CN115518952A

CN115518952A - Method for simultaneously cleaning a plurality of reaction vessels for preparing lactide and cleaning solvent thereof

Info

Publication number: CN115518952A
Application number: CN202211372631.7A
Authority: CN
Inventors: 鲁永弘; 向冬
Original assignee: Shenzhen Maiqi Biomaterial Co ltd
Current assignee: Shenzhen Maiqi Biomaterial Co ltd
Priority date: 2022-11-03
Filing date: 2022-11-03
Publication date: 2022-12-27

Abstract

The present disclosure provides a method for simultaneously cleaning a plurality of lactide preparation reaction vessels, comprising: preparing a cleaning solvent, wherein the cleaning solvent is a potassium hydroxide solution; adding a cleaning solvent into each reaction container respectively; a reflux condenser pipe is respectively arranged at the opening of each reaction container, and each reflux condenser pipe is connected with a condenser after being connected in series; starting a condenser, setting a preset cooling circulation temperature for condensation, heating a plurality of reaction containers until the cleaning solvent in each reaction container reaches the preset heating temperature, and maintaining the preset heating time to obtain a mixed liquid in which the reaction residual substances are dissolved; and taking down the reflux condenser pipe from the opening of each reaction vessel, and removing the mixed liquid to obtain the cleaned reaction vessel. According to the present disclosure, a method capable of simultaneously cleaning a plurality of reaction vessels for lactide production can be provided in a simple manner, at a low cost, and with high efficiency.

Description

Method for simultaneously cleaning a plurality of reaction vessels for preparing lactide and cleaning solvent thereof

Technical Field

The disclosure relates to the field of biodegradable high polymer materials, in particular to a method for cleaning a plurality of reaction vessels for preparing lactide simultaneously and a cleaning solvent thereof.

Background

The medical lactide is an important raw material for synthesizing medical polylactic acid. The medical polylactic acid has very good biocompatibility and good mechanical property, and the degradation products of the medical polylactic acid are carbon dioxide and water, so the medical polylactic acid is a safe and environment-friendly medical material. The medical polylactic acid has wide application in the fields of surgical operation suture lines, bone fixing materials, drug release, tissue engineering scaffolds and the like.

There are two main methods for synthesizing polylactic acid, the first is condensation reaction to obtain polylactic acid, and the other is ring-opening polymerization of lactide to obtain polylactic acid. The first one is that water in the reaction product is difficult to remove, so the molecular weight of the obtained polylactic acid is lower, and the second one is generally adopted at home and abroad at present, pure lactide is obtained by the polycondensation and the cracking of lactic acid, and then the medical polylactic acid is obtained by the ring-opening polymerization of the lactide.

The currently common method for preparing lactide is a two-step process, which comprises the specific steps of directly polycondensing lactic acid to obtain low molecular weight polylactic acid, and then cracking at a higher temperature to obtain lactide. When medical grade lactide is prepared on a small scale, a flask is usually used as a reaction vessel, reaction residual substances are basically polylactic acid (namely polylactic acid oligomer) which can not be cracked into lactide, the viscosity is high at high temperature, the lactide is difficult to pour out, the operation safety risk exists, the lactide can not be poured out after solidification after cooling, and the problem of resource waste and high cost exists when the flask is directly used as dangerous waste for treatment.

Disclosure of Invention

The present disclosure has been made in view of the above-described state of the art, and an object thereof is to provide a method capable of cleaning a plurality of reaction vessels for lactide production simultaneously in a simple manner, at low cost, and with high efficiency, and a cleaning solvent for cleaning the reaction vessels for lactide production.

To this end, a first aspect of the present disclosure provides a method for simultaneously cleaning a plurality of lactide production reaction vessels, comprising the steps of: preparing a cleaning solvent, wherein the cleaning solvent is a potassium hydroxide solution with the concentration of 0.1mol/L to 1 mol/L; adding the cleaning solvent into each reaction container respectively, wherein the ratio of the volume (unit is L) of the cleaning solvent in each reaction container to the mass (unit is kg) of reaction residual substances in each reaction container is not lower than 1; a reflux condenser pipe is respectively arranged at the opening of each reaction container, and each reflux condenser pipe is connected with a condenser after being connected in series; starting a condenser and setting a preset cooling circulation temperature for condensation, heating the reaction containers until the cleaning solvent in each reaction container reaches a preset heating temperature, and maintaining the preset heating time to obtain a mixed solution dissolved with the reaction residual substances, wherein the preset heating temperature is not lower than 150 ℃; and removing the reflux condenser pipes from the openings of the reaction containers, and removing the mixed liquid from the reaction containers to obtain the cleaned reaction containers.

In the first aspect of the present disclosure, by using a potassium hydroxide solution as a cleaning solvent and configuring the concentration of the potassium hydroxide solution to be 0.1mol/L to 1mol/L, the reaction residual substance can be promoted to be dissolved in the alkaline cleaning solvent, so that the cleaning effect of the reaction vessel can be improved; by configuring the ratio of the volume (in L) of the cleaning solvent in each reaction vessel to the mass (in kg) of the reaction residual substance in each reaction vessel to be not less than 1, the reaction residual substance and the cleaning solvent can be favorably fully reacted, and the dissolution of the reaction residual substance is favorably carried out; the reflux condenser pipes are respectively arranged at the openings of the reaction containers, so that steam of a cleaning solvent which is subsequently heated and evaporated can reenter the reaction containers through condensation reflux to participate in reaction, and the reflux condenser pipes are connected in series and then connected with the condenser; by configuring the predetermined heating temperature to be not lower than 150 ℃, the dissolution rate and solubility of the reaction residual substance in the cleaning solvent can be improved, thereby improving the cleaning effect of the reaction vessel. Thus, a method capable of cleaning a plurality of reaction vessels for lactide production simultaneously in a simple manner, at low cost and with high efficiency can be provided.

In the method according to the first aspect of the present disclosure, optionally, the predetermined heating temperature is 150 ℃ to 160 ℃, and the predetermined heating time is 6h to 24h. In this case, it is advantageous for the reaction residual substance to sufficiently react with the cleaning solvent, and thus for the reaction residual substance to be sufficiently dissolved in the cleaning solvent, whereby the cleaning effect of the reaction vessel can be improved.

In the method according to the first aspect of the present disclosure, the plurality of reaction vessels are optionally heated simultaneously by means of oil bath heating. In this case, by placing the reaction vessel in the heat transfer oil, the bottom region of the reaction vessel can be uniformly heated, thereby facilitating the reaction residual substance to be sufficiently dissolved in the cleaning solvent, and thus improving the cleaning effect of the reaction vessel.

In the method according to the first aspect of the present disclosure, optionally, the number of the plurality of reaction vessels is 2 to 4. In this case, 2 to 4 reaction vessels can be cleaned at the same time.

In the method according to the first aspect of the present disclosure, optionally, the predetermined cooling cycle temperature is not higher than 0 ℃. In this case, when the cleaning solvent is heated to evaporate and rise to the reflux condenser tube, the condensation reflux effect of the vapor of the cleaning solvent can be improved by setting the predetermined cooling cycle temperature to not higher than 0 ℃, whereby the vapor of the cleaning solvent can form droplets and re-enter the reaction vessel after being cooled, and thus the cleaning efficiency and cleaning effect of the reaction vessel can be improved.

In the method of the first aspect of the present disclosure, optionally, the reflux condenser tube is a serpentine reflux condenser tube. Under the condition, when the cleaning solvent is heated and evaporated and rises to the snake-shaped reflux condensation pipe, the steam of the cleaning solvent can form small drops in the snake-shaped reflux condensation pipe when contacting the snake-shaped reflux condensation pipe, gradually gather to form the small drops and finally fall down to enter the reaction container again when meeting cold, so that the reflux amount of the steam of the cleaning solvent is favorably improved, and the cleaning efficiency and the cleaning effect on the reaction container can be improved.

In the method according to the first aspect of the present disclosure, optionally, the reaction vessel is selected from one of a conical flask, a two-necked flask, and a three-necked flask, and the kinds of the respective reaction vessels are the same or different. From this, can add the washing solvent to reaction vessel to set up the backward flow condenser pipe at reaction vessel's opening part, thereby can be convenient for wash reaction vessel.

In the method according to the first aspect of the present disclosure, optionally, after obtaining the mixed solution, the mixed solution is removed from the reaction vessel while hot. In this case, by removing the mixed solution from the reaction vessel while it is hot, the possibility that the reaction residual substance in the mixed solution is deposited due to the temperature decrease of the mixed solution and the cleaning is incomplete can be effectively reduced, in other words, the cleaning effect of the reaction vessel can be advantageously improved.

In the method according to the first aspect of the present disclosure, optionally, the step of obtaining the mass of the reaction residual substance includes: weighing the reaction container before preparing lactide to obtain the mass of the reaction container; weighing a reaction vessel containing the reaction residue after preparing lactide to obtain the total mass; and subtracting the mass of the reaction container from the total mass to obtain the mass of the reaction residual substance. In this case, by obtaining the mass of the reaction residual substance, it is possible to easily determine the volume of the cleaning solvent to be added to the reaction vessel.

A second aspect of the present disclosure provides a cleaning solvent for cleaning a reaction vessel for lactide production, the reaction vessel having an opening and having an inner wall to which reaction residual substances left after the lactide production are attached, the reaction residual substances including polylactic acid oligomers, the cleaning solvent being a potassium hydroxide solution, and the cleaning solvent having a concentration of 0.1 to 1mol/L, a ratio of a volume (in units of L) of the cleaning solvent to a mass (in units of kg) of the reaction residual substances in the reaction vessel being not less than 1; when the reaction container is cleaned by the cleaning solvent, a reflux condensation pipe is arranged at an opening of the reaction container for condensation, the reaction container is heated until the cleaning solvent in the reaction container reaches a preset heating temperature, the preset heating time is maintained, mixed liquid with dissolved reaction residual substances is obtained, the mixed liquid is removed from the reaction container, and the cleaned reaction container is obtained, wherein the preset heating temperature is not lower than 150 ℃. In the second aspect of the present disclosure, by cleaning the reaction vessel with the cleaning solvent, a clean reaction vessel can be obtained.

According to the present disclosure, a method for simultaneously cleaning a plurality of lactide production reaction vessels, which has a simple cleaning method, low cost, and high efficiency, and a cleaning solvent for cleaning the lactide production reaction vessels can be provided.

Drawings

Fig. 1 is a flow diagram illustrating the preparation of lactide according to an example of the present disclosure.

Fig. 2 is a flow chart illustrating a method of simultaneously purging a plurality of lactide-producing reaction vessels in accordance with an example of the present disclosure.

Fig. 3 is a schematic view illustrating a condensate return apparatus according to an example of the present disclosure.

Description of the reference numerals:

1 … reaction vessel, 2 … condensing reflux device, 20 … refluxing condenser tube, 21 … channel, 22 … fourth opening, 30 … condenser.

Detailed Description

All references cited in this disclosure are incorporated by reference in their entirety as if fully set forth. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the following description, the same components are denoted by the same reference numerals, and redundant description thereof is omitted. The drawings are schematic and the ratio of the dimensions of the components and the shapes of the components may be different from the actual ones.

It should be noted that the terms "comprises" and "comprising," and any variations thereof, as used herein, are intended to cover any process, method, system, article, or apparatus that comprises or comprises a list of steps or elements without limitation, but may include or include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.

The first aspect of the present disclosure relates to a method for simultaneously cleaning a plurality of lactide production reaction vessels, which is simple in cleaning manner, low in cost, and high in efficiency, and by which a reaction vessel free from adhesion of reaction residual substances can be cleaned. The method of simultaneously cleaning a plurality of reaction vessels for lactide production in the present disclosure may be simply referred to as a "cleaning method", and may also be referred to as a method of cleaning a reaction vessel for lactide production, a method of cleaning a reaction vessel, a method of simultaneously cleaning a plurality of polylactic acid polymerization reaction apparatuses, or the like.

The reaction vessel cleaned by the cleaning method of the present disclosure without the adhesion of the reaction residual substance can be recovered and reused. For example, the washed reaction vessel can be used in a laboratory or can be reused for the preparation of lactide. The cleaning method of the present disclosure may also be used to clean a polylactic acid polymerization reaction apparatus. That is, the cleaning method of the present disclosure may be used to clean a container having a polylactic acid oligomer.

Hereinafter, a method for cleaning a plurality of reaction vessels for producing lactide according to the first aspect of the present disclosure will be described with reference to the drawings.

Fig. 1 is a flow diagram illustrating the preparation of lactide in accordance with an example of the present disclosure.

In this embodiment, the preparing the lactide may include: preparing a lactic acid raw material (step S11); preparing an oxide of an amphoteric metal as a catalyst (step S12); adding a catalyst into a lactic acid raw material, and polymerizing the lactic acid raw material to obtain a polylactic acid oligomer (step S13); the polylactic acid oligomer is cleaved to obtain lactide (step S14) (see fig. 1). The order of step S11 and step S12 is not sequential, for example, step S11 may be performed first and then step S12 may be performed, step S12 may be performed first and then step S11 may be performed, or step S11 and step S12 may be performed simultaneously. In this case, in step S14, the polylactic acid oligomer is generally not completely cleaved into lactide, and the polylactic acid oligomer not cleaved into lactide and the catalyst may adhere to the inner wall of the reaction vessel after cooling and solidification, and thus it is difficult to directly pour out the polylactic acid oligomer and the catalyst, and the reaction vessel cannot be reused. The substance adhering to the inner wall of the reaction vessel is referred to as a reaction residual substance. That is, the reaction residual substance may include polylactic acid oligomer.

The reaction vessel for producing lactide according to the present disclosure may produce lactide not only by the above-described method but also by other methods that may produce polylactic acid oligomers.

Fig. 2 is a flow diagram illustrating a method of simultaneously purging a plurality of lactide-producing reaction vessels in accordance with an example of the present disclosure.

In the present embodiment, the method of simultaneously cleaning a plurality of reaction vessels for lactide production may include: preparing a cleaning solvent (step S100); adding a cleaning solvent into each reaction vessel respectively (step S200); arranging a reflux condenser pipe at the opening of the reaction container, connecting the reflux condenser pipes in series and then connecting the reflux condenser pipes with a condenser (step S300); starting a condenser, setting a preset cooling circulation temperature for condensation, heating the reaction container until the cleaning solvent reaches the preset heating temperature, and maintaining the preset heating time to obtain a mixed solution in which reaction residual substances are dissolved (step S400); the mixed solution is removed from the reaction vessel to obtain a washed reaction vessel (step S500).

In this case, the reaction vessel for producing lactide can be cleaned by dissolving the reaction residual substance in the cleaning solvent and then removing the mixed solution in which the reaction residual substance is dissolved; in step S200, a plurality of reaction vessels for lactide production can be simultaneously cleaned by adding a cleaning solvent to each reaction vessel; in step S300, by disposing the reflux condenser tubes at the openings of the reaction vessels and connecting the reflux condenser tubes in series with the condenser, condensation reflux treatment can be conveniently performed on reactants in a plurality of reaction vessels at the same time, thereby facilitating improvement of cleaning efficiency of the reaction vessels and equipment utilization rate; in step S400, the reaction vessel is heated until the cleaning solvent reaches the predetermined heating temperature and is maintained for the predetermined heating time, so that the dissolution rate and solubility of the reaction residual substance in the cleaning solvent can be increased, thereby improving the cleaning effect of the reaction vessel.

In the present disclosure, the reaction vessel for preparing lactide may be simply referred to as a reaction vessel, and the reflux condenser tube may be simply referred to as a condenser tube.

In some examples, in step S100, the cleaning solvent may be a potassium hydroxide solution. In some examples, the concentration of the potassium hydroxide solution may be 0.1mol/L to 1mol/L. For example, the concentration of the potassium hydroxide solution may be 0.1mol/L, 0.2mol/L, 0.3mol/L, 0.4mol/L, 0.5mol/L, 0.6mol/L, 0.7mol/L, 0.8mol/L, 0.9mol/L, or 1mol/L. In this case, by using a potassium hydroxide solution as the cleaning solvent and setting the concentration of the potassium hydroxide solution to 0.1mol/L to 1mol/L, the reaction residual substance can be promoted to be dissolved in the alkaline cleaning solvent, and the cleaning effect on the reaction vessel can be improved.

In some examples, the cleaning solvent may be used to clean containers in a laboratory for lactide production. In some examples, the cleaning solvent may also be used to clean other containers having polylactic acid oligomers.

In some examples, the washing solvent may be separately added to each reaction vessel in step S200. This enables cleaning of a plurality of reaction vessels.

In some examples, in step S200, the ratio of the volume (in units of L) of the cleaning solvent in each reaction vessel to the mass (in units of kg) of the reaction residual substance in each reaction vessel may be not less than 1. In other words, the volume mass ratio of the washing solvent to the reaction residual substance may be not less than 1l. In this case, it is possible to facilitate the reaction residual substance to sufficiently react with the cleaning solvent, thereby facilitating the dissolution of the reaction residual substance. It can be understood that, when the reaction vessel is cleaned, the more the amount of the cleaning solvent is, the more sufficient cleaning of the reaction vessel can be performed, and in the present disclosure, by the condensation device in cooperation with a specific cleaning solvent, the reaction vessel can be cleaned in a condition that the volume-to-mass ratio of the cleaning solvent to the reaction residual substance can be not lower than 1l.

In some examples, in step S200, the volume-to-mass ratio of the washing solvent to the reaction residual substance may be 1l.

In some examples, the manner of obtaining the mass of the reaction residual substance may include the steps of: weighing the reaction container before reaction (namely before lactide preparation) to obtain the mass of the reaction container; weighing the reaction vessel containing the reaction residual substances after the reaction (i.e. after preparing lactide and pouring out the lactide in the vessel) to obtain the total mass; the mass of the reaction vessel was subtracted from the total mass to obtain the mass of the reaction residual material. In this case, the mass of the reaction residual substance can be obtained to determine the volume of the cleaning solvent to be added to the reaction vessel.

In some examples, in step S200, the number of reaction vessels may be preferably 2 to 4. For example, the number of reaction vessels may be 2, 3, or 4. In this case, 2 to 4 reaction vessels can be simultaneously cleaned, thereby improving the cleaning efficiency.

In some examples, in step S200, the reaction vessel may be selected from one of a conical flask, a two-necked flask, or a three-necked flask, and the kinds of the respective reaction vessels may be the same or different. From this, can be convenient for add the washing solvent to reaction vessel to set up the backward flow condenser pipe at reaction vessel's opening part, thereby can be convenient for wash reaction vessel. Of course, other containers with reaction residues can be cleaned by the cleaning method of the present disclosure, and only a few containers commonly used in experiments are exemplified and should not be construed as limiting. For example, in the process of producing lactide, it is generally necessary to add different kinds of reactants to a reaction vessel, and thus a three-necked flask is generally used as a reaction vessel for producing lactide.

In some examples, in step S300, a reflux condenser tube may be disposed at each opening of the reaction vessels. Under the condition, when the reaction vessel is heated subsequently, the steam of the heated and evaporated cleaning solvent can reenter the reaction vessel to participate in the reaction in a condensation reflux mode, so that the using amount of the cleaning solvent can be saved, the reaction vessel can be cleaned by using the cleaning solvent with a preset proportion, and meanwhile, the cost for cleaning the reaction vessel can be reduced.

In some examples, the reflux condenser tubes may be connected in series. Wherein, the reflux condenser pipe after the series connection can be connected with the condensing machine. In this case, when the reaction vessels are cleaned, the condensate required for the condensation reflux can be supplied to the plurality of reaction vessels simultaneously by one condenser, and the efficiency of cleaning the plurality of reaction vessels can be improved while the equipment utilization rate of the condenser is also improved. In other words, by providing one condenser, a plurality of reaction vessels can be cleaned at the same time.

In some examples, the reflux condenser tube may have a passage between an inner wall of its outer profile and an outer wall of the inner tube for vapor movement of the cleaning solvent. Under the condition, the condensed liquid flows in the inner pipe, so that the temperature of the space in the channel can be favorably reduced, when the steam of the cleaning solvent enters the channel with lower temperature, the steam of the cleaning solvent can be favorably condensed into small liquid drops when meeting the condensation and is further condensed on the outer wall of the inner pipe and the inner wall of the outer contour of the backflow condensation pipe to be converged into liquid drops to fall into the reaction container, the backflow amount of the steam of the cleaning solvent can be favorably improved, and the cleaning efficiency and the cleaning effect of the reaction container can be improved. In some examples, in step S300, the reflux condenser tube may be a serpentine reflux condenser tube. Under the condition, the inner pipe of the snakelike reflux condensation pipe is in a snakelike spiral shape, the inner pipe which is in the snakelike spiral shape has a larger surface area and is exposed in the space in the channel, when condensate flows through the inner pipe, the temperature of the space in the channel can be favorably and rapidly reduced, furthermore, when steam of a cleaning solvent enters the channel with lower temperature and meets the condensate to be condensed into small liquid drops, the small liquid drops can be gradually gathered on the outer wall of the inner pipe with lower temperature to form liquid drops, when the liquid drops are gathered to a certain amount, the liquid drops can slide down along the outer wall of the inner pipe which is in the snakelike spiral shape under the action of self gravity and continuously collect the liquid drops in the sliding process to form liquid flows and finally flow downwards into the reaction container, so that the reflux speed and reflux quantity of the cleaning solvent steam can be favorably improved, and the cleaning efficiency and the cleaning effect of the reaction container can be improved.

Fig. 3 is a schematic view showing a condensate return apparatus 2 according to an example of the present disclosure. In fig. 3, the reaction vessel 1, the reflux condenser 2 and the cooperation of the two are exemplarily described by taking an example in which the plurality of reaction vessels 1 are 4 three-necked flasks and the reflux condenser 20 is a serpentine-shaped reflux condenser, and the moving direction of the condensate is schematically indicated by an arrow in fig. 3.

In the example shown in fig. 3, each reflux condenser 20 may be provided at one of the openings (e.g., the middle opening in fig. 3) in each three-necked flask, each reflux condenser 20 may be connected to the condenser 30 by connecting pipes in series, and other openings of the three-necked flask to which the reflux condenser 20 is not connected may be in a closed state when heating, in which case vapor of the cleaning solvent can be guided to move from the opening connected to the reflux condenser 20 into the reflux condenser 20; one end of the reflux condenser pipe 20 relatively far away from the three-neck flask is provided with an opening (hereinafter referred to as a fourth opening 22), when the reaction vessel 1 is cleaned, the reflux condenser pipe 20 can be communicated with the outside through the fourth opening 22, when the cleaning solvent moves upwards due to heating and evaporation, even if the steam of the cleaning solvent cannot be completely condensed and refluxed in the channel 21 of the reflux condenser pipe 20, the steam of the cleaning solvent can be dissipated to the outside from the fourth opening 22, so that the pressure in the reaction vessel 1 and the reflux condenser pipe 20 and the outside pressure are in a balanced state, the reaction vessel 1 and/or the reflux condenser pipe 20 can be effectively prevented from being broken due to the overlarge internal pressure of the reaction vessel 1 and the reflux condenser pipe 20, and the safety of the cleaning process can be improved.

In some examples, the predetermined cooling cycle temperature may be set to not higher than 0 ℃ in step 400. For example, the predetermined cooling cycle temperature may be 0 ℃, -1 ℃, -2 ℃, -3 ℃, -4 ℃, or-5 ℃ or the like. In this case, when the cleaning solvent is heated to evaporate and rises to the reflux condenser tube, by setting the predetermined cooling cycle temperature to not higher than 0 ℃, the condensation reflux effect of the vapor of the cleaning solvent can be improved, thereby increasing the reflux amount of the vapor of the cleaning solvent.

In some examples, the reactor vessel for lactide production may also be purged without using a condensate return line. In this case, since the cleaning solvent is evaporated and dissipated by heating, the reaction vessel can be cleaned by adding a larger amount of the cleaning solvent to the reaction vessel or adding the cleaning solvent to the reaction vessel several times during the cleaning process so that an appropriate amount of the cleaning solvent is always maintained in the reaction vessel.

In some examples, a single reaction vessel may also be cleaned by the cleaning methods of the present disclosure. In this case, by arranging a reflux condenser tube at the opening of the reaction vessel, the vapor of the cleaning solvent which is subsequently heated and evaporated can enter the reaction vessel again to participate in the reaction through condensation reflux.

In some examples, a number of reaction vessels in excess of 4 may also be cleaned simultaneously by the cleaning methods of the present disclosure. For example, the number of reaction vessels that are simultaneously cleaned may be 5. Since the temperature of the condensate in the reflux condenser tube will rise with the movement of the condensate in the condenser tube, when the condensate flows through the condenser tube located at a position relatively back, for example, the 5 th condenser tube, the condensate with the rising temperature in the condenser tube may not achieve the desired condensation effect of the vapor of the cleaning solvent in the 5 th reaction vessel, so that a part of the vapor of the cleaning solvent is dissipated through the condenser tube, thereby affecting the cleaning effect of the reaction vessel. In this case, when it is necessary to clean reaction vessels in a number exceeding 4, the condensation reflux effect of the vapor of the cleaning solvent can be enhanced by setting a lower cooling cycle temperature. For example, the cooling cycle temperature may be set to-5 ℃. This improves the condensation/reflux effect of the vapor of the cleaning solvent, and improves the cleaning efficiency and cleaning effect of the reaction vessel.

In some examples, the predetermined heating temperature may be configured to be not lower than 150 ℃. For example, the predetermined heating temperature may be 150 ℃, 160 ℃, 170 ℃, 180 ℃, 190 ℃, or the like. In some examples, the predetermined heating temperature may be 150 ℃ to 160 ℃, preferably. In some examples, the predetermined heating time may be 6 to 24 hours. For example, the predetermined heating time may be 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h, 22h, or 24h. In this case, by setting a specific heating temperature and heating time, it is possible to facilitate the reaction residual substance to sufficiently react with the cleaning solvent, thereby facilitating the reaction residual substance to be sufficiently dissolved in the cleaning solvent, and thus it is possible to improve the cleaning effect of the reaction vessel. However, examples of the present disclosure are not limited thereto, and in other examples, the predetermined heating temperature may be configured to be lower than 150 ℃, and the cleaning effect may be improved by extending the predetermined heating time. For example, the predetermined heating temperature may be 140 ℃ and the predetermined heating time may be 48 hours.

In some examples, in step S400, a plurality of reaction vessels may be simultaneously heated by means of oil bath heating. In this case, by placing the reaction vessel in the conduction oil, the bottom region of the reaction vessel can be uniformly heated, thereby facilitating the reaction residual substance to be sufficiently dissolved in the cleaning solvent, whereby the cleaning effect of the reaction vessel can be improved.

In some examples, in step S500, after the reaction residual substance is sufficiently dissolved in the cleaning solvent, the condensation tube may be removed from the opening of the reaction container, and the mixed solution in the reaction container may be poured out.

In some examples, in step S500, the mixed liquor may be removed from the reaction vessel while hot. In this case, the mixed solution is removed from the reaction vessel while it is hot, so that the possibility that the reaction residual substance in the mixed solution is not completely washed due to precipitation of the mixed solution due to temperature reduction of the mixed solution can be effectively reduced, thereby contributing to improvement of the washing effect of the reaction vessel.

In some examples, in step S500, after the mixed liquid is removed from the reaction vessel, the reaction vessel may be washed with water several times. This can improve the cleanliness of the reaction vessel.

As described above, in the first aspect of the present disclosure, a method capable of simultaneously cleaning a plurality of reaction vessels for lactide production with a simple cleaning method, a low cost, and a high efficiency can be provided, in which the removal rate of reaction residual substances in the reaction vessels obtained by cleaning is 100%, and the reaction vessels after cleaning are free from the adhesion of reaction residual substances, and can be recovered and reused (for example, can be used in a laboratory, and can also be reused for lactide production).

A second aspect of the present disclosure relates to a cleaning solvent for cleaning a reaction vessel for lactide production. In the second aspect of the present disclosure, the reaction vessel after washing can be obtained by washing the reaction vessel with the washing solvent. The cleaning solvent in the second aspect of the present disclosure corresponds to the cleaning solvent in the cleaning method in the first aspect of the present disclosure, and the detailed description of the cleaning solvent may refer to the description of the cleaning solvent in the cleaning method, which is not repeated herein.

When the reaction vessel having the reaction residual substance is cleaned with the cleaning solvent according to the second aspect of the present disclosure, the cleaning may be performed using the cleaning method according to the first aspect of the present disclosure. Specifically, a reflux condenser tube may be disposed at an opening of the reaction vessel for condensation, the reaction vessel may be heated until the cleaning solvent inside the reaction vessel reaches a predetermined heating temperature, and the predetermined heating time is maintained to obtain a mixed solution in which the reaction residual substance is dissolved, and the mixed solution may be removed from the reaction vessel to obtain the cleaned reaction vessel, where the predetermined heating temperature is not lower than 150 ℃. The parameters, ratios and settings can be referred to the above description of the cleaning method, and are not repeated herein.

In summary, in the second aspect of the present disclosure, it is possible to provide a cleaning solvent for cleaning a reaction vessel for lactide production, which has no reaction residual substance attached thereto, can be recovered, and can be reused (for example, in a laboratory, and can be reused for lactide production).

Hereinafter, the cleaning method provided by the present disclosure will be described in detail with reference to examples and comparative examples, but they should not be construed as limiting the scope of the present disclosure.

[ examples ]

First, the reaction vessel was weighed before the preparation of lactide to obtain the mass of the reaction vessel.

Secondly, preparing lactide by the following specific steps: preparing a lactic acid raw material; preparing an oxide of an amphoteric metal as a catalyst; adding a lactic acid raw material and a catalyst into a reaction vessel, and polymerizing the lactic acid raw material to obtain a polylactic acid oligomer; and cracking the polylactic acid oligomer to obtain lactide.

And removing the prepared lactide from the reaction container, weighing the reaction container containing the reaction residual substances to obtain the total mass, and subtracting the mass of the reaction container from the total mass to obtain the mass of the reaction residual substances.

From now, the cleaning solvents of examples 1 to 12 were configured according to table 1.

Then, a cleaning solvent was added to the reaction vessel in the ratio shown in table 1.

Then, a reflux condenser pipe is respectively arranged at the opening of the reaction container of each of the embodiments 1 to 7, and the reflux condenser pipe is connected with a condenser; in each of examples 8 to 12, one reflux condenser tube was provided at each opening of 4 reaction vessels, and each reflux condenser tube was connected in series to a condenser.

Then, according to table 1, the condenser was turned on and a predetermined cooling cycle temperature was set for condensation, and the plurality of reaction vessels were heated until the cleaning solvent in each reaction vessel reached a predetermined heating temperature and maintained for a predetermined heating time, to obtain a mixed solution in which the reaction residual substances were dissolved.

Finally, the reflux condenser tube was removed from the opening of each reaction vessel, and the mixed solution was removed from the reaction vessel, thereby obtaining cleaned reaction vessels of examples 1 to 12.

TABLE 1

Comparative example

First, the reaction vessel was weighed using an electronic scale before the preparation of lactide to obtain the mass of the reaction vessel.

Secondly, preparing lactide by the following specific steps: preparing a lactic acid raw material; preparing an oxide of an amphoteric metal as a catalyst; adding a lactic acid raw material and a catalyst into a reaction container, and polymerizing the lactic acid raw material to obtain a polylactic acid oligomer; and (3) cracking the polylactic acid oligomer to obtain lactide.

And removing the prepared lactide from the reaction container, weighing the reaction container containing the reaction residual substances by using an electronic scale to obtain the total mass, and subtracting the mass of the reaction container from the total mass to obtain the mass of the reaction residual substances.

From the next, the cleaning solvents of comparative examples 1 to 27 were configured according to table 2.

Then, according to Table 2, the cleaning solvents were fed into the respective reaction vessels in such a ratio that the ratio of the volume (in terms of L) of the cleaning solvent in the respective reaction vessels to the mass (in terms of kg) of the reaction residual substances in the reaction vessels was not less than 1.

Then, a reflux condenser pipe was provided at the opening of the reaction vessel of each of comparative examples 1 to 6 and 11 to 27, and the reflux condenser pipe was connected to a condenser; and respectively arranging one reflux condensation pipe at the opening of each of the 4 reaction containers in the comparative examples 7 to 10, and connecting the reflux condensation pipes in series with a condenser.

Then, starting a condenser, and setting a preset cooling circulation temperature according to the table 2 for condensation; according to table 2, the plurality of reaction vessels were heated until the cleaning solvent in each reaction vessel reached a predetermined heating temperature (the predetermined heating temperature was room temperature, which means that the reaction vessel was placed in a room temperature environment of 25 ℃), and the heating was maintained for a predetermined time, thereby obtaining a mixed solution in which the reaction residual substances were dissolved.

Finally, the reflux condenser tube was removed from the opening of each reaction vessel, and the mixed solution was removed from the reaction vessel, to obtain cleaned reaction vessels of comparative examples 1 to 27.

TABLE 2

In the above-described operation, the reflux conditions of the cleaning solvent in the condensate reflux pipe of each example (example 1 to example 12) and each comparative example (comparative example 1 to comparative example 27) were observed and recorded. The observation of the reflux of the cleaning solvent in the example and the comparative example in which the number of the cleaning tanks is 4 means that the reflux of the cleaning solvent in the condensate return pipe positioned at the last among the 4 condensate return pipes connected in series is observed. Wherein total reflux means that the condensed liquid droplets were observed only in about 1/3 area of the lower portion of the reflux condenser tube during the washing, large reflux means that the condensed liquid droplets were observed only in about 2/3 area of the lower portion of the reflux condenser tube during the washing, and small reflux means that the condensed liquid droplets were observed in all areas of the reflux condenser tube during the washing, and the results were recorded as shown in table 3. Calculating the removal rate of the reaction residual substances in the cleaned reaction container, which is specifically as follows: the reaction vessels cleaned in each example and each comparative example were weighed by an electronic scale to obtain the total mass after cleaning, and the removal rate of the reaction residual substances was calculated from the weighing results, with the results shown in table 3. Wherein, the calculation formula of the removal rate of the reaction residual substances is as follows: removal rate = (mass of reaction residual substance-mass of reaction residual substance after washing)/mass of reaction residual substance × 100%. In calculating the removal rates of the reaction residual substances in each example and each comparative example in which the number of the cleaning vessels was 4, the average of the removal rates of the reaction residual substances in the 4 reaction vessels was taken as the removal rate of the reaction residual substances in each example and each comparative example.

In the examples, comparative examples, and the above measurement processes of the present disclosure, reagents and instruments used are commercially available products unless otherwise specified.

TABLE 3

	Reflux of cleaning solvent	Removal ratio of reaction residue (%)
			Example 1	All flows back	100
Example 2	All flows back	100
			Example 3	All flows back	100
Example 4	All flows back	100
			Example 5	All flows back	100
Example 6	All flows back	100
			Example 7	All flows back	100
Example 8	All flows back	100
			Example 9	All flows back	100
Example 10	All flows back	100
			Example 11	All flows back	100
Example 12	All flows back	100
			Comparative example 1	\	2
Comparative example 2	All flows back	74
			Comparative example 3	All flows back	91
Comparative example 4	A large amount of reflux	96
			Comparative example 5	All flows back	82
Comparative example 6	A large amount of reflux	92
			Comparative example 7	All flows back	67
Comparative example 8	All flows back	88
			Comparative example 9	A large amount of reflux	85
Comparative example 10	A small amount of reflux	77
			Comparative example 11	All flows back	55
Comparative example 12	A large amount of reflux	41
			Comparative example 13	\	2
Comparative example 14	All flows back	30
			Comparative example 15	All flows back	86
Comparative example 16	A large amount of reflux	72
			Comparative example 17	\	0
Comparative example 18	All flows back	2
			Comparative example 19	\	5
Comparative example 20	A large amount of reflux	24
			Comparative example 21	A small amount of reflux	16
Comparative example 22	\	10
			Comparative example 23	A large amount of reflux	67
Comparative example 24	A small amount of reflux	35
			Comparative example 25	\	11
Comparative example 26	A large amount of reflux	70
			Comparative example 27	A small amount of reflux	43

As can be seen from table 3, the removal rate of the reaction residue in each example (example 1 to example 12) was 100%.

Particularly, in a preferred embodiment, the predetermined heating time of example 5, example 6, example 7, example 11, and example 12 is 6 hours, and the removal rate of the reaction residual substance is 100%.

Particularly, in a preferred embodiment, 4 reaction vessels can be simultaneously cleaned in examples 8 to 12, and the removal rate of reaction residual substances is 100%.

The removal rate of the reaction residual substances in the reaction vessel obtained by the cleaning in example 3 was 100%, and the main reason is that when the single reaction vessel was cleaned, the vapor of the cleaning solvent was entirely refluxed in the reflux condenser tube at a predetermined heating temperature of 170 ℃, and the reaction residual substances were completely dissolved in the 0.1mol/L potassium hydroxide solution after a predetermined heating time of 12 hours.

The removal rate of the reaction residual substance in the reaction vessel cleaned in example 4 was 100%, mainly because the reaction residual substance was completely dissolved over a predetermined heating time of 12 hours, although the dissolution rate of the reaction residual substance in a 1mol/L potassium hydroxide solution under the predetermined heating temperature condition of 140 ℃ was low compared to the predetermined heating temperature condition of 150 ℃.

The removal rate of the reaction residual substance in the reaction vessel cleaned in comparative example 1 was only 2%, mainly because the predetermined heating temperature was low and the reaction residual substance had little solubility in a 0.1mol/L potassium hydroxide solution under room temperature conditions (25 ℃).

The removal rates of the reaction residual substances in the reaction vessels cleaned in comparative examples 2 and 3 were 74% and 91%, respectively, mainly due to the low predetermined heating temperatures, the low dissolution rates of the reaction residual substances in the 0.1mol/L potassium hydroxide solution at the predetermined heating temperatures of 130 ℃ and 140 ℃, and the incomplete dissolution of the reaction residual substances after the predetermined heating time of 24 hours.

The removal rate of the reaction residual substance in the reaction vessel cleaned in comparative example 4 was 96%, mainly because the predetermined heating temperature was low, the dissolution rate of the reaction residual substance in the 1mol/L potassium hydroxide solution was low under the predetermined heating temperature condition of 130 ℃, and the reaction residual substance could not be completely dissolved after the predetermined heating time of 24 hours.

The removal rates of the reaction residual substances in the reaction vessels cleaned in comparative examples 5 and 6 were 82% and 92%, respectively, mainly due to the fact that the predetermined heating temperature was high, and the cleaning solvent in the reaction vessel was evaporated at a high rate under the predetermined heating temperature condition of 180 ℃, and a large amount of vapor of the cleaning solvent was generated in a short time and was not completely refluxed in the condensation reflux pipe but was refluxed only in a small amount, so that the amount of the cleaning solvent in the reaction vessel was reduced and was not sufficient to completely dissolve the reaction residual substances.

The removal rates of the reaction residual substances in the reaction vessels cleaned in comparative examples 7 and 8 were 67% and 88%, respectively, mainly due to the low predetermined heating temperature, the low degradation rate of the reaction residual substances in the 0.1mol/L potassium hydroxide solution at the predetermined heating temperatures of 130 ℃ and 140 ℃, and the incomplete dissolution of the reaction residual substances after the predetermined heating time of 24 hours.

The removal rates of the reaction residual substances in the reaction vessels cleaned in comparative examples 9 and 10 are 85% and 77%, respectively, mainly because the preset heating temperature is high and the number of the cleaned reaction vessels is large, under the preset heating temperature conditions of 170 ℃ and 180 ℃, the cleaning solvent in the reaction vessels is high in evaporation speed, the condensate liquid is heated up due to the heat transfer effect of the steam of the cleaning solvent after entering the series-connected condensation return pipe, and the condensation effect of the heated condensate liquid on the cleaning solvent after entering the series-connected condensation return pipe is weakened, so that the steam of a large amount of cleaning solvent generated in a short time cannot completely return in the series-connected condensation return pipe and only slightly returns, and the amount of the cleaning solvent in the reaction vessels is reduced and is not enough to completely dissolve the reaction residual substances.

The removal rate of the residual matters in the reaction vessel cleaned in comparative example 11 was 55%, mainly because the concentration of the potassium hydroxide solution as the cleaning solvent was low and the solubility of the reaction residual matters in the 0.01mol/L potassium hydroxide solution was low enough to allow the reaction residual matters to be completely dissolved under the predetermined heating temperature condition of 150 ℃.

The removal rate of the residual substances in the reaction vessel cleaned in comparative example 15 was 86%, mainly because the hydrochloric acid solution as the cleaning solvent was poor in dissolving the reaction residual substances, and the solubility of the reaction residual substances in the hydrochloric acid solution of 0.1mol/L was low enough to allow the reaction residual substances to be completely dissolved under the predetermined heating temperature condition of 150 ℃.

The removal rates of the residual substances in the reaction vessels cleaned in comparative examples 20, 23 and 26 were 24%, 67% and 70%, respectively, mainly due to poor dissolution of the reaction residual substances by the potassium hydroxide ethanol solution, dichloromethane and chloroform as cleaning solvents, and the dissolution rates of the reaction residual substances in the 0.1mol/L potassium hydroxide ethanol solution, dichloromethane and chloroform were low under the predetermined heating temperature condition of 100 ℃, and the reaction residual substances could not be completely dissolved after the predetermined heating time of 24 hours.

The removal rates of the residual substances in the reaction vessels cleaned in comparative examples 21, 24 and 27 were 16%, 35% and 43%, respectively, mainly because the koh ethanol solution, dichloromethane and chloroform, which were the cleaning solvents, were relatively volatile, the koh ethanol solution, dichloromethane and chloroform, which were the cleaning solvents, evaporated at a relatively high rate under the predetermined heating temperature condition of 150 c, and a large amount of vapors of the cleaning solvents, which were generated in a short time, were not all refluxed but only slightly refluxed in the reflux condenser tube, so that the amount of the cleaning solvents in the reaction vessels was reduced and was not enough to completely dissolve the reaction residual substances.

In conclusion, the reaction vessels for preparing lactide obtained by cleaning in each example (example 1 to example 12) have no reaction residual substance left, the cleaning method is simple, and a plurality of reaction vessels for preparing lactide can be cleaned simultaneously in example 8 to example 12, so that the efficiency is high. In contrast, the method of cleaning the reaction vessel for the preparation of lactide in each of the comparative examples (comparative example 1 to comparative example 27) cannot simultaneously achieve the effect of the method of cleaning the reaction vessel for the preparation of lactide in each of the above-described examples (example 1 to example 12).

While the present disclosure has been described in detail above with reference to the drawings and examples, it should be understood that the above description is not intended to limit the disclosure in any way. Those skilled in the art can make modifications and variations to the present disclosure as needed without departing from the true spirit and scope of the disclosure, which fall within the scope of the disclosure.

Claims

1. A method for simultaneously cleaning a plurality of lactide production reaction vessels having openings and having reaction residual substances left after lactide production attached to the inner walls, the reaction residual substances including polylactic acid oligomers, comprising the steps of: preparing a cleaning solvent, wherein the cleaning solvent is a potassium hydroxide solution with the concentration of 0.1mol/L to 1 mol/L; adding the cleaning solvent into each reaction container respectively, wherein the ratio of the volume (unit is L) of the cleaning solvent in each reaction container to the mass (unit is kg) of reaction residual substances in each reaction container is not lower than 1; a reflux condenser pipe is respectively arranged at the opening of each reaction container, and each reflux condenser pipe is connected with a condenser after being connected in series; starting a condenser and setting a preset cooling circulation temperature for condensation, heating the reaction containers until the cleaning solvent in each reaction container reaches a preset heating temperature, and maintaining the preset heating time to obtain a mixed solution dissolved with the reaction residual substances, wherein the preset heating temperature is not lower than 150 ℃; and taking the reflux condenser pipes down from the openings of the reaction containers, and removing the mixed liquid from the reaction containers to obtain the cleaned reaction containers.

2. The method according to claim 1, wherein the predetermined heating temperature is 150 ℃ to 160 ℃ and the predetermined heating time is 6h to 24h.

3. The method of claim 1, wherein said plurality of reaction vessels are heated simultaneously by means of an oil bath.

4. The method of claim 1, wherein the plurality of reaction vessels is 2 to 4 in number.

5. The method of claim 1, wherein the predetermined cooling cycle temperature is no greater than 0 ℃.

6. The method of claim 1, wherein the reflux condenser is a serpentine reflux condenser.

7. The method according to claim 1, wherein the reaction vessel is selected from one of a conical flask, a two-necked flask and a three-necked flask, and the kinds of the respective reaction vessels are the same or different.

8. The method of claim 1, wherein the mixed liquor is removed from the reaction vessel while hot after the mixed liquor is obtained.

9. The method according to claim 1, characterized in that the means for obtaining the mass of the reaction residual substance comprise the steps of: weighing the reaction container before preparing lactide to obtain the mass of the reaction container; weighing a reaction vessel containing the reaction residue after preparing lactide to obtain the total mass; and subtracting the mass of the reaction container from the total mass to obtain the mass of the reaction residual substance.

10. A cleaning solvent for cleaning a reaction vessel for lactide production, the reaction vessel having an opening and having an inner wall to which reaction residual substances remaining after lactide production are attached, the reaction residual substances including polylactic acid oligomers, characterized in that the cleaning solvent is a potassium hydroxide solution, and the concentration of the cleaning solvent is 0.1 to 1mol/L, the ratio of the volume (in units of L) of the cleaning solvent to the mass (in units of kg) of the reaction residual substances in the reaction vessel is not less than 1; when the reaction container is cleaned by the cleaning solvent, a reflux condensation pipe is arranged at an opening of the reaction container for condensation, the reaction container is heated until the cleaning solvent in the reaction container reaches a preset heating temperature, the preset heating time is maintained, mixed liquid with dissolved reaction residual substances is obtained, the mixed liquid is removed from the reaction container, and the cleaned reaction container is obtained, wherein the preset heating temperature is not lower than 150 ℃.