CN107556331A

CN107556331A - The production technology of RMgBr

Info

Publication number: CN107556331A
Application number: CN201710786106.2A
Authority: CN
Inventors: 赵小林; 崔家乙; 伍有本; 郭鑫; 汪金柱; 廖朝庭
Original assignee: NANJING HABO MEDICAL TECHNOLOGY CO LTD
Current assignee: NANJING HABO MEDICAL TECHNOLOGY CO LTD
Priority date: 2017-09-04
Filing date: 2017-09-04
Publication date: 2018-01-09

Abstract

The invention belongs to organic chemical synthesis field, more particularly to a kind of production technology of RMgBr, using a diameter of 0.5 1cm magnesium ball as raw material magnesium；In an inert atmosphere, in anhydrous inert solvent, under the conditions of initiator is existing, grignard reaction occurs with organohalogen compound, after reaction completely, under the conditions of 8 12 DEG C, after quiescent settling 20 26 hours, by the RMgBr press-in steel cylinder of purifying, the separation of impurity and product is realized；The present invention selects 0.5 1cm magnesium balls, and control reduces the oxidation area of magnesium, reduces black suspension thing and sediment during the course of the reaction, can reduce the inventory of magnesium in process of production, cost-effective, green；Caused a small amount of black suspension thing and precipitation in reaction system are removed using low temperature sedimentation separation method, technique and device are simple, are advantageous to industrial scale production；The present invention have selected appropriate settling temperature and time simultaneously, can effectively impurity and product separation, the loss of less product.

Description

The production technology of RMgBr

Technical field

The invention belongs to organic chemical synthesis field, more particularly to a kind of production technology of RMgBr.

Background technology

RMgBr is in absolute solvent by organohalogen compound (alkyl halide, active halogenated aryl hydrocarbon) and magnesium metal Middle reaction forms organomagnesium reagent.The reaction in absolute ether or tetrahydrofuran (THF) is made conventional halogenated hydrocarbons with magnesium powder, prepares Process must have the material of active hydrogen (such as in absolute, without carbon dioxide, without ethanol etc.：Water, alcohol, ammonia NH3, hydrogen halides, End alkynes etc.) under the conditions of carry out.But the content of magnesium only has 95% or so in magnesium powder, the magnesium metal for having 4% is aoxidized, this portion Divide oxide-film to postpone the generation of grignard reaction, cause initiation difficult, the utilization rate of magnesium is low.

RMgBr is in process of production, conventional if magnesium from bad, can produce part black suspension thing and precipitation Filter, black suspension thing and sediment can hardly be effectively filtered to remove, and RMgBr is hygroscopic degenerates, pair set Standby and operation requires higher.

Chinese patent 201010605132.9 discloses a kind of preparation method of RMgBr, using bulky grain magnesium (1mm) Or magnesium ingot (50*50*500) is used as raw material magnesium, grignard reaction is carried out using still reaction mode or outer circulation reactive mode；Using Bulky grain magnesium (10*10*20), substantially belong to magnesium powder, can all increase oxidation area during production and storage, in scale Dust explosion is easily produced in production, oxidation area is still bigger, dangerous higher；Using magnesium ingot (50*50*500), chi It is very little too big, be difficult in a kettle stirring it is difficult to initiation reaction, need special reaction unit, equipment can only specific customization, use Stainless steel is made the screen cloth string bag and is fixed on reactor wall, it is difficult to clean, acid and alkali-resistance, the service life of equipment can not drop significantly It is low, it is difficult to operate.Destruction can be produced to reactor, produce potential safety hazard under high-speed stirred.

The content of the invention

The present invention is for above-mentioned technical problem present in prior art, there is provided a kind of production technology of RMgBr.

To solve the above problems, technical scheme is as follows：

A kind of production technology of RMgBr,

Using a diameter of 0.5-1cm magnesium ball as raw material magnesium；

The magnesium ball in an inert atmosphere, in anhydrous inert solvent, under the conditions of initiator is existing, with organic halogen Grignard reaction occurs for compound；Reaction equation is：

RX+Mg→RMg

Wherein RX is organohalogen compound, and X is halogen (F, Cl, Br, I).

Low temperature sedimentation separation is used after reaction completely.

Preferably, the reaction condition of the grignard reaction is：The magnesium ball that is put into grignard kettle, initiator and anhydrous lazy Property solvent, be heated to 60-65 DEG C of initiation reaction, under the conditions of 50-60 DEG C simultaneously organohalogen compound and anhydrous inert is added dropwise Solvent, backflow 2 hours is added dropwise, the light brown of clear is made to light grey liquid, acid base titration concentration.

Preferably, the condition of the low temperature sedimentation separation is：It is miscellaneous after quiescent settling 20-26 hours under the conditions of 8-12 DEG C Matter falls to reaction container bottom, and supernatant (RMgBr) is pressed into steel cylinder.As temperature be less than 8 degree, RMgBr 20 The solid that or so hour has 20% is separated out, and temperature can be lengthened or even can not settled completely higher than the time of 12 degree of impurity sedimentations； Under the conditions of 8-12 DEG C, the time is less than 20 hours, and impurity can not settle completely, more than 26 hours backward, the suspension of reaction solution With impurity not by time effects, thereby increases and it is possible to cause RMgBr to separate out, time cost increase.

Preferably, the mass ratio of the magnesium ball and organohalogen compound is 1:1-6, mass ratio 1:1.05 it is optimal.Examine The content of spherical magnesium is considered between 98-98%, and mass ratio is less than 1:1 has organohalogen compound reaction not exclusively, yield Reduce, impurity increases, and the complete raw material of unreacted can have an impact to next step reaction；Mass ratio is more than 1:6, there can be a large amount of magnesium Ball unreacted is complete, and this radix can be very big in industrialized production, is asked in the complete magnesium of unreacted it is difficult to recycling, handling With very high, and danger close,

Preferably, the mass ratio of the magnesium ball and initiator is 1:0.08.

Preferably, the initiator is iodine, high activity alkane halide or RMgBr；Make and draw of identical RMgBr It is optimal to send out agent.

Preferably, the organohalogen compound is alkane halide, phenyl halides or heterocycle halides.

Preferably, it is tetrahydrofuran, 2- methyltetrahydrofurans, ether or toluene that the anhydrous inert is molten.

Preferably, organohalogen compound is identical with the rate of addition of anhydrous inert solvent.

Relative to prior art, advantages of the present invention is as follows,

The present invention selects 0.5-1cm magnesium balls, and control reduces the oxidation area of magnesium, reduces black suspension thing during the course of the reaction And sediment, the inventory of magnesium can be reduced in process of production, it is cost-effective, the processing cost for discarding unreacted magnesium is reduced, Mitigate Environmental Inputs, it is green；

Caused a small amount of black suspension thing and precipitation in reaction system are removed using low temperature sedimentation separation method, instead of routine Filter method, avoid RMgBr because many more manipulations water suction degenerate；Artificial filter and filter plant device need not be put into Cost, technique and device are simple, are advantageous to industrial scale production；Simultaneously the present invention have selected appropriate settling temperature and when Between, black suspension thing and precipitation can be caused to be completely separated, avoid RMgBr to stand precipitation solid because of low temperature and for a long time again.

Embodiment

Embodiment 1：

Nitrogen displacement 3 times in 500L reactors, 25.25kg magnesium ball (0.5cm) is added, add 100L THF and initiator (iodine) 2kg, the backflow of 60-65 degree is heated to, is slowly passed through 50.5kg chloromethanes in 50-60 degree, while remaining 200L is added dropwise THF, backflow 2 hours being added dropwise, the light brown of clear is made to light grey liquid, acid base titration concentration is 3.05mol, 8 degree or so are cooled to, quiescent settling 20 hours, a small amount of black suspension thing and precipitation are deposited on reactor bottom, and solid without other Body is separated out, and supernatant is pressed into steel cylinder.

Embodiment 2：

Nitrogen displacement 3 times in 500L reactors, 25.25kg magnesium ball (1cm) is added, add 100L 2- methyl tetrahydrochysene furans Mutter and initiator (bromomethane) 2kg, be heated to the backflow of 60-65 degree, be slowly passed through 95kg bromomethanes in 50-60 degree, be added dropwise simultaneously Remaining 200kg2- methyltetrahydrofurans, ensure 2- methyltetrahydrofurans rate of addition as the same period speed of chloromethanes, 2- methyltetrahydrofurans need first to be added dropwise simultaneously, and backflow 2 hours is added dropwise, and the light brown of clear is made to light gray Color liquid, acid base titration concentration are 3.06mol, are cooled to 12 degree or so, quiescent settling 26 hours, a small amount of black suspension thing and heavy Deposit is separated out in reactor bottom, and without other solids, and supernatant is pressed into steel cylinder.

Embodiment 3：

Nitrogen displacement 3 times in 1000L reactors, 25.25kg magnesium ball (0.7cm) is added, add 200L THF and initiation Agent (2 cbloropropane isopropyl chloride RMgBr) 2kg, be heated to 60-65 degree backflow, slowly 50-60 degree be added dropwise 78.5kg2- chloropropanes and 200L THF mixed liquor, backflow 2 hours is added dropwise, the light brown of clear is made to light grey liquid, acid base titration Concentration is 2.04mol, is cooled to 10 degree or so, quiescent settling 24 hours, a small amount of black suspension thing and precipitation are deposited on reactor Bottom, and separated out without other solids, supernatant is pressed into steel cylinder.

Embodiment 4：

Nitrogen displacement 3 times in 500L reactors, 25.25kg magnesium ball (0.8cm) is added, add 100L 2- methyl tetrahydrochysenes Furans and initiator (2- N-Propyl Bromides RMgBr) 2kg, the backflow of 60-65 degree is heated to, 123kg 2- slowly are added dropwise in 50-60 degree The mixed liquor of N-Propyl Bromide and 120L 2- methyltetrahydrofurans, the light brown of clear is made to light grey liquid, is added dropwise Backflow 2 hours, acid base titration concentration is 3.02mol, is cooled to 10 degree or so, quiescent settling 24 hours, a small amount of black suspension thing Reactor bottom is deposited on precipitation, and is separated out without other solids, supernatant is pressed into steel cylinder.

Embodiment 5：

Nitrogen displacement 3 times in 1000L reactors, 25.25kg magnesium ball (0.8cm) is added, add 200L THF and initiation Agent (tert-butyl chloride RMgBr) 2kg, the backflow of 60-65 degree is heated to, 92.6kg tert-butyl chlorides slowly are added dropwise in 50-60 degree With 280L THF mixed liquor, backflow 2 hours is added dropwise, light brown to light grey liquid, the soda acid that clear is made drips It is 1.75mol to determine concentration, is cooled to 10 degree or so, quiescent settling 24 hours, a small amount of black suspension thing and precipitation are deposited on reaction Bottom portion, and separated out without other solids, supernatant is pressed into steel cylinder.

Embodiment 6：

Nitrogen displacement 3 times in 100L reactors, 2.44kg magnesium ball (0.8cm) is added, add 15L tetrahydrofurans and initiation Agent (bromobenzene RMgBr) 0.2kg, the backflow of 60-65 degree is heated to, 15kg bromobenzenes and 23L tetrahydrochysene furans slowly is added dropwise in 50-60 degree The mixed liquor muttered, backflow 2 hours is added dropwise, acid base titration concentration is 2.08mol, and the light brown of clear is made to light gray Color liquid, 10 degree or so being cooled to, quiescent settling 24 hours, a small amount of black suspension thing and precipitation are deposited on reactor bottom, and Separated out without other solids, supernatant is pressed into steel cylinder.

Comparative example 1：

With embodiment 5, except that, the condition of low temperature sedimentation separation is：6 degree or so are cooled to, quiescent settling 20 is small When, the tert-butyl group magnesium chloride solids for having 20% separate out.

Comparative example 2：

With embodiment 5, except that, the condition of low temperature sedimentation separation is：16 degree or so are cooled to, quiescent settling 60 is small When, still there is a small amount of black suspension thing to be dispersed in system.

Comparative example 3：

With embodiment 5, except that, the condition of low temperature sedimentation separation is：10 degree or so are cooled to, quiescent settling 18 is small When, still there is a small amount of black suspension thing to be dispersed in system.

Comparative example 4：

With embodiment 5, except that, the condition of low temperature sedimentation separation is：10 degree or so are cooled to, quiescent settling 40 is small When, there are a small amount of tert-butyl group magnesium chloride solids to separate out.

It should be noted that above-described embodiment is only presently preferred embodiments of the present invention, it is not used for limiting the present invention's Protection domain, the equivalent substitution or replacement made on the basis of the above belong to protection scope of the present invention.

Claims

A kind of 1. production technology of RMgBr, it is characterised in that

Using a diameter of 0.5-1cm magnesium ball as raw material magnesium；

The magnesium ball in an inert atmosphere, in anhydrous inert solvent, under the conditions of initiator is existing, with organohalogen compound Generation grignard reaction；

Low temperature sedimentation separation is used after reaction completely.
2. the production technology of RMgBr as claimed in claim 1, it is characterised in that the reaction condition of the grignard reaction For：Magnesium ball, initiator and the anhydrous inert solvent put into grignard kettle, is heated to 60-65 DEG C of initiation reaction, in 50-60 Organohalogen compound and anhydrous inert solvent is added dropwise simultaneously under the conditions of DEG C, backflow 2 hours, acid base titration concentration is added dropwise.
3. the production technology of RMgBr as claimed in claim 1, it is characterised in that the condition of the low temperature sedimentation separation For：Under the conditions of 8-12 DEG C, after quiescent settling 20-26 hours, supernatant is pressed into steel cylinder.
4. the production technology of the RMgBr as described in claim any one of 1-3, it is characterised in that the magnesium ball and organic halogen The mass ratio of plain compound is 1:1-6.
5. the production technology of the RMgBr as described in claim any one of 1-3, it is characterised in that the magnesium ball and initiator Mass ratio be 1:0.08.
6. the production technology of the RMgBr as described in claim any one of 1-3, it is characterised in that the initiator be iodine, High activity alkane halide or RMgBr.
7. the production technology of the RMgBr as described in claim any one of 1-3, it is characterised in that the organic halogen chemical combination Thing is alkane halide, phenyl halides or heterocycle halides.
8. the production technology of the RMgBr as described in claim any one of 1-3, it is characterised in that the anhydrous inert is molten to be Tetrahydrofuran, 2- methyltetrahydrofurans, ether or toluene.
9. the production technology of the RMgBr as described in claim any one of 1-3, it is characterised in that organohalogen compound and The rate of addition of anhydrous inert solvent is identical.