METHOD FOR PREPARATION OF MONONITRATED AROMATIC COMPOUNDS

The invention discloses a method for preparation of mononitrated aromatic compounds in a liquid-liquid biphasic solvent system with aqueous nitric acid as one phase and ionic liquids (ILs) as the second phase, wherein the nitric acid is continuously exchanged during the reaction.

Mononitrated aromatic compounds and methods for their preparation are known. These compounds represent intermediates in a wide range of methods for preparation e.g. of aromatic amines and other aromatic compounds.

EP 1 324 973 B discloses a process for the nitration of an aromatic compound, wherein the aromatic compound is admixed with a nitrating agent in the presence of an ionic liquid. The reaction system consists of only one phase. The range of ionic liquids where the disclosed nitration reaction succeeds is limited to those where the corresponding acid form of the anion is stronger, or at least as strong as nitric acid. Prominent examples given are the hydrogen sulfate anion and trifluoromethane sulfonate anion. As cations of the ILs imidazolium cations are disclosed. In the example the nitrotoluene/residual nitric acid is distilled off at 140°C at 1 mbar. The preferred distillation method is steam distillation, optionally by the addition of water before the steam distillation.

Since water is not removed during the reaction, the concentration of the nitric acid

continuously decreases, thereby the turnover rate of the reaction slows down. The ionic liquid mentioned contains a cationic, imidazolium moiety, which is prone to nitration, thereby undesired byproducts can be formed, which results in reduced long term stability of the IL.

DE 2 622 313 A discloses a method for the preparation of mononitrated aromatic compounds by nitration of aromatic compounds with nitric acid without the use of sulfuric acid, wherein the nitration is done in 40% to 68% (w/w) nitric acid, the reaction mixture is separated mechanically into an inorganic and an organic phase. The inorganic phase is separated by rectification into one phase with lower nitric acid concentration and another phase with higher nitric acid concentration.

The inorganic phase and the organic phase in this method show high solubility among each other, which can be as high as 45%. Therefore cooling and/or dilution before the phase separation are/is required as well as elaborate rectification with several steps after phase separation. This is energetically and ecologically unfavorable and leads to prolonged process times.

The DE 2 622 313 A suggests increasing the temperature near the end of the reaction in order to shorten reaction times and to obtain higher conversion rates, but hints at the problem of dinitration. The problematic and undesired possibility of dinitration, which represent toxicologically problematic substances, which can even pose a security risk, necessitates in the disclosed method specific technical provisions, such as higher number of steps, such as purification and/or distillation steps, a specific flow profile and other measures. Explicit recommendation is even to stop the reaction already when the turnover rate has exceeded 90% in order to avoid by products such as deriving from dinitration.

There was a need for a method for preparation of mononitrated aromatic compounds, which provide for improved process control, which generates an ecologically unproblematic waste stream, and which uses inexpensive reactants and a minimum number of substances. The use of sulfuric acid should be avoided in order to avoid waste water containing sulfate. The reaction rate should be high, the reaction should be fast. The desired method should have a simple and energetically advantageous work-up procedure for the reaction mixture. The recovery rate of the desired products should be high. Any waste stream should be small. In this text,

alkyl means linear or branched alkyl;

halogen means F, CI, Br or I, preferably F, CI or Br;

OTf trifluoromethane sulfonate, triflate;

IL Ionic Liquid;

if not stated otherwise.

Subject of the invention is a method for the preparation of a mononitrated aromatic compound by a reaction of an aromatic compound with nitric acid,

wherein the reaction is done in a liquid liquid biphasic system with a phase (A) and a phase (B);

phase (A) is an ionic liquid (A),

ionic liquid (A) is selected from the group consisting of nitrate, hydrogen sulfate and

trifluoromethane sulfonate of [N(R1)(R2)(R3)R4] ⁺ , and nitrate, hydrogen sulfate and trifluoromethane sulfonate of [P(R1)(R2)(R3)R4] ⁺ ; Rl and R2 are identical or different and independently from each other Ci

R3 is C4-14 alkyl;

R4 is C4-14 alkyl or C4-14 alkyl substituted by SO3H;

with the proviso, that the total number of carbon atoms in Rl, R2, R3 and R4 is at least 16; and

with the proviso, that if Rl and R2 are Ci_ ₂ alkyl, then R3 and R4 are Cio-14 alkyl; phase (B) is aqueous nitric acid (B),

aqueous nitric acid (B) has a concentration (CONC) at the beginning of the reaction, concentration (CONC) is from 50% to 70% of nitric acid, the % being weight percent and are based on the total weight of the aqueous nitric acid (B);

the average residence time of aqueous nitric acid (B) in phase (B) is smaller than the reaction time by exchange of aqueous nitric acid (B) by an aqueous nitric acid (C) during the reaction;

the aqueous nitric acid (C) has a concentration (C) from concentration (CONC) to 100%, the %> being weight percent and are based on the total weight of the aqueous nitric acid (C); the aromatic compound is selected from the group consisting of benzene, naphthalene,

biphenyl and diphenyl ether;

wherein the aromatic compound is unsubstituted or substituted with 1, 2, 3 or 4 substituents; and

wherein the substituents are identical or different and independently from each other selected from the group consisting of Ci_io alkyl, C5-6 cycloalkyl, and halogen. The average residence time can also be called average staying time or average dwell time, and specifies the average time how long a specific part of phase (B), that is a specific part of aqueous nitric acid (B), stays in the reaction before it is exchanged during the reaction by aqueous nitric acid (C).

An exchange can be done once or more than once during the reaction.

An exchange can be done continuously.

The amount of phase (B), i.e. of aqueous nitric acid (B), which is exchanged, can be a part of the amount of phase (B), it can be the total amount of the amount of phase (B), or phase (B) can be exchanged more than once during the reaction. Preferably, exchange of phase (B), i.e. of aqueous nitric acid (B), is done during the reaction 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20 times or continuously.

Preferably, any batchwise exchange exchanges 50 to 100%, more preferably 75 to 100%, even more preferably 90 to 100%, of phase (B), the % are weight % and are based on the total amount of phase (B).

In another more preferred embodiment, phase (B), i.e. aqueous nitric acid (B), is exchanged during the reaction 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20 times or continuously, and, in case of non-continuous exchange, any batchwise exchange exchanges 90 to 100% of phase (B), the % are weight % and are based on the total amount of phase (B).

Continuous exchange is preferred over batchwise exchange. During the reaction, nitric acid is spent by the nitration reaction and water is produced as a side product, therefore the concentration of nitric acid in phase (B) would continuously drop during the reaction, if no phase (B) was exchanged. Exchange of phase (B) serves the purpose to remove the side product water from the reaction mixture. Simultaneously, by exchanging phase (B), the concentration of nitric acid in phase (B) is kept either equal to or at least as near as possible to concentration (CONC). When choosing a continuous exchange of phase (B), the concentration of nitric acid in phase (B) can even be kept constant. By this exchange of phase (B), the reaction rate does no longer drop as much as it would drop without exchange, and often, in case of no exchange, the reaction even stops altogether before full conversion of the substrate.

It is actually possible to even increase the concentration of nitric acid in phase (B) by the exchange, if the concentration of aqueous nitric acid (C) is above concentration (CONC) and the amount of exchanged phase (B) is adapted to serve the purpose of increase of the concentration of nitric acid in phase (B) over concentration (CONC). But this, i.e. the increase of the concentration of nitric acid in phase (B) during the reaction, is usually not a preferred embodiment, since one can as well start right from the beginning with the desired higher concentration (CONC). Preferably, also the amount of phase (B) is kept constant during the reaction by said exchange of part of phase (B) with the aqueous nitric acid (C).

Preferably, ionic liquid (A) is selected from the group consisting of [N(R1)(R2)(R3)R4] ⁺ N0 ₃ ^" , [P(R1)(R2)(R3)R4] ⁺ N0 ₃ ^" , [N(R1)(R2)(R3)R4] ⁺ HS0 ₄ ^~ , [P(R1)(R2)(R3)R4] ⁺

HS0 ₄ ^" , [N(R1)(R2)(R3)R4] ⁺ (OTf) ^" and [P(R1)(R2)(R3)R4] ⁺ (OTff;

more preferably, ionic liquid (A) is selected from the group consisting of

[N(R1)(R2)(R3)R4] ⁺ N0 ₃ ^" , [P(R1)(R2)(R3)R4] ⁺ N0 ₃ ^" , [N(R1)(R2)(R3)R4] ⁺ (OTf) ^" and

[P(R1)(R2)(R3)R4] ⁺ (OTf) ^" ;

even more preferably, ionic liquid (A) is selected from the group consisting of

[N(R1)(R2)(R3)R4] ⁺ N0 ₃ ^" and [N(R1)(R2)(R3)R4] ⁺ (OTf) ^" .

In case that the ionic liquid (A) is [N(R1)(R2)(R3)R4] ⁺ N0 ₃ ^" or [P(R1)(R2)(R3)R4] ⁺ N0 ₃ ^" , it can be generated from the corresponding hydrogen carbonate or carbonate. The corresponding hydrogen carbonate or carbonate is converted to the nitrate when coming into contact with the nitric acid in phase (B), therefore preferably said conversion is done in situ.

With respect to the substituents Rl, R2, R3 and R4,

preferably, Rl, R2, R3 and R4 are linear alkyl residues;

preferably, R3 and R4 are identical, and Rl and R2 are identical;

more preferably Rl, R2, R3 and R4 are linear alkyl residues, R3 and R4 are identical and Rl and R2 are identical.

Even more preferably, R3 and R4 are identical and are linear C ₄ _i ₂ alkyl, and Rl and R2 are identical and are linear C _1-12 alkyl.

Even more preferably, the ionic liquid (A) is selected from the group consisting of [N(n- butyl) ₄ ] ⁺ N0 ₃ ^" , [P(n-butyl) ₄ ] ⁺ N0 ₃ ^" , [N(n-hexyl) ₄ ] ⁺ N0 ₃ ^" , [P(n-hexyl) ₄ ] ⁺ N0 ₃ ^" , [N(n- octyl) ₄ ] ⁺ N0 ₃ ^" , [P(n-octyl) ₄ ] ⁺ N0 ₃ ^" , [N(n-dodecyl) ₄ ] ⁺ N0 ₃ ^" , [P(n-dodecyl) ₄ ] ⁺ N0 ₃ ^" , [N(CH ₃ )(n-octyl) ₃ ] ⁺ N0 ₃ ^" , [P(CH ₃ )(n-octyl) ₃ ] ⁺ N0 ₃ ^" , [N(n-butyl) ₄ ] ⁺ (OTf) ^" , [P(n- butyl) ₄ ] ⁺ (OTf) ^" , [N(CH ₃ )(n-octyl) ₃ ] ⁺ (OTf) ^" , [P(CH ₃ )(n-octyl) ₃ ] ⁺ (OTf) ^" , [N(n- butyl) ₃ ((CH ₂ ) ₄ S0 ₃ H)] ⁺ N0 ₃ ^" , [P(n-butyl) ₃ ((CH ₂ ) ₄ S0 ₃ H)] ⁺ N0 ₃ ^" , [N(CH ₃ ) ₂ (n-decyl) ₂ ] ⁺ N0 ₃ ^" and [P(CH ₃ ) ₂ (n-decyl) ₂ ] ⁺ N0 ₃ ^" ; especially, the ionic liquid (A) is selected from the group consisting of [N(n-butyl) ₄ ] ⁺ N0 ₃ , [N(CH ₃ )(n-octyl) ₃ ] ⁺ (OTf) ^" , [N(n-butyl) ₄ ] ⁺ (OTf) ^" , [N(n-butyl) ₃ ((CH ₂ ) ₄ S0 ₃ H)] ⁺ N0 ₃ ^" and

[N(CH ₃ ) ₂ (n-decyl) ₂ ] ⁺ N0 ₃ ^" .

Preferably, concentration (CONC) is from 60% to 70%, more preferably from 61% to 69%, even more preferably from 61 > to 68%>, especially 65%>, of nitric acid, the %> being weight percent and are based on the total weight of the aqueous nitric acid (B).

Preferably, concentration (C) is from concentration (CONC) to 70%, the % being weight percent and are based on the total weight of the aqueous nitric acid (C). Preferably, the molar amount of nitric acid (B) in phase (B) is 1 to 10 fold, more preferably 1 to 6 fold, of the molar amount of aromatic compound.

Preferably, the aromatic compound is selected from the group consisting of benzene,

naphthalene, biphenyl and diphenyl ether;

wherein the aromatic compound is unsubstituted or with 1 , 2, 3 or 4 substituents substituted; and

wherein the substituents are identical or different and independently from each other selected from the group consisting of Ci_io alkyl, C5-6 cycloalkyl, and halogen;

more preferably, the aromatic compound is selected from the group consisting of toluene, xylene, chlorobenzene, naphthalene, biphenyl and diphenyl ether;

even more preferably, the aromatic compound is selected from the group consisting of

toluene, m-xylene, chlorobenzene, naphthalene, biphenyl and diphenyl ether;

especially, the aromatic compound is selected from the group consisting of toluene, m-xylene, chlorobenzene, naphthalene and diphenyl ether;

more especially, the aromatic compound is selected from the group consisting of toluene, m- xylene and chlorobenzene. Preferably, the molar amount of ionic liquid (A) is 0.01 to 100 fold, more preferably 0.05 to 50 fold, even more preferably 0.1 to 10 fold, especially 0.2 to 2 fold, of the molar amount of aromatic compound (A).

The reaction can be done under pressure, such as from atmospheric pressure to 400 bar.

Preferably, the reaction is done at a temperature (A) of -25 °C to 250 °C, more preferably of 0 °C to 200 °C, even more preferably 20 °C to 200 °C, especially of 25 °C to 180 °C.

Preferably, the reaction time of the reaction is from 1 min to 72 h, more preferably from 15 min to 12 h, even more preferably from 30 min to 3h, especially from 30 min to 90 min.

The reaction can be done under inert atmosphere. Preferably, an inert atmosphere is made from a gas (A) selected from the group consisting of nitrogen, helium, neon, argon, carbon dioxide and mixtures thereof.

More preferably, gas (A) is nitrogen or carbon dioxide.

The exchange of part of phase (B) with the aqueous nitric acid (C) during the reaction is done by removal of a part of phase (B) during the reaction and addition of the aqueous nitric acid (C).

Further subject of the invention is the method as described above, also with all its preferred embodiments, wherein the part of phase (B), which was removed during the reaction from the reaction mixture, is regenerated after its removal from the reaction mixture, the regeneration is done by contacting the removed part of phase (B) with N0 ₂ and an oxidizing agent, the oxidizing agent is 0 ₂ or air.

N0 ₂ and the oxidizing agent are added preferably in a molar ratio of 2 mol equivalents N0 ₂ to 0.5 mol equivalents oxidizing agent.

Preferably, the amount of N0 ₂ and oxidizing agent, which is contacted with the removed part of phase (B), is such that concentration (C) is attained in the removed part of phase (B) by this regeneration. Preferably, the removed part of phase (B) after regeneration is used as aqueous nitric acid (C), which is added to the reaction mixture during the reaction in exchange for the removed part of phase (B).

In another embodiment, the removed part of phase (B) is regenerated by distillation.

In another embodiment, the removed part of phase (B) is regenerated by a combination of contacting with N0 ₂ and an oxidizing agent as described above, also in all its described embodiments, and distillation.

Therefore further subject of the invention is the method as described above, also with all its preferred embodiments, wherein the part of phase (B), which was removed during the reaction from the reaction mixture, is regenerated after its removal from the reaction mixture, the regeneration is done by a combination of contacting the removed part of phase (B) with N0 ₂ and an oxidizing agent, the oxidizing agent is 0 ₂ or air, and distillation.

Preferably, the regeneration is done first by contacting with N0 ₂ and the oxidizing agent, until a concentration of nitric acid of 60 to 64 % is attained, and then the distillation is done to attain a concentration of nitric acid of 65%, which represents preferably concentration (CONC) and concentration (C).

Further subject of the invention is the method as described above, also with all its preferred embodiments, wherein phase (A) is distilled after the reaction, in this distillation the mononitrated aromatic compound is distilled off; a distillation residue remains, this distillation residue contains the ionic liquid.

Preferably, an entrainer is present in the distillation, the entrainer is water or aqueous nitric acid.

More preferably, the entrainer is water or part of phase (B), with phase (B) as defined above, also with all its preferred embodiments.

The distillation can be done under reduced pressure. When an entrainer is present, the entrainer and the mononitrated aromatic compound form after the distillation two phases and can therefore easily be separated; preferably, the entrainer and the mononitrated aromatic compound are separated after the distillation. The amount of entrainer can vary.

Preferably, the amount of entrainer is 0.001 to 10 fold, more preferably 0.01 to 5 fold, of the weight of phase (A).

The entrainer can be recycled during distillation. The ionic liquid (A) does not distill and therefore represents the distillation residue or distillation sump. After distillation, the said distillation residue can be added to the reaction mixture as phase (A).

Preferably, the distillation residue is used for phase (A), with phase (A) as defined above, also with all its preferred embodiments; preferably without further treatment.

This is preferably done, when the method is done in a continuous way. A continuous way is described further down below.

Preferably, the entrainer, which was separated from the mononitrated compound after the distillation, is used for phase (B), with phase (B) as defined above, also with all its preferred embodiments. For this purpose, the entrainer can e.g. be added to the removed part of phase (B), or to the reaction mixture.

Preferably, the entrainer removed during the distillation is used to attain the concentration (C) and/or to adjust the amount of the aqueous nitric acid (C) in the removed part of phase (B) for regeneration.

The concentration (C) is attained in the removed part of phase (B) by the amount of N0 ₂ and oxidizing agent.

The main reaction stoichiometries are: a) aromatic compound + ITNO ₃ -> mononitrated aromatic compound + H ₂ 0 b) H ₂ 0 + 2 NO2 -> HNO3 + HNO2

c) HNO3 + HNO2 + 1/2 O2 -> 2 HNO3 The overall reaction stoichiometry therefore is: aromatic compound + N0 ₂ + 1/4 0 ₂ -> mononitrated aromatic compound + 1/2 H ₂ 0 The stoichiometric amount of water, which inherently is generated in the reaction, can be discharged from the whole reaction system e.g. by the distillation.

By the two parameters, i.e. firstly the amount of entrainer added to the reaction mixture or added to the removed phase (B) for regeneration, and secondly the amount of N0 ₂ and oxidizing agent added to the removed phase (B) for regeneration, the concentration of nitric acid in phase (B) can be kept constant during the reaction, preferably the concentration of nitric acid in phase (B) and the amount of phase (B) are kept constant simultaneously.

When part of phase (B) is used as entrainer, the method in total produces a minimal amount of nitric acid as a waste stream.

When the entrainer is water and is added before the distillation of phase (A), the method in total can consume water and produces nitric acid as a waste stream

Therefore preferably an entrainer is present in the distillation and the entrainer is aqueous nitric acid; preferably the entrainer is part of phase (B).

Therefore further subject of the invention is said method comprising said distillation, wherein the water, which is extracted from the reaction mixture by the distillation, and which is extracted after the distillation, preferably in form of an aqueous nitric acid, and the N0 ₂ and the oxidizing agent, which are used for the regeneration of the part of phase (B) after its removal from the reaction mixture, are used to keep the concentration of nitric acid in phase (B) constant during the reaction;

preferably to keep the concentration of nitric acid in phase (B) and the amount of phase (B) constant during the reaction;

said distillation is preferably done with an entrainer, with the entrainer as described above, also with all its preferred embodiments. The method or the reaction can be done batch wise or continuously. Continuously means, that the reaction is done in a continuous way in a reactor for continuous reactions, called continuous reactor in the following. The following describes possible embodiments of a continuous reaction apparatus.

A continuous reaction apparatus has two domains: a reactor R, where the two phases are mixed, and a separator S, where the two phases are allowed to separate.

The aromatic compound and the ionic liquid as a stream R(in A), and the aqueous nitric acid as a stream R(in B) are continuously fed into reactor R; from separator S part of the two phases S(out A) and S(out B) are continuously discharged, S(out A) contains ionic liquid, unreacted aromatic compound and mononitrated aromatic compound. S(out B) contains water and nitric acid and is regenerated with N0 ₂ and oxidizing agent for use as R(in B).

The content of R is being fed into S continuously. The streams are adjusted in such a way, that a steady state condition is realized. After distillation of S(out A), the distillation residue or distillation sump is used for R(in A), the optional entrainer for R(in B).

It is possible to use more than one of such a system in a row, i.e. a cascade consisting of R ⁿ - S ^p , with n = 1 to i, with p = 1 to (i - 1), and with n = p for n = 1 to (i - 1), n being the number of a specific reactor unit in the cascade, with the last reactor in the cascade not being followed by a separator, i being the total number of units in the cascade. Steady state means, that S ^m (out A)) = R ^(m+1) (in A)), with m = 1 to (i - 1).

Through the phases S ^p (out B), preferably after having combined them, N0 ₂ and oxidizing agent is passed for regeneration of the concentration of the nitric acid, then the thus regenerated aqueous nitric acid is used for R(in B). Part of the thus regenerated aqueous nitric acid can be purified in counter current extraction with the aromatic compound, said aromatic compound is then used for feeding into R ¹ .

After the last reactor, i.e. after R ¹ , there is no separator, instead the two phases are distilled. Here a distillation column can be chosen, which provides no or provides a separation of the residual aromatic compound from the mononitro aromatic compound. The aqueous nitric acid from this distillation is treated in the same way as the phases S ^p (out B). The sump of the distillation can be used for feeding R ¹ .

In case of a continuous method, the process parameters can be adjusted in such a way, that a high conversion of aromatic compound into mononitrated aromatic compound is attained, but the amount of byproducts is kept low. In another embodiment, a continuous method can be done in such a way, that only a low, preferably from 10% to 40%, conversion rate of aromatic compound into mononitrated aromatic compound is attained, the conversion rate in % are mol % of mononitrated aromatic compound based on the total molar amount of aromatic compound used for the reaction.

Optionally in case of a continuous method, the crude product mixture comprising

mononitrated aromatic compound, aromatic compound, phase (A) and phase (B) can be fed again into the continuous reactor and be subjected again to the conditions of the reaction. Such a technique would be suitable for a continuous loop reactor set-up.

A loop reactor functions in principle in the same way as a continuous reactor set up, except for the fact, that R and S are separated by time rather than by space, i.e. the reaction mixture is fed from the separator S back into the reactor R.

A continuous method or continuous reaction has the advantage, that residence time of the product at the elevated temperature can be minimized, thereby side reactions can be further avoided or at least further minimized. The method of the present invention uses inexpensive starting materials such as aqueous nitric acid, N0 ₂ and as oxidizing agent air or 0 ₂ . No toxicologically problematic waste streams are generated, actually the only waste generated is the water, that is generated due to the overall stoichiometry of the whole reaction system, and which is therefore inherently unavoidable, and which is the only side product which needs to be discarded off. This water is obtained from the distillation in form of aqueous nitric acid and recycled into the regeneration of the removed part of phase (B), and therefore can be discharged from the reaction system e.g. in form of aqueous nitric acid of concentration (C), which represents actually not a waste, but a substance useful in chemical reactions. This discharged aqueous nitric acid can further be purified from residual ionic liquid and from product, i.e. mononitrated aromatic compound, by extraction with the substrate, i.e. with the aromatic compound.

The method uses a minimum number of substances, the anion of the ionic liquid is preferably N0 ₃ , therefore derived from nitric acid, which is the nitrating agent, and therefore no additional anion is introduced into the system in the preferred embodiment, thereby inherently reducing the amount of possible side reactions. Due to the use N0 ₂ and 0 ₂ for the regeneration of the nitric acid, also from this process step no waste stream results.

When the regenerated part of phase (B) is used as aqueous nitric acid (C), which is added to the reaction mixture during the reaction in exchange for the removed part of phase (B), any traces of ionic liquid, of aromatic compound or of mononitrated aromatic compound, which are dissolved in the removed part of phase (B) due to inherent solubilities, are fed back into the reaction mixture. Thereby the work-up is considerably simplified. Since the concentration of the nitric acid in phase (B), i.e. the concentration (CONC), is kept constant during the reaction, the turnover rate of the reaction does not slow down.

The ionic liquid (A) is not prone to nitration, thereby no undesired by products can be formed, the long term stability is provided. Since phase (A) and phase (B) show low solubilities among each other, good phase separation is observed, no cooling or dilution before the phase separation is mandatorily required. The distillation is simple, does not require multiple column plates, and the process is energetically and ecologically favorable with short overall process times. Furthermore the low cross solubilities of phase (A), phase (B) and the product, i.e. the mononitrated aromatic compound, provide a high recovery rate of the product, only up to 10% of product was observed to be discharged via phase (B). Due to the regeneration of phase (B) and its recycling back into the process, the thus discharged product is not lost, does not require a separate isolation or complex rectification, but is simply fed back into the process. No sulfuric acid is used for the nitration reaction, therefore no sulfate containing waste is generated; in case that the anion of the ionic liquid (A) is not nitrate, the respective amount of said anion different from nitrate is still considerably lower than the amount of sulfate when sulfuric acid would be used in the nitration reaction. The method provides for constant reaction parameters such as concentration of nitric acid, which can be selected to fit optimal for the targeted reaction and substrate, thereby dinitration and other side reactions are effectively controlled and reduced, without requiring special technical provisions, and thereby also high conversion rates do not increase side reactions. This results in improved selectivity of the method. Actually only mono nitration and no dinitration was observed in any of the inventive examples described below.

The method of the present invention can be performed continuously, which provides a more constant product quality than batch wise processes. A continuous method is also more convenient for the large scale production of compounds, because fewer operations and fewer operators are required, because no dangerous accumulation of starting materials occurs, and because the process is easier to control. Alternatively, the method of the present invention can be conducted batch wise.

Examples

List of Abbreviations and Raw materials

The ionic liquids were purchased, since they are commercially available, if not otherwise stated.

The amounts of aromatic and nitrated aromatic compounds were determined by NMR or by gas chromatography (GC), if not otherwise stated.

For the determination of aromatic and nitrated aromatic compounds by GC, an aqueous or organic phase was extracted with dibutyl ether, the resulting extract was neutralized and used for GC, if not otherwise stated.

For the determination of aromatic and nitrated aromatic compounds by NMR in an organic phase, the organic phase was used for the measurement as is without neutralization, if not otherwise stated.

The conversion in the examples is a molar conversion rate and is given in %, the % being based on the total molar amount of aromatic compound used for the reaction; of not stated otherwise.

The conversion rate and the ratio of isomers were detected by gas chromatography, if not stated otherwise. The ratio of isomers is given in form of the ratio of the areas of the peaks of the isomers in the GC chromatogram, with the biggest area normalized to 100%.

100% conversion means, that no substrate was detectable by GC.

The values for amount in percent or for concentration were measured by NMR in case of the amount or concentration of ionic liquid, by acid titration in case of the concentration of nitric acid and by Karl Fischer titration in case of the amount of water, if not otherwise stated. Comparative Example 1

Nitration of toluene in the presence of ionic liquid without exchange of phase B

Toluene (10.4 g, 113.3 mmol), 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%> based on substrate), and [N(n-butyl) ₄ ] ⁺ N0 ₃ (10.2 g, 30 mol-%> based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for 60 min. The concentration of nitric acid in the aqueous phase at the end of the reaction was 57.0 % (w/w). The reaction mixture was cooled to room temperature, extracted with dibutyl ether (once with 20 ml) to provide a mixture of toluene, nitrotoluene isomers and dibutylether, which was neutralized and analyzed by gas chromatography to show a conversion of 62.8 % (ratio between 2-, 3- and 4-nitrotoluene is 1 : 0.08 : 0.62). Example 1

Nitration of toluene in the presence of ionic liquid with batch wise exchange of phase B every 15 min, using 50% HNO ₃

Toluene (10.4 g, 113.3 mmol), 50 % (w/w) aqueous nitric acid (42.8 g, 300 mol-% based on substrate), and [N(n-butyl) ₄ ] ⁺ N0 ₃ (10.2 g, 30 mol-% based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 50 % (w/w) aqueous nitric acid (42.8 g, 300 mol-% based on substrate). Average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 48.1 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml) to provide a mixture of nitrotoluene isomers and dibutyl ether, the conversion was 39.1 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.09 : 0.64. Example 2

Nitration of toluene in the presence of ionic liquid with batch wise exchange of phase B every 15 min

Toluene (20.9 g, 226.6 mmol), 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-%> based on substrate), and [N(n-butyl) ₄ ] ⁺ NO ₃ (20.4 g, 30 mol-%> based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-%>). Average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 56.9 % (w/w). A total of 11.9 mol-% of aromatics, the % based on the molar amount of toluene at the beginning, were stripped out by the exchanges of the aqueous phases. The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase and which represents phase (A), was extracted with dibutyl ether (once with 20 ml) to provide a mixture of nitrotoluene isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.07 : 0.67.

Example 3

Nitration of toluene in the presence of ionic liquid with batch wise exchange of phase B every 10 min

Toluene (10.44 g, 113.3 mmol), 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%> based on substrate), and [N(n-butyl) ₄ ] ⁺ N0 ₃ (10.2 g, 30 mol-%> based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 10, 20, 30, 40 and 50 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%>). Average residence time of aqueous nitric acid (B) therefore was 10 min.

The concentration of aqueous nitric acid in these five lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 56.9 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml) to provide a mixture of nitrotoluene isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.06 : 0.56.

Example 4

Nitration of toluene in the presence of ionic liquid with batch wise exchange of phase B every 5 min

Toluene (10.44 g, 113.3 mmol), 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-% based on substrate), and [N(n-butyl) ₄ ] ⁺ N0 ₃ (10.2 g, 30 mol-% based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 55 min. After 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%). Average residence time of aqueous nitric acid (B) therefore was 5 min.

The concentration of aqueous nitric acid in these ten lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 56.7 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml) to provide a mixture of nitrotoluene isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.07 : 0.56.

Example 5 to 8

Examples 5 to 8 were done according to example 2 with the following differences:

1. only half of the batch size of example 2 was used (i.e. toluene (10.4 g, 113.3 mmol); 65 %

(w/w) aqueous nitric acid (33.4 g, 300 mol-% based on substrate); ionic liquid (30 mol-%> based on substrate); 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%>) for exchange); and

2. the type of ionic liquid (A) was changed according to Table 1.

Table 1 gives further details. In each example the reaction mixture was a liquid-liquid biphasic mixture as it was in example 2.

The minimal concentration of aqueous nitric acid in % (w/w) in the various lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), is given in column (3).

Column (1) gives the total amount of aromatics stripped out with aqueous phases

Column (2) gives the ratio of 2- : 3- : 4-nitrotoluene

"Ex" means "Example", "conv" means "conversion", "PATE" means "prepared according to example" Table 1

Ex Ionic liquid (A) conv (3) (2) (1)

5 100 % 55.9 % 1 : 0.09 : 0.68 10.1 %

[N(CH ₃ ) ₂ (n-decyl) ₂ ] ⁺ N0 ₃ ^~

PATE 5a

6 4 %

[N(n-butyl) ₃ ((CH ₂ ) ₄ S0 ₃ H)] ⁺ N0 ₃ ^" 100 % 57. 1 : 0.12 : 0.69 n.a. PATE 6a

7 100 % 58.8 % 1 : 0.08 : 0.80 n.a.

[N(n-butyl) ₄ ] ⁺ (OTff

PATE 7a

8 100 % 59.6 % 1 : 0.09 : 0.75 n.a.

[N(CH ₃ )(n-octyl) ₃ ] ⁺ (OTff

PATE 8a

9 [N(n-hexyl) ₄ ] ⁺ N0 ₃ 100 % 57.2 % 1 : 0.08 : 0.61 7.4 %

PATE 9a

10 [N(n-octyl) ₄ ] ⁺ N0 ₃ 100 % 59.8 % 1 : 0.10 : 0.68 4.7 %

PATE 10a

11

[N(n-octyl) ₃ ((CH ₂ ) ₄ S0 ₃ H)] ⁺ N0 ₃ ^" 100 % 57.3 % 1 : 0.07 : 0.62 10.6 % PATE 11a

12 [P(n-octyl) ₄ ] ⁺ N0 ₃ 99.8 % 57.9 % 1 : 0.10 : 0.65 8.2 %

PATE 12a

Example 5a

Preparation of N-decyl-N,N-dimethyldecan-l-ammonium nitrate

To commercially available N-decyl-N,N-dimethyldecan-l -ammonium carbonate/hydrogen carbonate (10.0 g), 65 % (w/w) aqueous HN0 ₃ was added until pH was between 6.0 and 7.0. A biphasic system was obtained. The organic phase was washed with distilled (once with 20 ml) water to yield N-decyl-N,N-dimethyldecan-l -ammonium nitrate.

Example 6a

Preparation of N,N,N-tributyl-4-sulfobutane-l-ammonium nitrate

Tri-n-butyl amine (10.0 g, 54.0 mmol) and 1,4-butane sultone (5.5 mL, 100 mol-%) were mixed. The mixture was heated to 160 °C, refluxed at 160 °C for 3 days and cooled to room temperature. 65 % (w/w) aqueous HN0 ₃ (5.2 g, 100 mol-%) was added. Extraction with dichloromethane (once with 20 ml) and evaporation of dichloromethane yields Ν,Ν,Ν- tributyl-4-sulfobutane- 1 -ammonium nitrate.

Example 7a

Preparation of tetra-n-butyl ammonium trifluoromethane sulfonate

Tetra-n-butyl ammonium bromide (10.0 g, 31.0 mmol) was dissolved in 100 ml water, and lithium trifluoromethane sulfonate (5.3 g, 110 mol-%) was dissolved in 20 ml water. Both solutions were mixed at room temperature, stirred for 30 min at room temperature and extracted with dichloromethane (once with 20 ml) to yield tetra-n-butyl ammonium

trifluoromethane sulfonate upon evaporation of dichloromethane.

Example 8a

Preparation of N-methyl-N,N-dioctyloctan-l-ammonium trifluoromethane sulfonate

Tri-n-octyl amine (10.0 g, 28.3 mmol) was dissolved in dichloromethane and cooled to 0 °C. Methyl trifluoromethane sulfonate (5.6 g, 120 mol-%) was added dropwise at 0 °C. The mixture was then heated to 50 °C and refluxed at 50 °C for 24 h. Evaporation of

dichloromethane and of unreacted methyl trifluoromethane sulfonate yields N-methyl-N,N- dioctyloctan-1 -ammonium trifluoromethane sulfonate. Example 9a

Preparation of tetra-n-hexyl ammonium nitrate

Commercially available tetra-n-hexyl ammonium bromide (12.8 g, 29.5 mmol) was dissolved in 100 ml dichloromethane. Silver nitrate (5.0 g, 29.4 mmol), dissolved in 100 ml water was added. After stirring for 30 min at room temperature, the mixture was filtered and the two liquid phases separated. Evaporation of dichloromethane from the organic phase yielded tetra- n-hexyl ammonium nitrate.

Example 10a

Preparation of tetra-n-octyl ammonium nitrate

Commercially available tetra-n-octyl ammonium bromide (10.0 g, 18.2 mmol) was dissolved in 100 ml dichloromethane. Silver nitrate (3.1 g, 18.2 mmol), dissolved in 100 ml water was added. After stirring for 30 min at room temperature, the mixture was filtered and the two liquid phases separated. Evaporation of dichloromethane from the organic phase yielded tetra- n-octyl ammonium nitrate. Example 11a

Preparation of N,N-dioctyl-N-(4-sulfobutyl)octan-l-ammonium nitrate

Tri-n-octyl amine (19.1 g, 54.0 mmol) and 1,4-butane sultone (5.5 mL, 100 mol-%) were mixed. The mixture was heated to 170 °C, refluxed at 170 °C for 5 days and cooled to room temperature. 65 % (w/w) aqueous HN0 ₃ (5.2 g, 100 mol-%) was added. Extraction with dichloromethane (once with 20 ml) and evaporation of dichloromethane yields N,N-dioctyl- N-(4-sulfobutyl)octan- 1 -ammonium nitrate . Example 12a

Preparation of tetra-n-octyl phosphonium nitrate

Commercially available tetra-n-octyl phosphonium bromide (25.8 g, 45.8 mmol) was dissolved in 100 ml dichloromethane. Silver nitrate (7.8 g, 45.9 mmol), dissolved in 100 ml water was added. After stirring for 30 min at room temperature, the mixture was filtered and the two liquid phases separated. Evaporation of dichloromethane from the organic phase yielded tetra-n-octyl phosphonium nitrate.

Comparative Example 2

Nitration of toluene in the absence of ionic liquid with batch wise exchange of aqueous phase every 15 min

Toluene (10.4 g, 133.3 mmol) and 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%>) were mixed. A liquid- liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%>), average residence time of aqueous nitric acid (B) therefore was 15 min. A total of 45.1 mol-% of aromatics, the % based on the molar amount of toluene at the beginning, were stripped out by the exchanges of the aqueous phases.

The concentration of aqueous nitric acid in the various lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 58.1 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml), to provide a mixture of nitrotoluene isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.09 : 0.65.

Example 13

Regeneration of spent aqueous nitric acid phase B by discharging gaseous N0 ₂ and air

N0 ₂ and air was passed through 100 g of spent aqueous phase B, said spent aqueous phase B was a collection of exchanged aqueous nitric acid phase from repetitions of example 2, which was the so called lower phase as described in example 2. While collecting said spent aqueous phases B, small amounts of water were used to wash the spent aqueous phases B from the apparatus, which caused the concentration of nitric acid in the such collected spent aqueous phase B at the beginning to be lowered to 48.4 % by weight of nitric acid.

The two gases were passed through the spent phase B in alternation with 6 liter gas per minute, each for 15 min and starting with N0 ₂ ; while the spent phase B was stirred at room temperature. Nitric acid concentration is measured by titration and reached 65 % by weight of nitric acid after a total time of 90 min.

Example 14

Example 2 was repeated with the following differences:

1. only half of the batch size of example 2 was used (i.e. toluene (10.4 g, 113.3 mmol); 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-% based on substrate); ionic liquid (30 mol-% based on substrate); and

2. the regenerated aqueous nitric acid (33.4 g, 300 mol-%) produced according to example 7 was used for exchange of the aqueous phase, and not fresh aqueous nitric acid as was used example 2. The reaction mixture is a liquid-liquid biphasic mixture as in example 2.

Conversion was found to be 100 % (ratio between 2-, 3- and 4-isomer is 1 : 0.07 : 0.65).

Example 15

Entrainer distillation of phase A after reaction

Phase (A) was prepared according to example 2, where, after the reaction mixture was cooled to room temperature and before any extraction with dibutyl ether, the two phases of the reaction mixture were separated. The upper phase was phase (A). To this phase (A), 40 mL water were added. The mixture was distilled at 130 °C and ambient pressure using a Dean- Stark-apparatus, which allowed recycling of the water during the distillation, which acted as entrainer. The distillation in a Dean-Stark-apparatus represents a distillation with only one column plate.

After the distillation, the sump (i.e. the distillation residue) contained 50.3 % ionic liquid, 42.2 % nitric acid and 7.5 % water, the % being weight percent and are based on the total weight of the sump.

The distillate was biphasic. The lower phase was the organic phase, 99.2 % of the organic phase was a mixture of nitrotoluene isomers. The upper phase was the aqueous phase and contained 11.0 % (w/w) aqueous nitric acid, both % values are weight percent and are based on the total weight of the respective phase.

Example 16

Nitration of chlorobenzene in the presence of ionic liquid with batch wise exchange of phase B every 15 min

Chlorobenzene (13.3 g, 118.3 mmol), 65 % (w/w) aqueous nitric acid (36.2 g, 316 mol-% based on substrate) and [N(n-butyl) ₄ ] ⁺ OTf (13.9 g, 30 mol-% based on substrate) were mixed. A liquid- liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 120 min. After 15, 30, 45, 60, 75, 90 and 105 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (36.2 g, 316 mol-% based on substrate), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these various lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 62.5 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml), to provide a mixture of chlorobenzene, chloro nitrobenzene isomers and dibutyl ether, the conversion was 97.9 % and the ratio between l-chloro-2-nitrobenzene : l-chloro-3- nitrobenzene : l-chloro-4-nitrobenzene was 1 : 0.02 : 2.53.

Example 17

Nitration of m-xylene in the presence of ionic liquid with batch wise exchange of phase B every 15 min m-Xylene (12.0 g, 113.4 mmol), 65 % (w/w) aqueous nitric acid (36.2 g, 320 mol-% based on substrate) and [N(n-butyl) ₄ ] ⁺ OTf (13.3 g, 30 mol-% based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (36.2 g, 320 mol-% based on substrate), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these various lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 58.8 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml), to provide a mixture of nitro xylene isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-nitro-m-xylene : 4-nitro-m-xylene : 5-nitro-m-xylene was 1 : 6.41 : 0.07 This mixture contains 2% of unidentified byproducts.

Example 18

Nitration of naphthalene in the presence of ionic liquid with batch wise exchange of phase B every 15 min

Naphthalene (14.5 g, 113.4 mmol), 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%> based on substrate) and [N(n-butyl) ₄ ] ⁺ N0 ₃ (10.2 g, 30 mol-%> based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-% based on substrate), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these various lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 51.5 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, a sample of the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 2 ml), to provide a mixture of nitro naphthalene isomers and dibutyl ether, the conversion was 100 % and the ratio between 1-nitro-naphthalene : 2-nitro-naphthalene was 1 : 0.02. This mixture contains 4.7% 1,5-dinitro-naphthalene. Entrainer distillation of the organic phase according to example 11 at 140 °C gave a mixture of nitro naphthalene isomers in the lower phase of the distillate.

Example 19

Nitration of biphenyl in the presence of ionic liquid with batch wise exchange of phase B every 15 min

Biphenyl (17.5 g, 113.4 mmol), 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-% based on substrate) and [N(n-butyl) ₄ ] ⁺ N0 ₃ (10.2 g, 30 mol-% based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-%> based on substrate), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these various lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 55.8% (w/w).

The reaction mixture was cooled to room temperature. After phase separation, a sample of the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 2 ml), to provide a mixture of nitro biphenyl isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-nitro-biphenyl : 4-nitro-biphenyl was 1 : 1.19. This mixture contains 6.6% dinitro-biphenyl.

Example 20

Nitration of diphenyl ether in the presence of ionic liquid with batch wise exchange of phase B every 15 min

Diphenyl ether (19.3 g, 113.4 mmol), 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-% based on substrate) and [N(n-butyl) ₄ ] ⁺ N0 ₃ (10.2 g, 30 mol-% based on substrate) were mixed. A liquid- liquid biphasic mixture was obtained. The mixture was heated to 100 °C and stirred at 100 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (33.4 g, 300 mol-% based on substrate), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these various lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 59.9 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, a sample of the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 2 ml), to provide a mixture of nitrophenyl phenyl ether isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-nitrophenyl phenyl ether : 4-nitrophenyl phenyl ether was 1 : 3.3. Entrainer destination of the organic phase according to example 11 at 140 °C gave a mixture of nitro phenyl phenyl ether isomers in the lower phase of the distillate.

Example 21

Nitration of toluene in the presence of 20 mol-% ionic liquid with batch wise exchange of phase B every 15 min

Toluene (10.4 g, 113.3 mmol), 65 % (w/w) aqueous nitric acid (36.2 g, 330 mol-% based on substrate), and [N(n-butyl) ₄ ] ⁺ (OTf) (8.9 g, 20 mol-%> based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (36.2 g, 330 mol-%>), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 58.1 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml) to provide a mixture of nitrotoluene isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.11 : 0.81. Example 22

Nitration of toluene in the presence of 10 mol-% ionic liquid with batch wise exchange of phase B every 15 min

Toluene (10.4 g, 113.3 mmol), 65 % (w/w) aqueous nitric acid (36.2 g, 330 mol-% based on substrate), and [N(n-butyl) ₄ ] ⁺ (OTf) (4.4 g, 10 mol-% based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (36.2 g, 330 mol-%>), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 57.1 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml) to provide a mixture of nitrotoluene isomers and dibutyl ether, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.11 : 0.80. Example 23

Nitration of toluene in the presence of a once recycled ionic liquid with batch wise exchange of phase B every 15 min

To create a once recycled ionic liquid, phase (A) was prepared according to example 2 and distilled according to example 9. After the distillation, the sump (i.e. the distillation residue) contained 75.4 % ionic liquid, 18.3 % nitric acid and 6.1 % water, the % being weight percent and are based on the total weight of the sump.

Toluene (20.9 g, 226.6 mmol), 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-% based on substrate), and [N(n-butyl) ₄ ] ⁺ N0 ₃ (24.9 g of said sump containing 18.8 g recycled ionic liquid, 1.6 g of fresh ionic liquid, altogether 30 mol-%) were mixed.

A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-%), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 57.3 % (w/w).

A total of 14.6 mol-% of aromatics, the % based on the molar amount of toluene at the beginning, were stripped out by the exchanges of the aqueous phases. The reaction mixture was cooled to room temperature. After phase separation, 40 mL of water were added to the organic phase, which was the upper phase. The mixture was distilled at 130 °C and ambient pressure using a Dean-Stark-apparatus, which allowed recycling of the water during the distillation, which acted as entrainer. The distillation in a Dean-Stark-apparatus represents a distillation with only one column plate.

After the distillation, the sump (i.e. the distillation residue) contained 68.4 % ionic liquid, 24.9 % nitric acid and 6.7 % water, the % being weight percent and are based on the total weight of the sump.

The distillate was biphasic. The lower phase was the organic phase, which was a mixture of nitrotoluene isomers, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.07 : 0.67.. The upper phase was the aqueous phase. Example 24

Nitration of toluene in the presence of a twice recycled ionic liquid with batch wise exchange of phase B every 15 min

Toluene (20.9 g, 226.6 mmol), 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-%> based on substrate), and [N(n-butyl) ₄ ] ⁺ N0 ₃ (21.3 g of sump (i.e. the distillation residue) prepared according to example 14 containing 14.6 g recycled ionic liquid, 3.3 g of fresh ionic liquid, altogether 26 mol-%) were mixed.

A liquid- liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-%>), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 51.8 % (w/w). A total of 24.8 mol-% of aromatics, the % based on the molar amount of toluene at the beginning, were stripped out by the exchanges of the aqueous phases. The reaction mixture was cooled to room temperature. After phase separation, to the organic phase, which was the upper phase, 40 mL of water were added. The mixture was distilled at 130 °C and ambient pressure using a Dean-Stark-apparatus, which allowed recycling of the water during the distillation, which acted as entrainer. The distillation in a Dean-Stark-apparatus represents a distillation with only one column plate.

After the distillation, the sump (i.e. the distillation residue) contained 69.6 % ionic liquid, 23.9 % nitric acid and 6.5 % water, the % being weight percent and are based on the total weight of the sump.

The distillate was biphasic. The lower phase was the organic phase, which was a mixture of nitrotoluene isomers, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.08 : 0.67. The upper phase was the aqueous phase. Example 25

Nitration of toluene in the presence of a three times recycled ionic liquid with batch wise exchange of phase B every 15 min

Toluene (20.9 g, 226.6 mmol), 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-% based on substrate), and [N(n-butyl) ₄ ] ⁺ N0 ₃ (16.7 g of sump (i.e. the distillation residue) prepared according to example 15 containing 11.7 g recycled ionic liquid, 8.7 g of fresh ionic liquid, altogether 30 mol-%) were mixed.

A liquid- liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-%>), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 58.6 % (w/w).

A total of 12.4 mol-% of aromatics, the % based on the molar amount of toluene at the beginning, were stripped out by the exchanges of the aqueous phases. The reaction mixture was cooled to room temperature. After phase separation, to the organic phase, which was the upper phase, 40 mL of water were added. The mixture was distilled at 130 °C and ambient pressure using a Dean-Stark-apparatus, which allowed recycling of the water during the distillation, which acted as entrainer. The distillation in a Dean-Stark-apparatus represents a distillation with only one column plate.

After the distillation, the sump (i.e. the distillation residue) contained 62.8 % ionic liquid, 31.1 % nitric acid and 6.0 % water, the % being weight percent and are based on the total weight of the sump.

The distillate was biphasic. The lower phase was the organic phase, which was a mixture of nitrotoluene isomers, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.07 : 0.63. The upper phase was the aqueous phase. Example 26

Nitration of toluene in the presence of a four times recycled ionic liquid with batch wise exchange of phase B every 15 min

Toluene (20.9 g, 226.6 mmol), 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-% based on substrate), and [N(n-butyl) ₄ ] ⁺ N0 ₃ (28.9 g of sump (i.e. the distillation residue) prepared according to example 16 containing 18.2 g recycled ionic liquid, no fresh ionic liquid, altogether 26 mol-%) were mixed.

A liquid- liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 65 % (w/w) aqueous nitric acid (66.7 g, 300 mol-%>), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 56.9 % (w/w).

A total of 15.2 mol-% of aromatics, the % based on the molar amount of toluene at the beginning, were stripped out by the exchanges of the aqueous phases. The reaction mixture was cooled to room temperature. After phase separation, to the organic phase, which was the upper phase, 40 mL of water were added. The mixture was distilled at 130 °C and ambient pressure using a Dean-Stark-apparatus, which allowed recycling of the water during the distillation, which acted as entrainer. The distillation in a Dean-Stark-apparatus represents a distillation with only one column plate.

After the distillation, the sump (i.e. the distillation residue) contained 65.1 % ionic liquid, 28.7 % nitric acid and 6.1 % water, the % being weight percent and are based on the total weight of the sump. The distillate was biphasic. The lower phase was the organic phase, which was a mixture of nitrotoluene isomers, the conversion was 100 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.08 : 0.68. The upper phase was the aqueous phase. Example 27

Nitration of toluene in the presence of ionic liquid with batch wise exchange of phase B every 15 min, using 60% HNO ₃

Toluene (10.4 g, 113.3 mmol), 60 % (w/w) aqueous nitric acid (35.7 g, 300 mol-% based on substrate), and [N(n-butyl) ₄ ] ⁺ NO ₃ (10.2 g, 30 mol-% based on substrate) were mixed. A liquid-liquid biphasic mixture was obtained. The mixture was heated to 110 °C and stirred at 110 °C for a total reaction time of 60 min. After 15, 30 and 45 min of stirring, the stirring was stopped and the aqueous phase, which was the lower phase, was exchanged with 60 % (w/w) aqueous nitric acid (35.7 g, 300 mol-% based on substrate), average residence time of aqueous nitric acid (B) therefore was 15 min.

The concentration of aqueous nitric acid in these three lower phases, which were removed and exchanged during the reaction, and which represent the above mentioned exchanged part of phase (B), was at least 57.6 % (w/w).

The reaction mixture was cooled to room temperature. After phase separation, the organic phase, which was the upper phase, was extracted with dibutyl ether (once with 20 ml) to provide a mixture of nitrotoluene isomers and dibutyl ether, the conversion was 99.0 % and the ratio between 2-, 3- and 4-isomer was 1 : 0.09 : 0.66.