RU2840015C1 - Plant for continuous production of paracetamol by acylation of para-aminophenol with acetic anhydride - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: present invention relates to chemical engineering, specifically to an apparatus for continuously producing paracetamol by acylation of p-aminophenol with acetic anhydride obtained in situ by pyrolysis of acetone. Plant includes a unit for producing acetic anhydride by pyrolysis of acetone, a reactor for preparing a solution of para-aminophenol, a para-aminophenol acylation reactor, a paracetamol suspension concentration reactor, a continuous-action separating device for separating solid paracetamol from the mother solution and a mother solution storage vessel, wherein ratio of working volumes of reactor for acylation of para-aminophenol and reactor for concentration of suspension of paracetamol ranges from 1:3 to 1:10.

EFFECT: provision of a plant for production of paracetamol which is stable in operation in continuous mode for a long period of time.

18 cl, 2 dwg, 2 ex

Description

The present invention relates to the field of chemical technology, in particular to an installation intended for the continuous production of paracetamol by acylation of para-aminophenol with acetic anhydride obtained in situ by pyrolysis of acetone.

para-Acetylaminophenol (acetaminophen, paracetamol) is a medicinal product, analgesic and antipyretic from the anilide group, which has an antipyretic effect. According to the mechanism of action, paracetamol blocks cyclooxygenase 1 and cyclooxygenase 2 mainly in the central nervous system, affecting the pain and thermoregulation centers. In inflamed tissues, cellular peroxidases neutralize the effect of paracetamol on cyclooxygenase, which explains the almost complete absence of an anti-inflammatory effect. The absence of a blocking effect on the synthesis of prostaglandins in peripheral tissues determines the absence of a negative effect on water-salt metabolism and the mucous membrane of the gastrointestinal tract.

Paracetamol is included in the list of essential drugs of the World Health Organization, as well as in the list of vital and essential drugs of the Russian Federation. Therefore, to this day, in the research and production areas, there is significant interest in the development and implementation of new effective methods for synthesizing paracetamol that meet the modern realities of ever-increasing raw materials and increasingly stringent requirements for ensuring the environmental friendliness of production.

The traditional method for synthesizing paracetamol is the acylation reaction of para-aminophenol. Acetic anhydride is widely used as an acylating agent (e.g., the Mallinckrodt process, the Sterling process, and the Monsanto process). The use of this reagent has clear advantages over other synthetic approaches. The reaction proceeds smoothly in a wide variety of solvents (ethyl acetate, acetic acid, water), with high yields.

A method for producing paracetamol from p-aminophenol by reaction with acetic anhydride in acetic acid is known from Chinese patent CN 108689871 A. This method is part of a synthetic chain for producing paracetamol from nitrobenzene, including the intermediate production and isolation of purified p-aminophenol as an individual product. The p-aminophenol obtained from nitrobenzene and purified in a rectification column is reacted with an acetic anhydride/acetic acid mixture. The reaction is carried out by heating the mixture consisting of p-aminophenol, acetic anhydride and acetic acid at a temperature of 30-50°C for 1-1.5 hours. Then the reaction mixture is transferred to a bubbling crystallizer and a gas stream (nitrogen) with a temperature of 0-5°C is passed through it for crystallization and isolation of solid paracetamol. Under such conditions, paracetamol is crystallized for 30-120 minutes, resulting in paracetamol with a yield of 97-98% and a purity of 90-99%.

The apparatus for obtaining paracetamol from p-aminophenol by acylation in acetic acid in CN 108689871 A is not described in detail. It is only indicated that after the acylation reaction, the reaction mixture is transferred to a crystallizer to isolate solid paracetamol.

From the publication of R.W. Kurnianto et al., Jurnal Rekayasa Proses 2021, Vol. 15, No. 1, pp. 49-58, a method is known for producing paracetamol by reacting p-aminophenol with acetic anhydride in an aqueous solution, which is carried out in a batch reactor, which is a three-necked flask with overhead stirring, the isolation of paracetamol is carried out during crystallization and pure white crystals of paracetamol are obtained. The acylation reaction is carried out at a temperature of 86 ° C, 90 ° C and 108 ° C with a stirrer rotation speed of 250 rpm or 350 rpm. The publication notes that an increase in the intensity of stirring leads to an increase in the reaction rate. Commercial acetic anhydride is used in the reaction.

Among the general shortcomings of the described approaches, one can note the periodic mode of obtaining paracetamol using commercial acetic anhydride, which has a relatively high cost and strict regulation of the turnover of this reagent, as well as mixing performed by conventional laboratory stirrers. However, for carrying out such processes in a continuous mode, and especially with significant scaling, an extremely important aspect is the issues of mass and heat exchange, which affect the selectivity and speed of the process.

In addition, the indicated methods are carried out in laboratory quantities and involve performing synthetic operations on available equipment, without attaching special importance to the optimization and efficiency of the devices used.

At the same time, the combination of obtaining acetic anhydride from cheap and accessible initial reagents and carrying out the acylation reaction within the framework of a single unit would make it possible to obtain and use acetic anhydride of the required concentration for the acylation reaction, as well as easily regulate the specified concentration, without the need to accumulate large quantities of semi-finished products, which would simplify the process flow chart and reduce the need to dispose of the resulting waste.

Currently, there are three main industrial approaches to the production of acetic anhydride: acetaldehyde oxidation (CN 105732361 A; New J. Chem., 2017, 41, 931; Ukr. Khim. Zhurn., 1985, 51(11), 1208-13), carbonylation (US 9012683 B2) and the ketene process (J. Appl. Chem., 1953, 3, 6, 241-252; CN 113636930 A).

Thus, patent CN 105732361 A describes the catalytic oxidation of ethanol or acetaldehyde with gaseous oxygen at a relatively low temperature of 50-200°C using a palladium catalyst.

The process of obtaining acetic anhydride by carbonylation of methyl acetate on rhodium catalysts has been described quite widely, for example in US patents US 8653303 B2 and US 6222070 B1.

These methods use expensive catalysts that have a limited lifespan and require replacement or complex regeneration. Methyl acetate carbonylation uses toxic carbon monoxide, and the reaction is carried out in the liquid phase at elevated pressure.

The most effective method for synthesizing acetic anhydride can be considered the ketene method (Scheme 1), since in this case the simplest hardware is used and expensive catalysts are not required.

For example, ketene can be obtained by catalytic dehydration of acetic acid at 650-700°C using tungstophosphoric acid supported on SiO ₂ (CN 103570519 A). When the ketene vapor is cooled to 150°, it is trapped by acetic acid to form acetic anhydride. A similar pyrolysis method for generating ketene from acetic acid at 725°C on a phosphorus-containing catalyst has been described (JP 6100442 B1). These papers describe the complete sequence for producing acetic anhydride from acetic acid.

The key unit in ketene production units is the pyrolysis reactor, where acetone or acetic acid vapors are heated to a temperature of >720°C. When analyzing designs, two main methods for creating such conditions for pyrolysis can be identified: internal or external heating of vapors.

The internal method of heating the reagent vapors to generate ketene is achieved by using the so-called "ketene lamp" - a metal coil with a high electrical resistance value, with which the reagent vapors come into direct contact.

For example, patent application US 20140245658 A1 for the production of ethanol by hydrogenation describes a method for generating ketene from acetone using a similar ketene lamp.

"Ketene lamp" is quite an effective technical solution for providing high-temperature heating, and it can be used to precisely regulate the pyrolysis temperature. However, when using the spiral, a large temperature difference inevitably occurs, since the lower part of the heated spiral is cooled by incoming fresh reagent vapors. The resulting difference in heating has a negative effect on durability, the spiral can burn out relatively easily. Because of this, it is impossible to guarantee many hours of uninterrupted operation of such a unit.

A device with an electric heating coil is described in patent RO 112353 B1. In this solution, the heating coil is located inside a quartz tube and does not directly contact the vapors. It is difficult to ensure high productivity in such a solution, and such a device is only suitable for laboratory conditions.

External heating of the pyrolysis reactor is much easier to provide. Thus, in the classical laboratory method of generating ketene from acetone, described in the work of C.D. Hurd, Org. Synth. 1925, 4, 39, the heating of the tube with acetone vapors is carried out by external gas burners.

Patent GB 1109523 A describes a similar approach, but discloses in more detail the design of a gas furnace, which consists of four compartments for sequentially heating a coil reactor.

In patent GB 627810 A the pyrolysis apparatus is not described in detail, but according to the drawing it is a similar device.

A method for obtaining ketene by pyrolysis of acetone in a copper pyrolysis chamber at a temperature of 760-810°C is known from the UK patent document GB 472988 A. The chamber is a tube located in an electric furnace.

Patent CN 114931903 A proposes to use acetic acid as the initial reagent; during pyrolysis in the presence of a triethyl phosphate catalyst, it decomposes to form ketene and water. The pyrolysis apparatus is heated in a furnace.

With the furnace heating method, it is possible to provide the required temperature in the reactor, the device can operate continuously for a long time. However, furnaces are not economical enough and have high thermal inertia, which inevitably leads to significant difficulties in bringing the installation into operation.

Thus, at present, there still remains a significant need for the development of new devices for both the continuous production of acetic anhydride and the continuous acylation of para-aminophenol, eliminating or at least minimizing the previously indicated disadvantages of the prior art and providing the person skilled in the art with a wider choice of means and technologies for realizing the production of the valuable pharmaceutical product paracetamol with excellent yields and high purity.

Therefore, the objective of the present invention was to provide a new plant for producing paracetamol by acylating para-aminophenol with acetic anhydride, which would allow for the continuous production of acetic anhydride by pyrolysis of acetone and the acylation of para-aminophenol with the possibility of effectively heating the vapors of the reagent subjected to pyrolysis in a given temperature range, and would be characterized by stable operation in continuous mode over a long period of time and effective mixing, guaranteeing improved heat and mass transfer of the acylation reaction mixture, with a simple design that ensures high productivity and energy efficiency.

The authors managed to solve this problem using a new installation for the continuous production of paracetamol by acylation of para-aminophenol with acetic anhydride, including

a unit for producing acetic anhydride by pyrolysis of acetone, comprising an evaporation tank for evaporating acetone; a pyrolysis reactor configured to pyrolyze acetone to form a gas mixture containing ketene, at least one refrigerator for condensing unreacted acetone, a line for returning condensed unreacted acetone to the evaporation tank, a gas-liquid separator, at least one absorption tank configured to react gaseous ketene with liquid acetic acid, wherein the pyrolysis reactor has several successively arranged heating zones with their own heating filament in each zone, in which gradient heating of acetone vapor is ensured, and at least one absorption tank is equipped with an inlet for acetic acid, an outlet for exhaust gases and an outlet for an acetic anhydride solution; a reactor for preparing a para-aminophenol solution, equipped with a stirrer, a temperature maintenance system, a temperature sensor, an inlet for feeding solid para-aminophenol, inlets for feeding water and fresh acetic acid solution, and an outlet for gravity-flowing removal of part of the prepared solution, located in the upper part of the reactor;

a reactor for acylating para-aminophenol, equipped with a stirrer, at least one inlet for feeding a para-aminophenol solution, connected via a fluid medium to a reactor for preparing a para-aminophenol solution, and an inlet for feeding acetic anhydride, connected via a fluid medium to an outlet for acetic anhydride solution of at least one absorption tank of an acetic anhydride production unit, and an outlet for gravity-flowing removal of a portion of the acylation reaction mixture, located in the upper part of the reactor;

a paracetamol suspension concentration reactor equipped with a stirrer and a cooling device, a temperature sensor, at least one inlet for the para-aminophenol acylation reaction mixture, fluidly connected to the para-aminophenol acylation reactor, an outlet for the suspension concentration reaction mixture, located in the upper part of the reactor;

a continuous separating device for separating solid paracetamol from the mother liquor, equipped with at least one inlet for the reaction mixture from the suspension concentration reactor, a drain for the mother liquor and an outlet for unloading solid paracetamol;

container for storing the mother liquor,

wherein the ratio of the working volumes of the para-aminophenol acylation reactor and the paracetamol suspension concentration reactor is in the range from 1:3 to 1:10.

The presented installation allows to continuously obtain paracetamol by acylation of para-aminophenol with acetic anhydride obtained in situ, under very mild conditions (low temperature) and in a short time, with obtaining paracetamol with a high yield, selectivity and with a low content of colored resins. At the same time, the combination of two processes within one installation allows to refuse accumulation of large quantities of semi-finished products, to regulate on-site the concentration of the prepared solution of acetic anhydride in acetic acid required for the acylation process in the widest range (from 1 to 99%). The ratio of reaction volumes of the reactors of the installation developed by the authors of this technical solution allows to implement a short reaction stage at a given reaction temperature and a longer stage of concentration of the product suspension at a reduced temperature, and the small volume of the reaction stage allows to refuse the use of energy-consuming temperature maintenance systems, regulating the temperature only by the feed rate of the initial reagents, which became possible due to the absence of inertia of temperature change inherent in large reaction volumes.

In addition, due to the use of several heating zones in the pyrolysis reactor, long-term stable operation of the acetic anhydride production unit by acetone pyrolysis and, accordingly, the entire installation as a whole is realized; energy-efficient heating of acetone vapors is carried out in a precisely specified temperature range with easy temperature regulation inside the pyrolysis reactor and a short response time, which ensures high productivity and energy efficiency of the installation.

This installation also allows you to realize the following advantages:

cheap acetone is used as a feedstock for generating the acylating reagent;

ketene generation is organized according to the recycling principle, where acetone vapors are returned to the original reaction vessel, which increases the efficiency of the process;

the installation operates in continuous mode, which increases the efficiency and quality of paracetamol, since it is easier to control the process conditions, and during production the product is not broken down into separate batches;

A depleted mother liquor in acetic acid can be used as a reaction medium for acylation, which increases the overall efficiency and reduces liquid waste.

Detailed description of the essence of the technical solution

The production of paracetamol in the claimed plant is based on the reaction of acylation of para-aminophenol with acetic anhydride, and acetic anhydride for the conversion is also produced in this plant. Thus, two parallel processes are carried out in the plant: production of a solution of acetic anhydride and synthesis of paracetamol (scheme 1).

The production of acetic anhydride is based on the pyrolysis reaction of acetone to form ketene and methane, after which the highly reactive gaseous ketene reacts with liquid acetic acid to form acetic anhydride.

To implement such a production scheme, the claimed installation generally includes a unit for producing acetic anhydride, a reactor for preparing a para-aminophenol solution, a reactor for acylating para-aminophenol, a reactor for concentrating a paracetamol suspension, a separating device, and a container for storing the mother liquor.

This arrangement allows for the implementation of various advantages of the proposed technical solution, such as the use of recirculation flows to improve the efficiency and productivity of the plant.

Figure 1 shows one of the preferred embodiments of the claimed installation for producing paracetamol by acylating para-aminophenol with acetic anhydride obtained by pyrolysis of acetone.

The detailed description of the claimed installation presented below is given for clarity with reference to the preferred embodiment shown in Fig. 1, but does not impose any limitations on the scope of the claims.

The acetic anhydride production unit BP3.1 generally includes equipment for the pyrolysis decomposition of acetone: an evaporation tank and a pyrolysis reactor with several heating zones, equipment for separating unreacted acetone from gaseous ketene: a refrigerator for condensing a portion of the unreacted acetone, a low-temperature refrigerator, a gas-liquid separator and a line for returning unreacted acetone, as well as devices for carrying out the interaction of ketene with acetic acid: at least one absorption tank.

In one embodiment, the acetic anhydride production unit BP3.1 is equipped with a gas supply for creating an inert atmosphere, preferably selected from nitrogen or argon, said supply is intended for purging all units of the unit in order to remove air from all units when starting the plant, as well as to prevent unwanted air suction during operational operation.

For generating acetone vapors, the acetic anhydride production unit BP3.1 includes an evaporation tank IS3.1 equipped with a heating jacket designed to create a temperature above the boiling point of acetone, an inlet for fresh acetone and an inlet for recirculated acetone, as well as at least one outlet for boiling acetone vapors connected to at least one inlet of the pyrolysis reactor.

The evaporation tank IS3.1 is connected to the tank for fresh acetone (not shown) via line L1, through which fresh acetone is supplied to the inlet for fresh acetone in an amount equal to the acetone spent during pyrolysis. This ensures continuous, uninterrupted operation of the apparatus.

As a rule, the evaporation tank of the IS3.1 is filled with acetone to 2/3 of its internal volume and, by means of a heating jacket, the acetone is heated to a temperature sufficient to maintain constant vigorous boiling of the acetone, which guarantees the removal of acetone vapors through the outlet at the top of the evaporation tank, connected to the inlet of the pyrolysis reactor.

The pyrolysis reactor PR1 is designed with the possibility of pyrolysis of acetone with the formation of a gas mixture containing ketene, and in general is a reaction vessel equipped with an internal reaction space and walls. The pyrolysis reactor PR1 is designed with the possibility of withstanding a heating temperature of at least in the range from 700 to 1200°C for a long time.

According to the present technical solution, the pyrolysis reactor PR1 is made of heat-resistant material, in particular heat-resistant metal or quartz.

Metals and alloys that can be used as a material for creating the PR1 pyrolysis reactor can be used that can be used at high temperatures and in various aggressive environments, i.e. materials that are chemically inert under the reaction conditions in order to minimize chemical corrosion of the reactor walls. Examples of suitable structural materials include special grades of heat-resistant stainless steels (for example, according to GOST 5632), steel-based materials, materials based on titanium, tungsten, nickel, chromium, beryllium, their alloys, superalloys such as Monel, Inconel, Incoloy, Hastelloy, etc.

In one embodiment, the walls of the pyrolysis reactor are made of heat-resistant stainless steels, preferably of AISI 316 stainless steel (08X17H13M2T according to GOST 5632-2014).

In another embodiment, the walls of the pyrolysis reactor are made of heat-resistant quartz glass.

In one preferred embodiment, the pyrolysis reactor PR1 is a pyrolysis tubular reactor.

In the internal space of the PR1 reactor there are several successively arranged heating zones with their own heating filament in each zone, in which gradient (gradual) heating of acetone vapors from 56°C in the lower part of the reactor to 795°C in the upper part is provided. Heating zoning leads to the fact that in each zone the temperature difference between the passing acetone vapors and the temperature of the heated heating filament decreases; a decrease in the temperature difference leads to a decrease in the thermal stress of the heating coil material and, accordingly, increases the working life of the heating coil.

The use of several controlled heating zones allows for a gradient increase in the temperature of acetone vapors with different rates of increase in different sections of the reactor. In the case of maximally uniform heating, the entire temperature range, starting from the temperature of boiling acetone to the temperature of the pyrolysis reaction (56°C - 795°C), is divided into equal intervals by the number of heating elements used (for example, in the case of three heating elements: the first spiral 300°C, the second spiral 547°C, the third spiral 795°C). In this case, the temperature difference in the lower and upper parts on each heating element will be minimal. However, it is also possible to carry out an uneven heating method. In this case, one of the temperature ranges is narrowed, respectively, increasing the others. This allows for a more optimal adjustment of the device operation in specific conditions. Thus, when increasing the flow of input acetone vapors, it is advisable to slightly increase the highest temperature range in order to increase productivity (for example, in the case of three heating elements: the first spiral 240°C, the second spiral 440°C, the third spiral 790°C).

In a preferred embodiment, the pyrolysis reactor has two to five heating zones arranged in series, more preferably three heating zones arranged in series, each having its own heating filament.

In a preferred embodiment with a pyrolysis reactor having three successively arranged heating zones, the temperature at the outlet of the first heating zone is in the range of 240 to 350°C, the temperature at the outlet of the second heating zone is in the range of 400 to 500°C, and the temperature at the outlet of the third heating zone is in the range of 740 to 795°C.

In a preferred embodiment, the filaments (heating coils) are made of nichrome wire, since nichrome alloys with a high nickel content have high heat resistance in an oxidizing atmosphere. The wire is wound on a porcelain holder for greater mechanical stability of the structure; more preferably, nichrome wire with a diameter of at least 1 mm in the form of a spiral is used for the filaments.

It is known that acetone pyrolysis does not occur below 740°C, and its carbonization begins above 790°C. The catalytic addition of triethyl phosphate to the reaction mixture allows the pyrolysis temperature to be lowered by 6-8 degrees. Thus, the working pyrolysis temperature of 770-780°C is maintained in the reaction zone of the PR3.1 reactor.

In contrast to the standard "ketene lamp" of the state of the art, such heating, carried out by means of several heating zones, is distinguished by increased reliability, since such a technical solution significantly reduces the thermal stress associated with the temperature difference within one spiral, which is experienced by the heating spiral material. Reducing temperature differences becomes a particularly urgent task in the case of uneven flow of acetone vapors into the reactor due to beating during the boiling process. In the case of using a "ketene lamp" with one heating spiral, the resulting large temperature jumps lead to mechanical destruction of the spiral material. The proposed scheme using several heating elements levels out this negative effect and ensures long-term uninterrupted operation.

Also, unlike external heating of the pyrolysis reactor, for example in a furnace, when heating by means of several heating zones there is no thermal inertia, which allows easy regulation of the temperature inside the pyrolysis reactor in a precisely specified temperature range with a short response time, in addition, higher energy efficiency of the process is ensured due to contact of the heating elements with acetone vapors. All this allows the unit to be operated in a continuous mode, without interruption, for a long period of time.

To regulate the heating power, the pyrolysis reactor can be equipped with a temperature sensor for each heating zone, for example, a thermocouple.

In the internal reaction space of the pyrolysis reactor, thermal decomposition of gaseous acetone occurs with the formation of a gas mixture containing ketene, which mainly consists of ketene, methane, ethylene, carbon dioxide and vapors of unreacted acetone. Ethylene and carbon dioxide are formed as a result of partial decomposition of ketene and are present in the gas mixture in an insignificant amount. The pyrolysis reactor of the claimed installation is equipped with an outlet for the reaction mixture of gases containing ketene, which in a preferred embodiment can be connected to the inlet for the pyrolysis reaction mixture of the heat exchanger for preheating fresh acetone TO3.1 to increase the energy efficiency of the process.

The specified heat exchanger TO3.1 includes an internal heat exchange space and an external jacket. The hot gas mixture containing ketene enters the internal heat exchange space through the inlet for the pyrolysis reaction mixture, cools as a result of heat exchange, and leaves it through the outlet for the cooled gas mixture containing ketene. In the preferred embodiment, the internal heat exchange space is made in the form of a cylindrical pipe. Fresh acetone passes through the external jacket of this heat exchanger, which, as a result of indirect heat exchange with the hot gas mixture containing ketene, undergoes preliminary heating and is directed through line L1 to the evaporation tank IS3.1. This technological solution increases the overall energy efficiency of the installation.

To control the degree of cooling of the gas mixture containing ketene, the heat exchanger for preheating fresh acetone TO3.1 can be equipped with a temperature sensor or thermometer TT3.4.

For separating unreacted acetone from gaseous ketene, the acetic anhydride production unit includes two condensers connected in series, preferably two descending condensers. In the first descending condenser HX3.1, for condensing a portion of the unreacted acetone from the gas mixture containing ketene, a heat carrier, preferably water, with a temperature in the range from 5 to 15°C is used as a cooling medium. The inlet of this descending condenser HX3.1 is connected either to the outlet for the reaction mixture of gases of the pyrolysis reactor PR3.1, or, in the preferred embodiment, to the outlet for the cooled gas mixture containing ketene, of the heat exchanger for preheating fresh acetone TO3.1. In the lower part, the descending condenser HX3.1 is equipped with an outlet for the gas phase and an outlet for the liquid phase.

In the descending condenser HX3.1, the main part of the unreacted acetone from the gas mixture containing ketene is condensed, the condensed acetone in the form of a liquid phase flows down and enters through the liquid phase outlet into the line for returning condensed unreacted acetone L2. The cooled gas mixture containing ketene enters through the gas phase outlet via line L3 to the inlet of the low-temperature descending condenser HX3.2.

In a preferred embodiment, the low-temperature downdraft condenser HX3.2 is a spiral downdraft condenser that uses a coolant with a temperature in the range of -20 to -35°C.

Water-alcohol mixtures, ethylene glycol-based antifreezes and other coolants with a low freezing point can be used as a coolant.

In this low-temperature descending cooler HX3.2, complete condensation of the remaining portion of unreacted acetone from the gas mixture containing ketene occurs, and a cooled two-phase flow is formed, which enters the gas-liquid separator SP3.1 through the fluid outlet.

The gas-liquid separator SP3.1 is designed with the ability to remove condensed acetone from a gas mixture containing ketene and to form a gaseous mixture enriched in ketene.

In one embodiment, the gas-liquid separator SP3.1 is a container with an internal space and a cooling jacket, equipped with an inlet for a fluid medium, an outlet for a gas phase and an outlet for a liquid phase, wherein the inlet for the fluid medium is designed with the possibility of introducing a cooled two-phase flow from a low-temperature descending cooler HX3.2 into the lower half of the internal space of the container, the outlet for the gas phase is designed in the upper half of the internal space of the container, and the outlet for the liquid phase is designed in the immediate vicinity of the bottom or on the bottom of the internal space of the container.

A heat carrier with a temperature in the range from -20 to -35°C is used as a cooling medium in the cooling jacket; in particular, the same heat carriers can be used as in the case of the low-temperature descending refrigerator HX3.2.

The liquid phase outlet of the gas-liquid separator SP3.1 is connected to the line for returning condensed unreacted acetone L2.

Condensed acetone is fed from the gas-liquid separator SP3.1 back to the evaporation tank IS3.1 via this line L2 (if necessary, the flow rate is regulated by valve 3.5). As already indicated above, condensed acetone is also fed to this line L2 from the descending condenser HX3.1. Thus, complete recirculation of unreacted acetone is achieved.

In a preferred embodiment, the line for returning condensed unreacted acetone L2 to the evaporation tank IS3.1 is equipped before the inlet for recirculated acetone of the evaporation tank IS3.1 with a siphon C3.1, which has a reduced cross-section and prevents the release of vapors from the evaporation tank into line L2.

The use of such a combination of two successively located descending condensers and a gas-liquid separator ensures complete separation of acetone from the gas mixture containing ketene and allows for the efficient use of unreacted acetone, thereby increasing the productivity of the plant as a whole.

To carry out the reaction of ketene with acetic acid, the acetic anhydride production unit includes at least one absorption tank designed with the possibility of carrying out the interaction of gaseous ketene from a gaseous mixture enriched with ketene with liquid acetic acid to produce a solution of acetic anhydride in acetic acid and a stream of exhaust gases.

In one embodiment, at least one absorption vessel is provided with a cooling system, a temperature sensor, a bubbling device for introducing a gaseous mixture enriched with ketene, a paddle stirrer, an inlet for acetic acid, an outlet for exhaust gases and an outlet for an acetic anhydride solution.

In a preferred embodiment, the acetic anhydride production unit includes two absorption tanks connected in series for more complete capture of ketene. In this embodiment, the outlet for exhaust gases of the first absorption tank E3.1 is connected to the bubbling device of the second absorption tank E3.2.

Since the reaction of acetic anhydride formation occurs with the release of heat, forced cooling is provided in the absorption tanks using a cooling system. In the preferred embodiment, the cooling system is a cooling jacket with a heat carrier.

Excessive increase in temperature reduces the selectivity of the reaction and decreases the solubility of ketene in the reaction solution, therefore the temperature in the absorption tanks is maintained in the range of 25-35°C. The temperature of the reaction solutions is monitored using reaction mixture temperature sensors. In the preferred embodiment, thermometers TT3.5 and TT3.6 are used as reaction mixture temperature sensors in the absorption tank.

In a preferred embodiment with two absorption tanks, the bubbling device BR3.1 of the first absorption tank E3.1 is connected to the outlet for the gas phase of the gas/liquid separator SP3.1 via line L4. Through this line L4, the gaseous mixture enriched in ketene enters the absorption tank E3.1 through the bubbling device BR3.1 and then through the outlet for exhaust gases along line L5 through the bubbling device BR3.2 into the absorption tank E3.2. For better contact of the gas with the liquid, tanks E3.1 and E3.2 are equipped with paddle mixers M3.1 and M3.2.

For the introduction of acetic acid, an acetic acid inlet is provided in the absorption tank, to which acetic acid is supplied via line L6. In the preferred embodiment, the acetic acid is glacial acetic acid.

For unloading the obtained acetic anhydride in the acetic acid solution, an outlet for the acetic anhydride solution is provided in the absorption tank, connected to line L7, through which the prepared acetic anhydride solution is fed to the inlet for the acetic anhydride solution of the para-aminophenol acylation reactor P3.1. By regulating the rate of unloading the reaction mixture from the absorption tank, it is possible to obtain a solution of acetic anhydride in acetic acid in the widest range of concentrations, for example from 1 to 99% by weight, preferably from 60 to 98% by weight.

Each absorption tank in the claimed installation is equipped with an outlet for exhaust gases; in the embodiment of the installation with several successively located absorption tanks, the outlet for exhaust gases of the last absorption tank in the series (and in the case of a single absorption tank directly) is connected to line L8, through which exhaust gases exit the acetic anhydride production unit for disposal (into the atmosphere or for incineration).

In the preferred embodiment, the line is equipped with a rotameter RT3.1. Since the two-stage separation of acetone in the refrigerators HX3.1, HX3.2 and the separator SP3.1 captures all acetone vapors, and the absorption unit completely removes ketene from the gas mixture, then practically pure methane is removed at the outlet. The rate of its release can be used to judge the intensity of pyrolysis and, accordingly, the amount of ketene obtained. Thus, based on the readings of the rotameter RT3.1, it is possible to determine the required amount of fresh acetone, which should be fed to the evaporation tank IS3.1 via line L1.

The reactor for preparing a para-aminophenol solution R3.1 of the claimed installation is designed to dissolve solid para-aminophenol in a mixture of water and a fresh solution of acetic acid and/or a recycled mother solution of acetic acid and to form a heated solution of para-aminophenol.

The reactor for preparing a solution of para-aminophenol P3.1 is a reaction vessel equipped with a stirrer M3.3, a temperature maintenance system, a temperature sensor, an inlet for feeding solid para-aminophenol, inlets for feeding water and fresh acetic acid solution, and an outlet for the gravity discharge of part of the prepared solution, located in the upper part of the reactor;

In a preferred embodiment, for feeding solid para-aminophenol, the claimed installation may additionally include a solid para-aminophenol feeding apparatus B3.1. The candy type of feeding apparatus B3.1 is selected based on the characteristics of the raw material used (its moisture content, flowability, etc.), for example, the feeding apparatus B3.1 may be selected from a cell dispenser or a screw with a hopper.

In a preferred embodiment, lines L9 and L20 are primarily used to create a feedstock of pure aqueous acetic acid solution at the start of plant operation.

To obtain a solution of para-aminophenol, acetic acid with a concentration of 70-80% is used, since in this range the maximum solubility of para-aminophenol is achieved at the process temperature.

In a preferred embodiment, the reactor for preparing a para-aminophenol solution P3.1 is equipped with an input for feeding a recycled mother liquor, which is connected via line L16 to a container for storing the mother liquor E3.4, which allows the collected mother liquor to be sent again as a medium for dissolving solid para-aminophenol, ensuring an increase in the productivity of the claimed installation and a reduction in the amount of liquid waste.

In order to give the para-aminophenol solution the required temperature, as well as for the most complete dissolution of para-aminophenol, heating to 45-50°C is provided in reactor R3.1 using the temperature maintenance system СО3.1, the temperature is controlled by the temperature sensor readings, preferably the thermocouple TT3.7. For intensive mixing, the reactor for preparing the para-aminophenol solution R3.1 is equipped with an effective paddle stirrer. For the resulting excess of the prepared solution, reactor R3.1 is equipped with an outlet for the gravity discharge of a portion of the prepared solution, located in the upper part of the reactor, in the preferred embodiment representing a natural overflow to line L10.

In a preferred embodiment, before the outlet for the prepared para-aminophenol solution, located in the upper part, a catching/filtering device is provided in the reactor R3.1, which prevents the entrainment of the solid fraction into the line L10 and ensures the supply of a clean para-aminophenol solution. In a particularly preferred embodiment, the catching/filtering device is selected from a mesh filter or an internal separator shelf.

The reactor for preparing a solution of para-aminophenol P3.1 is designed with the ability to operate in a self-regulating mode, i.e. the excess of the prepared solution without a solid fraction is removed naturally (by gravity) through the outlet for removing part of the prepared solution TP3.1 and the reactor for acylation of para-aminophenol passes along line L10.

The reactor for acylation of para-aminophenol P3.2 of the claimed installation is intended for efficient mixing of a solution of para-aminophenol and a solution of acetic anhydride and subsequent implementation of the reaction of acylation of para-aminophenol.

The reactor for acylation of para-aminophenol P3.2 is a reaction vessel equipped with an effective mixer M3.4, at least one inlet for feeding a para-aminophenol solution, connected via a fluid medium to a reactor for preparing a para-aminophenol solution, and an inlet for feeding acetic anhydride, connected via a fluid medium to an outlet for the acetic anhydride solution of at least one absorption tank of the acetic anhydride production unit, and an outlet for gravity removal of a portion of the acylation reaction mixture, located in the upper part of the reactor.

It was found that under the given conditions the para-aminophenol acylation reaction proceeds relatively quickly, so the authors proposed to use a reduced volume reactor P3.2. In this case, the required acylation reaction rate is ensured by full contact of the reagents, which occurs in the conditions of a small reaction volume. In a large reaction volume, it is extremely difficult to achieve full mass transfer even with the use of specialized mixers. In turn, in a small volume of the reaction medium, it is easy to ensure the most effective mixing of the components. It is this solution that allows achieving high chemical conversion rates in a shorter time when operating in a continuous mode.

The reaction of para-aminophenol acylation is slightly exothermic, in addition, a hot initial solution of para-aminophenol is supplied from reactor R3.1. Thus, due to the selected reaction volume, the operating temperature in the range from 45 to 50°C is created and self-maintained in reactor R3.2, the process intensity is controlled using sensor TT3.8. Excessive increase in temperature has a negative effect on the purity of the product, in case of exceeding 50°C, the temperature of the reaction mass in reactor R3.2 can be reduced by proportionally reducing the feed rates of the initial reagents through lines L1, L2 and dispenser B3.1.

The inlet for feeding the acetic anhydride solution of the reactor P3.2 is connected to the outlet for the acetic anhydride solution of the acetic anhydride production unit, from which the acetic anhydride solution in acetic acid is fed into the reactor via line L7. When fed into the reactor P3.2, the acetic anhydride solution may have a concentration in the range from 1 to 99% by weight, preferably from 60 to 98% by weight.

The heated para-aminophenol solution is fed into the para-aminophenol acylation reactor P3.2 through the inlet for feeding the para-aminophenol solution, which is connected via a fluid medium to the outlet for removing part of the prepared para-aminophenol solution.

The reactor for acylation of para-aminophenol P3.2 of the claimed installation is designed with the ability to operate in a self-regulating mode, i.e. the excess reaction mass is removed naturally (by gravity) through the outlet for removing part of the acylation reaction mixture, located in the upper part of the reactor, and through line L11 passes into the reactor for concentrating the paracetamol suspension P3.3, while the remaining part of the acylation reaction mixture remains in the reactor P3.2, where the acylation reaction continues and where a new batch of reagents is continuously supplied.

The reactor for concentrating the paracetamol suspension R3.3 of the claimed installation is intended to achieve the complete course of the acylation reaction and to cool the reaction mixture for the crystallization of paracetamol with the formation of a suspension of paracetamol in a solution of aqueous acetic acid.

The paracetamol suspension concentration reactor P3.3 is a reaction vessel equipped with a stirrer and a cooling device, a temperature sensor, at least one inlet for the para-aminophenol acylation reaction mixture, connected via a fluid medium to the para-aminophenol acylation reactor, an outlet for the suspension concentration reaction mixture, located in the upper part of the reactor;

The M3.5 stirrer provides an upward flow, maintains the homogeneity of the medium and does not allow the sediment to settle. The temperature in the P3.3 reactor is controlled using the TT3.9 temperature sensor.

Using the cooling device TO3.2, the temperature in the reactor R3.3 is maintained in the range from 10 to 15°C. In the preferred embodiment, the cooling device is an immersion cooling coil or an external cooling jacket connected to a thermostat.

Such temperature conditions allow the most complete isolation of crystalline paracetamol from the reaction solution with the formation of a concentrated suspension of paracetamol in an aqueous-acetic medium, and at the same time ensure the passage of the chemical reaction of acylation with a conversion of >99%. The said full passage of the acylation reaction is ensured by the detected ratio of the working volumes of the acylation reactor and the paracetamol suspension concentration reactor, which should be in the range from 1:3 to 1:10. The increased volume of the suspension concentration reaction mixture compared to the volume of the acylation reaction mixture in the continuous mode allows for an increase in the acylation reaction time and at the same time to combine this process with the isolation of the crystalline product, thereby not increasing the total process time.

Within the framework of the present invention, the term “working volume of the reactor” means the maximum volume of the reaction mixture that can be in the reactor at the moment of occurrence of a natural overflow into another apparatus of the plant.

Thus, the working volume of the reactor will be determined by the location of the upper outlet for the reaction mixture. According to the present technical solution, the outlet for the reaction mixture in reactors P3.2 and P3.3 is located in the upper third of the height of the corresponding reactor. The height of the reactor is determined inside the reactor from the lowest point on the bottom of the reactor to the highest point on the reactor cover.

The reactor for concentrating the paracetamol suspension R3.3 of the claimed installation is designed with the ability to operate in a self-regulating mode, i.e. the excess of the formed suspension is removed naturally (by gravity) through the outlet for the reaction mixture for concentrating the suspension, located in the upper part of the reactor, and through line L12 passes into a continuous separating device, while the remaining part of the reaction mixture for concentrating the suspension remains in the reactor R3.3, where the formation of the paracetamol suspension continues and where a new batch of the reaction mixture for acylation is continuously supplied.

According to the present technical solution, a continuous separating device is any device that allows for the continuous efficient separation of a solid crystalline precipitate and a liquid mother liquor.

In a preferred embodiment, the continuous separating device is a horizontal centrifuge with scraper discharge CG3.1.

The horizontal centrifuge with scraper discharge CG3.1 according to the present technical solution is equipped with an input for feeding the suspension leaving the paracetamol suspension concentration reactor R3.3, as well as an output for removing solid paracetamol and an output for removing the mother liquor.

In a preferred embodiment, the horizontal centrifuge CG3.1 is equipped with an additional supply of acetic acid for washing the product, through which glacial acetic acid is fed into the centrifuge CG3.1 via line L13.

The squeezed and washed solid paracetamol is discharged from the centrifuge through the solid paracetamol discharge outlet and is sent via line L14 either for storage or for further drying and purification.

The pure centrate is removed from the centrifuge through the outlet for removing the mother liquor and is sent via line L15 to the storage tank for the recycled mother liquor E3.4.

The storage tank for the recycled mother liquor E3.4 is a tank of suitable size, provided with an inlet for feeding the mother liquor from the separating device, and an outlet for removing the mother liquor.

The mother liquor in container E3.4 is diluted aqueous acetic acid with a minimum content of paracetamol. As a rule, the residual content of dissolved paracetamol in the mother liquor is 5-13%.

In a preferred embodiment, the outlet for removing the mother liquor from the tank E3.4 is connected via line L16 to the inlet for feeding the circulating mother liquor of the para-aminophenol solution preparation reactor. Pump H3.1 is located on line L16, by means of which a portion of the circulating mother liquor contained in the tank E3.4 is fed into the circulation circuit for preparing the para-aminophenol solution.

The remaining part of the mother liquor is stored in tank E3.4, after a sufficient amount of solution has accumulated, it is redirected to the processing stage - evaporation with the release of residual paracetamol (not shown in the diagram). The watered acetic acid obtained during evaporation is subjected to additional distillation, after which it is reused in the process. This allows for a significant increase in the product yield and avoidance of additional liquid waste.

In the preferred embodiment of the claimed installation, reactors P3.1, P3.2 and P3.3 are equipped with additional outlets for the reaction mixture, located in the lower part of the reactor, to lines L17, L18 and L19 for complete emptying of the apparatuses in order to completely eliminate mechanical losses of raw materials. These flows are regulated by the corresponding three-way valves 2.1, 2.2 and 2.3, they are used only at the stage of completion of the operation of the entire installation and for technical maintenance of the apparatuses. After the addition of the initial reagents is complete, the valves are opened in turn (starting with 2.1), transferring all working solutions along the descending cascade. This allows not to lose the reaction mass. Also, in reactors P3.1, P3.2 and P3.3, external drain lines can be provided for servicing the reactors.

All process lines through which connection and/or communication via liquid, fluid, bulk and/or gaseous medium is carried out between individual devices and units in the claimed installation are pipelines of sufficient cross-section to ensure unimpeded transportation of the working medium.

Thus, the claimed plant is designed with the ability to operate in a continuous mode without the need to stop any devices to isolate the product. At the same time, due to the use of its own acetic anhydride production unit, which guarantees a continuous and stable supply of acetic anhydride solution of the required concentration, the plant does not require additional storage tanks for intermediate products, and ensures the output of a product with unchanged quality characteristics over a long period of operation.

Moreover, the acylation reaction is carried out using spatially separated reaction media that differ in volume and are aimed at achieving a specific goal. Thus, due to the small reaction volume during acylation, high homogeneity of the medium is achieved in the reaction mass and, accordingly, the same conditions for the process throughout the volume. Effective mass transfer in a small volume guarantees maximum contact of the reagents, which ensures an increased reaction rate. As a result, high conversion is achieved in a short time of residence in the reaction volume. On the other hand, the reaction medium for concentrating the suspension has an increased volume, which allows it to be used simultaneously for two processes under continuous conditions: bringing the acylation reaction to completion and fully removing the resulting product from the liquid phase to form a concentrated suspension.

The figures presented show:

Fig. 1 shows one of the preferred embodiments of the claimed installation;

Fig. 2 shows one of the preferred embodiments of a pyrolysis reactor with a tubular working part containing three successively located heating zones, a general view of the reactor is presented, as well as a sectional view of the reactor and a separate view of the heating element with a holder and a spiral.

Legend:

BP3.1 Acetic anhydride production unit

IS3.1 Evaporative tank with heating jacket

PR3.1 Pyrolysis reactor

NS3.1 First heating coil for heating vapors

НС3.2 Second heating coil for heating vapors

НС3.3 Third heating coil of the reaction zone

TO3.1 Heat exchanger for heating fresh acetone

TO3.2 Immersion coil for cooling the solution in the reactor R3.3.

СО3.1 Immersion coil of the temperature maintenance system in the reactor Р3.1

TP3.1 Outlet for removing pure prepared para-aminophenol solution from reactor R3.1

НХ3.1 Downward Cooler

НХ3.2 Low Temperature Descending Refrigerator

C3.1 Siphon for return of condensed acetone vapors

SP3.1 Gas-liquid separator for removing acetone residues

E3.1 First absorption tank

E3.2 Second absorption tank

E3.3 Storage tank for mother solution

M3.1 Mechanical stirrer

M3.2 Mechanical stirrer

BR3.1 Bubbling device

BR3.2 Bubbling device

P3.1 Reactor for preparation of para-aminophenol solution

P3.2 Para-aminophenol acylation reactor

P3.3 Reactor for concentrating paracetamol suspension

B3.1 Cellular dispenser with hopper for feeding solid para-aminophenol

M3.3 Mechanical stirrer in reactor P3.1

M3.4 Mechanical stirrer in reactor P3.2

M3.5 Mechanical stirrer in reactor P3.3

H3.1 Pump for feeding the circulating depleted mother liquor

CG3.1 Continuous horizontal centrifuge with scraper discharge for solid paracetamol

TT3.1 Temperature sensor at the outlet of the first vapor heating zone

TT3.2 Temperature sensor at the outlet of the second vapor heating zone

TT3.3 Temperature sensor at the outlet of the third (reaction) zone of vapor heating

TT3.4 Temperature sensor for outgoing vapors from PR3.1

TT3.5 Temperature sensor of the solution in the absorption tank E3.1

TT3.6 Temperature sensor of the solution in the absorption tank E3.2

TT3.7 Temperature sensor in reactor R3.1

TT3.8 Temperature sensor in reactor R3.2

TT3.9 Temperature sensor in reactor R3.3

RT3.1 Rotameter for measuring the flow of methane coming out of the plant

L1 Line for feeding fresh acetone to the evaporation tank IS3.1

L2 Acetone recirculation line into the evaporation tank IS3.1

L3 Line for feeding cooled vapors to NH3.2 for final removal of residual acetone

L4 Line for feeding gaseous mixture of ketene-methane into absorption tank E3.1

L5 Line for feeding gaseous mixture of ketene-methane into absorption tank E3.2

L6 Line for feeding glacial acetic acid to absorption tanks E3.1 and E3.2

L7 Line for feeding acetic anhydride solution in acetic acid from absorption tanks E3.1 and E3.2 to reactor R3.2

L8 Line for removal of gaseous waste (methane/ethylene) for disposal

L9 Line for supplying clean water to reactor R3.1

L10 Line for supplying prepared pure para-aminophenol solution from reactor R3.1 to reactor R3.2

L11 Line for feeding reaction mass from reactor R3.2 to reactor R3.3

L12 Line for feeding paracetamol suspension from reactor R3.3 to centrifuge CG3.1

L13 Line for supplying washing acetic acid

L14 Line for unloading squeezed paracetamol from the centrifuge CG3.1

L15 Line for draining mother liquor from centrifuge CG3.1 into tank E3.4

L16 Line for feeding the circulating depleted mother liquor from tank E3.4 to reactor R3.1

L17 Line for complete drainage of solution from reactor R3.1 to reactor R3.2

L18 Line for complete discharge of reaction mass from reactor R3.2 to reactor R3.3

L19 Line for complete drainage of paracetamol suspension from reactor R3.3 into centrifuge CG3.1

L20 Line for feeding glacial acetic acid to reactor R3.1

3.1 Tap for supplying fresh acetic acid to the absorption tank E3.1 (initial position - closed)

3.2 Tap for supplying fresh acetic acid to the absorption tank E3.2 (initial position - closed)

3.3 Tap for discharging acetic anhydride from the absorption tank E3.1 (initial position - closed)

3.4 Tap for discharging acetic anhydride from the absorption tank E3.2 (initial position - closed)

3.5 Valve for returning condensed acetone from the separator SP3.1 to the evaporation tank IS3.1 (initial position - closed)

3.6 Valve for purging the unit with argon before starting work (initial position - closed)

3.7 Tap for supplying fresh acetone to the evaporation tank IS3.1 (initial position - closed)

3.8 Tap for supplying fresh acetone to the preheating heat exchanger TO3.1 (initial position - closed)

3.9 Clean water supply tap to reactor P3.1

3.10 Three-way valve for complete draining of reactor contents P3.1

3.11 Three-way valve for complete draining of the reactor contents P3.2

3.12 Three-way valve for complete drainage of the reactor contents P3.3

3.13 Shut-off valve for draining filtrate from centrifuge ЦГ3.1

3.14 Shut-off valve for feeding the recycled depleted mother liquor from tank E3.4 to reactor P3.1

3.15 Shut-off valve for supplying washing acetic acid from tank E3.3

3.16 Valve for feeding glacial acetic acid into reactor P3.1

A Upper mounting flange of the pyrolysis reactor

In Reactor Vessel Mounting Studs

With a sealed plug in the reactor body for the output of power wires and a thermocouple sensor

D Temperature sensors

E Quartz body of the pyrolysis reactor

F Gaskets for hermetically sealing the pyrolysis reactor body with mounting flanges

G Internal heating element

H Lower mounting flange of the pyrolysis reactor

I Porcelain heating coil holder

J Heating electric coil

The technical solution is further explained in more detail using implementation examples, which, however, do not impose limitations on the scope of the claims of this invention.

EXAMPLES

Example 1 Obtaining paracetamol by acylation of para-aminophenol with acetic anhydride in the claimed installation according to Fig. 1

To implement this example, a setup was used that was created in accordance with the diagram shown in Figure 1. The PR3.1 pyrolysis reactor was created in accordance with the diagram shown in Figure 2 and was a tube made of heat-resistant glass (quartz) with a wall thickness of 5 mm, an internal diameter of 0.80 mm and a height of 200 mm.

Inside, three heating elements were successively arranged to create three heating zones with an ever-increasing temperature. Each heating element was provided with its own power source. Before starting work, all heating elements were calibrated to determine the required supplied power to create a given temperature: lower 240-250°C; middle 440-450°C; upper 775-785°C. Each heating element was made of nichrome wire 0.1 mm. The wire was formed into 16 successive spirals with a turn diameter of ~7 mm and a pitch of four turns per centimeter of length. The spirals were fixed on cross-shaped porcelain holders 60 mm high. The heating elements were arranged so that the wires did not touch each other.

For the synthesis of paracetamol, a cascade of reactors with working volumes of the reactors was used: P3.1 - 5 l; P3.2 - 2 l; P3.3 - 10 l.

Before starting the work, the BP3.1 block was purged with argon through line L1 for 15 minutes to completely eliminate the presence of air in the working volume. Then, fresh acetone (400 g) with the addition of triethyl phosphate as a catalyst (200 mg, 0.05% by weight) was loaded into the IS3.1 container, uniform stable boiling was ensured, acetone vapors continuously entered the PR3.1 pyrolysis reactor with a mass flow rate of 18 g/min.

The temperature at the outlet of the first heating zone according to the readings of TT3.1 was 240-245°C, the temperature at the outlet of the second heating zone according to the readings of TT3.2 was 444-447°C, the temperature at the outlet of the third heating zone according to the readings of TT3.3 was 780-783°C. The total power consumption of the pyrolysis reactor was 1300-1420 watts to maintain the set temperature in an empty unit, and 1800-1920 watts when acetone vapors entered the PR3.1 reactor and the reactor entered the operating mode.

The conversion of acetone vapors in the pyrolysis reactor PR3.1 was 8.29%, unreacted acetone vapors were completely condensed in the condensers HX3.1 and HX3.2 and were recycled into the evaporation tank IS3.1. The mass flow rate of acetone was 88.6 g/hour (1.52 mol/hour), respectively, fresh acetone with the addition of triethyl phosphate as a catalyst (44.3 mg per 88.6 g of acetone, 0.05% by weight) was continuously fed through line L1 at a rate of 88.6 g/hour to compensate for the consumption of the starting material.

The gas mixture purified from acetone was fed to the cascade of tanks E3.1 and E3.2 with glacial acetic acid (2×500 ml), where ketene was completely absorbed with the formation of acetic anhydride with a quantitative yield. The temperature in tanks E3.1 and E3.2 was maintained at 30°C. Upon reaching a concentration of 98% acetic anhydride in acetic acid, the finished 98% solution was removed from the tanks via line L7 with a total flow rate of 89 g/hour. At the same time, glacial acetic acid was fed to the tanks via line L6 with a total flow rate of 52.8 g/hour. In the first absorption tank, ketene was absorbed more intensively than in the second one; accordingly, the input (E3.1 ~37 g/hour; E3.2 ~15.8 g/hour acetic acid) and output (E3.1 ~62.3 g/hour; E3.2 ~26.7 g/hour 98% acetic anhydride) flows in E3.1 were slightly greater than in E3.2. The intensity of the input flows was regulated by valves 3.1 and 3.2, and the output flows were regulated by valves 3.3 and 3.4. The concentrations in the tanks and at the outlet of line L7 were monitored by NMR using an internal standard.

The gas flow at the unit outlet on line L8, according to the readings of the gas flow sensor RT3.1, was 0.68-0.73 l/min (the main components of the mixture at the outlet were methane and ethylene). Acetic anhydride was obtained with a total productivity of 87.22 g/hour (0.85 mol/hour) based on the pure substance. The resulting 98% acetic anhydride solution was continuously fed to reactor R3.2 through line L9 at a rate of 89 g/hour (0.85 mol/hour, 1.1 equiv).

In parallel with the operation of the BP3.1 unit, solid dry para-aminophenol was continuously dosed from the bin with the B3.1 cell feeder into the R3.1 feed solution preparation reactor at a rate of 84 g/hour (0.77 mol/hour), water was fed through line L9 at a rate of 80 g/hour, and glacial acetic acid was fed through line L20 at a rate of 187 g/hour. After the unit had reached steady-state operation, instead of water through line L9 and glacial acetic acid through line L20, the circulating mother liquor of acetic acid was fed into the para-aminophenol solution preparation reactor through line L16 from tank E3.4 at a rate of 444 g/hour. The water content in the circulating solution was 30%, the residual content of dissolved paracetamol was ~10%.

In the reactor for preparing the feed solution P3.1, a temperature of 45°C was maintained using the temperature maintenance system CO3.1. The prepared hot para-aminophenol solution was continuously fed through the overflow via line L10 into the reactor P3.2, where it was effectively mixed with the 98% solution of acetic anhydride in acetic acid (1.1 equiv) fed at a rate of 89 g/hour. In the acylation reactor, the reaction proceeded at a high rate, and the reaction mass was fed to the suspension concentration reactor P3.3 through the overflow via line L11. In reactor P3.3, a temperature of 10°C was maintained by means of a submersible coil, and a suspension of crystalline paracetamol in the mother liquor was formed. Excess reaction mass from the suspension concentration was continuously fed through the overflow via line L12 into the continuous horizontal centrifuge with scraper discharge CG3.1. To wash the pressed sediment, acetic acid was fed from tank E3.3 at a rate of 82 g/hour to CG3.1. Part of the mother liquor collected in tank E3.4 was sent via line L16 to reactor R3.1 to prepare a para-aminophenol solution at a rate of 444 g/hour.

The squeezed crystalline paracetamol was unloaded from CG3.1 and sent for additional drying in a vacuum.

Paracetamol was obtained with a productivity of 111.7 g/hour (yield 96%, purity 99%).

The paracetamol synthesis unit operated continuously at the specified parameters and productivity for 48 hours, after which the unit was forcibly stopped. After the unit was finished, the collected mother liquor was evaporated, resulting in a total product yield of 98% (of theory).

Acetic acid:

¹ H NMR (90 MHz, CDCl ₃ ) δ 2.09 (s, 3H), 11.42 (br s, 1H).

Acetic anhydride:

¹ H NMR (300 MHz, CDCl ₃ ) δ 2.22 (s, 6H).

Paracetamol:

¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.99 (s, 3H), 6.68 (d, 2H, J=8.8 Hz), 7.34 (d, 2H, J=8.8 Hz), 9.12 (s, 1H), 9.64 (s, 1H).

¹³ C NMR (300 MHz, DMSO-d ₆ ) δ 24.2, 115.5, 121.3, 131.5, 153.6, 168.0.

Example 2 Implementation of acetone pyrolysis in the acetic anhydride production unit of a plant with a pyrolysis reactor in the form of a “ketene lamp” with one heating coil from the prior art (comparative example)

For comparison, a setup with an alternative design of the pyrolysis reactor was launched, with one heating element three times longer (180 mm) and, accordingly, with a single heating coil, not divided into sections. The heating coil was made in a similar way: from nichrome wire ∅ 1 mm, the wire was formed into 16 consecutive coils with a coil diameter of ~7 mm, a pitch of four coils per centimeter of length and fixed on a porcelain cross-shaped holder. The pyrolysis reactor body, the rest of the hardware of the entire setup and the process parameters remained unchanged to ensure a correct comparison of the two technological solutions.

The total power consumption of the pyrolysis reactor was 2500-2650 watts to maintain the set temperature in an empty unit, and the energy consumption for the reaction was 750 watts. At the same time, the productivity of 94-103 g/hour of acetic anhydride was achieved with a higher conversion of acetone (13.5%) and a lower product yield (35%), which is due to stronger local superheating of vapors and subsequent decomposition of ketene. However, the total time of uninterrupted operation of the pyrolysis reactor did not exceed four hours due to the burnout of the heating coil.

Thus, the presented results of the conducted experiments clearly demonstrate that the installation according to the invention allows for the continuous production of acetic anhydride by means of acetone pyrolysis, while effective heating of acetone vapors is realized in a precisely specified temperature range with easy temperature regulation inside the pyrolysis reactor, while it is distinguished by the possibility of long-term stable operation in continuous mode, and the use of reactors of different volumes due to highly effective mixing and subsequent holding ensures an excellent overall reaction rate and, as a result, high productivity.

Claims (25)

1. A plant for the continuous production of paracetamol by acylation of para-aminophenol with acetic anhydride, comprising a unit for producing acetic anhydride by acetone pyrolysis, comprising an evaporation tank for evaporating acetone, a pyrolysis reactor configured to pyrolyze acetone to form a gas mixture containing ketene, at least one refrigerator for condensing unreacted acetone, a line for returning condensed unreacted acetone to the evaporation tank, a gas-liquid separator, at least one absorption tank configured to react gaseous ketene with liquid acetic acid, wherein the pyrolysis reactor has several successively arranged heating zones with their own heating filament in each zone, in which gradient heating of acetone vapor is ensured, and at least one absorption tank is equipped with an inlet for acetic acid, an outlet for exhaust gases and an outlet for an acetic anhydride solution; a reactor for preparing a para-aminophenol solution, equipped with a stirrer, a temperature maintenance system, a temperature sensor, an inlet for feeding solid para-aminophenol, inlets for feeding water and fresh acetic acid solution, and an outlet for gravity-flowing removal of part of the prepared solution, located in the upper part of the reactor; a reactor for acylating para-aminophenol, equipped with a stirrer, at least one inlet for feeding a para-aminophenol solution, connected via a fluid medium to a reactor for preparing a para-aminophenol solution, and an inlet for feeding acetic anhydride, connected via a fluid medium to an outlet for acetic anhydride solution of at least one absorption tank of an acetic anhydride production unit, and an outlet for gravity-flowing removal of a portion of the acylation reaction mixture, located in the upper part of the reactor; a paracetamol suspension concentration reactor equipped with a stirrer and a cooling device, a temperature sensor, at least one inlet for the para-aminophenol acylation reaction mixture, fluidly connected to the para-aminophenol acylation reactor, an outlet for the suspension concentration reaction mixture, located in the upper part of the reactor; a continuous separating device for separating solid paracetamol from the mother liquor, equipped with at least one inlet for the reaction mixture from the suspension concentration reactor, a drain for the mother liquor and an outlet for unloading solid paracetamol; container for storing mother liquor; wherein the ratio of the working volumes of the para-aminophenol acylation reactor and the paracetamol suspension concentration reactor is in the range from 1:3 to 1:10. 2. The installation according to item 1, characterized in that it additionally includes a device for feeding solid para-aminophenol, which is preferably selected from a cell dispenser or a screw with a hopper. 3. The installation according to item 1, characterized in that the pyrolysis reactor has three heating zones located in series. 4. The installation according to item 3, characterized in that the temperature at the outlet of the first heating zone is in the range from 240 to 350°C, the temperature at the outlet of the second heating zone is in the range from 400 to 500°C, and the temperature at the outlet of the third heating zone is in the range from 740 to 795°C. 5. The installation according to item 1, characterized in that in the reactor for preparing the para-aminophenol solution, the temperature is maintained in the range from 45 to 50°C by means of a temperature maintenance system. 6. The installation according to item 1, characterized in that a catching/filtering device is installed in front of the outlet for the prepared para-aminophenol solution, located in the upper part of the reactor, which prevents the entrainment of the solid fraction and ensures the flow of a clean para-aminophenol solution. 7. The installation according to item 6, characterized in that the catching/filtering device is selected from a mesh filter or an internal separator shelf. 8. The installation according to item 1, characterized in that the reactor for preparing a para-aminophenol solution, the reactor for acylating para-aminophenol, and the reactor for concentrating the paracetamol suspension are equipped at the bottom with an additional outlet for the reaction mixture, intended for completely emptying the reactor upon completion of operation of the entire installation. 9. The installation according to item 1, characterized in that the continuous separating device is a horizontal centrifuge with a scraper discharge. 10. The installation according to item 1, characterized in that the reactor for preparing the para-aminophenol solution is additionally equipped with an input for feeding the acetic acid circulating mother liquor. 11. The installation according to item 10, characterized in that the container for storing the mother liquor is connected via a fluid medium to the inlet for feeding the acetic acid mother liquor of the reactor for preparing the para-aminophenol solution. 12. The installation according to paragraph 1, characterized in that the pyrolysis reactor of the acetic anhydride production unit is made of a heat-resistant material, in particular, a heat-resistant metal or quartz. 13. The installation according to item 1, characterized in that the pyrolysis reactor is a pyrolysis tubular reactor. 14. The installation according to item 1, characterized in that the acetic anhydride production unit includes two series-connected condensers for condensing unreacted acetone, preferably two descending condensers. 15. The installation according to item 1, characterized in that at least one absorption tank of the acetic anhydride production unit is equipped with a cooling system, a temperature sensor, a bubbling device for introducing a gaseous mixture enriched with ketene, a paddle stirrer, an inlet for acetic acid, an outlet for exhaust gases and an outlet for a liquid reaction mixture. 16. The installation according to item 15, characterized in that the acetic anhydride production unit includes two absorption tanks connected in series. 17. The installation according to item 16, characterized in that the outlet for the exhaust gases of the first absorption tank is connected to the bubbling device of the second absorption tank. 18. The installation according to item 1, characterized in that the continuous separating device is additionally equipped with an input for feeding acetic acid used for washing solid paracetamol.

Images