparation technology of a kind of lithium diisopropylamide according to claim 1, is characterized in that, described inert gas replacement number of times is 3-4 times. 4. the preparation technology of a kind of lithium diisopropylamide according to claim 1, is characterized in that, the mass volume ratio of styrene and THF in the described mixed solvent is (1-1.5) g: 1ml. 5. the preparation technology of a kind of lithium diisopropylamide according to claim 1, is characterized in that, the mass volume ratio of described metal lithium, diisopropylamine and tetrahydrofuran is (1.4-1.8) g: (12- 15) g: (32-34) ml. 6. the preparation technology of a kind of lithium diisopropylamide according to claim 5 is characterized in that, the mass volume ratio of described metal lithium, diisopropylamine and tetrahydrofuran is 1.5g:12.65g:32.5ml. 7. The preparation process of a kind of lithium diisopropylamide according to claim 1, characterized in that, the stirring speed of the lithium metal, diisopropylamine and tetrahydrofuran is 100-200r/min, and the cooling temperature is 0°C the following. 8. The preparation process of a kind of lithium diisopropylamide according to claim 7, characterized in that, the cooling temperature is -4°C. 9. the preparation technology of a kind of lithium diisopropylamide according to claim 1, is characterized in that, the volume ratio of tetrahydrofuran and mixed furan in the mixed solvent is 6-7:1 in the mixed system.