KR20070058562A - Process for producing heteroaromatic carboxylic acids - Google Patents

Abstract

A process for the production of a heteroaromatic carboxylic acid comprising contacting in the presence of a catalyst, a precursor of said carboxylic acid with an oxidant, such contact being effected with said precursor and the oxidant in an aqueous solvent comprising water under supercritical conditions or near supercritical conditions close to the supercritical point.

Description

Process for Producing Heteroaromatic Carboxylic Acids

The present invention relates to a process for the selective partial oxidation of alkyl heteroaromatic compounds, especially nitrogen-containing heteroaromatics, for the production of heteroaromatic carboxylic acids such as nicotinic acid.

Pyridinecarboxylic acids derived from methylpyridine are important intermediates in the pharmaceutical industry. In particular, 3-pyridinecarboxylic acid or nicotinic acid used as precursor of vitamin B3 has been produced on a large scale. For the synthesis of pyridinecarboxylic acids, two basic methods are used. One method is based on hydrolysis of pyridinecarboxamides derived from pyridinecarbonitrile and the other method is based on the oxidation of alkylpyridine by air, nitric acid, selenium dioxide and the like. Pyridinecarbonitrile is formed by ammonia oxidation of methylpyridine, which is subsequently hydrolyzed to pyridinecarboxylic acid via pyridinecarboxamide. 3-pyridinecarboxylic acid has been commercially produced by nitric acid oxidation of 5-ethyl-2-methylpyridine.

Selective oxidation of alkyl heteroaromatic compounds to carboxylic acids is known to be significantly more difficult than the corresponding carbocyclic compounds. The residence time required for the oxidation of alkyl heteroaromatic compounds to carboxylic acids is considerably longer than for equivalent carbocyclic alkyl aromatic compounds. For example, JP-07233150 (Nissan Chemical International) describes a process for preparing nicotinic acid from 3-methylpyridine by oxidation in acetic acid using a cobalt manganese cerium bromide catalyst with a required reaction time of 3 hours. To start. Studies on p-xylene similar to that of terephthalic acid oxidation suggest that the required residence time is 40 minutes or less (US-3354202).

Conventional methods require long residence times and produce significant amounts of undesirable byproducts. By-products include partially oxidized intermediates of the target carboxylic acid, such as aldehyde intermediates. For example, the preparation of 3-pyridinecarboxylic acid (3-PyA) by oxidation of 3-methylpyridine (3-Mpy) generates a significant concentration of 3-pyridinecarboxaldehyde (3-PyAl). In addition, decarboxylation of the product can result in the unsubstituted heteroaromatic compound itself, which is pyridine in the oxidation of 3-methylpyridine.

JP-2002-226404 (Daicel Chemical Industries, Ltd.) produces nicotinic acid from 3-methyl pyridine in acetic acid using N-hydroxyphthalimide as an accelerator for oxidation in acetic acid. The method is disclosed. However, this method is economically undesirable because it requires a long residence time and generates a significant amount of phthalimide and phthalate impurities from the added accelerator.

Commercial gas phase processes for the oxidation of 3-methylpyridine to nicotinic acid described in DE-19822788 (Lonza AG) present several drawbacks. Since the reaction is exothermic, carrying it out in the gas phase results in heat transfer limitations that reduce the energy removal efficiency from the reaction. In addition, since the reaction is carried out with a fixed bed heterogeneous catalyst, the reaction can only occur at the surface of the catalyst and not throughout the fluid medium.

There is still a need to provide an improved process for the preparation of heteroaromatic carboxylic acids, in particular a method in which reaction time and by-product formation are reduced.

It may be desirable to avoid the use of significant amounts of organic solvents, such as acetic acid, which are relatively expensive and may require recovery and recycling due to environmental constraints. Another problem with the use of acetic acid is that it is flammable when mixed with air or oxidation under certain conditions. Another problem with the use of organic solvents is that the oxidant may have low solubility. For example, when dioxygen is used as the oxidizing agent, dioxygen will be present primarily as separate bubbles in the reaction medium in which only a small fraction of dioxygen in the solvent is dissolved. The reaction between the precursor and the dioxygen is caused by the diffusion of dioxygen into the bulk liquid from the bubble, so that the reaction rate is limited by the low solubility of dioxygen in the solvent.

It has now been found that heteroaromatic carboxylic acids can be synthesized by oxidation of precursors in supercritical water.

Holliday RL et al. (J. Supercritical Fluids 12, 1998, 255-260) describe a batch process for the synthesis of aromatic carboxylic acids, particularly aromatic carboxylic acids, from alkyl aromatics in a supercritical water reaction medium using molecular oxygen as the oxidant. do. The dielectric constant of water, as it as it approaches the critical point (374 ℃ and 220.9 bara), around 80C ² / Nm decreases rapidly, and the value at room temperature of ² to a value of 5C ² / Nm ^2, it should not solubilize organic molecules. As a result, the water then behaves like an organic solvent to such an extent that the hydrocarbons such as toluene become fully miscible with water under supercritical or near supercritical conditions. For example, terephthalic acid is substantially insoluble in water below about 200 ° C. Dioxide is also very soluble in subcritical and supercritical water.

International patent application WO 02/06201 comprises the production of aromatic carboxylic acids, such as terephthalic acid or isophthalic acid, comprising oxidizing at least one precursor of carboxylic acid in an aqueous solvent under supercritical conditions or near supercritical conditions near the supercritical point. Disclosed is a continuous method for.

One object of the present invention is to provide a process which eliminates the need for the use of organic materials as solvents as an alternative and improved method for producing heteroaromatic carboxylic acids with high yields and selectivity, and also with reduced reaction times. Another object of the present invention is to provide an alternative and improved method for the preparation of heteroaromatic carboxylic acids wherein substantially all of the reactants and products are kept in a common phase during the reaction.

Summary of the Invention

According to the present invention, a process for preparing heteroaromatic carboxylic acids comprising contacting a precursor of heteroaromatic carboxylic acid with an oxidizing agent in the presence of a catalyst in an aqueous solvent comprising water under supercritical conditions or near supercritical conditions near the supercritical point. To provide.

The process of the present invention is advantageous in that the residence time is short and shows high yield and good selectivity of product formation. In addition, by using water under supercritical or near supercritical conditions, the desired heteroaromatic carboxylic acid can be produced without using aliphatic carboxylic acids such as acetic acid as the primary solvent.

Substantially all the resulting carboxylic acid is kept in solution during the reaction, after which the carboxylic acid is recovered from the reaction medium.

Preferably, the method is carried out using a reactant and a solvent to form a substantially single homogeneous fluid phase in which the components in question are mixed at the molecular level. This is in contrast to existing methods where dioxygen is present in individual bubbles in the reaction medium. In that the reaction between the precursor and dioxygen comes from dioxygen which diffuses from the bubble into the bulk liquid, the reaction rate of the conventional process is limited by the solubility of dioxygen in organic solvents that are not high. The use of water under supercritical or near supercritical conditions as a solvent modifies the reaction kinetics because the concentration of dioxygen in water increases significantly as the supercritical point approaches and exceeds it. In addition, the reaction kinetics are further enhanced by the high temperatures encountered mainly when the water solvent is under supercritical or near supercritical conditions. The combination of high temperature, high concentration and homogeneity means that the reaction of converting the precursor to carboxylic acid can occur extremely rapidly compared to the residence time used in conventional methods.

Under these conditions, intermediate impurities such as aldehyde intermediates are immediately oxidized to the desired carboxylic acid. In addition, autocatalytic destruction reactions between the precursor and the oxidant that consume the catalyst are minimized.

Preferably, the contacting is performed such that the precursor, oxidant and aqueous solvent constitute a substantially single homogeneous phase in the reaction zone, wherein at least a portion of the precursor is in contact with the oxidant such that the catalyst is at least of the oxidant. It happens simultaneously with contact with some.

Preferably the contacting is carried out in a continuous flow reactor. In one alternative embodiment, the process may be carried out as a batch reaction in a batch reactor.

The method is a heteroaromatic carboxylic acid, preferably selected from nitrogen and oxygen, containing one, two or three heteroatoms, preferably nitrogen, preferably one or two heteroatoms, more preferably one heteroatom. It can be used to prepare. Preferably, the heteroaromatic carboxylic acid comprises a 5 or 6-membered ring system, preferably a 6-membered ring system. Preferably, the heteroaromatic carboxylic acid is monocyclic or bicyclic, preferably monocyclic. The method is particularly applicable to the preparation of nitrogen-containing heteroaromatic compounds, in particular those containing 1, 2 or 3 nitrogen atoms, in particular those containing 6-membered rings. In one preferred embodiment, the heteroaromatic carboxylic acid comprises a pyridine or pyrimidine ring, preferably a pyridine ring. In one preferred embodiment, the heteroaromatic carboxylic acid is nicotinic acid.

Suitable precursors are alkyl-substituted heteroaromatic compounds, in particular methyl-substituted heteroaromatic compounds. In one preferred embodiment, the precursor is alkylpyridine or alkylpyrimidine, preferably alkylpyridine, preferably methylpyridine, preferably 3-methylpyridine. In the methods described herein, preferably only one precursor of the desired carboxylic acid is used. However, alternatively more than one precursor of the desired carboxylic acid can be used. In addition to the alkyl substituents, the heterocyclic precursor may optionally have one or more other substituents such as hydroxyl groups, nitrate groups and halide group (s).

Detailed description of the invention

In the process of the invention, the pressure and temperature of the process are selected to ensure supercritical or near supercritical conditions. Thus, the operating temperature is typically in the range of a lower limit of 300 to 480 ° C., more preferably of 330 to 450 ° C., typically of about 340 to 370 ° C. to an upper limit of about 370 to about 420 ° C. The operating pressure is typically in the range of about 40 to 350 bara, preferably 60 to 300 bara, more preferably 200 to 280 bara.

As used herein, "near supercritical conditions" means that the reactants and the solvent constitute a substantially single homogeneous phase, which in practice can be achieved under conditions below the critical temperature of water. In one embodiment, the term “near supercritical conditions” means that the solvent is at least 100 ° C. below the critical temperature of water at 220.9 bara, preferably at least 50 ° C. below, more preferably at least 35 ° C. below, in particular It means the temperature is lower than 20 ℃.

As used herein, "continuous flow reactor" refers to a reactor in which the reactants are introduced and mixed, and the products are simultaneously drawn in a continuous manner as opposed to a batch reactor. For example, the reactor may be a tubular flow reactor (vortex or laminar flow), but the various aspects of the invention as defined herein are not limited to this particular type of continuous flow reactor. The residence time in a continuous flow reactor is defined as the reactor volume divided by the volume flow rate of the reactants at operating conditions.

As used herein, "carboxylic acid precursor" or "precursor" means an organic compound, preferably a hydrocarbon, capable of being oxidized to a particular carboxylic acid in high yield in the presence of selective oxidation conditions. One example of a pyridinecarboxylic acid precursor is methylpyridine, for example the nicotinic acid precursor is 3-methylpyridine. Accordingly, methylpyrimidine can be used to produce pyrimidine carboxylic acids.

As used herein, reference to the production of carboxylic acids includes reference to the production of its anhydrides. As will be apparent to those skilled in the art, whether the method of the present invention produces a carboxylic acid or anhydride thereof will depend on the conditions of the reaction and / or the conditions used to isolate or isolate the product.

Preferably, in the process of the invention, substantially all, also in any case, at least 98% by weight of the heteroaromatic carboxylic acids produced in the reaction are kept in solution during the reaction and the solution leaves the oxidation reaction zone to cool down. Do not start to precipitate until.

The residence time for the reaction may be suitable for achieving the conversion of the precursor to the desired heteroaromatic carboxylic acid without significantly producing decomposition products. The residence time of the reaction medium in the reaction zone is generally 10 minutes or less, usually about 2 minutes or less, preferably 1 minute or less, more preferably 30 seconds or less.

In one preferred embodiment, the selectivity to the target carboxylic acid is at least 90%, preferably at least 95%, more preferably at least 98%, wherein the selectivity is determined by the weight yield of the target acid, the target acid and Divided by the total weight yield of partially oxidized aldehyde impurities, and other reaction products except degradation products, expressed as a percentage.

In a preferred embodiment, the yield of the target carboxylic acid is preferably at least 50% by weight, preferably at least 60% by weight, preferably at least 70% by weight, preferably at least 80% by weight, preferably at least 90% by weight of the precursor. to be.

Suitable reactor systems for carrying out the process of the invention may generally be configured as follows. The discussion below relates to a preferred embodiment of the continuous flow reactor. However, as mentioned above, the present invention is not limited to such a configuration, and the following discussion is for illustrative purposes only.

There may be more than one reaction zones in series or in parallel. For example, where multiple reaction zones in parallel are used, reactants and solvents may form separate flow streams, which may pass through the reaction zone and, if desired, product streams from such multiple reaction zones may be integrated to yield a single product. A stream can be formed. If more than one reaction zone is used, conditions such as temperature may be the same or different in each reactor. Each reactor can be operated adiabatically or isothermally. Isothermal or controlled temperature rises may be maintained by heat exchange to define a predetermined temperature profile as the reaction proceeds through the reactor.

In one embodiment of the present invention, the heat of reaction is in accordance with conventional techniques known to those skilled in the art, for example in accordance with the techniques described in WO-02 / 06201 which discloses the techniques cited by reference herein. It is removed from the reaction by heat exchange using a heat-accepting fluid. Suitably, the heat-receiving fluid comprises water.

The oxidant in the process of the invention preferably comprises molecular oxygen, such as air or oxygen enriched air, but preferably a gas containing oxygen as the main constituent, more preferably pure oxygen, or oxygen dissolved in a liquid. . The use of air is not preferred because of the large compression costs incurred and the waste gas handling equipment needed to treat large amounts of waste gas due to the high nitrogen content of the air, but this is also not excluded from the scope of the present invention. Pure oxygen or oxygen rich gas, on the other hand, allows the use of fewer compressors or smaller waste gas treatment equipment. The use of dioxygen as an oxidant in the process of the invention is particularly advantageous because it is very water soluble under supercritical or near supercritical conditions. Thus, at some point in time, the oxygen / water system will be in a single homogeneous phase.

Instead of molecular oxygen, the oxidant may include atomic oxygen derived from a compound, such as a compound that is liquid at room temperature, containing one or more oxygen atoms per molecule. One such compound is, for example, hydrogen peroxide, which acts as an oxygen source by reaction or decomposition as described by Lin, Smith et al. (International Journal of Chemical Kinetics, Vol. 23, 1991, p.971).

The process of the invention is carried out in the presence of an oxidation catalyst. The catalyst may be soluble in the reaction medium comprising the solvent and the heteroaromatic carboxylic acid precursor, or alternatively a heterogeneous catalyst may be used. The catalyst, whether homogeneous or heterogeneous, typically comprises one or more heavy metal compounds such as cobalt and / or manganese compounds, preferably manganese compound (s) alone, and may optionally comprise an oxidation promoter. For example, the catalyst can take any form used in the liquid phase oxidation reaction to produce aromatic carboxylic acids (eg, terephthalic acid) in aliphatic carboxylic acid solvents, for example cobalt and / or manganese bromide , Bromoalkanoate or alkanoate (primarily C ₁ -C ₄ alkanoate, such as acetate). Compounds of other heavy metals such as vanadium, chromium, iron, molybdenum, lanthanides such as cerium, zirconium, hafnium, and / or nickel may be used in place of cobalt and / or manganese. Advantageously, the catalyst system may comprise manganese bromide (MnBr ₂ ). When oxidation promoters are used, they are atomic bromine, ionic bromide (such as HBr, NaBr, KBr, NH ₄ Br) and / or organic bromide (such as bromobenzene, benzyl-bromide, mono- and di-bromine Mother acetic acid, bromoacetyl bromide, tetrabromoethane, ethylene-di-bromide, etc.). Alternatively, the oxidation promoter may comprise a ketone such as methylethyl ketone, or an aldehyde such as acetaldehyde.

If the catalyst is used in heterogeneous form, it may be suitably located in the reaction zone to ensure contact between the continuous flow reaction medium and the catalyst. In this case, the catalyst may be appropriately supported and / or confined within the reaction zone to ensure such contact without unduly limiting the flow cross section. For example, the heterogeneous catalyst may be coated on, or otherwise applied to, or embodied in, a static element (eg, an element that forms an openwork structure) located in the reaction zone so that the reaction medium flows thereon. can do. The static element may additionally serve to promote the mixing of reactants through the reaction zone. Alternatively, the catalyst may be in the form of moving pellets, particles, finely divided form, metal sponge form, and the like, and if necessary, means are provided to confine the catalyst to the reaction zone such that the catalyst pellets, etc., in operation may be Suspended or immersed in the reaction medium flowing through the. The use of heterogeneous catalysts in any of the above manners provides the advantage of limiting the catalytic effect to clearly defined zones so that once the reaction medium crosses the zones, further oxidation occurs at a reduced rate. Or considerably suppressed.

After initiating the oxidation reaction by heating and pressurizing the reactants, the heated and pressurized reactants are merged into the reaction zone. This can be done in a number of ways to mix either or both of the reactants with the aqueous solvent before or after achieving supercritical or near supercritical conditions, and the mixing isolating the reactants from each other until incorporated into the reaction zone. It is done in ways to keep it intact.

In the batch method of the present invention, the water, precursor and catalyst solution are mixed in the autoclave before heating to the reaction temperature and reaching the reaction pressure. The oxidant may optionally be added to the mixture under reaction conditions or it may be added before sealing and heating the batch reactor autoclave. After the desired reaction time, the reaction autoclave is cooled down and the product is released. The heteroaromatic carboxylic acid product can then be recovered using any suitable product recovery system such as extraction, concentration and recrystallization.

In the continuous process of the present invention, the reactor system is preferably a reactor such that contact of at least a portion, preferably substantially all of the oxidant and precursor is such as contact of at least a portion, preferably substantially all of the catalyst and the oxidant. The system is configured to take place at the same point in time.

In a first embodiment, after heating and pressurizing the aqueous solvent to ensure a supercritical or near supercritical state, the oxidant is mixed with the aqueous solvent and the oxidant is moderately pressurized before mixing with the aqueous solvent and heated if desired. The precursor is pressurized and heated if desired. In the case of a method using a homogeneous catalyst, the catalyst component is pressurized and heated if desired. The precursor, catalyst and oxidant / solvent mixture are then contacted simultaneously. In the case of a method using a heterogeneous catalyst, the precursor is contacted with an oxidant / solvent mixture in the presence of the catalyst.

In a second embodiment of the invention, after heating and pressurizing the aqueous solvent to an appropriate pressure to ensure a supercritical or near supercritical state, the precursor is mixed with the aqueous solvent, the precursor is moderately pressurized before mixing with the aqueous solvent, Heat if desired. In one batch, the homogeneous catalyst component is contacted with the aqueous solvent while simultaneously contacting the precursor with the aqueous solvent after pressurization and optional heating. In an alternative arrangement, a heterogeneous catalyst is used and limited to the reaction zone as described above. After heating and pressurizing the aqueous solvent to ensure a supercritical or near supercritical state, the oxidant after pressurization and, if desired, heating is mixed with the aqueous solvent. In the case of a method using a homogeneous catalyst, the oxidant / aqueous solvent mixture is then contacted with a mixture comprising the precursor, the catalyst and the aqueous solvent. In the case of a method using a heterogeneous catalyst, the oxidant / aqueous solvent mixture is contacted with the mixture comprising the precursor and the aqueous solvent in the reaction zone, ie in the presence of the heterogeneous catalyst.

The contacting of the various streams may be performed as a separate feed of the device in which the feed is integrated to form a single homogeneous fluid phase, allowing the oxidant and precursor to react. The apparatus in which the feed is integrated has, for example, Y, T, X or other configuration such that the separate feed is integrated in a single flow passage constituting a continuous flow reactor, or in some cases two or more continuous flows. It can be integrated in multiple flow passages forming the reactor. Flow passages or passageways into which the feed is integrated may comprise sections of tubular configuration with or without internal dynamics or static mixing elements.

In one preferred embodiment, in-line or static mixers are advantageously used to ensure fast speed and homogeneity, for example to promote dissolution in the aqueous solvent of the oxidant and the formation of a single phase.

The oxidant feed and the precursor feed may be merged in a single location, or contacting may be performed in two or more stages such that at least some of either feed or both feeds are in a progressive manner, such as in a reactor. It can be introduced through multiple injection points for the flow direction through. For example, one feed can be passed along a continuous flow passage, where the other feed is fed at multiple points apart in the longitudinal direction of the continuous flow passage, allowing the reaction to be carried out gradually. The feed passed through the continuous flow passage may comprise an aqueous solvent like the feed introduced at multiple points.

Similarly, the addition of catalysts, in particular homogeneous catalysts, can be carried out in a gradual manner, for example via multiple injection points for the flow direction through the reactor.

In one embodiment, the oxidant is introduced to the reaction at two or more positions. Such locations are conveniently located relative to the bulk flow of solvent and reactants through the oxidation zone, whereby the oxidant is introduced into the reactants at the initial location and at one or more additional locations downstream of the initial location.

The reaction mixture comprises a solution of heteroaromatic carboxylic acid after crossing the continuous flow reactor. The solution may also include a catalyst (if used), and relatively small amounts of byproducts such as intermediates (such as aldehydes), decarboxylation products and degradation products, and any unused reactants.

The invention will now be described with reference to the accompanying drawings, which are by way of example only.

1A and 1B are schematic flow charts showing the basic arrangement described for the first embodiment, where FIG. 1A shows the use of a homogeneous catalyst and FIG. 1B shows the use of a heterogeneous catalyst.

2A-2D are schematic flow charts showing the basic arrangement described for the second embodiment, where FIGS. 2A and 2B show the use of homogeneous catalysts and FIGS. 2C and 2D show the use of heterogeneous catalysts. . In Figures 2B and 2D, the oxidant is introduced in a progressive manner along the reaction zone at multiple injection points.

FIG. 3 is a schematic flow diagram illustrating more specifically the arrangement in which the precursor is added to a premixed stream of oxygen and water (ie, the device according to the method shown in FIGS. 1A and 1B).

4A, 4B, 4C, 4D and 5 show the configuration of various premixers that can be used to effect mixing of one or more of the reactants with an aqueous solvent.

6 is a schematic diagram illustrating the multi-stage injection of an oxidant.

7 is described later in connection with the examples.

With reference to FIG. 1A, the dioxygen after pressurization is mixed with the water after heating, the mixture is pressurized and optionally further heated in the preheater 1 to achieve a supercritical state. After pressurization the precursor and catalyst are added to the O ₂ / water stream at or just before the reactor 2 starts and the mixture is passed through the reactor. Upon exiting the reactor, the stream is cooled and depressurized in back pressure regulator 3. The product is generated in a coolant stream. In the corresponding FIG. 1B the catalyst already exists as a heterogeneous catalyst in the reactor.

2A and 2B, the precursor and catalyst after pressurization are mixed with water after being pressurized and optionally heated and optionally further heated in preheater 1A to achieve a supercritical state. The dioxygen gas after pressurization is mixed with water in a supercritical state and optionally further heated in the premixer 1. In FIG. 2A, the two streams are mixed at or just before the reactor 2 starts and the mixture is passed through the reactor. In FIG. 2B, the O ₂ / water stream is added to the reactor in a gradual manner at multiple injection points. Upon exiting the reactor, the stream is cooled and depressurized in back pressure regulator (3). The product is generated in a stream of cooling water. In the corresponding FIGS. 2C and 2D, the catalyst is already present as a heterogeneous catalyst in the reactor.

With reference to FIG. 3, the feedstock component comprising water, precursor and dioxygen gas is pressurized to an operating pressure and the components are pressed from 300 ° C. to 480 ° C., more preferably from 330 ° C. to 450 ° C., typically about 340 ° C. Continuously supplied from each of the sources 10, 12 and 14 via a preheater 16 which heats to a temperature between the lower limit of from 370 ° C. and the upper limit of about 370 ° C. to about 420 ° C., the pressure and temperature being supercritical or near seconds. It is chosen to ensure a threshold condition. Part of the heat used to preheat the feedstock component may be derived from the exotherm generated during the subsequent reaction between the precursor and the oxidant. Heat from other sources may be in the form of high pressure steam, for example, and / or heating may be performed by direct ignition heating of the water stream. The heat of reaction can be recovered in any suitable manner, for example by heat exchange between the fluid after the reaction and a suitable heat-receiving fluid such as water. For example, the heat-receiving fluid can be arranged to flow in a heat exchange relationship, with countercurrent and / or rectification with reactants and solvents passing through the reaction zone. The passage or passages through which the heat-receiving fluid flows across the reaction zone may be outside of the reaction zone and / or may extend inwardly through the reaction zone. Such internally extending flow passage (s) may generally extend parallel to and / or across the general flow direction of the reactant / solvent, for example through the reaction zone. For example, the heat-receiving fluid may traverse the reaction zone by passage through one or more coil tubes located inside the reactor. The reaction enthalpy can be used to recover power through a suitable power recovery system such as a turbine; For example, a heat-receiving fluid such as water may be used to elevate the high pressure saturated steam at a temperature and pressure, for example of about 300 ° C./100 bara, which is then overheated by external heat and fed to the high efficiency condensation steam turbine. The power can be recovered. In this way, the reactor can be kept at an optimum temperature and effective energy efficiency can be achieved. In an alternative approach, the reactor can be operated under adiabatic conditions and a moderately high flow rate of water through the reaction zone can be used to suppress temperature rise throughout the reactor in operation. If desired, a combination of both approaches can be used, ie a combination of recovery of the reaction enthal ratio through the heat-receiving fluid and a suitable water flow rate through the reaction zone.

After heating of the feedstock component, the oxygen is brought under supercritical or near supercritical conditions as a result of preheating and pressurization, thus mixing the feedstock with water capable of solubilizing the feedstock. In the embodiment shown in FIG. 3, oxygen and water are mixed in premixer 18A. The precursor is also mixed with water in premixer 18B. Of course, the precursors may also be premixed separately with water before introduction into the preheater 16.

The premixer (or premixer in which the premix of each reactant and water is carried out) may be of various forms, such as Y, L or T pieces, a double T configuration, or as shown in FIGS. 4A, 4B, 4C, 4D and 5, respectively. It may take the form of a static mixer. In Figures 4A-4D and 5, the symbol A represents the preheated water feed to the premixer, B represents the reactant (precursor or oxygen) and P represents the mixed stream obtained. In the dual T configuration of FIG. 4D, two mixed streams P1 and P2 are produced. They may be passed through separate continuous flow reactors or combined into a single stream and then through a single continuous flow reactor. As is known to those skilled in the art, X piece configurations can also be used.

Instead of premixing either or both of the reactants with water prior to introduction into the reaction zone, the reactants and water are introduced separately into the reaction zone to react using some form of mixing device (eg, static mixer). It will be appreciated that mixing in a zone will result in mixing substantially all of the components in the reaction zone.

If a homogeneous catalyst is to be used for the reaction, the catalyst is added to the premixed oxygen / water stream as a solution from source 19, and at the same time the premix is added immediately before entering the reactor or at the point where the reactor starts. To the oxygen / water stream (ie, as shown in FIG. 1A).

After preheating and premixing, the feedstock components are combined in the reaction zone 20 to form a single homogeneous fluid phase where the reactants are merged. The reaction zone 20 is combined with a flow rate of a single mixer device, such as a combined reactant, in the form of a tubular plug flow reactor, with a suitable reaction time to ensure the conversion of precursors to carboxylic acids with high conversion efficiency and low intermediate aldehyde content. It may be composed of a pipe of a certain length to provide.

If the reaction is carried out in the presence of a heterogeneous catalyst system (ie as shown in FIG. 1B), the catalyst system can be distributed longitudinally with respect to the flow direction and is co-extensive with the reaction zone so that once If a supercritical or near supercritical fluid passes through a section of the pipe occupied by the catalyst system, the reaction rate can be significantly lowered, thereby suppressing the production of decomposition products.

The reactants may be combined upstream of the "one shot" of the reactor 20. Alternatively, they can be combined in a gradual manner by injecting one reactant into the stream containing the other reactants at multiple points along the length of the reactor. One way to implement multiple injection batches is shown in the continuous flow reactor of FIG. 6, where the reactor consists of a pipe P. FIG. In one embodiment in which the premixed oxygen / water stream is added to the premixed precursor / water stream (as shown in FIG. 2D), the premixed precursor / supercritical or near supercritical water stream W is a pipe (P). To the upstream end of In the case of a method in which a homogeneous catalyst is used, the water stream W will also contain a catalyst; In a method using a heterogeneous catalyst, the catalyst will be present in the pipe P. The stream passes through reactor pipe (P), and in a series of positions spaced apart along the length of pipe (P), preheated and compressed oxygen dissolved in supercritical or near supercritical water inlet passages A through E Feed through to produce a product stream (S) comprising the desired heteroaromatic carboxylic acid in a supercritical or near supercritical aqueous solution. In this way, the oxygen needed to fully oxidize the precursor to the carboxylic acid is injected gradually to control oxidation and to minimize side reactions and possible combustion of the precursor, carboxylic acid product or carboxylic acid intermediate.

Referring again to FIG. 3, after reacting to a desired degree, the supercritical or near supercritical fluid is passed through a heat exchanger 22 through which the heat exchange fluid is purified via a closed loop 24, whereby the heat is preheated. It may be recovered for use at (16).

The cooled solution is then fed to the product recovery section 26 where the carboxylic acid is recovered from the solution. Any suitable product recovery method known to those skilled in the art can be used.

Experimental work was performed on a laboratory scale by continuously oxidizing precursors in supercritical water with MnBr ₂ catalyst. Exotherm was minimized by using a relatively diluted solution (<5% organic w / w). The basic configuration of the system is shown in FIG. 1A. A more detailed description of the system used for this lab scale experiment is shown in FIG. 7.

Hydrogen peroxide (100 vol) was diluted to a suitable concentration, such as a 2% solution, fed to the pump and cooled to 5 ° C. or less. Hydrogen peroxide was then heated in preheater 152 consisting of a 5 m coil of ¼ inch OD stainless steel pipe, molded from aluminum blocks. By using a relatively long coil in the preheater 152, proper mixing of the oxidant and water was achieved. The oxidant / water fluid was then passed through a crosspiece 154 where it was contacted with the precursor and the MnBr ₂ catalyst solution supplied via its own pump.

Other components are shown in Figure 7 as follows: 162 A-E: valve; 163 A-B: pressure relief valve; 164 A-E: non return valve; 165 A-F: pressure transducer; T: Thermocouple (the aluminum heater block of the preheater 152 contains a thermocouple not shown). Preheaters were obtained from NWA GmbH; Pumps were Gilson 302, 305, 306 and 303; Back pressure regulators were obtained from Tescom (Model 26-1722-24-090).

Maximum corrosion occurred in the region of the crosspiece 154 where the oxidant, precursor and catalyst solution meet, especially in the incoming unheated catalyst feed pipe, where the hot gradient coincides with the bromide ions. Hastelloy C276 (or titanium), if a NaOH solution was used, was used in the final section of the reactor downstream and in the catalyst feed-pipe, before the mixer section for the addition of the solution, at approximately 100 ° C. The temperature gradient occurred at a length of approximately 5 cm and also for the other components in 316 L stainless steel. All pipe work that was prone to corrosion failure was protected inside the polycarbonate shield.

Prior to each run, the apparatus was hydrostatically pressure tested on cooling and then heated with a flow of pure 18 Mohm water (5-10 ml / min). Once the operating temperature was reached, the hydrogen peroxide feed and pumps for the precursor and MnBr ₂ were started. Typically, experiments were conducted for 4-5 hours. The product was collected and analyzed mainly for sequential time of 15 or 30 minutes. Purity was mainly verified by HPLC. The yield of solid product was calculated by dividing the molar concentration of the different products in the solution by the molar concentration of the feedstock fed to the reactor.

Example  One

Using 100 volumes of hydrogen peroxide, the diluted stock was prepared with 56 ml of peroxide and 760 ml of nanopure water (18.3 megohm resistance). Dilute catalyst stocks were prepared by dissolving manganese bromide in a nanopure water at a Br concentration of 5000 ppm w / w. 3-methylpyridine was kept undiluted separately. Sodium hydroxide stock solution (0.5 M) was prepared and fed downstream of the reactor, but before the back pressure regulator.

Deionized water alone was pumped through a preheater, mixed-piece, reactor, caustic mixer, cooler and back pressure regulator at a rate such that the final residence time through the reactor was 10 seconds. The residence time is the volume of tubular reactor, pipework and fittings between the mixing pieces (first to start the reaction by mixing the reactants and second to quench the reaction with the addition of sodium hydroxide). It is defined as divided by volume flow rate. Volumetric flow rates were based on the physical properties of the water under mixed conditions, as published by the International Steam Tables, and also by the U.S. National Institute of Standards and Technology.

The back pressure regulator was set to adjust the reactor pressure to 220 bar. The mixing piece was adjusted to 380 ° C. and the heater was set to control the reactor to 374 ° C.

Each reaction was pumped to the mixing pieces separately. Methylpyridine was fed to the reactor at a concentration of 0.50% w / w, oxygen was fed at a rate slightly above the stoichiometric rate required for oxidation of 3-methylpyridine to nicotinic acid, and the catalyst solution was fed to the mixing piece, A Br concentration of 1640 ppm was generated in the reactor.

After reaching a stable set point condition, samples were collected over 15 minute intervals and then analyzed. This experiment was conducted for 1.5 hours. The results show good selectivity for nicotinic acid (about 95%) at a conversion of about 30%. Some 3-pyridine carboxaldehyde was detected in a yield of 1-2%. Unreacted precursor was stable in the reaction medium and recovered at the end of the reaction.

Claims (10)

A method of making a heteroaromatic carboxylic acid comprising contacting a precursor of a heteroaromatic carboxylic acid with an oxidizing agent in the presence of a catalyst in an aqueous solvent comprising water under supercritical conditions or near supercritical conditions near the supercritical point. The method of claim 1 wherein said contacting is performed in a continuous flow reactor. The method of claim 2, wherein the contacting of the precursor occurs in a reaction zone having a residence time of less than 2 minutes. The process of claim 3, wherein substantially all of the resulting heteroaromatic carboxylic acid is maintained in solution during the reaction. The method of claim 1 wherein the heteroaromatic carboxylic acid is a nitrogen-containing heteroaromatic compound. The method of claim 1 wherein the heteroaromatic carboxylic acid comprises a six-membered ring. The method of claim 1 wherein the heteroaromatic carboxylic acid comprises a pyridine ring. The method of claim 1 wherein the heteroaromatic carboxylic acid is nicotinic acid. The method of claim 1 wherein the precursor to the heteroaromatic carboxylic acid is alkylpyridine. The method of claim 1 wherein the precursor to the heteroaromatic carboxylic acid is 3-methylpyridine.

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