CN218458670U

CN218458670U - Special device for synthesizing bulk drug methyl salicylate

Info

Publication number: CN218458670U
Application number: CN202222844699.2U
Authority: CN
Inventors: 杨海洋
Original assignee: Wudi Rongchuan Chemical Technology Co ltd
Current assignee: Wudi Rongchuan Chemical Technology Co ltd
Priority date: 2022-10-27
Filing date: 2022-10-27
Publication date: 2023-02-10
Anticipated expiration: 2032-10-27

Abstract

The utility model discloses a special device for synthesizing bulk drug methyl salicylate, which comprises an esterification kettle arranged at the front end; the esterification kettle is respectively connected with a methanol storage tank, a salicylic acid turnover tank and a concentrated sulfuric acid head tank through pipelines; the rear end of the esterification kettle 1 is connected with a distillation kettle through a pipeline; the rear end of the distillation kettle is connected with a first condenser through a pipeline; the rear end of the first condenser is connected in parallel with a front fraction receiving tank and a finished product receiving tank through a pipeline. The device's use can improve the product yield, and reduces the influence of production to the environment, and production system arranges more rationally, and production efficiency is high.

Description

Special device for synthesizing bulk drug methyl salicylate

Technical Field

The utility model belongs to bulk drug production facility field, concretely relates to synthetic isolated plant of bulk drug methyl salicylate.

Background

Methyl salicylate is also called methyl salicylate, is mainly used for perfuming oral cavity medicines and solvents in perfume pharmaceutical preparations, also is used as a pharmaceutical intermediate or solvent, is widely used in daily use or medical fields such as insecticides, bactericides, cosmetics, printing ink, fiber dyeing assistance and the like, salicylic acid is generally adopted to react with methanol in industry, concentrated sulfuric acid is used as catalysis or dehydration, and the process improvement of the methyl salicylate is mainly the improvement of a catalyst due to the corrosion problem of sulfuric acid and the influence on the environment, for example, the use of the concentrated sulfuric acid is replaced by p-toluenesulfonic acid, sodium bisulfite, heteropoly acid and strong acid resin, but the methods are not suitable for industrial production, so the production process of the methyl salicylate is optimized, and a novel production device of the pharmaceutical intermediate with wide application is developed by means of the method to meet the market demand.

SUMMERY OF THE UTILITY MODEL

The utility model provides a synthetic isolated plant of bulk drug methyl salicylate, the device's use can improve the product yield, and reduction production is more reasonable to the influence of environment, and production system arranges that production efficiency is high.

In order to achieve the above object, the utility model provides a following technical scheme: a special device for synthesizing bulk drug methyl salicylate comprises an esterification kettle arranged at the front end; the esterification kettle is respectively connected with a methanol storage tank, a salicylic acid transfer tank and a concentrated sulfuric acid head tank through pipelines; the rear end of the esterification kettle 1 is connected with a distillation kettle through a pipeline; the rear end of the distillation kettle is connected with a first condenser through a pipeline; the rear end of the first condenser is connected in parallel with a front row fraction receiving tank and a finished product receiving tank through a pipeline.

Preferably, the rear end of the finished product receiving groove is connected with a vacuum system through a pipeline.

Preferably, the vacuum system comprises a filter with the front end connected with the finished product receiving tank; the rear end of the filter is connected with a filling kettle through a pipeline; the filling kettle is connected with a second condenser through a pipeline.

Preferably, the front end of the concentrated sulfuric acid head tank is connected with a concentrated sulfuric acid storage tank through a pipeline.

Preferably, the esterification kettle is connected with a third condenser through a pipeline; the rear end of the third condenser is connected with a methanol solvent recovery tank through a pipeline.

Preferably, the finished product receiving tank is connected with a nitrogen gas steel cylinder through a pipeline.

Compared with the prior art, the beneficial effects of the utility model are that: the new synthesis device is firstly applied to industrial production, the total yield reaches 90%, the quality meets the national standard or the customer standard, the yield is greatly improved compared with the known production process and the literature data, and the yield of the known traditional process and the literature is not more than 80% at most and is about 70% at most. The new device is matched with a new catalyst to greatly reduce the reaction temperature and the feeding amount of methanol, and a large amount of methanol recovery process is saved due to the accurate molar ratio of the methanol, so that the raw material loss and the energy loss are reduced, and the equipment investment and the personnel allocation are also reduced; the technical progress improves the production safety of the product and minimizes the influence of the product on the environment.

Other features of the present disclosure and advantages thereof will become apparent from the following detailed description of exemplary embodiments thereof, which proceeds with reference to the accompanying drawings.

Drawings

In order to more clearly illustrate the embodiments of the present disclosure or technical solutions in related arts, the drawings used in the description of the embodiments or related arts will be briefly introduced below, it is obvious that the drawings in the description below are only embodiments of the present disclosure, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

FIG. 1 is an overall view of the special device of the present invention;

in the figure: 1. the system comprises an esterification kettle, 2 a methanol storage tank, 3 a salicylic acid turnover tank, 4 a concentrated sulfuric acid elevated tank, 5 a distillation kettle, 6 a first condenser, 7 a prostate fraction receiving tank, 8 a finished product receiving tank, 9 a vacuum system, 91 a filter, 92 a filling kettle, 93 a second condenser, 10 a concentrated sulfuric acid storage tank, 11 a third condenser, 12 a methanol solvent recovery tank, 13 and a nitrogen steel cylinder.

Detailed Description

The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. Based on the embodiments of the present invention, all other embodiments obtained by a person skilled in the art without making creative efforts belong to the protection scope of the present invention.

Unless specifically stated otherwise, the relative arrangement of parts and steps, numerical expressions, and numerical values set forth in these embodiments do not limit the scope of the present invention. Meanwhile, it should be understood that the sizes of the respective portions shown in the drawings are not drawn in an actual proportional relationship for the convenience of description. Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate. In all examples shown and discussed herein, any particular value should be construed as exemplary only and not as limiting. Thus, other examples of the exemplary embodiments may have different values. It should be noted that: like reference numbers and letters refer to like items in the following figures, and thus, once an item is defined in one figure, it need not be discussed further in subsequent figures.

For ease of description, spatially relative terms such as "over 8230 \ 8230;,"' over 8230;, \8230; upper surface "," above ", etc. may be used herein to describe the spatial relationship of one device or feature to another device or feature as shown in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is turned over, devices described as "above" or "on" other devices or configurations would then be oriented "below" or "under" the other devices or configurations. Thus, the exemplary terms "at 8230; \8230; above" may include both orientations "at 8230; \8230; above" and "at 8230; \8230; below". The device may be otherwise variously oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.

Referring to fig. 1, the present invention provides a technical solution: a special device for synthesizing bulk drug methyl salicylate comprises an esterification kettle 1 arranged at the front end; the esterification kettle 1 is respectively connected with a methanol storage tank 2, a salicylic acid turnover tank 3 and a concentrated sulfuric acid head tank 4 through pipelines; the rear end of the esterification kettle 1 is connected with a distillation kettle 5 through a pipeline; the rear end of the distillation kettle 5 is connected with a first condenser 6 through a pipeline; the rear end of the first condenser 6 is connected in parallel with a front fraction receiving tank 7 and a finished product receiving tank 8 through a pipeline.

The rear end of the finished product receiving groove 8 is connected with a vacuum system 9 through a pipeline. The vacuum system 9 comprises a filter 91 with the front end connected with the finished product receiving tank 8; the rear end of the filter 91 is connected with a filling kettle 92 through a pipeline; the filling vessel 92 is connected to a second condenser 93 through a pipe. The front end of the concentrated sulfuric acid head tank 4 is connected with a concentrated sulfuric acid storage tank 10 through a pipeline. The esterification kettle 1 is connected with a third condenser 11 through a pipeline; the rear end of the third condenser 11 is connected with a methanol solvent recovery tank 12 through a pipeline. The finished product receiving tank 8 is connected with a nitrogen steel cylinder 13 through a pipeline.

The reaction process of the special device is as follows:

esterification: adding a catalyst into a 2000L esterification kettle 1, then sequentially adding quantitative salicylic acid and methanol from a salicylic acid turnover tank 3 and a methanol storage tank 2, starting stirring after the completion, controlling the rotating speed to be 58 +/-2 rpm, and stirring until the solution is clear. Opening a chilled water inlet and outlet valve of a jacket of the esterification kettle 1, and cooling to below 20 ℃. Opening a dropping valve of the concentrated sulfuric acid head tank 4, slowly dropping a certain amount of concentrated sulfuric acid, and controlling the temperature to be less than or equal to 20 ℃ in the dropping process. After the dripping is finished, the temperature is raised to 70-75 ℃, and the reflux reaction is carried out for more than 6 hours. The reaction was monitored by HPLC for endpoint.

And (3) distillation: and after the reaction is finished, stopping heating, cooling the system to 40-50 ℃, removing the residual methanol by reduced pressure distillation, allowing the residual methanol to enter a methanol solvent recovery tank 12, and performing reduced pressure distillation until no obvious liquid drops are evaporated.

Primary water washing: and after the distillation is finished, washing the concentrate with process water, stirring for 30min, standing for 30min, separating, discarding the water phase, and collecting the lower organic phase. And (3) secondary water washing: and washing the organic phase with the process water again to be neutral, stirring for 30min, standing for 30min, separating, discarding the water phase, and collecting the lower organic phase, namely the crude product. Transferring the crude methyl salicylate product obtained in the last step to a distillation still 5, distilling under reduced pressure, collecting the front fraction with the temperature lower than 100 ℃ (vacuum is less than or equal to-0.09 MPa) in a front fraction receiving tank 7, discarding the front fraction, collecting the fraction with the temperature of 141-145 ℃ (vacuum is less than or equal to-0.09 MPa) in a finished product receiving tank 8, pressing the collected fraction into a clean area, and filling in a vacuum system to obtain the finished methyl salicylate product.

The catalyst in the esterification kettle 1 adopts 4-dimethylamino pyridine (DMPA) and NN-cyclic carbonyl imide (DCC) as mixed catalysts, the catalytic effect of the catalytic combination on the esterification reaction of alcohols with large space resistance and low activity is particularly ideal, the reflux reaction temperature is reduced from 80-90 ℃ to 20-25 ℃ due to the catalysts, although the reaction time is basically the same as that of the general process, the reduction of the reaction temperature greatly reduces the energy consumption, the DMPA can be recycled, the reaction temperature of salicylic acid and methanol in the traditional process is 80-90 ℃, the loss caused by the vaporization of methanol is serious (the boiling point of methanol is 64.7) due to the high reaction temperature, the feed ratio of salicylic acid and methanol in the traditional process is 1: 1.5 (excessive methanol), the defect of the overhigh reaction temperature is that the loss of methanol and the vaporization of methanol are not beneficial to the formation of ester, the new process basically does not consider the loss caused by the vaporization of methanol under the room temperature condition, the ratio of salicylic acid to methanol is 1: 1, the feed ratio of methanol in the traditional process is greatly reduced compared with the traditional process, the molar ratio of the distillation to the distillation is also the molar ratio of methanol, the distillation process, the preparation of methanol is not considered, and the equipment is not required by the traditional process, and the precise production process is not only the saving the investment of methanol and saving the production process. Although the reaction principle of the method is consistent with that of the traditional process and belongs to a simple esterification process, the proportion of the mixed catalyst, the accurate molar ratio of the salicylic acid to the methanol and the like are the biggest optimization points of the process, and the special device is developed for matching with a new process.

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

Claims

1. A bulk drug methyl salicylate synthetic isolated plant which characterized in that: the special device comprises an esterification kettle (1) arranged at the front end; the esterification kettle (1) is respectively connected with a methanol storage tank (2), a salicylic acid turnover tank (3) and a concentrated sulfuric acid head tank (4) through pipelines; the rear end of the esterification kettle (1) is connected with a distillation kettle (5) through a pipeline; the rear end of the distillation kettle (5) is connected with a first condenser (6) through a pipeline; the rear end of the first condenser (6) is connected in parallel with a front fraction receiving tank (7) and a finished product receiving tank (8) through a pipeline.

2. The special device for synthesizing methyl salicylate as a raw material drug according to claim 1, wherein: the rear end of the finished product receiving groove (8) is connected with a vacuum system (9) through a pipeline.

3. The special device for synthesizing bulk drug methyl salicylate of claim 2, which is characterized in that: the vacuum system (9) comprises a filter (91) with the front end connected with the finished product receiving groove (8); the rear end of the filter (91) is connected with a filling kettle (92) through a pipeline; the filling kettle (92) is connected with a second condenser (93) through a pipeline.

4. The special device for synthesizing methyl salicylate as a raw material drug according to claim 1, wherein: the front end of the concentrated sulfuric acid head tank (4) is connected with a concentrated sulfuric acid storage tank (10) through a pipeline.

5. The special device for synthesizing methyl salicylate as a raw material drug according to claim 1, wherein: the esterification kettle (1) is connected with a third condenser (11) through a pipeline; the rear end of the third condenser (11) is connected with a methanol solvent recovery tank (12) through a pipeline.

6. The special device for synthesizing methyl salicylate as a raw material drug according to claim 1, wherein: the finished product receiving groove (8) is connected with a nitrogen steel cylinder (13) through a pipeline.