FIELD OF THE INVENTION

The invention is in the field of the (continuous) production of ozonides using ozone and unsaturated hydrocarbons, in particular olefins and aromatics, in one or more microreactors.

BACKGROUND OF THE INVENTION

Industrial oxidation processes increasingly asks for environmentally friendly oxidizing agents. The use of oxygen - as ozone - as the oxidizing agent represents an alternative to reagents used so far, such as chromic acid or potassium permanganate. Additionally, oxidation using ozone, i.e. ozonolysis, advantageously avoids the production of waste materials, which when using the above-mentioned metal-based oxidizing agents must be very cost-intensively disposed of. However, ozonolysis involves extreme conditions and often yields instable products (see e.g. P. Bailey, Ozonation in organic Chemistry, Academic Press, New York, 1978); it is the intricate character of this type of reaction that has prevented ozonolysis of being successful at industrial levels.

The hazard potential in the conversion of e.g. olefins using ozone comes from the exothermic reaction of the substrate with the oxidizing agent. Furthermore, the intermediate product from the ozonide reaction can be classified as highly-energetic, which can be unstable and/or poorly resistant to thermal changes. Therefore, the extreme heat developed during reaction (350 kJ/mol) must be removed from the reaction mixture, to avoid decomposition of the thermally unstable ozonolysis intermediates. This decomposition can, apart from the formation of undesired byproducts, also lead to critical conditions in the reaction process.

Another drawback associated with ozonolysis of olefins is the formation of aerosols, a phenomenon referred to in the art as film evaporation. Aerosols contain the substrate to be oxidized and/or the ozonide, and are extraordinarily reactive, due to their highly reactive surface and the prevailing unfavourable reaction conditions.

Yet a further problem associated with ozonolysis can be low space-time yields (yield of product per volume of the reactor and time), due to poor mass transfer rates. This is for instance the case with aromatics, for which mass transfer phenomena determine the ozonolysis rate. Low conversion rates are for instance reported in CH 673.456 and US 6,346,623, their contents herein incorporated by reference. In all cases exemplified there, yields were lower than 80 %.

These negative aspects attached to ozonolysis are for instance discussed in US 6,545,186, on the ozonolysis of β-Pinen for the synthesis of Nopinone, reporting the risk of explosion. In the art, the reactions are performed using cryogenic conditions, thus circumventing the problem of decomposition. Likewise, GB 872,355 and GB 823,840 describe the ozonolyses of dicyclopentadiene to tricarboxycyclopentylacetic acid being hindered by aerosol formation. There, it is solved by using non-combustible solvents, such as water, with the aid of emulsifying agents. Their contents are herein incorporated by reference.

WO-2008/077769 deals with control of the flammable oxygen concentrations in ozonolysis of organic compounds. The solution is sought in ozone-carrying inert gas/02 stream with limited oxygen concentrations. It involves conventional reaction conditions such as reaction pressure that never exceeds 2 bar abs. The type of reactor is unspecified.

WO-02/072518 discloses a process for producing monocarbonyl, biscarbonyl or hydroxyl compounds involving ozonization. By making use of equipment consisting of one to two absorption apparatuses, devices for dissipating heat of the reaction and devices for separating the gas and liquid phase, with countercurrent reactant streams it appears possible to circumvent low reaction temperatures - and associated low yields - and to ease the separation of the free carbonyl compounds from the phosphate esters which form during the preceding reduction step. In a preferred embodiment, the continuous ozonolysis is carried out in two bubble columns as absorption apparatuses. At present, the above-discussed low conversation rates, delicate reaction conditions, formation of aerosols and risk of explosion, heat production and - therewith associated - instable intermediate products still make ozonolysis a poor alternative for heavy-metal based oxidizing agents.

US-A-2007/0276165 attempts to improve ozonolysis conditions using a structured reactor. It finds improved exchange of heat and material, higher selectivities, and reduced risk of explosion. Its contents are herein incorporated by reference. Since it makes use of conventional microreactors, the pressure applied is about 1 - 2 bar, which is the limit for standard microreactors. In the examples the ozonide is produced by combining ozone and unsaturated reactants at ambient temperatures and at 1.3 bar. Reported yields are at best 52%, or about 1.1 m ³ /hr in terms of the empty reactor volume. In terms of reaction velocity and volume rate, results are still unsatisfactory. This is demonstrated in the accompanying examples.

WO-2007/134847 likewise addresses the hazardous conditions involved in producing amines, alcohols, aldehydes and acids. It discloses a multi-step process for oxidizing organic compounds via an organic azide or peroxo compound, making use of a series of microreactors. Example 3 describes ozono lysis of naphthalene at 4 bar using a compressor especially designed for ozone compression. Yields were still unsatisfactorily low, i.e. at most 49.9 % of stable end product was obtained. Hence, there is a need in the art to render oxidation of olefins, aromatics and annelated aromatics accessible to ozonolysis, without being hampered by the aforementioned drawbacks. Apart from being safe and selective, such a process should also result in high space-time yields.

SUMMARY OF THE INVENTION

The inventors have found that ozonolysis of olefins and aromatics can be improved and the above problems reduced or even avoided if the ozone is supplied to a microreactor in compressed form, at a pressure above 5 bar, and subsequent ozonolysis is performed in the compressed stage. It makes it possible to mix large gas volumes with small liquid volumes, and achieve satisfactory contact between the gas and liquid reactants. This dramatically improves yields, as demonstrated in the accompanying examples.

However, conventional ozone generators cannot build up such pressures. Without aid, pressure levels typically reach 1.3 bar, as evidenced in US-A-2007/0276165.

Therefore, the inventors first fed the ozone through a compressor, prior to the microreactor. The adjustment of the volume sizes is preferably obtained by compression of the ozone-containing gas at an overpressure of at least 4 bar, preferably to about 10 bar.

The compressed ozone allows for the production of dry ozone-containing gas without loss of ozone concentration. It was surprisingly found that the ozone- containing gas can be compressed under industrial conditions without any measurable decomposition.

The process of the present invention makes it possible to produce ozonides from olefins and/or aromatics continuously. Above all, the compressed ozone gives far better results in terms of yields, reaction velocity and volume rates between the liquid and gas phase than reported in case of the ozone supply to conventional microreactors. Further, with the use of stoichiometric quantities of the reactive gas no multiphase reaction mixings are observed. The present invention thus enables ozonolysis even at industrial scales.

DETAILED DESCRIPTION OF THE INVENTION

The invention thus pertains to a process for oxidizing unsaturated starting materials, comprising:

(i) providing a liquid composition containing an olefin and/or aromatic starting compound,

(ii) compressing an ozone-containing gas to a pressure of at least 5 bar absolute,

(iii) introducing the compressed ozone-containing gas in one or more microreactors, bringing said gas into contact with said liquid composition (i), to obtain an ozonide, (iv) and optionally subjecting said ozonide to oxidative or reductive degradation.

Given the incapacity of conventional microreactors to build up the pressure to a required minimum level, it is preferred to perform step (ii) in a compressor, prior to step (iii).

Basically, the choice of the unsaturated starting materials is not critical; on the contrary, it is another advantage of the process that it can be applied to very different substrates. The term "unsaturated starting material" preferably comprises olefins and/or aromatics.

The liquid composition containing an olefin and/or aromatic starting compound provided in step (i) preferably contains 2 to 50 % by weight, more preferably 4 - 25 wt%, most preferably 7.5 to 10 wt% of olefin, based on the total weight of the liquid reaction mixture submitted to step (iii). Alternatively or additionally, the reactant is diluted with a solvent in a weight ratio of olefin and/or aromatic starting compound to solvent of 1 :2 to 2: 1.The dilution reduces the viscosity of the ozonides formed. For the production of the ozonides, it is preferred to use oxidation-stable aromatic or non-aromatic solvents. The solvent must be suitable for use in ozonolysis. Preferred solvents include substituted or non-substituted aromatic hydrocarbons or solvents which possess oxygen in the form of carbonyl, ether or alcohol functions. Halogenated aromatic and non-aromatic solvents have proved suitable for performing the reaction. Solvents with other oxidizable hetero-atoms (for example nitrogen) are likewise suitable, as a result of the high selectivity of the process. Because of the solubility of the reaction participants in toluene or alcohols, or mixtures of them, they are particularly preferred.

Olefin

In case the starting compound, i.e. the compound to be oxidized, is an olefin, it is preferably an aliphatic C3_4o and preferably C _6- I ₈ hydrocarbons containing 1 to 4 double bonds. The olefin is preferably generally represented by formula I:

in which Rl, R2, R3 and R4 represent, independently, hydrogen or an organic component (with preferably no more than 100 C-atoms), preferably a substituted component selected from the group comprising alkyl, heteroalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, cycloalkenyl, cycloalkenylalkyl, alkinyl, cycloalkylalkinyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aryl, heteroaryl, arylalkyl, cycloalkylaryl, cycloalkenylaryl, cycloalkylheteroaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heterocycloalkenylheteroaryl and hetero arylalkyl, and/or two or more of Rl, R2, R3, R4 are covalently interconnected, provided that the olefin is not ethene (i.e. at least one of Rl - R4 is not hydrogen).

If one or more of Rl - R4 are aromatically or non-aromatically substituted, the substituent(s) is/are preferably selected from the group consisting of:

- hydroxy, - Ci-Cs-Alkyl, preferably Methyl, Ethyl, n-Propyl, iso-Propyl, n-Butyl, iso- Butyl, tert- Butyl,

- C ₃ -Ci ₈ -Cycloalkyl, preferably Cyclopropyl, Cyclopentyl, Cyclohexyl, Cyclooctyl, Cyclododecyl, Cyclopentadecyl, Cyclohexadecyl,

- C ₂ -Cs-AIkUIyI, preferably Ethinyl, Propinyl, - Ci-C ₈ -Perfluoralkyl, preferably Trifluormethyl, Nonafluorbutyl, - Ci-C8-Alkoxy, preferably Methoxy, Ethoxy, iso-Propoxy, n-Butoxy, iso-Butoxy, tert.- Butoxy,

- C3-Ci2-Cycloalkoxy, preferably C3-Cycloalkoxy, Cs-Cycloalkoxy, Cβ-Cycloalkoxy, Cs-Cycloalkoxy, C^-Cycloalkoxy, Cis-Cycloalkoxy, Ciβ-Cycloalkoxy,

- Ci -C ₂ O-AIkO xyalkyl, in the 1 to 5 CH ₂ -groups are replaced by oxygen

- -[-O-CH ₂ -CH ₂ -]v-Q or -[-O-CH ₂ -CHMe-] _v -Q, where Q may be OH or CH ₃ , and v represents 1, 2, 3 or 4,

- Ci-C ₄ -ACyI, preferably acetyl,

- Ci-C ₄ -Carboxy, preferably CO ₂ Me, CO ₂ Et, CO ₂ iso-Pr, C0 ₂ tert.-Bu,

- Ci-C ₄ -ACyIoXy, preferably Acetyloxy,

- halogen, preferably F or Cl,

- Sii-Siio-Silyl, and

- Sii-Si3o-Siloxy or Polysiloxy.

If one or more of the components of Rl, R2, R3, R4 contain nitrogen, sulphur or phosphorus, then the N, S or P-containing component is preferentially stable with respect to the oxidation.

Aromatic

In case the starting compound is an aromatic compound, it is represented by formula (II):

in which Rl, R2, R3, R4, R5 and R6 represent, independently, hydrogen or an organic component (with preferably no more than 100 C-atoms), preferably a substituted component selected from the group comprising alkyl, heteroalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, cycloalkenyl, cycloalkenylalkyl, alkinyl, cycloalkylalkinyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aryl, heteroaryl, arylalkyl, cycloalkylaryl, cycloalkenylaryl, cycloalkylheteroaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heterocycloalkenylheteroaryl and heteroarylalkyl, and/or two or more of Rl, R2, R3, R4, R5 and R6 are covalently interconnected.

If one or more of Rl - R6 are aromatically or non-aromatically substituted, the substituent(s) is/are preferably selected from the group consisting of:

- hydroxy,

- d-Cg-Alkyl, preferably Methyl, Ethyl, n-Propyl, iso-Propyl, n-Butyl, iso- Butyl, tert- Butyl,

- C ₃ -Ci ₈ -Cycloalkyl, preferably Cyclopropyl, Cyclopentyl, Cyclohexyl, Cyclooctyl, Cyclododecyl, Cyclopentadecyl, Cyclohexadecyl,

- C ₂ -C ₈ -Alkinyl, preferably Ethinyl, Propinyl,

- Ci-Cs-Perfluoralkyl, preferably Trifluormethyl, Nonafluorbutyl,

- Ci-Cs-Alkoxy, preferably Methoxy, Ethoxy, iso-Propoxy, n-Butoxy, iso-Butoxy, tert.- Butoxy, - C3-Ci2-Cycloalkoxy, preferably C3-Cycloalkoxy, Cs-Cycloalkoxy, Cβ-Cycloalkoxy, Cs-Cycloalkoxy, Ci2-Cycloalkoxy, Cis-Cycloalkoxy, Ciβ-Cycloalkoxy,

- Ci -C ₂ O-AIkO xyalkyl, in the 1 to 5 CH2-groups are replaced by oxygen

- -[-0-CH ₂ -CH ₂ -Jv-Q or -[-O-CH ₂ -CHMe-] _v -Q, where Q may be OH or CH ₃ , and v represents 1, 2, 3 or 4, - Ci-C ₄ -ACyI, preferably acetyl,

- Ci-C ₄ -Carboxy, preferably CO ₂ Me, CO ₂ Et, CO ₂ iso-Pr, C0 ₂ tert.-Bu,

- Ci-C4-Acyloxy, preferably Acetyloxy,

- halogen, preferably F or Cl,

- Sii-Siio-Silyl, and - Si ₁ -Si ₃ O-SiIo xy or Po lysiloxy.

If one or more of the components of Rl, R2, R3, R4, R5, R6 contain nitrogen, sulphur or phosphorus, then the N, S or P-containing component is preferentially stable with respect to the oxidation.

Ozone

Ozone may be produced using pure oxygen or mixtures of oxygen and inert gas(es) in varying volumetric ratios to oxygen, preferably between 1 and 80 vol.% oxygen.

The gaseous ozone is first compressed, before introduction into the micro-reactor. The ozone-containing gas is preferably compressed to the desired pressure range by the o

use of an appropriate ozone-resistant compressor. The absolute pressure of the compressed ozone preferably ranges between 5 and 12 bar, more preferably at least 5.1, 5.2, 5.3, more preferably at least 5.5 bar absolute, and most preferably between 6 and 10 bar, preferably up to 8 bar. The ozone compressor is preferably a four head high flow ozone compressor, designed for high concentration ozone gas. It is made oil- and waterfree with teflon diaphragms and can bring the ozone from an ozone generator into the microreactor system by compressing it up to the aforementioned range.

The compressed ozone is added to the reaction mixture containing the olefin and/or aromatic in step (iii). Therein, the ozone concentration in the gas supplied to the reaction mixture lies preferably within the range of 1 to 12 % by weight in relation to the total gas used. Especially preferred are ozone concentrations in the range of 4 to 8 % by weight.

Ozonolysis; reactor

The reaction is conducted in one or more microreactors. A microreactor is generally defined as a miniaturized reactor (mini- or microreactor) with characteristic dimensions (channel or plate width) in micrometers to millimetres (preferably from 0.01 mm to 10.0 mm). The characteristic feature of a microreactor is preferably that at least one of the three spatial dimensions of the reaction space is dimensionalized in the range from 1 to 2000 μm. Microreactors are distinguished from other reactors by a high transfer- specific inner surface, short residence times of the reactants and high specific heat and mass transfer levels. The microreactor is preferably a continuous microreactor, i.e. a microreactor suitable for use in a continuous process. A continuous process is defined as a method of manufacturing in which new materials are added and products removed continuously at a rate that maintains the reaction volume at a specific level. In other words, continuous reactors are reactors that may be used to carry out steady state operations.

The micro reactor preferably comprises a device allowing the reactants (gaseous or liquid) to enter and continuously flow through. The reactants are contacted with each other in the device, allowing a chemical reaction to take place in a narrow confined space like a channel or between two plates. One (in the case of plates) or two (in case of channels or grooves) dimensions of the micro reactor are chosen in such a way that the characteristic times for heat transfer and/or mass transfer are very low. Herewith high rates of reaction and heat transfer can be handled in a controlled fashion. The heat is transferred to or from a heat transfer fluid that does not come into contact with the reactants or the products. The walls of the micro reactor may contain catalytic activity. A (bio)catalyst may be deposited, immobilized or coated on the wall.

A number of microreactors may be combined in parallel to form a "structured reactor", thus a mere arrangement of microreactors. Entering reactants are distributed over manifold systems or other distribution systems to the individual microreactors. Each micro- reactor may include mixing zones to mix the entering reactants and/or the reaction medium. Each microreactor may contain residence zones to allow the reaction medium to obtain sufficient conversion. The micro- reactor may be constructed of, or may contain, a number of parallel sub-units (mixing zones with residence zones) in a numbering-up concept to obtain sufficient production capacity.

Thus, the volume, available for reaction depends on the diameter and length of the microreactor, or in case a microreactor is used on the dimension of the parallel channels and the number of parallel channels. The volume of micro -reactors or microreactors typically lies in the range of 1 ml to 1 m ³ , preferably from 10 ml to 50 1. Preferably, a microreactor is defined as a reactor having a channel with a hydraulic diameter of 20 mm or less. The hydraulic diameter Dh is defined as 4A/U, wherein A is the cross sectional area of the reactor channel and U is the perimeter of said cross section.

For a round tube, the hydraulic diameter Dh equals the diameter of the tube. For a rectangular duct, that has a cross section with a rectangular shape, the hydraulic diameter equals 4LW/2(L+W), wherein L is the length of the longest side of the rectangle and W is the width of the rectangle. For the special case of a square duct, the hydraulic diameter Dh equals L. For an annulus, the hydraulic diameter is Dh = (4 * 0.25π(D _o ² - D ₁ ² ))/ (π(D ₀ - D ₁ )) = D ₀ -D ₁ , wherein D ₀ is the outer diameter of the annulus and D ₁ is the inner diameter. However, it should be noted that the general formula 4A/U, wherein A is the cross sectional area of the reactor channel and U is the perimeter of said cross section, allows calculation of the hydraulic diameter for any shape of reactor channel.

A detailed account on microreactors and their arrangement in structured reactors is presented, for example, by Jahnisch et al. in Angewandte Chemie, Vol. 116, 410-451 (2004), herein incorporated by reference. Reference is also made, by way of example, to European patent application EP 0903174 Al (Bayer), which describes the liquid phase oxidation of organic compounds in a microreactor consisting of a bundle of parallel reaction channels. The aforementioned WO-2007/134847 also describes microreactors that are suited. Again, its contents is herein incorporated by reference.

Inside the microreactor or structured reactor, ozonolysis is preferably performed at a temperature of -78°C to +30 ⁰ C, in particular at -30 ⁰ C to +10 ⁰ C, and most preferably at -10 ⁰ C to 0 ⁰ C. Under these conditions secondary reactions of the ozonolysis and a potential hazard caused by exceeding the ignition temperature of one the reaction components can be avoided.

Ozone can be introduced to the reaction mixture in step (iii) in a molar range of 1 to 5, or preferably in the range of 1 to 3 and most preferably in the range of 1.1 to 2 molar equivalents, calculated on the molar amount of olefin and/or aromatic to be oxidized. Under these conditions any undesired side-products of ozonolysis are minimized.

The whole of step (iii) is preferably performed at a pressure in the aforementioned range.

The reaction of ozone with the olefin and/or aromatic preferably takes place at a flow rate of 0.1-200 g/minute, and preferably at flow rates of 10 - lOOg/minute. The best results are obtained with flow rates within the range of 10- 50g/minute.

Ozonide

The ozonide obtained from the ozonlysis of an olefin according to formula (I) may schematically be represented by formula (III)

in which Rl, R2, R3, R4 have the meaning as given above. In the literature, the ozonide is sometimes alternatively drawn up as:

The invention is not regarded being tied by the exact structural representation of the ozonide. Hence, where ozonide is mentioned in the context of the invention, it encompasses either of the above schematic representations. Similar structures may be drawn for the ozono lysis of an aromatic schematically represented by formula (II).

Conversion

The ozonide obtained in step (iii) is optionally converted, i.e. oxidatively or reductively degraded, to a thermodynamically stable product in a subsequent conversion step (iv). The conversion takes place using techniques known to the expert and as e.g. described in detail in the literature by J. March, Advanced Organic Chemistry, Fourth edition, Wiley, New York, 1992 and the Organikum, chemistry publishing house, New York, Weinheim, 21st edition.

Oxidative cleavage of the ozonisation products generally takes place at temperatures of 20 - 140 ⁰ C and preferably at temperatures of 80 - 100 ⁰ C, either in the absence of pressure, or under a slight excess pressure, preferably in the range of from about 1 to about 10 bar. Oxygen or an oxygen-containing gas stream is normally used for the oxidation. The reaction is generally carried out in the presence of a catalyst, metal salts and immobilized heterogeneous catalysts being used. The reactants are also generally present in dilute form. Compounds such as aldehydes, ketones or alcohols may be obtained. The oxidation products can in addition be transferred by consecutive reaction steps into the oxidized compounds such as carbonic acids or carbonic acid esters, and even beyond.

Reductive cleavage of the ozonization products generally takes place at temperatures of 20 - 100 ⁰ C and preferably at temperatures of 50 - 80 ⁰ C, in the absence of pressure, or under excess pressure, preferably in the range of from 1 to 10 bar. The reaction is carried out with a suitable reducing agent, preferably hydrogen or a hydrogen-containing gas stream. The reduction is preferably carried out in the presence of a metallic catalyst, particularly palladium. Each of the three process steps of ozonolysis, oxidative and reductive cleavage can be carried out independently or in combination with at least one of the other two. Accordingly, in practice, it is recommended to carry out the reaction as a whole in two microreactors arranged in tandem. The reaction of the unsaturated reactant with ozone takes place in the first reactor. The ozonides formed may then be introduced into the second microreactor where, for example, they are oxidized with air or reduced with hydrogen in the presence of a catalyst, or by another suitable reducing agent, such as, for example, zinc in glacial acetic acid or sodium hydrogen sulfite. The reaction may be carried out with or without dilution by inert solvents. The second reactor does not necessitate a preceding compressor.

EXAMPLES

Unless stated otherwise, percentages are understood as weight percentages; quantity data specifications refer to mass ratios; and ambient temperature corresponds to about 20 ⁰ C.

Example 1 : Production of Cyclocitral from Ionone

A solution of Ionone in methanol was pumped through a -10 ⁰ C pre-cooled Starlam microreactor, commercially available with Microinnova (Graz, Austria). The concentration amounts to 12%. The reaction mixture in the reactor is held at about 30 ⁰ C by cooling. When temperature and flow conditions (27g/minute) reaches constant levels, 1.1 molar equivalents of ozone were fed to the reaction mixture, at a pressure of 6 bar using a four head high flow ozone compressor, and at an ozone concentration of 110g/Nm3, or about 8% ozone in oxygen. With subsequent conversion a temperature rise of approximately 40 ⁰ C was observed. The solution of ozonised products leaving the equipment was collected under cooled conditions, and subsequently transformed by means of steam distillation into the desired product, Cyclocitral (formula V):

Throughput: 100% Yield: 80% Concentration: 95% Example 2: Production of Nopinone from β-Pinene

A 10 % solution of β-Pinene in methanol was pumped through a -10 ⁰ C pre-cooled microreactor. The reaction mixture in the reactor was maintained at about 30 ⁰ C by cooling. After setting both constant temperature and flow conditions (20g/minute), 1.1 molar equivalents of ozone were fed at the same time into the reaction mixture under a pressure of 6 bar and at an ozone concentration of 90 g/Nm ³ (grams per m ³ at standard "N" conditions). The conversion of the substrate with ozone resulted in a temperature rise of approximately 40 ⁰ C. The ozonide leaving the equipment was collected under cooled conditions and subsequently transformed by means of a reduction reaction into the desired product, Nopinone, represented by formula (VI):

Thereto, the solution was cooled down to a reaction temperature of -20 ⁰ C. 1.1 mol equivalents of dimethylsulfϊde was dosed to the ozonide from the first stage of the reaction, to obtain a ketone. The peroxide-free reaction mixture was then concentrated, charged with MTBE, and the resulting solution washed 5 times with water. From the reaction, after the removal of the solvent by distillation, a colourless oil remains.

Throughput: 100% Yield: 97% Concentration: 97%

Example 3 : Production of Pyridine-2.3 dicarboxylic acid from quinoline A 5 - 10 % solution of quinoline in methanol was pumped through the 0 ⁰ C pre-cooled microreactor. The reaction mixture in the reactor was held at about 25°C by cooling. After setting both constant temperature and flow conditions (25g/minute), 2.1 molar equivalents of ozone were added in one time to the reaction mixture at a pressure of 6 bar and at an ozone concentration of 130 g/Nm ³ . The conversion of the substrate with ozone in the microreactor system yielded a temperature rise of 25 to 30 ⁰ C. The yellow ozonide solution leaving the equipment was collected under cooled conditions and subsequently transformed by means of an oxidation reaction into the desired product, Pyridine-2.3 dicarboxylic acid (VII):

Thereto, the reaction solution was cooled with ice to a reaction temperature of 2°C, and 3 mol equivalents of a 35% solution of hydrogen peroxide was added thereto. At the same temperature, the mixture was then discharged into caustic soda. After a reaction time of 2h the products of the reaction were precipitated by bringing the aqueous solution to a pH-value of 1 to 2 by adding acid.

Throughput: 100% Yield: 73% Concentration: 97%

Comparative example I - atmospheric conditions The reaction schemes of examples 1 - 3 were reproduced, with the exception that the compressor was left out and ozone was now added to the reaction mixture at ambient pressure. In all three cases the yield was considerably lower, i.e. 20 - 30 %, and more than 50 % unreacted substrate remained.