CN110156638A

CN110156638A - The preparation process of etocrilene

Info

Publication number: CN110156638A
Application number: CN201910579027.3A
Authority: CN
Inventors: 胡林林
Original assignee: Wuhan Benjamin Pharmaceutical Ltd By Share Ltd
Current assignee: Wuhan Benjamin Pharmaceutical Ltd By Share Ltd
Priority date: 2019-06-28
Filing date: 2019-06-28
Publication date: 2019-08-23

Abstract

The invention discloses a kind of preparation process of etocrilene, comprising: benzophenone, ethyl cyanoacetate, ammonium acetate and acetic acid are put in proportion into reaction vessel by step 1), are dissolved by heating；Step 2) gradually vacuumizes, until predetermined vacuum degree, is continuously heating to the first preset temperature, and keep the temperature, the acetic anhydride of predetermined amount, reaction time 8-12h are added in reaction vessel；Step 3) is cooled to the second preset temperature, washes, and stands, layering；Upper layer oil reservoir is taken, decrease temperature crystalline filters, and drying obtains target product etocrilene；Etocrilene purity is high prepared by the present invention, impurity are few；And acetic anhydride is added in midway, and uses catalyst 1, and the dual catalyst mode that 3- dialkylimidazolium oxometallate and acetic acid, ammonium acetate combine is substituted traditional single catalyst mode, substantially increases conversion ratio.

Description

The preparation process of etocrilene

Technical field

The present invention relates to etocrilene preparation fields.It is more particularly related to a kind of preparation of etocrilene Journey.

Background technique

Ultraviolet absorbing agent etocrilene, chemical name: Uvinul N35, chemical structure are shown:Appearance: white crystalline powder, English name: Etocrilene, english abbreviation ETO；For plastics, Coating, vehicle glass, cosmetics, is used as ultraviolet absorbing agent in sun-screening agent at dyestuff, is also synthesis ultraviolet absorbing agent Losec A kind of important intermediate of vertical woods.

Application number 201811381161.4 discloses a kind of preparation process of etocrilene, takes away reaction by vacuum distillation The water that process generates can also take away acetic acid while taking away moisture, to cause the reduction of reaction yield.

Summary of the invention

In order to achieve the goal above, the present invention provides a kind of preparation process of etocrilene, comprising:

Benzophenone, ethyl cyanoacetate, ammonium acetate and acetic acid are put in proportion into reaction vessel by step 1), heating Dissolution；

Step 2) gradually vacuumizes, until predetermined vacuum degree, is continuously heating to the first preset temperature, and keep the temperature, toward reaction The acetic anhydride of predetermined amount is added in container, cancels vacuum, reaction time 8-12h；

Step 3) is cooled to the second preset temperature, washes, and stands, layering；

Upper layer oil reservoir is taken, decrease temperature crystalline filters, and drying obtains target product etocrilene；

Preferably, the preparation process of the etocrilene, the matter of benzophenone, ethyl cyanoacetate, ammonium acetate, acetic acid Amount is than being 500-600:500-600:60-100:60.

Preferably, the preparation process of the etocrilene, in step 1), the heating for dissolving temperature control be so that Reaction raw materials can melt, and specially 40-50 DEG C.

Preferably, the preparation process of the etocrilene, in step 2 predetermined vacuum degree be -0.09~- 0.095MPa。

Preferably, the preparation process of the etocrilene, in step 2), the first preset temperature is 70-75 DEG C.

Preferably, the preparation process of the etocrilene, in the step 1), ionic-liquid catalyst is thrown in synchronization Enter in reaction vessel, the dispensing quality of the catalyst is the 1/95 of benzophenone.

Preferably, the preparation process of the etocrilene, the catalyst are 1,3- dialkylimidazolium oxometallic acid Salt, structure are shown as follows:

Preferably, the preparation process of the etocrilene in the step 2), gradually vacuumizes, until condenser In have a fraction appearance, start calculating reacting time.

Preferably, the preparation process of the etocrilene, the second preset temperature are 55-65 DEG C.

Preferably, the preparation process of the etocrilene, in the step 2), reaction vessel is connected to condenser pipe, It realizes and is condensed back.

The present invention is include at least the following beneficial effects:

1, etocrilene purity is high prepared by the present invention, impurity are few；

2, the present invention adds acetic anhydride on the way in the reaction, and acetic anhydride is reacted with the water that reaction process generates, not only consumed Water avoids water from causing reaction (water will promote balanced reaction mobile to reverse direction) to reaction, can also produce acetic acid, can be with Ammonium acetate is further dissolved, the progress of reaction is promoted, and avoiding will while directly emitting water in existing method Acetic acid is taken away, so that bring yield reduces problem；

3, the present invention is in the dual catalyst combined with catalyst 1,3- dialkylimidazolium oxometallate and acetic acid, ammonium acetate Mode is substituted traditional single catalyst mode, substantially increases conversion ratio.

Further advantage, target and feature of the invention will be partially reflected by the following instructions, and part will also be by this The research and practice of invention and be understood by the person skilled in the art.

Detailed description of the invention

Fig. 1 is the nuclear magnetic resonance figures of etocrilene in embodiment 2；

Fig. 2 is the HPLC high phase liquid chromatogram of etocrilene in embodiment 2.

Specific embodiment

Present invention will be described in further detail below with reference to the accompanying drawings, to enable those skilled in the art referring to specification text Word can be implemented accordingly.

Reaction equation of the invention is as follows:

(T6, T7 respectively represent acetic acid and ammonium acetate)

Embodiment 1 (adds acetic acid) halfway

580kg benzophenone, 520kg ethyl cyanoacetate, 70kg ammonium acetate and 60kg acetic acid are put in proportion into synthesis In kettle, 45 DEG C are warming up to, stirring and dissolving；And take vacuum, gradually vacuumize, until have in condenser appropriate fraction (- 0.088Mpa or so), start calculating reacting time, be continuously heating to 72 DEG C, and keep the temperature, step up vacuum degree until up to- 0.095Mpa；

The acetic acid 50kg of predetermined amount is added in reaction vessel, cancels vacuum, reaction time 10h；

After reaction, open cycle water is cooled to 60 DEG C hereinafter, addition 300kg water, stirring 20 in the case where band vacuum Minute, stop stirring, heat preservation stands 30 minutes this processes and will be layered；Extracting lower layer's oil reservoir, (upper layer waste water layer is discharged at waste water Reason system), by lower layer's oil reservoir in 25 DEG C of decrease temperature crystallines, and with 10-15 DEG C of centrifugal filtration, be again heated to 58 DEG C of dissolutions, while hot mistake , for circulating water cooling to 35 DEG C, switching cryosel, centrifugal filtration obtains filtrate, dries 4h at 60 DEG C to get final goal is arrived Product etocrilene 540kg, product yield are 65% (on the basis of benzophenone), are analyzed through chromatograph-mass spectrometer coupling, purity 92%.

Embodiment 2 (adds acetic anhydride) halfway

After reaction, open cycle water is cooled to 60 DEG C hereinafter, addition 300kg water, stirring 20 in the case where band vacuum Minute, stop stirring, heat preservation stands 30 minutes this processes and will be layered；Extracting lower layer's oil reservoir, (upper layer waste water layer is discharged at waste water Reason system), by lower layer's oil reservoir in 25 DEG C of decrease temperature crystallines, and with 10-15 DEG C of centrifugal filtration, be again heated to 58 DEG C of dissolutions, while hot mistake , for circulating water cooling to 35 DEG C, switching cryosel, centrifugal filtration obtains filtrate, dries 4h at 60 DEG C to get final goal is arrived Product etocrilene 723.5kg, product yield are 90% (on the basis of benzophenone), are analyzed through chromatograph-mass spectrometer coupling, purity 92%.

Embodiment 3 (adds acetic anhydride+catalyst 1,3- dialkylimidazolium oxometallate) halfway

By 580kg benzophenone, 520kg ethyl cyanoacetate, 70kg ammonium acetate, 60kg acetic acid, 6.1kg1,3- dialkyl group miaow Azoles oxometallate is put in proportion into synthesis reactor, is warming up to 45 DEG C, stirring and dissolving；And vacuum is taken, gradually vacuumize, until Have in condenser appropriate fraction (- 0.088Mpa or so), starts calculating reacting time, be continuously heating to 72 DEG C, and keep the temperature, gradually Vacuum degree is improved until reaching -0.095Mpa；

After reaction, open cycle water is cooled to 60 DEG C hereinafter, addition 300kg water, stirring 20 in the case where band vacuum Minute, stop stirring, heat preservation stands 30 minutes this processes and will be layered；Extracting lower layer's oil reservoir, (upper layer waste water layer is discharged at waste water Reason system), by lower layer's oil reservoir in 25 DEG C of decrease temperature crystallines, and with 10-15 DEG C of centrifugal filtration, be again heated to 58 DEG C of dissolutions, while hot mistake , for circulating water cooling to 35 DEG C, switching cryosel, centrifugal filtration obtains filtrate, dries 4h at 60 DEG C to get final goal is arrived Product etocrilene 799.7kg, product yield are 96% (on the basis of benzophenone), are analyzed through chromatograph-mass spectrometer coupling, purity 98%.

Although the embodiments of the present invention have been disclosed as above, but its is not only in the description and the implementation listed With it can be fully applied to various fields suitable for the present invention, for those skilled in the art, can be easily Realize other modification, therefore without departing from the general concept defined in the claims and the equivalent scope, the present invention is simultaneously unlimited In specific details and legend shown and described herein.

Claims

1. a kind of preparation process of etocrilene characterized by comprising

Benzophenone, ethyl cyanoacetate, ammonium acetate and acetic acid are put in proportion into reaction vessel by step 1), are dissolved by heating；

Step 2) gradually vacuumizes, until predetermined vacuum degree, is continuously heating to the first preset temperature, and keep the temperature, toward reaction vessel The acetic anhydride of predetermined amount is inside added, vacuum, reaction time 8-12h are cancelled；

Upper layer oil reservoir is taken, decrease temperature crystalline filters, and drying obtains target product etocrilene.

2. the preparation process of etocrilene as described in claim 1, which is characterized in that benzophenone, ethyl cyanoacetate, acetic acid Ammonium, acetic acid mass ratio be 500-600:500-600:60-100:60.

3. the preparation process of etocrilene as described in claim 1, which is characterized in that in step 1), the heating for dissolving temperature Degree control is specially 40-50 DEG C so that reaction raw materials can melt.

4. the preparation process of etocrilene as described in claim 1, which is characterized in that predetermined vacuum degree is -0.09 in step 2 ~-0.095MPa.

5. the preparation process of etocrilene as described in claim 1, which is characterized in that in step 2), the first preset temperature is 70-75℃。

6. the preparation process of etocrilene as described in claim 1, which is characterized in that synchronous by ion in the step 1) Liquid catalyst is put into reaction vessel, and the dispensing quality of the catalyst is the 1/95 of benzophenone.

7. the preparation process of etocrilene as claimed in claim 6, which is characterized in that the catalyst is 1,3- dialkyl group miaow Azoles oxometallate, structure are shown as follows:

8. the preparation process of etocrilene as described in claim 1, which is characterized in that in the step 2), gradually vacuumize, Until there is fraction appearance in condenser, start calculating reacting time.

9. the preparation process of etocrilene as described in claim 1, which is characterized in that the second preset temperature is 55-65 DEG C.

10. the preparation process of etocrilene as described in claim 1, which is characterized in that in the step 2), reaction vessel with Condenser pipe connection, realizes and is condensed back.