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Title:
PROCESS FOR MANUFACTURING AN ALKYL SUBSTITUTED CYCLOHEXANECARBONITRILE
Document Type and Number:
WIPO Patent Application WO/2021/048365
Kind Code:
A1
Abstract:
A process for manufacturing an alkyl substituted cyclohexanecarbonitrile, said process comprising the following steps: - reaction of cyanoisophorone with an organometallic compound comprising an alkyl group in order to transform the ketone moiety into its corresponding alcohol; - reduction of the alcohol in order to obtain the alkyl substituted cyclohexanecarbonitrile.

Inventors:
LORENT KAROL (BE)
Application Number:
PCT/EP2020/075485
Publication Date:
March 18, 2021
Filing Date:
September 11, 2020
Export Citation:
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Assignee:
SOLVAY (BE)
International Classes:
C01B15/023; C07C255/46
Domestic Patent References:
WO2011094953A12011-08-11
WO2010109011A12010-09-30
WO2010011010A12010-01-28
WO2013053617A12013-04-18
WO2011095576A12011-08-11
WO2015049327A12015-04-09
WO2010139728A12010-12-09
Foreign References:
US4299775A1981-11-10
US2158525A1939-05-16
US2215883A1940-09-24
EP0529723A11993-03-03
EP0965562A11999-12-22
EP3052439A12016-08-10
US3617219A1971-11-02
EP2019056761W2019-03-19
US4299775A1981-11-10
GB841323A1960-07-13
Other References:
CHEMICAL ABSTRACTS, Columbus, Ohio, US; abstract no. 64742-94-5
SHIVE ET AL., JACS, vol. 64, 1942, pages 385 - 389
DISCHINO ET AL., JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, vol. 42, 1999, pages 965 - 974
Attorney, Agent or Firm:
VANDE GUCHT, Anne et al. (BE)
Download PDF:
Claims:
1. A process for manufacturing an alkyl substituted cyclohexanecarbonitrile, said process comprising the following steps:

- reaction of cyanoisophorone with an organometallic compound comprising an alkyl group in order to transform the ketone moiety into its corresponding alcohol;

- reduction of the alcohol in order to obtain the alkyl substituted cyclohexanecarbonitrile.

2. The process according to claim 1, said process comprising the additional step of synthesizing the cyanoisophorone through cyanation of isophorone.

3. The process according to claim 1 or 2, wherein the alkyl substituted cyclohexane carbonitrile is 1,3,3,5-tetramethylcyclohexanecarbonitrile (C11G).

4. The process according to claim 2, wherein the cyanation uses KCN and/or NaCN. 5. The process according to claim 2 or 4, wherein the cyanation takes place in a polar solvent like DMF, DMSO or sulfolane.

6. The process according to any of claims 1 to 5, wherein the organometallic compound is a Grignard reagent or DMZ (DiMethylZinc).

7. The process according to claim 6, wherein the organometallic compound is methylMgBr or methylMgCl.

8. The process according to any of claims 1 to 7, wherein the reaction of the cyanoisophorone with the organometallic compound takes place in an ether solvent (THF or methyl THF for instance), in anhydrous conditions.

9. The process according to any of claims 1 to 8, wherein the step of reducing the alcohol uses an organosilane reducing agent like Et3SiH, A1C13,

TiC14 or Boron trifluoride etherate (strictly boron trifluoride diethyl etherate, or boron trifluoride-ether complex) preferably assisted by TFA (TriFluoro Acetic Acid).

10. 1,3,3,5-tetramethylcyclohexanecarbonitrile (C11G) obtainable by a process according to any of claims 1 to 9.

11. A process for manufacturing hydrogen peroxide comprising the following steps: - hydrogenating a working solution which comprises an alkylanthraquinone and/or 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 obtained by a process according to any of claims 1 to 9 and/or is the compound according to claim 10.

12. The process according to claim 11, said process having a production capacity of hydrogen peroxide of up to 100 kilo tons per year. 13. The process according to claim 11 or 12, said process being operated in a plant located at an industrial end user site.

Description:
Process for manufacturing an alkyl substituted cyclohexanecarbonitrile

The present invention relates to a process for manufacturing an alkyl substituted cyclohexanecarbonitrile, to a specific alkyl substituted cyclohexanecarbonitrile and to its use as solvent in the manufacture of an aqueous hydrogen peroxide solution. 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-alkylanthraquinone, 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 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 oxygen-enriched air 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). Hydrogen peroxide is then typically extracted with water and recovered in the form of a crude aqueous hydrogen peroxide solution, and the quinone is returned to the hydrogenator to complete the loop. The use of di-isobutyl-carbinol (DIBC) 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, A150, 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 H202 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 EP2019/056761 to 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).

The synthesis of such solvents has been reported in literature. For instance 2,2,6-trimethyl-cyclohexane-carbonitrile was synthesized by Shive et al. (JACS, 1942, vol. 64, pp.385-389) starting from geranic acid which was first cyclized using formic acid (1); was then hydrogenated to the corresponding saturated acid (2,2,6-trimethylcyclohexanecarboxylic acid) (2), which was then transformed in the corresponding acyl chloride using thionyl chloride (3), then in the corresponding amide using ammonia (4) and finally, in the corresponding carbonitrile by dehydration using phosphorus pentoxide (5).

This way of synthesis hence implies 5 reaction steps. Besides, the solvent generated only has IO C atoms (hence, is a CIO) while we found out that better results in terms of hydrogenated quinone solubility and insolubility in H202 (hence higher purity level of the H202) can be obtained with nitriles having a higher number of C atoms i.e. Cl 1 or Cl 1+ (i.e. more than 11C atoms).

However, the synthesis of such kind of solvents has up till now not been reported in literature. Therefore, in a first aspect, the present invention relates to a process for manufacturing an alkyl substituted cyclohexanecarbonitrile from the a, b- unsaturated cyclohexenone 3,3,5-trimethylcyclohex-2-enone also called isophorone, said process comprising the following steps:

- isophorone cyanation to cyanoisophorone; - reaction of said cyanoisophorone with an organometallic compound comprising an alkyl group in order to transform the ketone moiety into its corresponding alcohol;

- reduction of the alcohol in order to obtain the alkyl substituted cyclohexanecarbonitrile. Since cyanoisophorone, also called IsoPhoroneNitrile or IPN also is commercially available, the present invention also relates to a process for manufacturing an alkyl substituted cyclohexanecarbonitrile from cyanoisophorone, said process comprising the following steps:

- reaction of said cyanoisophorone with an organometallic compound comprising an alkyl group in order to transform the ketone moiety into its corresponding alcohol;

- reduction of the alcohol in order to obtain the alkyl substituted cyclohexanecarb onitril e .

In a preferred embodiment, said process comprising the additional step of synthesizing the cyanoisophorone through cyanation of isophorone.

The alkyl substituted cyclohexanecarbonitrile that can be obtained by the process according to the invention comprises 4 substituents namely: 3 methyl groups coming from the (cyano)isophorone and the alkyl group coming from the organometallic compound, which preferably is a methyl or an ethyl group, more preferably a methyl group. Hence, the preferred alkyl substituted cyclohexane carbonitrile that can be obtained in the frame of the invention is 1, 3,3,5- tetramethyl cyclohexanecarbonitrile (Cl 1G).

An advantage of the process according to the invention is to start from a cheap and widely available chemical namely either isophorone which is produced on a multi-thousand ton scale by basic or acid catalysed condensation of acetone; or IPN which is also widely available on the market especially in China.

Cyanation of said isophorone has been reported in literature like for instance in the article to Dischino et al. in the Journal of Labelled Compounds and Radiopharmaceuticals, 42, 965-974 (1999), in US4299775 and in WO 2011/095576. It generally involves the use of compounds like KCN, NaCN, CuCN, Zn(CN)2, AlEt2CN and the like. KCN and/or NaCN are preferred for an industrial process mainly for economic reasons.

Cyanation preferably takes place in a polar solvent like DMF, DMSO or sulfolane. The reaction temperature preferably is from 50 to 150°C, preferably between 100 and 140°C, most preferably about 120°C. The reaction generally happens at a pressure from atmospheric pressure up till 10 bar, mots preferably at atmospheric pressure and until full conversion is reached. Alternatively, and even more preferably especially in case AlEt2CN is used, cyanation can take place in a non-polar organic solvent like toluene, at lower temperature, typically from -10°C until ambient temperature, preferably between 0 and 20°C.

The organometallic compound that can be used to transform the ketone group into a ternary alcohol can be a Grignard reagent (i.e. an organo-Mg compound), DMZ (DiMethylZinc)... A Grignard reagent is preferred, more particularly methylMgBr or methylMgCl. The reaction preferably takes place in an ether solvent (THF or methyl THF for instance), in anhydrous conditions. The reaction temperature preferably is below 0°C. The reaction is advantageously performed at atmospheric pressure.

The step of reducing the alcohol in order to obtain the alkyl substituted cyclohexanecarbonitrile preferably uses an organosilane reducing agent like Et3SiH, A1C13, TiC14 or Boron trifluoride etherate (strictly boron trifluoride diethyl etherate, or boron trifluoride-ether complex) preferably assisted by TFA (TriFluoroAcetic Acid). The reaction temperature preferably is from 20 to 100°C, more preferably from 30 to 80°C, most preferably about 50°C. The reaction if preferably conducted at atmospheric pressure and can be conducted solvent free or in a polar solvent like DCM or DCE.

The present invention also concerns a specific alkyl substituted cyclohexanecarbonitrile which can be obtained by the above described process namely compound Cl 1G described above. The synthesis of this compound has not been reported yet in literature. Finally, the present invention also relates to a process for manufacturing hydrogen peroxide comprising the following steps:

- hydrogenating a working solution which comprises an alkylanthraquinone and/or 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 obtained by a process as described above and/or has the formula Cl 1G as described above.

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-/.vopropylanthraquinone, 2 -sec- and 2-tert- butylanthraquinone (BQ), 1,3-, 2,3-, 1,4- and 2,7-dimethylanthraquinone, amylanthraquinones (AQ) like 2 -iso- and 2-/er/-amylanthraquinone and mixtures of these quinones. The term "tetrahydroalkylanthraquinone" is intended to denote the 9, 10- tetrahydroquinones corresponding to the 9,10-alkylanthraquinones specified above. Hence, for EQ and AQ, they respectively are designated by ETQ and ATQ, their reduced forms (tetrahydroalkylanthrahydroquinones) being respectively ETQH and ATQH. Preferably, an AQ or EQ is used, the latter being preferred.

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 solvents mixture, and more preferably at least 40wt%. Generally, there is not more than 80wt% of this non-polar solvent, preferably not more than 60wt% of it in the organic solvents 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, /cvV-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 hydro- carbons 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 (nButAc=100) of 5.3.

As explained above, 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 m3 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.

The term "washing" is intended to denote any treatment, which is well known in the chemical industry (as disclosed in GB841323A, 1956 (Laporte), for instance), of a crude aqueous hydrogen peroxide solution with an organic solvent which is intended to reduce the content of impurities in the aqueous hydrogen peroxide solution. 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 former 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 an H202 concentration within the range of 30- 50% by weight. The solvents of the invention make it is possible to achieve a higher solubility and thus there is less polar solvent needed to achieve a higher partition coefficient. With this higher partition coefficient it is possible to reduce the capex (capital expenditure) required for the extraction sector.

The solvents of the invention are particularly suitable for the manufacture of hydrogen peroxide by the AO-process wherein said process has a production capacity of hydrogen peroxide of up to 100 kilo tons per year (ktpa). Preferably said process is a small to medium scale AO-process operated 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 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 a small to medium scale 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 their partition coefficient is more favourable, less emulsion is observed in the process and a purer H202 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 degradates, like epoxy or anthrone derivatives, back into useful quinones. Here also, the solvents of the invention are favourable because the quality of the H202 solution can be maintained within the specifications namely in terms of TOC for a longer period of time.

The following example illustrates some preferred embodiments of the present invention.

Example

Step 1 - Synthesis of IsoPhorone Nitrile (IPN): In a 21 jacketed reactor fitted with mechanical stirring, thermostatically controlled at 15-10°C,

93 g (0.66 mol) of isophorone were introduced and diluted with 150 ml of hexane.

11 AlEt2CN (IN) in toluene (1.2 Eq ) were fed over three hours without exceeding 15°C then stirring was maintained for two hours at room temperature.

Once the reaction was complete, the reactor was drained slowly in 21 of NaOH solution (IN).

The solution obtained was stirred until two phases were separated.

The aqueous phase was extracted twice with 300 ml of MTBE and the organic phase was washed with 300 ml of water and then with 300 ml of water saturated with NaCl (26%). The organic phase was then dried over Mg sulfate and concentrated under vacuum.

103 g of a slightly yellow compound were obtained, which crystallized after several hours; GC confirmed the purity of the IPN was OK and a complete conversion with a Yield of 96%

Step 2 - Synthesis of l,3,5,5-tetramethyl-5-Hydroxy- cyclohexylcarbonitrile :

In a 500 ml reactor 24.8 g (0.15 mol) of IPN are dissolved in 300 ml of dry THF, under inert atmosphere. The medium was cooled to -40 ° C.

Once at temperature, 60 ml solution of a solution of CEBMgBr (3N) (1.2 Eq ) was added without exceeding -30°C (1.5 h).

The medium was stirred for one hour at -40 ° C.

The cold medium was poured onto ice (300 g) and 20 ml of concentrated HC1 were added.

Once at room temperature, the medium was diluted with 350 ml of MTBE.

The organic phase is set aside.

200 ml of a 26% (weight) NaCl solution were added to the aqueous phase, which was then extracted twice by 200 ml of MTBE (methyl tertbutyl ether). The two organic phases were combined and dried over Mg sulfate before being concentrated.

24.8 g of an oily substance were obtained which crystallized on cooling.

NMR analysis showed a 79/17 alcohol / ketone ratio was obtained.

Step 3 - Synthesis of 1,3,5,5-tetramethyl-cyclohexylcarbonitrile (C11G) :

In a 500 ml reactor 16.7 g (100% 0,lmole) of 1,3, 5, 5 -tetramethyl-5- Hydroxy-cyclohexylcarbonitrile were dissolved in 150 ml of dry DCM.

2 Eq (0.2 mol) (23.26 g) of triethylsilane were added, followed by 15 ml of trifluoroacetic acid. The medium was stirred at room temperature for 24 hours.

The medium was then poured into 250 ml of water; the organic phase was set aside and the aqueous phase extracted with 200 ml of DCM, generating a second organic phase.

The organic phases were combined and washed with 200 ml of a 10% KOH solution, then concentrated.

14 g of an oily substance were obtained, composed of Cl 1G and IPN. Placed in 25 ml of petroleum ether and cooled, the IPN precipitated; after filtration and evaporation of the petroleum ether, Cl 1G were obtained. (8.2 gr).