Novel Synthesis for Nitrile Solvents

This application claims priority filed on November 10, 2022 in Europe with Nr 22206518.7.

TECHNICAL FIELD

The present invention relates to a novel synthesis for cyclohexane carbonitrile solvents and their use as polar solvents in a hydrogen peroxide production process using alkylanthraquinones and/or their tetrahydro form.

TECHNICAL BACKGROUND

Hydrogen peroxide is one of the most important inorganic chemicals to be produced worldwide. Its industrial applications include textile, pulp and paper bleaching, organic synthesis (propylene oxide), the manufacture of inorganic chemicals and detergents, environmental and other applications.

Synthesis of hydrogen peroxide is predominantly achieved by using the Riedl-Pfleiderer process (originally disclosed in U.S. Pat. Nos. 2,158,525 and 2,215,883), also called anthraquinone loop process or AO (auto-oxidation) process.

This well-known cyclic process makes use typically of the auto-oxidation of at least one alkylanthrahydroquinone and/or of at least one tetrahydroalkylanthrahydroquinone, most often 2-alkylanthrahydroquinone, to the corresponding alkylanthraquinone and/or tetrahydroalkylanthraquinone, which results in the production of hydrogen peroxide.

The first step of the AO process is the reduction in an organic solvent (generally a mixture of solvents) of the chosen quinone (alkylanthraquinone or tetrahydroalkylanthraquinone) into the corresponding hydroquinone (alkylanthrahydroquinone or tetrahydroalkylanthrahydroquinone) using hydrogen gas from any source and a catalyst. The mixture of organic solvents, hydroquinone and quinone species (working solution, WS) is then separated from the catalyst and the hydroquinone is oxidized using oxygen, air or a mixture of oxygen with other gases thus regenerating the quinone with simultaneous formation of hydrogen peroxide. The organic solvent of choice is typically a mixture of two types of solvents, one being a good solvent of the quinone derivative (generally a non-polar solvent for instance a mixture of aromatic compounds) and the other being a good solvent of the hydroquinone derivative (generally a polar solvent for instance a long chain alcohol or an ester or a tetraalkylurea or a trialkylphosphate). Hydrogen peroxide is then typically extracted with water and recovered in the form of a crude aqueous hydrogen peroxide solution, and the working solution with quinone species is returned to the hydrogenator to complete the loop.

The use of for example di-isobutylcarbinol (DBC) as polar solvent is namely described in Patent applications EP 529723, EP 965562 and EP 3052439 in the name of the Applicant. The use of a commercial mixture of aromatics sold under the brand Solvesso®-150 (CAS no. 64742-94-5) as non-polar solvent is also described in said patent applications. This mixture of aromatics is also known as Caromax, Shellsol, Al 50, Hydrosol, Indusol, Solvantar, Solvarex and others, depending on the supplier. It can advantageously be used in combination with sextate (methyl cyclohexyl acetate) as polar solvent (see namely US Patent 3617219).

Most of the AO processes use either 2-amylanthraquinone (AQ), 2- butylanthraquinone (BQ) or 2-ethylanthraquinone (EQ). Especially in the case of EQ, the productivity of the working solution is limited by the lack of solubility of the reduced form of ETQ (ETQH). It is namely so that EQ is largely and relatively quickly transformed in ETQ (the corresponding tetrahydroalkylanthraquinone) in the process. Practically, that ETQ is hydrogenated in ETQH to provide H2O2 after oxidation. The quantity of EQH produced is marginal in regards of ETQH. It means that the productivity of the process is directly proportional to the amount of ETQH produced. The reasoning is the same for a process working with AQ or BQ instead of EQ.

The hydrogenated quinone solubility issue is known from prior art and some attempts were made to solve it. Namely co-pending PCT application EP 2019/056761 of the Applicant, discloses the use of non-aromatic cyclic nitrile type solvents as polar solvent in the mixture, more specifically the use of cyclohexane carbonitriles, and especially substituted ones (in which the nitrile function is protected from chemical degradation).

Although some molecules of this kind are known, their market availability is currently only very limited and anyway too small to satisfy the needs of an industrial AO process. Besides, they are often synthesized starting from expensive and/or non-environmentally friendly raw materials. In WO 2021/048368 the Applicant of the present invention refers to the use of a novel polar organic nitrile solvent - 5-methyl-2-isopropyl-cyclohexane carbonitrile (Cl IF) - in AO processes and three possible production methods thereof. In these production methods 5-methyl-2-isopropyl-cyclohexane carbonitrile (Cl IF) is obtained by mesylation or tosylation of menthol followed by cyanation, or chlorination of menthol followed by cyanation, or esterification of menthol followed by cyanation.

However, the cyanation of the intermediates produced by mesylation, tosylation, chlorination or esterification of menthol has several disadvantages: the reaction (1) is a high consuming energy reaction due to the high temperature of reaction; (2) requires high excess of cyanide that complicates their separation from effluent at an acceptable cost to avoid impact on environment; (3) produces besides the Cl IF 20-30% of alkenes obtained by elimination of leaving group (e.g. mesylate, tosylate etc.), which are difficult to separate from Cl IF due their close boiling points; (4) requires anhydrous conditions to avoid loss of yield by hydrolysis of above intermediates, and further (5) the total yield of the produced solvent is sometimes too low to be interesting for industrial processes.

In Organic Synthesis, A Publication of Reliable Methods for the Preparation of Organic Compounds, Coll. Vol. 9, page 281 (1998); Vol. 74, page 217 (1997) a method is described by Reid et al., which provides another nitrile solvent - 3,3,5-trimethyl-cyclohexane carbonitrile (C10C). However, in this method the mesitylenesulfonylhydrazine is prepared by two successive steps, which are energy intensive due to the wide range of operating temperature, and which require a control and, if necessary, a regulation of the operating temperature to ensure a safe control of heat release and to minimize loss of yield of the desired intermediate produced in the first step. Moreover, in the first step an excess of chlorosulfonic acid is used, which is not recyclable due to its losses by hydrolysis. In the third step, the acid catalysed reaction between mesitylenesulfonylhydrazine, 3,3,5-trimethyl-cyclohexanone and potassium cyanide will generate besides C10C potassium mesitylenesulfmate that is not recycled. Hence, also this production method has several disadvantages.

In the scientific publication of Barbier (Helvetica Chimica Acta, 1940, vol. 23, p. 519-521) another production method for 3,3,5-trimethyl-cyclohexane carbonitrile (C10C) is described. This method requires 5 steps each of which required at least one purification by distillation, and thus also this method is also complex and energy intensive. Among these steps, someone generates high amount of effluents. Hence, also this method is less interesting for industrial processes.

Another problem of AO-processes known in the prior art is the formation of the undesired epoxide 2-ethyl-5,6,7,8-tetrahydro-8a,10a-epoxy-9,10- anthraquinone (ETEQ) during the oxidation of ETQH to obtain hydrogen peroxide. ETEQ does not participate significantly in the formation of hydrogen peroxide and reduces the amount of active ETQ, and thus the yield of hydrogen peroxide. The reasoning is the same for a process working with ATQ or BTQ instead of ETQ.

Consequently, there was still the need to provide polar solvents, in particular nitrile solvents, and production methods thereof, which overcome the disadvantages of the prior art, and through their use the productivity of the AO process can be improved. In particular, the aim was to provide a polar solvent, by which the hydrogenated quinone of the working solution shows an improved solubility in comparison to polar solvents usually used in AO processes, which facilitates the extraction of the produced hydrogen peroxide from the organic phase to the aqueous phase, and/or which minimizes the formation rate of the epoxide 2-ethyl-5,6,7,8-tetrahydro-8a,10a-epoxy-9,10-anthraquinone (ETEQ), in order to produce a hydrogen peroxide solution in sufficient quantity and which has an improved purity level, e.g. having a low total organic carbon (TOC) content.

SUMMARY OF THE INVENTION

The present invention relates to a method for the preparation of cyclohexane carbonitrile solvents, in particular for the preparation of 5-methyl-2- isopropyl-cyclohexane carbonitrile (Cl IF) and 3,3,5-trimethyl-cyclohexane carbonitrile (C10C), comprising the following steps:

(a) condensation of an alkyl- or arylcarbazate with a cyclohexanone having the formula (I) wherein Ri is isopropyl and R2 and R3 are hydrogens, or Ri is a hydrogen and R2 and R3 are methyl, to generate a first intermediate of formula (II) or (Ila) followed by cyanation of the first intermediate (II) or (Ila) to obtain a second intermediate of formula (III) or (Illa) b) oxidation of second intermediate (III) or (Illa) with the aid of an oxidant to generate a third intermediate of formula (IV) or (IVa) followed by decomposition of the third intermediate (IV) or (IVa) performed with the aid of a base to obtain 5-methyl-2-isopropyl-cyclohexane- carbonitrile (Cl IF) having the formula (V)

(V), or to obtain 3,3,5-trimethyl-cyclohexane carbonitrile (C10C) having the formula (Va) wherein in all intermediates R is an alkyl or aryl residue.

Furthermore, the present invention relates to the cyclohexane carbonitrile solvents 5-methyl-2-isopropyl-cyclohexane carbonitrile (Cl IF) and 3,3,5- trimethyl-cyclohexane carbonitrile (C10C), preferably produced by the method according to the invention, and their use as polar solvents or a combination thereof in a process for the production of hydrogen peroxide using alkylanthraquinones and/or tetrahydroalkyl-anthraquinones (AO process), wherein Cl IF is obtained by the method of the invention and C IOC is obtained by the method of the invention or any suitable production method thereof.

The AO process of the invention comprises the following steps:

- hydrogenating a working solution, which comprises an alkylanthraquinone and/or a tetrahydroalkylantraquinone and a mixture of a non-polar organic solvent and a polar solvent, which is Cl IF, C10C, or a combination, wherein Cl IF is obtained by the method of the invention and C IOC is obtained by the method of the invention or any suitable production method thereof,

- oxidizing the hydrogenated working solution to produce hydrogen peroxide, and

- isolating the hydrogen peroxide.

DETAILED DESCRIPTION OF THE INVENTION Before the process of the invention and the use of the polar solvents, which are obtained by the process of the invention, in an AO process will be described in detail, it is to be understood that this invention is not limited to specific process conditions described herein, since such conditions may, of course, vary.

It is also to be understood that the terminology used herein is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

As used herein, the singular forms "a", "an", and "the" include both singular and plural referents unless the context clearly dictates otherwise. By way of example, "a compound" means one compound or more than one compound.

The terms "containing", "contains" and "contained of' as used herein are synonymous with "including", "includes" or " comprising", "comprises", and are inclusive or open-ended and do not exclude additional, non-recited members, elements or process steps. It will be appreciated that the terms “containing”, “contains”, "comprising", "comprises" and "comprised of' as used herein comprise the terms "consisting of', "consists" and "consists of'.

Throughout this application, the term "about" is used to indicate that a value includes the standard deviation of error for the device or method being employed to determine the value.

As used herein, the term “average” refers to number average unless indicated otherwise.

As used herein, the terms “% by weight”, “wt.- %”, “weight percentage”, or “percentage by weight” are used interchangeably. The same applies to the terms “% by volume”, “vol.- %”, “vol. percentage”, or “percentage by volume”, or “% by mol”, “mol- %”, “mol percentage”, or “percentage by mol”.

The recitation of numerical ranges by endpoints includes all integer numbers and, where appropriate, fractions subsumed within that range (e.g. 1 to 5 can include 1, 2, 3, 4 when referring to, for example, a number of elements, and can also include 1.5, 2, 2.75 and 3.80, when referring to, for example, measurements). The recitation of end points also includes the end point values themselves (e.g. from 1.0 to 5.0 includes both 1.0 and 5.0). Any numerical range recited herein is intended to include all sub-ranges subsumed therein. Should the disclosure of any patents, patent applications, and publications conflict with the description of the present application to the extent that it may render a term unclear, the present description shall take precedence.

Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.

In the following passages, different alternatives, embodiments and variants of the invention are defined in more detail. Each alternative and embodiment so defined may be combined with any other alternative and embodiment, and this for each variant unless clearly indicated to the contrary or clearly incompatible when the value range of a same parameter is disjoined. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

Furthermore, the particular features, structures or characteristics described in present description may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and from different embodiments, as would be understood by those in the art.

5-methyl-2-isopropyl-cyclohexane carbonitrile (Cl IF) and 3,3,5-trimethyl- cyclohexane carbonitrile (C10C) are polar solvents, which are interesting for using them in an AO process. In order to provide a production process for these cyclohexane carbonitrile solvents suitable for industrial applications, the method according to the invention comprises two main method steps, wherein in the first method step

(a) a condensation of an alkyl- or arylcarbazate with a cyclohexanone having the formula (I) as defined above is carried out to generate a first intermediate of formula (II) or (Ila), followed by cyanation of the first intermediate (II) or (Ila) to obtain a second intermediate of formula (III) or (Illa), wherein R of all intermediates is an alkyl or aryl residue, (Step 1):

(Ha), and in the second method step (Step 2)

(b) an oxidation of the second intermediate (III) or (Illa) with the aid of an oxidant is carried out to generate a third intermediate of formula (IV) or (IVa), wherein R is also an alkyl or aryl residue, followed by decomposition of the third intermediate (IV) or (IVa) performed with the aid of a base to obtain Cl IF (see formula (V)) or C10C (see formula (Va)) (Step 2):

(Illa), (IVa) (Va) The method of the invention overcomes the disadvantages of the prior art methods as discussed above, i.e. the method of the invention is less energy intensive, less complex and thus less expensive than the known processes. Furthermore, the method of the invention is more environmentally friendly, and the yields and purity levels of Cl IF and C10C, produced according to the method of the invention, are in the desired ranges or even improved.

In a preferred embodiment of the invention, the two main method steps (a) and (b) are carried out in different reactors. Preferably, the two sub-reactions of the first method step (a) are carried out in one reactor without isolating the first intermediate of formula (II)/(IIa) before cyanation. After cyanation of the first intermediate of formula (II)/(IIa), it is possible to purify the second intermediate (III)/(IIIa).

According to the invention, before the second method step (b) is carried out the reaction mixture including the second intermediate (III/IIIa) is washed as described below to remove interfering impurities. Afterwards, the second intermediate (III)/(IIIa) is introduced into a second reactor, wherein the second method step (b) is carried out to obtain Cl IF or C 10C without isolating the third intermediate of formula (IV)/(IVa). Afterwards, the produced Cl IF or C 10C may be further purified.

Furthermore, it is preferred that the cyclohexanone of formula (I), wherein Ri is hydrogen and R2 and R3 are methyl, and which is used for producing C10C, is obtained in a pre-reaction, carried out before the two main method steps of the invention, by hydrogenation of isophorone in the presence of a catalyst. The catalyst used in this pre-reaction can be any hydrogenation catalyst as known in the prior art. However, it is preferred that the catalyst is a heterogeneous catalyst comprising at least one element. Preferably, the catalyst comprises at least one element selected from the group consisting of elements of families 8, 9, 10, 11 and 12 of the IUPAC Periodic Table of The Elements. More preferably, the at least one element is selected from the group consisting of nickel, palladium, platinum, ruthenium and rhodium; even more preferred the at least one element is Pd. The at least one element of catalyst can be supported or not on at least one carrier. Examples of non-supported catalyst are metal blacks like for example platinum black and palladium black, oxide catalysts as for example palladium oxide, platinum oxide, and ruthenium oxide and skeletal metals, like Raney® metals as Nickel Raney®. The carrier is usually selected from the group consisting of inorganic materials, organic materials and any combination thereof. Suitable inorganic materials are preferably selected form the group consisting of inorganic oxides, inorganic sulfates, inorganic hydrogenosulfates, inorganic carbonates, inorganic hydrogenocarbonates, and mixture thereof. Examples of inorganic oxides are kieselguhr, silica, aluminum oxides (aluminas), alkali metal and alkaline earth metal silicates, aluminum silicates (silica-aluminas), clays like montmorillonite and kaolin, zeolites like ZSM-5, spinels, magnesium silicates, magnesium oxide, zirconium oxide, sulfated or not, titanium oxide, tungsten oxide, zinc oxide, asbestos and mixed oxides like zirconia-silica or zirconia- tungsten oxide. Examples of inorganic carbonates are dolomite, barium carbonate and calcium carbonate. Barium sulfate is an example of inorganic sulfate. Suitable organic materials are preferably selected from the group consisting of active carbon, organic materials naturally occurring or organic synthetic compounds having high molecular weights, such as silk, polyamides, polystyrenes, cellulose or polyurethanes. Inorganic oxides, inorganic sulfates, inorganic carbonates, active carbons, and mixture thereof are preferred carriers. Active carbon is also convenient. The hydrogenation is carried out under conditions usually used in the prior art. For example, the hydrogenation is conducted at a temperature of between 10 and 50 °C, more preferably between 20 and 30°C. Furthermore, the hydrogenation may be conducted at a pressure of from 5 to 30 bar, for example at 10 bar. Hydrogen is typically fed into the reactor with a constant pressure, preferably during a period between 3.0 and 5.0 hours, more preferably between 3.5 and 4.5 hours, whereby the reaction period depends on the amount of the catalyst used therein, i.e. the lower the amount the longer the reaction period.

Furthermore, according to the invention, it is preferred that the menthone, i.e. the cyclohexanone of formula (I), wherein Ri is isopropyl and R2 and R3 are hydrogens, and which is used for producing Cl IF, is L-menthone. The L- menthone has preferably a cis/trans configuration ratio of 2-10 : 98-90, more preferably of 3 : 97.

By using the method of the invention, it is possible to provide a Cl IF or C10C having a high purity, preferably a purity of at least 95.0 % or at least 97%, more preferably of at least 98.0% or of at least 99.0% measured by gas chromatography (GC).

The alkyl and the aryl residue of the alkyl- or arylcarbazate, and thus the residue “R” of formulas (II)/(IIa) to (IV)/(IVa) referring to the intermediates of the invention, can be any alkyl/aryl residue, which does not hinder the condensation of the carbazate with the cyclohexanone of formula (I) to generate the first intermediate of formula (II)/(IIa).

Preferably the alkyl- or aryl-carbazate of the invention is selected from the group consisting of methyl-, ethyl-, t-butyl-, and phenyl-carbazate, more preferably the residue of the carbazate is methyl or ethyl, and even more preferably the residue is methyl.

According to the invention, the condensation of the alkyl- or arylcarbazate with the cyclohexanone of formula (I) may be carried out by reacting the alkyl- or arylcarbazate with the cyclohexanone of formula (I) in the presence of an inorganic and/or organic acid (acid catalyst), and, optionally, with the additional use of a solvent. The solvent can be any solvent typically used in condensation reactions. It is preferred that the solvent partially solves the alkyl-or arylcarbazate, the cyclohexanone of formula (I) and acid

The inorganic and/or organic acid used in this sub-reaction step of the first main method step (a) of the invention is selected preferably from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, propionic acid, methane sulfonic acid, benzenesulfonic acid, p- toluensulfonic acid, hydrogen cyanide, pyridine hydrochloride, ammonium chloride, triethylamine hydrochloride, pyridinum paratoluenesulfonate, and a combination thereof. In a preferred embodiment the acid is acetic acid.

The solvent is selected preferably from the group consisting of an alcohol, an aliphatic hydrocarbon, a cyclic hydrocarbon, a halogenated hydrocarbon, an aromatic hydrocarbon, an ether, a linear or cyclic amide, a nitrile solvent, dimethyl sulfoxide, sulfolane, a mixture of organic solvent and water with or without phase transfer catalyst, and a combination thereof. More preferably the solvent is selected from the group consisting of methanol, ethanol, one of isomers of propanol or butanol or pentanol, cyclopentanol, hexanol, ethylene glycol, propylene glycol, glycerol, pentane, hexane, heptane, cyclohexane, methylene chloride, chloroform, benzene, monoalkyl-benzene e.g. toluene, polyalkyl-benzene e.g. as one of isomers of xylene, chlorobenzene, polychlorobenzene e.g. dichlorobenzene, diethyl ether, cyclopentyl methylether, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, N-methyl-2- pyrrolidone, acetonitrile, propionitrile, dimethyl sulfoxide, sulfolane, and a mixture of organic solvent and water with or without phase transfer catalyst as aliquat 336 or tetrabutyl-ammonium bromide. Even more preferred the solvent is an alcohol selected from the group consisting of methanol, ethanol, one of isomers of propanol or butanol or pentanol. In a most preferred embodiment, the solvent is methanol.

In the condensation reaction of the first method step (a), cyclohexanone of formula (I) and the alkyl- or arylcarbazate may be used in a ratio of 1 : 1.20, more preferably in a ratio of 1 : 1.15, 1 : 1.07, even more preferably in a ratio of 1 : 1.03.

The inorganic and/or organic acid is used in sufficient amount to carry out the condensation. It is preferred that the inorganic and/or organic acid is used in amount of 0.5 to 4.0 mol %, more preferred in an amount of 1.0 to 3.5 mol%, even more preferred in an amount of 1.5 and 3.0 mol %, based on the total amount of cyclohexanone of formula (I) used in this method step.

In one embodiment of the invention, the condensation reaction is carried out such that the alkyl- or arylcarbazate is at least partially solved in a solvent as defined above. Afterwards, this solution may be cooled down. Subsequently, the cyclohexanone of formula (I) and the inorganic and/or organic acid (acid catalyst) are successively added to the solution. However, according to the invention, the condensation can be carried by any order of introduction of the reactants to the reactor, for example the cyclohexanone of formula (I) and the acid may be introduced into the reactor and afterwards the alkyl- or arylcarbazate is added to the reaction mixture. Moreover, as mentioned above, the use of a solvent in this sub-method step of the invention is optional. Furthermore, the reactant may be solved in a solvent as defined above prior to their introduction to the reactor used in the first method step of the invention, this prior dissolution may be done for example in a dissolution reactor, alternatively, the reactants may be introduced into the reactor in their solid form.

As mentioned above, in one embodiment of the invention, in particular in case the cyclohexanone is menthone, the reaction mixture is cooled down, preferably the reaction mixture is cooled down to 5 to -25°C, more preferably to 1 to -15°C, even more preferably to 0 to -5°C.

Furthermore, according to the invention, the condensation reaction is preferably conducted for 8 to 25 hours, more preferably for 10 to 22 hours, even more preferably for 15 to 20 hours.

After the condensation of the alkyl- or arylcarbazate with the cyclohexanone of formula (I) has been carried, preferably is completed, a cyanation reaction is conducted to obtain the second intermediate having the formula (III)/ (Illa). Preferably, the cyanation of method step (a) is performed by directly introducing HCN into the reactor, or by an in-situ production of HCN in the reactor. In industrial processes, it is preferred to introduce HCN directly.

If the HCN is directly introduced into the reactor, it is preferred to carry out the reaction in a reactor equipped with a condenser to condense HCN vapour in reaction medium or in an autoclave by using liquid or gas hydrogen cyanide or aqueous hydrocyanic acid and optionally a solvent. The main advantage of that embodiment is that the main inorganic at the end of reaction is the unreacted HCN that can be recycled while in the embodiment below using in-situ production of HCN, the inorganics obtained after the reaction are also the unreacted HCN but more importantly the stoichiometric amount of salt produced concomitantly in situ with HCN which increases considerably the amount of effluent to be treated. That particular advantage allows to consider the realization of the reaction with higher excess of HCN when it is introduced in one time, compared to the sequential addition described below to reduce reaction time.

The in-situ production of HCN may be carried out by using NaCN, KCN and/or tetraalkylammoniumcyanide, in the presence of an inorganic and/or organic acid and a solvent suitable to solve at least partially NaCN, KCN and/or tetraalkylammoniumcyanide, the produced HCN and intermediate (II) or (Ila).

The inorganic/organic acid as well as the solvent used in said sub-step of the method of the invention is preferably selected from the appropriate group as defined above regarding the condensation of the alkyl- or arylcarbazate with cyclohexanone of formula (I) according to the invention. The acids and solvents used in the two sub-steps of the first method step (a) of the invention may be the same or different. It is preferred that they are the same.

According to the invention, the cyanation may be carried out such that NaCN, KCN and/or tetraalkylammoniumcyanide and optionally the appropriate solvent is added to the reaction mixture of the conducted condensation as described above. Afterwards, the reaction mixture is brought up to preferably room temperature and the acid used in order to produce HCN in-situ is added to the reaction mixture. The in-situ production of HCN is an exothermic reaction, which has to be controlled. This may be done by adding the acid to the reaction mixture over a period of preferably 1.0 to 4.0 hours, more preferably of 1.5 to 3.5 hours carefully to the reaction mixture with a flow rate so that a temperature of 35 °C, preferably of 30 °C is not exceeded. After the addition of the acid to the reaction mixture, or after introducing HCN directly into the reactor, the mixture may be stirred for 15 to 36 hours, more preferably for 20 to 25 hours. Subsequently, in order to complete the cyanation reaction, NaCN, KCN and/or tetraalkyl-ammoniumcyanide and an acid as defined above, or as alternative HCN may be additionally added to the reaction mixture, wherein the acid is added preferably to the reaction mixture over period of 0.5 to 2.0, more preferably for 1.0 to 1.5 hours. Afterwards, the reaction mixture may be stirred for 20 to 36 hours, more preferably for 24 to 20 hours.

In order to produce HCN in-situ in a sufficient amount to carry out the cyanation reaction according to the invention, NaCN, KCN and/or tetraalkylammonium-cyanide and the inorganic and/or organic acid are used in an amount of 1.0 to 3.5 eq., more preferably of 1.5 to 3.2 eq., most preferably of 2.0 to 3.0 eq. to 1 eq. of menthone or the first intermediate (Ila).

After the cyanation has been conducted, the crude reaction mixture may be diluted with organic solvent and then washed with water, preferably demineralized water, then aqueous and organic phases may be separated. The organic solvent used in this method step is an organic solvent that is not miscible with water to allow separation between organic and water phase, such as for example dichloromethane, Furthermore, it is preferred to extract impurities from the aqueous phase by means of an organic solvent, for example dichloromethane, for several times, preferably for 2 to 4 times.

The washing and the extraction steps are intended to denote any treatment which is well known in the chemical industry and for example may be done in a mixer-settler or in a counter-current column.

Afterwards, the obtained organic phases are combined and the aqueous may be further purified.

The entire organic phase may be further washed with water and/or a mixture of for example water, preferably with demineralized water, and/or an aqueous alkali hydroxide solution, like sodium hydroxide solution, and/or an aqueous alkali chloride solution, like aqueous sodium chloride solution.

The organic solutions obtained by these washing steps are combined. According to the invention, this organic solution may contain the second intermediate (III)/(IIIa) of the invention in an amount of 8 to 25 wt.-%, more preferably of 10 to 20 wt.-%, even more preferably of 11 to 15 wt.-%, based on the total amount of the solution. For further use, the second intermediate of formula (III)/(IIIa) may be isolated or not from the organic solution obtained by the above-described washing steps. However, according to the invention, it is preferred to introduce the organic solution containing the second intermediate (III)/(IIIa) obtained by the above-described washing steps into a second reactor to carry out the second main method step (b) of the invention.

In a particular embodiment of the invention after cyanation, the remaining HCN may be removed from the crude mixture under vacuum or by a stripping with inert gas bubbling in mixture. Then the mixture containing salt by in-situ production of HCN may be treated as described above before to introduce it into a second reactor to carry out the second main method step (b) of the invention. The mixture from HCN directly introduced into the reactor may be sent directly to the second reactor.

According to the invention, the condensation and cyanation reaction of method step (a) as described above can be carried out successively or simultaneously. In the second method step (b) of the invention, an oxidation of the second intermediate (III)/ (Illa) with the aid of an oxidant to generate a third intermediate of formula (IV)/(IVa) is conducted followed by a decomposition of the third intermediate of formula (IV)/(IVa) with the aid of a base to obtain Cl IF or ClOC.

The oxidant used to generate the third intermediate (IV)/(IVa) of the invention can be any oxidant suitable to oxidize the hydrazinyl group of the second intermediate (III)/(IIIa) to the diazenyl group of the third intermediate (IV)/(IVa). In particular it is preferred that the oxidant is selected from the group consisting of halogenated oxidants, cerium ammonium nitrate, pyridinium chlorochromate, manganese (IV) oxide, potassium or barium permanganate, silver oxide or lead (IV) acetate, tetraalkylammonium nitrite, ammonium nitrite, alkali nitrite, tert-butylhypochlorite, sodium hypochlorite, or -bromite, hypohalous acid, hydrogen peroxide, air, oxygen, salts of peroxomonosulfuric acid, for example peroxomonosulfates of the alkali, alkaline earth, and other metals, or the triple salt 2 KHSO5.KHSO4.K2SO4 (sold under the trade names Oxone or Caroat), peracid compound and combinations thereof.

If the oxidant is a halogenated oxidant, it is preferred that the halogenated oxidant is selected from the group consisting of halogen such as chlorine, bromine, iodine, a combination of two halogens, N-halogen succinimide as N- bromo, N-chloro or N-iodo, l,3-dihalo-5,5-dimethylhydation with halo- corresponding to chloro, bromo, and iodo, (diacetoxyiodo)benzene, trichloroisocyanuric acid, and tetraalkyl-ammonium-periodate as tetrabutyl- or tetraethyl- and alkaliperiodate as lithium, sodium or potassium.

Furthermore, it is preferred that the halogenated oxidant is used in combination with an organic or inorganic base. The organic base may be selected from the group consisting of pyridine, dimethylaminopyridine and polyalkylamine for example triethylamine. The inorganic base may be an aqueous buffer or an aqueous solution selected from the group consisting of alkali hydroxide, alkali carbonate, alkali hydrogencarbonate, alkali phosphate and mono-or di-hydrogenophosphate. The alkali metal is preferably lithium, sodium or potassium.

In a preferred embodiment tetraalkylammonium nitrite or ammonium nitrite or alkali nitrite is used as oxidant in the method of the invention, wherein the alkali metal is lithium, sodium or potassium. Additionally, it is preferred that tetraalkylammonium nitrite, or ammonium nitrite, or alkali nitrite is used in combination with an acetic anhydride.

In another embodiment tert-butylhypochlorite or aqueous sodium hypochlorite is used as oxidant in combination with a catalytic amount of tetraalkylamonium, ammonium, alkali- or alkaline earth metal-bromide or iodide.

In a further embodiment, as oxidant a peracid is used, preferably in this embodiment the oxidant is meta-chloroperoxybenzoic acid or peracetic acid.

If the oxidant is hydrogen peroxide, air, oxygen, salts of peroxomonosulfuric acid as peroxomonosulfates of the alkali, alkaline earth, and other metals, or oxone, the following combinations of components are preferred:

Hydrogen peroxide, air or oxygen (atmospheric or under pressure) in presence of homogeneous or heterogeneous metal catalyst and an additive in catalytic amount such as hydrogen halide or base.

Hydrogen peroxide in combination with a catalytic amount of one of hydrogen halide or halide where the halide is bromine or iodine. In a more preferred embodiment hydrogen peroxide is used in combination with hydrogen bromide.

Salts of peroxomonosulfuric acid as peroxomonosulfates of the alkali, alkaline earth, and other metals alone, or Oxone alone, or in combination with a catalytic amount of one of hydrogen halide, halide or alkali halide where halide is bromine or iodine. Air or oxygen (atmospheric or under pressure) in presence of organic catalyst such as 2,2,6,6-Tetramethylpiperidine-l-oxyl.

Air or oxygen (atmospheric or under pressure) in presence of catalytic amount of tetraalkylammonium, ammonium or alkali nitrite and nitric acid or in presence of tert-butyl nitrite in non-stoichiometric amount.

Air or oxygen (atmospheric or under pressure) in presence of a catalytic amount of tetraalkylammonium, ammonium or alkali nitrite and bromine or alkali metal bromide or alkaline earth metal bromide or ammonium bromide or quaternary alkyl ammonium bromide or quaternary alkyl ammonium tribromide. That chemistry can be extended to iodine analogues.

According to the invention, the oxidation reaction, but also the decomposition reaction as described below, may be performed in the presence of one or several organic solvents suitable to dissolve the second and/or third intermediate of the invention, preferably the solvent is a solvent as described above with respect to the first main method step (a) of the invention and subsequent solvent used for aqueous phase extraction. In particular, it is preferred that in all method steps of the invention, i.e. in the two sub-steps of the first main method step (a) and in the two sub-steps of the second main method step (b) according to the invention, the same solvent is used. It is even more preferred that the solvent is methanol in combination with extraction solvent.

In a more preferred embodiment of the invention, as mentioned above, the oxidation is carried out with the aid on a hydro-halogen acid, for example hydrobromic acid, in combination with hydrogen peroxide, whereby preferably 0.05 to 0.35, more preferably 0.10 to 0.25 eq., even more preferred 0.15 to 0.2 eq. of hydro-halogen acid and preferably 1.5 to 2.5, more preferably 2 eq. of hydrogen peroxide to 1 eq. of menthone or the first intermediate (Ila) is added to the solution of the second intermediate (III)/(IIIa).

The oxidation reaction as described above is an exothermic reaction, which have to be controlled. Therefore, the oxidants and combinations thereof are preferably added to the second intermediate (III)/ (Illa) or solution carefully, for example dropwise, to the second intermediate (III)/(IIIa), under stirring over a period of preferably 0.5 to 3.0 hours, more preferably between 1 and 2 hours. The resulting mixture may be further stirred for 1.0 to 5 hours, preferably for 2 to 3 hours to obtain the third intermediate (IV)/(IVa) of the invention.

Afterwards, the mixture including the third intermediate is combined with a base to decompose the third intermediate (IV)/(IVa) and thus to obtain Cl IF or C10C. The base may be an alkali hydroxide, an alkali alcoholate or aqueous sodium hypochlorite or combinations thereof,. More preferably, the base is sodium or potassium hydroxide, or lithium, sodium or potassium methanolate or ethanolate, or combinations thereof. It is further preferred to use an aqueous solution of the base, a solution of the base and alcohol such methanol or ethanol or a solution of the base and another organic solvent.

In particular embodiments of the invention, the base is used as a solution of

NaOH or KOH in water or alcohol as for example MeOH or EtOH; MeONa in MeOH or EtONa in EtOH; or MeOLi in 1,2-dimethoxy ethane.

It is further preferred that the third intermediate (IV)/ (IVa) and the base are dissolved in one or several organic solvents as described above with respect to the first main method step (a) of the invention.

Furthermore, according to the invention the decomposition may be done with or without a phase transfer catalyst. Phase transfer catalyst which are usually used in such decomposition reactions are well known in the art.

According to the invention, the decomposition reaction is preferably carried out for 0.2 to 3 hours, preferably for 0.5 to 2 hours.

In another embodiment of the invention, the oxidation of intermediate (III/IIIa) and decomposition of intermediate (IV/IVa) are carried out simultaneously. In that case the oxidation and decomposition are conducted in the presence of a solvent as described above and the following oxidation/decomposition system may be used:

Aqueous sodium hypochlorite;

Aqueous hydrogen peroxide in presence of copper complex as catalyst and at one controlled pH regulated with aqueous ammonia or another buffer; or

Air or oxygen (at atmospheric or under pressure) in presence of copper complex as catalyst and at one controlled pH regulated with aqueous ammonia or other buffers.

After the decomposition of intermediate (IV/IVa), the reaction mixture may be washed. Therefore, water, preferably demineralized water, is added to the reaction mixture and the resulted organic and water phase are separated from each other. Afterwards, the water phase is preferably extracted with an organic solvent, like dichloromethane. The extraction may be carried out for several times, preferably for at least 2 or 3 times. The organic phases are preferably combined and again washed by using for example water, more preferably demineralized water, optionally in combination or sequentially with an aqueous hydro-halogen acid solution, for example, aqueous hydrochloride acid solution, and an aqueous alkali halogen solution, for example aqueous sodium chloride solution. Afterwards, it is preferred to remove the solvents from the organic phase by vacuum distillation. In doing so, Cl IF or C 10C may be obtained in a yield of between 80 and 95 %, preferably of between 84 and 90 %.

If necessary, the Cl IF or C 10C obtained after method step (b) (“crude” Cl IF or C10C) can be further purified. This may be done by a vacuum distillation at a temperature between 100 and 120 °C, more preferably between 105 to 118 °C, even more preferred between 107 to 117 °C at 100 mbar. The such purified Cl IF or purified C10C has a purity level of at least 95.0 % or at least 97%, more preferably of at least 98.0% or of at least 99.0% measured by gas chromatography (GC).

The overall yield of the method of the invention including also the last purification step as described above may be between 65 to 85 %, preferably between 70 and 80 %.

The method of the invention may be carried out in a batch mode, as described above, or in a continuous mode.

The following chemical equations summarize the method and its conditions according to the invention. However, these equations only refer to specific examples and does not limit the claimed invention:

Step 1 Step 2

Furthermore, the present invention relates to a process for manufacturing an aqueous hydrogen peroxide solution by using Cl IF, C 10C or a combination thereof as polar solvent, wherein Cl IF is obtained by the method of the invention and C 10C is obtained by the method of the invention or any suitable production method thereof. This process comprises the following steps: hydrogenating a working solution which comprises an alkylanthraquinone and/or a tetrahydroalkylanthraquinone and a mixture of a non-polar organic solvent and a polar organic solvent; oxidizing the hydrogenated working solution to produce hydrogen peroxide; and isolating the hydrogen peroxide, wherein the polar organic solvent is a 5-methyl-2-isopropyl-cyclohexane carbonitrile (Cl IF), 3,3,5-trimethyl-cyclohexane carbonitrile (C10C), or a combination thereof, wherein Cl IF is obtained by the method of the invention as described above and C 10C is obtained by the method of the invention as described above or by any other suitable method.

Hence, the production process for hydrogen peroxide according to the invention is an AO process. In the AO process of the invention, which preferably is a continuous process operated in loop, a working solution is used which is hence preferably circulated in a loop through the hydrogenation, oxidation and extraction steps.

The term "alkylanthraquinone" is intended to denote a 9,10-anthraquinone substituted in position 1, 2 or 3 with at least one alkyl side chain of linear or branched aliphatic type comprising at least one carbon atom. Usually, these alkyl chains comprise less than 9 carbon atoms and, preferably, less than 6 carbon atoms. Examples of such alkylanthraquinones are ethylanthraquinones like 2- ethylanthraquinone (EQ), 2-isopropylanthraquinone, 2-sec- and 2-tert- butylanthraquinone (BQ), 1,3-, 2,3-, 1,4- and 2,7-dimethylanthraquinone, amylanthraquinones (AQ) like 2-sec-iso- and 2-tert-amylanthraquinone and mixtures of these quinones.

The term "tetrahydroalkylanthraquinone" is intended to denote the tetrahydro-9, 10-anthraquinones corresponding to the 9,10-alkylanthraquinones specified above. Hence, for EQ and AQ, they are respectively designated by ETQ and ATQ, their reduced forms (tetrahydroalkylanthrahydroquinones) being respectively ETQH and ATQH.

Preferably, an AQ or EQ or a mixture of both is used.

In order to be able to also solubilize the quinone, the polarity of the solvent mixture is preferably not too high. Hence, there is preferably at least 30wt% of non-polar solvent in the organic solvent mixture, and more preferably at least 40 wt.-%. Generally, there is not more than 80 wt.-% of this non-polar solvent, in the organic solvent mixture.

The non-polar solvent preferably is an aromatic solvent or a mixture of aromatic solvents. Aromatic solvents are for instance selected from benzene, toluene, xylene, tert-butylbenzene, trimethylbenzene, tetramethylbenzene, naphthalene, methylnaphthalene mixtures of polyalkylated benzenes, and mixtures thereof. The commercially available aromatic hydrocarbon solvent of type 150 from the Solvesso® series (or equivalent from other supplier) gives good results. S-150 (Solvesso®- 150; CAS no. 64742-94-5) is known as an aromatic solvent of high aromatics which offer high solvency and controlled evaporation characteristics that make them excellent for use in many industrial applications and in particular as process fluids. The Solvesso® aromatic hydrocarbons are available in three boiling ranges with varying volatility, e.g. with a distillation range of 165-181 °C, of 182-207 °C or 232-295 °C. They may be obtained also naphthalene reduced or as ultra-low naphthalene grades. Solvesso® 150 (S-150) is characterized as follows: distillation range of 182-207 °C; flash point of 64 °C; aromatic content of greater than 99 % by wt.; aniline point of 15 °C; density of 0.900 at 15 °C; and an evaporation rate (n-butylacetate = 100) of 5.3.

The hydrogenation reaction takes place in the presence of a catalyst (like for instance the one object of WO 2015/049327 in the name of the Applicant) and as for instance described in WO 2010/139728 also in the name of the applicant (the content of both references being incorporated by reference in the present application). Typically, the hydrogenation is conducted at a temperature of at least 45 °C and preferably up to 120 °C, more preferably up to 95 °C or even up to 80 °C only. Also typically, the hydrogenation is conducted at a pressure of from 0.2 to 5 bar. Hydrogen is typically fed into the vessel at a rate of from 650 to 750 normal m ³ per ton of hydrogen peroxide to be produced.

The oxidation step may take place in a conventional manner as known for the AO process. Typical oxidation reactors known for the anthraquinone cyclic process can be used for the oxidation. Bubble reactors, through which the oxygen-containing gas and the working solution are passed co-currently or counter-currently, are frequently used. The bubble reactors can be free from internal devices or preferably contain internal devices in the form of packing or sieve plates. Oxidation can be performed at a temperature in the range from 30 to 70 °C, particularly at 40 to 60 °C. Oxidation is normally performed with an excess of oxygen, so that preferably over 90%, particularly over 95%, of the alkyl anthrahydroquinones contained in the working solution in hydroquinone form are converted to the quinone form.

After the oxidation, during the purification step, the hydrogen peroxide formed is separated from the working solution generally by means of an extraction step, for example using water, the hydrogen peroxide being recovered in the form of a crude aqueous hydrogen peroxide solution. The working solution leaving the extraction step is then recycled into the hydrogenation step in order to recommence the hydrogen peroxide production cycle, eventually after having been treated/regenerated.

In a preferred embodiment, after its extraction, the crude aqueous hydrogen peroxide solution is washed several times i.e. at least two times consecutively or even more times as required to reduce the content of impurities at a desired level, for example, the crude aqueous hydrogen peroxide solution is washed with an organic solvent, which is intended to reduce the content of impurities in the aqueous hydrogen peroxide solution as disclosed for example in GB 841323 A. This washing can consist, for example, in extracting impurities in the crude aqueous hydrogen peroxide solution by means of an organic solvent in apparatuses such as centrifugal extractors or liquid/liquid extraction columns, for example, operating counter-current wise. Liquid/liquid extraction columns are preferred. Among the liquid/liquid extraction columns, columns with random or structured packing (like Pall rings for instance) or perforated plates are preferred. The formers are especially preferred.

In a preferred embodiment, a chelating agent can be added to the washing solvent in order to reduce the content of given metals. For instance, an organophosphorus chelating agent can be added to the organic solvent as described in the above captioned patent application EP 3052439 in the name of the Applicant, the content of which is incorporated by reference in the present application.

The expression "crude aqueous hydrogen peroxide solution" is intended to denote the solutions obtained directly from a hydrogen peroxide synthesis step or from a hydrogen peroxide extraction step or from a storage unit. The crude aqueous hydrogen peroxide solution can have undergone one or more treatments to separate out impurities prior to the washing operation according to the process of the invention. It typically has a H2O2 concentration within the range of 30- 50% by weight.

By using Cl IF and/or C10C, which are produced according to the invention, it is possible to achieve a higher solubility of the hydrogenated quinone of the working solution, in particular in comparison to sextate and diisobutylcarbinol (DBC), which are usually used as polar solvents in an AO process. The maximum solubility of a hydrogenated quinone (QH) in a solvent mixture is directly correlated with the productivity of the working solution. The higher is QH solubility, the higher will be theoretically quantity of hydrogen peroxide achievable per kg of WS (productivity).

The degree of QH solubility can be indicated as test level (TL), which refers to the produced amount of H2O2 per kg working solution (g ^CL/kg of WS) at a specific temperature for a specific concentration of the polar solvent. According to the invention, it is preferred that at 70 °C and a polar solvent concentration in the working solution of 15 wt.-% the test level (TL) is above 5.9, preferably above 6.0 g H2O2/kg WS. Additionally, it is preferred that at 70 °C and a polar solvent concentration in the working solution of 25 wt.-% the test level (TL) is 9.0 or higher, more preferably 10.0 or higher, most preferably 11.0 or higher. This is fulfilled by using Cl IF and/or C10C produced by the method of invention as polar solvent(s) in the AO process.

Due to the higher solubility obtained by using Cl IF and/or C10C produced according to the invention, less amounts of the polar solvent is needed to achieve a higher partition coefficient called kb ratio at same QH solubility. With this higher partition coefficient called kb ratio it is possible to reduce the capex (capital expenditure) required for the extraction sector.

The use of Cl IF and/or C10C according to the invention as polar solvent(s) in the AO process results into a better extraction of hydrogen peroxide from the organic phase to the aqueous phase in comparison to an AO process, wherein as polar solvent for example sextate or DBC is used. Indeed, hydrogen peroxide concentration in organic phase is lower when using Cl IF and/or C10C instead of the two other solvents. This effect can be indicated for example by the kb ratio of the solvent. The determination of the kb ratio according to the invention is described below in the examples. The kb ratio of the Cl IF or C 10C produced according to the invention is higher than of sextate or DBC. In particular, it is preferred that at a concentration of 30 wt.-% of the polar solvent in the mixture of non-polar solvent and polar solvent, the kb ratio of Cl IF according to the invention is at least 300, at least 500, or at least 700.

Furthermore, as mentioned above, it is state of the art that the epoxide 2- ethyl-5,6,7,8-tetrahydro-8a,10a-epoxy-9,10-anthraquinone (ETEQ) is an undesired by-product in the AO process obtained during the oxidation of 2-ethyl- 5,6,7,8-tetrahydro-9,10-anthrahydroquinone. Consequently, it is desired to minimize its formation rate. As demonstrated in the examples, by using Cl IF and/or C 10C of the invention instead of for example sextate or DBC the ETEQ formation rate can be minimized. According to the invention it is preferred that the epoxide formation rate (g ETEQ/kg of total H2O2 produced) is less than 2.9, more preferably less than 2.7, even more preferably 2.5 or lower.

It has been further found out that due to the use of the Cl IF and/or C10C produced according to the invention, the TOC content in aqueous hydrogen peroxide is lower than the TOC content of an aqueous hydrogen peroxide by using sextate or DBC as polar solvents. In particular the TOC content of the aqueous hydrogen peroxide solution by using the Cl IF and/or C 10C of the invention as polar solvent is lower than 400 ppm, in many cases lower than 350 ppm, preferably lower than 300 ppm, more preferably lower than 280 ppm, or lower than 250 ppm, or lower than 200 or even lower than 150 ppm. The TOC content can be measured as described in the examples below.

Hence, a higher purity level of the hydrogen peroxide solution can be obtained.

The Cl IF and/or C10C according to the invention is suitable for the manufacture of hydrogen peroxide by the AO process wherein said process has a production capacity of hydrogen peroxide of up to 300 or 100 kilo tons per year (ktpa), i.e. the solvents are suitable for large scale AO-processes. Furthermore, the solvents are also suitable for small to medium scale AO-processes operating with a production capacity of hydrogen peroxide of up to 50 kilo tons per year (ktpa), and more preferably with a production capacity of hydrogen peroxide of up to 35 kilo tons per year (ktpa), and in particular with a production capacity of hydrogen peroxide of up to 20 kilo tons per year (ktpa). The dimension ktpa (kilo tons per annum) relates to metric tons.

A particular advantage of such scales AO process is that the hydrogen peroxide can be manufactured in a plant that may be located at any, even remote, industrial end user site and the solvents of the invention are therefore especially suitable. It is namely so that since the QH solubility and the partition coefficient , called kb ratio, is more favourable with less amount of polar solvent, less emulsion is observed in the process and a purer H2O2 solution can be obtained (namely containing less TOC) and this for a longer period of time compared to when solvents known from prior art are used.

In a preferred sub-embodiment of the invention, the working solution is regenerated either continuously or intermittently, based on the results of a quality control, regeneration meaning conversion of certain degradants, like epoxy or anthrone derivatives, back into useful quinones. Here also, the Cl IF and/or C10C according to the invention is favourable because the amount of epoxide to be regenerated is reduced, the quality of the H2O2 solution can be maintained within the specifications namely in terms of TOC as mentioned above for a longer period of time.

The present invention is further illustrated by the following examples. It should be understood that the following examples are for illustration purposes only, and are not used to limit the present invention thereto.

EXAMPLES Abbreviations

AO: autooxidation

DBC: di-isobutylcarbinol

Cl IF: 2-isopropyl-5-methyl-cyclohexane carbonitrile

C10C: 3,3,5-trimethyl-cyclohexane carbonitrile

ETQ: 2-ethyl-5,6,7,8-tetrahydro-9, 10-anthraquinone

ETEQ: 2-ethyl-5, 6, 7, 8-tetrahydro-8a, 10a-epoxy-9, 10-anthraquinone

GC: Gas chromatography

NMR: Nuclear magnetic resonance

OP: organic phase r.t: room temperature

TOC: total organic carbon

WS: working solution

Production of Cl IF (according to the invention)

First Method Step (a)

A 2L double-jacketed reactor was equipped with a mechanical stirrer, a temperature probe and a condenser fitted with a nitrogen-inlet and a gas-outlet connected to a scrubber flask containing aqueous potassium hydroxide.

The reactor was charged with methylcarbazate (193 g, 2.14 mol) and methanol (400 ml).

To the resulting solution stirred and cooled down to 0°C was added successively 1-menthone (308 g, 2.0 mol) and acetic acid (3 g, 0.05 mol). The reaction progress was monitored by gas chromatography. After 15 hours, methanol (100 ml) then potassium cyanide (260 g, 4.0 mol) was added to the reactor. Cooling is stopped and the reaction media is heated to room temperature. Acetic acid (240 g, 4.0 mol) was added dropwise for two hours to control the exotherm by maintaining temperature below 30°C. After 24 h, all the solid particles was dissolved and KCN (130 g, 2.0 mol) was added followed by the introduction of acetic acid (120 g, 2.0 mol) for one hour. After additional 24 h, the mixture was poured into water (2.5 L), the reactor was washed with dichloromethane (500 ml) and water (500 ml). All the phases were mixed for a few minutes then the organic phase was separated. The aqueous phase was extracted three times with 500 ml of dichloromethane. The combined organic phases were washed with two 1-L portions of demineralized water, one 0.5L portion of aqueous sodium hydroxide solution (0.5 N) and one 50 mL portion of aqueous sodium chloride solution (15-20 wt.-%). The combined organic solution (~3 kg) contained 15 wt.-% of desired intermediate product (III) and 1 wt.-% of menthyl carbomethoxyhydrazone (II).

Second Method Step (b)

The solution was poured in a 5 L reactor equipped with a mechanical stirrer, a temperature probe and a condenser fitted with a nitrogen-inlet and a gas-outlet connected to a scrubber flask containing aqueous potassium hydroxide solution.

Aqueous hydrobromic acid solution (48 wt.-%, 80 g, 1.0 mol) and water (200 g) were introduced successively to this solution. To the resulting mixture under vigorous stirring was added dropwise aqueous hydrogen peroxide solution (32.2 wt.- %, 422 g, 4.0 mol) over one hour to control the exotherm and the reflux. After 3 h, the solution became red/deep orange and the reflux was stopped. The solution was kept under stirring and pumped at a rate of lOOml/min into a solution of potassium hydroxide in methanol (2 L, 2N, 4.0 mol) to decompose the intermediate and obtain Cl IF. During this operation, a large volume of gas was evolved (nitrogen and carbon dioxide). After 2 hours, the media was diluted by demineralized water (2.5 L). The layers were separated and the aqueous phase was extracted twice with dichloromethane (2 X 500 ml). The combined organic layers were washed with demineralized water (1 X 1 L), aqueous hydrochloric acid solution (1 X 1 L, 1 N) and aqueous sodium chloride solution (1 X 1 L, 15-20 wt.-%). The solvents were removed from the organic layer using a rotary evaporator under vacuum to give 320 g of crude mixture with a Cl IF content between 84-87 wt.-% as assessed by H ¹ NMR.

The residue was purified by vacuum distillation to afford 248 g of a colourless liquid corresponding to pure Cl IF (Overall yield including distillation: 75%, GC purity: 99.6%, boiling point: 114-117 °C at 100 mbar).

Production of C10C (according to the invention)

Pre-reaction

A IL autoclave regulated at room temperature and equipped with a mechanical stirrer, a temperature probe, a nitrogen inlet, a hydrogen outlet, a drain valve and a manometer was successively charged with isophorone (600 g, 4.34 mol) and 10 wt.-% Pd/C (20 g, 18.8 mmol). The autoclave was next sealed and purged with nitrogen (6 bar) by pressurizing and depressurizing five times. The resulting mixture was stirred at 25°C and then purged with hydrogen (10 bar) by pressurizing and depressurizing five times. It was then kept at this temperature for four hours by maintaining a pressure of 10 bar with hydrogen. When the hydrogen consumption was stopped, the autoclave was depressurized and then purged with nitrogen by pressurizing and depressurizing several times (5-10 times). The reaction mixture was filtered to recover the used catalyst. The filtrate was distilled under reduced pressure (75-81°C, 100 mbar) to afford 547 g of pure 3, 3, 5 -trimethyl cyclohexanone.

First Method Step (a)

A 10L double-jacketed reactor regulated at room temperature and equipped with a mechanical stirrer, a temperature probe, a condenser fitted with a nitrogen-inlet and gas phase-outlet connected to a scrubber flask containing aqueous sodium hydroxide solution (3N, 5 L) was successively charged with 3, 3, 5 -trimethyl cyclohexanone (2 Kg, 14 mol, 1 eq), methanol (3L) and methylcarbazate (1.352 Kg, 15 mol, 1.06 eq). The resulting solution was stirred and after dissolution of methlycarbazate, acetic acid (42.5 g, 0.05 Eq) was carefully added for 1 hour to control the large exotherm below 45°C. The reaction media was stirred at room temperature until full conversion after 19 h to give a solution of intermediate (Ila) used without further purification. For practical reason, this solution was divided in several portions whose volume is compatible with the reactor size of next reaction.

In a 2L double-jacketed reactor regulated at room temperature and equipped with a mechanical stirrer, a temperature probe, a condenser fitted with a nitrogen-inlet and a gas phase-outlet connected to a scrubber flask containing aqueous sodium hydroxide (3N, 5 L), was introduced a solution of intermediate (Ila) (564 g of solution, 301.5 g of intermediate Ila, 1.42 mole, 1 eq). To this solution under stirring was added solid KCN (185 g, 2.84 mol, 2 eq) followed by the introduction of acetic acid (168 g, 2.84 mol, 2 eq) for 3 h using a metering pump to keep the exotherm between 4 and 8°C and maintain a temperature below 35°C. After 24 h, a translucent slightly yellow solution was obtained. To this solution was added the third equivalent of KCN (90 g, 1.38 mol, 1 eq) followed by the addition of acetic acid (83 g, 1.38 mol, 1 eq) for 1.5 h. The resulting mixture was maintained under stirring at room temperature for 24 h to give a brown solution. To this solution was introduced 100 mL of demineralized water in order to dissolve the salts. The excess of HCN was partially stripped from reaction mixture using a nitrogen flow for 2 hours. The solution was poured with a pump in 1.5 L of demineralized water contained in a 5 L reactor (connected to the scrubber flask). The 2 L reactor was rinsed with 500 ml of water and 500 ml of dichloromethane. This aqueous and organic phases were sent to the 5 L reactor.

The phases in the 5 L reactor were stirred for 10 min in order to dissolve the organics then the organic phase was separated. The aqueous phase was extracted three times with 500ml of dichloromethane. The combined organic phases were successively washed two times with 1 L of demineralized water, once with 1 L of aqueous sodium hydroxide solution (IN) and once with 1 L of aqueous sodium chloride solution (20 wt%) in order to get approximately 2760 g of solution containing intermediate Illa. The conversion of intermediate Ila was around 90%.

Second Method Step (b)

The solution was placed in a 5 L reactor equipped with a mechanical stirrer, a temperature probe and a condenser fitted with a nitrogen-inlet and a gas-outlet connected to a scrubber flask containing aqueous sodium hydroxide solution (3N, 5 L).

To this solution was successively added aqueous hydrobromic acid solution (48 wt.-%, 50 g, 0.3 mol, 0.21 eq) and demineralized water (100 g). To the resulting mixture under vigorous stirring (800-1000 rpm) was added aqueous hydrogen peroxide solution (50.0 wt.-%, 165 g, 2.42 mol, 1.7 eq) over two hours to control the exotherm and the reflux. After two additional hours the solution became red/deep orange (meaning that oxidation was achieved). The biphasic solution was kept under stirring and transferred with a pump over 2h into a solution of potassium hydroxide in methanol (2N, IL, 2.0 mol, 1.41 eq) to decompose the intermediate IVa and obtain C10C. During the decomposition, an important reflux was observed and a large volume of gas was evolved (nitrogen and carbon dioxide). The mixture was stirred one additional hour. Then the layers were separated and the aqueous phase was extracted with 500ml of dichloromethane. The combined organic phases were washed with demineralized water (1 X 1 L) and aqueous sodium chloride solution (1 X 1 L, 20 wt.-%). The solvents were removed from the organic layer using a rotary evaporator under vacuum to afford 200-205 g of crude mixture containing C10C and 3,3,5- trimethyl cyclohexanone in a 85/15 weight ratio (wt/wt %). The crude mixture was purified by vacuum distillation (100 mbar) using an Oldershaw column to give 146 g of pure C10C (Overall yield including distillation: 70%, GC purity: 99%, boiling point: 107-113°C at 100 mbar). Pure 3, 3, 5 -trimethyl cyclohexanone (boiling point : 75-81 °C at 100 mbar) was recovered during distillation and could be recycled.

AO Process

1. AO Process

The AO process was carried out in a lab pilot. Therefore, the pilot was composed of a hydrogenation reactor with a slurry of palladium catalyst, an oxidation column and an extraction column. It was run with a closed loop of organic working solution composed initially by a mixture of alkylated anthraquinone (ethylanthraquinone and ethyltetrahydroanthraquinone), Solvesso™ 150 and as polar solvent Cl IF, C10C, sextate or DBC. It was monitored periodically to evaluate the formation of the epoxide ETEQ with the total production of hydrogen peroxide.

2. Determination of OH solubility in working solutions

The determination of the QH solubility was performed on synthetic

EQZETQ working solutions. These quinones mixed in the tested solvents have been hydrogenated to a fixed level and cooled down successively to 4 different temperatures before the measurements (min 3 hours to stabilize the system between each measurement). The conditions applied for these tests were

EQ concentration 100g/kg

ETQ concentration 140 g/kg

Polar solvent variable (*)

Level of hydrogenation 10.8 NI H ₂ /kg WS (~ 116g of QH/kg of WS or a TL (Test Level) of 16.3g of H ₂ O ₂ /kg WS (= maximum theoretical value of TL if all QH is dissolved)

Temperature of hydrogenation 75 °C

The temperature of precipitation is indicated as temperature at which QH was measured. The QH solubility have been determined at 70 °C, 65, 60 and 55 °C. The theoretical values designated by the term “ Test Level g LhC /kg WS) ” were calculated as follows: 1 mole (240g) ETQH (which actually is QH in the examples) per kg of WS will produce 1 mole (34g) of H2O2 per kg of WS.

Hence, the level in the examples equals: 34*QH/240.

3. Estimation of kb ratio from equilibration between aqueous hydrogen peroxide and organic solutions

An aqueous hydrogen peroxide solution (25 ml, 35 wt.-%) and an organic solution (25 ml) prepared from Solvesso™ 150 and polar solvent were stirred together in a flask for 30 minutes. After decantation and separation of phases by centrifugation, the hydrogen peroxide content was determined in organic phase using suitable analytical method and expressed in g per kg of phase. The hydrogen peroxide concentration in aqueous phase is equal before and after equilibration.

The water concentration in aqueous phase (AP) and the total solvent concentration in organic phase (OP) both expressed in g per kg of phase were calculated by following formulas:

[H ₂ O] ^AP = 1000 - [^02]^

[Total solvent] ^op = 1000 - [H2O2] ^op

The kb ratio was calculated as: kb = { [ O^ / [ O } / { [H ₂ O ₂ ] ^OP / [Total solvent] ^op }

4. Formation rate of ETEQ

The epoxide formation rate observed in AO process lab pilot was determined by measuring periodically (minimum 5 consecutive measurements spaced out in time at regular intervals) the concentration of ETEQ and hydrogen peroxide in the working solution after oxidation. The concentration of ETEQ and H2O2 were measured respectively by high performance liquid chromatography and spectrophotometry using potassium titanium (IV) oxalate. The concentrations of these species were expressed in g of species per kg of working solution.

The total amount of H2O2 produced after one specified time (M ¹ ) was obtained by following formula and expressed in kg :

M ^t = F * ([H ₂ 0 ₂ ]/1000) * At + M ¹ ' ¹ where F is the flow of working solution in kg per hour, [H2O2] is the concentration of H2O2 in working solution in g per kg, At is the elapsed time (expressed in hour) between time t and the time t-1 of the previous measurement and M ¹ ' ¹ is the total amount of H2O2 expressed in kg and produced at previous measurement at time t-1.

The total amount of H2O2 produced per kg of working solution after one specified time (M) is calculated by following formula and expressed in kg of total H2O2 produced per kg of working solution :

M = M ^t / m ^ws where m ^ws is the mass of working solution expressed in kg.

It was observed that the relationship between the ETEQ concentrations ([ETEQ]) and the total amounts of H2O2 (M) was linear with a slope corresponding to the epoxide formation rate expressed in g of ETEQ per kg of total H2O2 produced.

5. Determination of TOC content

The TOC content was measured in a test by mimicking the final stage of the water extraction of hydrogen peroxide from oxidized working solution of the AO process.

Therefore, a 50 ml penicillin flask equipped with a magnetic stir bar was charged with 20 g of aqueous hydrogen peroxide solution (45 wt.-%), 5 g of Solvesso™ 150 and 5 g of polar solvent. The resulting mixture was stirred for 10 minutes at 650 rpm and 60°C in the closed flask. The mixture was decanted at room temperature for 30 minutes. The tubing of the total organic carbon (TOC) analyser was introduced in the aqueous phase. The total carbon (TC) measurement was repeated three times and is equal to the TOC.

Results

1. OH solubility

In Figures 1-4 the QH solubilities by using Cl IF, C10C, sextate or DBC as polar solvent in the AO process at a temperature of 70 °C, 65 °C, 60 °C and 55 °C are depicted.

Based on curve it can be observed that at 70°C, the test level is higher with Cl IF or C 10C than DBC and sextate, in particular, at a polar solvent concentration of 15 wt.-% the TL of Cl IF or C10C is above 6 g H2O2 / kg WS. At temperatures below 70 °C the test level is higher with Cl IF or C10C than DBC and sextate above a polar solvent concentration of 30 wt.-%. Between 15 wt.-% and 30 wt.-% of the polar solvent concentration and depending on the curve, the test level with Cl IF is in most of the cases similar to DBC but always higher than sextate, and with C10C always higher.

2. Kb ratio

In Table 1 and in Figure 5 the kb ratio by using Cl IF, C10C, sextate or DBC as polar solvent in the AO process are depicted.

As can be seen from the graph, the kb ratio is higher when using Cl IF or C10C instead of sextate and DBC. It means that the extraction of hydrogen peroxide from organic phase to aqueous phase is better with Cl IF or C10C. Indeed, hydrogen peroxide concentration in organic phase is lower when using Cl IF or C 10C instead of the two other solvents.

Table 1

3. Formation rate of ETEQ

As can be seen from Table 2 the lowest formation rate of ETEQ was obtained by using Cl IF as polar solvent.

Table 2

4. TOC measurement Based on the results of Table 3 below, the following can be observed:

The TOC value in aqueous hydrogen peroxide is lower with the nitrile solvent Cl IF or C IOC than with the sextate or DBC which means that Cl IF or C IOC is less soluble in aqueous hydrogen peroxide and hence allows reaching a higher purity level of hydrogen peroxide solution.

Table 3