Mechanochemical synthesis of 2-(4'-c2-c10-alkylbenzoyl)benzoic acid

Abstract

The invention provides a process for the manufacture of a 2-(4'-C2-C10-alkylbenzoyl)benzoic acid, said process comprising causing a C2-C10-alkylbenzene and phthalic anhydride to undergo a mechanochemical Friedel-Crafts acylation in the presence of a Lewis acid to obtain a 2-(4'-C2-C10-alkylbenzoyl)benzoic acid. The invention also relates to processes for the manufacture of 2-(C2-C10)-alkyl-9,10-anthraquinones from 2-(4'-C2-C10- alkylbenzoyl)benzoic acid and for the manufacture of hydrogen peroxide using such anthraquinones.

Description

MECHANOCHEMICAL SYNTHESIS OF 2-(4'-C2-C10-ALKYLBENZOYL)BENZOIC ACIDFIELD OF THE INVENTION

[0001] The invention relates to the mechanochemical synthesis of 2-(4’-C2-C10- alkylbenzoyl)benzoic acid, that is to a process for preparing 2-(4’-C2-C10- alkylbenzoyl)benzoic acid by mixing reagents (C2-C10-al kyl benzene, phthalic anhydride and Lewis acid) mechanically in the absence of a solvent. The invention also relates to processes for the manufacture of 2-(C2-C10-alkyl)-9,10-anthraquinones from 2-(4’-C2-C10- alkylbenzoyl)benzoic acid and for the manufacture of hydrogen peroxide using such anthraquinones.BACKGROUND OF THE INVENTION

[0002] Hydrogen peroxide is produced industrially by the anthraquinone auto-oxidation process in which a 2-alkyl-9,10-anthraquinone is hydrogenated and its hydrogenated form oxidized in a cyclic process. Different alkyl-9,10-anthraquinones are reactive in the autooxidation process, including, 2-ethyl-, 2-butyl, 2-hexenyl-, diethyl- and 2-amyl-9,10- anthraquinone. 2-Amyl-9,10-anthraquinone is the most useful of these due to the high solubility in the working solution of that compound and its hydrogenated form and due to its high stability. It is a mixture comprising 2-tert-amyl- and 2-sec- / so-amyl-9,10-anthraquinone due to isomerization that occurs during the first step of the anthraquinone synthesis.

[0003] In general, 2-alkyl-9,10-anthraquinones are synthesized by a Friedel-Crafts acylation reaction between phthalic anhydride and an alkylbenzene in presence of a Lewis acid. The resulting 2-alkylbenzoylbenzoic acid is cyclized to the corresponding 2-alkyl-9, 10- anthraquinone by reaction with oleum, or concentrated sulfuric acid at an elevated temperature.

[0004] Generally, the process for the synthesis of 2-(4’-amylbenzoyl)benzoic acid uses Friedel-Crafts acylation between phthalic anhydride and tert-amylbenzene in a halogenated solvent such as dichloromethane with aluminum chloride as the Lewis acid. However, dichloromethane is a CMR (carcinogenic, mutagenic or toxic for reproduction) substance according to REACH Regulation (Regulation (EC) No. 1907 / 2006) and a substance of very high concern (SVHC) according to the definition introduced by REACH Regulation (Regulation (EC) No. 1907 / 2006). Hence, there is an incentive to synthesize 2-(mono- orpoly-alkylbenzoyl)benzoic acids without requiring a carcinogenic solvent like dichloromethane (cf. EP0429863, CN 104326896).

[0005] Besides dichloromethane, other halogenated solvents can be used in similar Friedel- Crafts acylation reactions. 2-(4’-Amylbenzoyl)benzoic acid has also been synthesized in chlorobenzene (cf. US4087458, JP2010105942), o-dichlorobenzene (cf. US4087458, US5107004), trichlorobenzene (cf. US4035396), 4-fluorobromobenzene (cf. CN116120160) and 1 ,2-dichloroethane (cf. CN109320414). 2-(4’-tert-Butylbenzoyl)benzoic acid has been synthesized in 1 ,2-dichloroethane (cf. CN115991642). And 2-(4’-ethylbenzoyl)benzoic acid has been synthesized in chlorobenzene, p-dichlorobenzene, fluorobenzene, p- difluorobenzene and 4-fluorobromobenzene (cf. CN116120160). However, these halogenated solvents are either also SVHC’s, as they are carcinogenic substances (dichloromethane, 1 ,2-dichloroethane, p-dichlorobenzene) or persistent bioaccumulative substances (trichlorobenzene). Or there is a significant risk that they will be characterized as such in the future (chlorobenzene, o-dichlorobenzene, fluorobenzene, p-difluorobenzene and 4-fluorobromobenzene). 2-(4’-Ethylbenzoyl)benzoic acid has also been synthesized in nitrobenzene (cf. CN111747839), but this is also a carcinogenic SVHC substance. Moreover, all of these alternative solvents are more expensive than dichloromethane.Med. Chem. Res. Vol. 22(1) pp 453-465 (2012) discloses the synthesis of 2-(4- isopropylbenzoyl)benzoic acid from phthalic anhydride and cumene using carbon disulphide as solvent. JP S61 158949 and US-A-4,792,551 disclose similar reactions using dichloroethane and ethyl benzene as solvents, respectively.

[0006] Rather than using a halogenated solvent, an aluminum chloride based ionic liquid can be used as both the Lewis acid and the solvent of these Friedel-Crafts acylation reactions (cf. J. Chem. Res. (S) 2003, 650-651 ; J P61176537; CN101921189; CN103896756). However, ionic liquids are difficult to prepare, to dry and to recycle making them expensive alternatives for dichloromethane.

[0007] Alternatively, the (alkyl)benzene reagent can be used in excess to function as both reagent and solvent. Thus, 2-benzoylbenzoic acid has been synthesized in 7-10 equivalents benzene (cf. Comptes rendus 1878, 86, 1368-1371 ; Ann. chim. phys. 1888, 14, 433-472; Ber. Dtsch. Chem. Ges. 1908, 41, 3627-3638; Acta Chem. Scand. 1996, 50, 954-957; US2009012116); 2-(4-methylbenzoyl)benzoic acid has been synthesized in 3-11 equivalents toluene (cf. Bull. soc. chim. 1881 , 35, 503-509; Ann. chim. phys. 1888, 14, 433-472; Ber. Dtsch. Chem. Ges. 1908, 41, 3627-3638; Org. Synth. 1925, 4, 73; Aust. J. Chem. 1990, 43, 593-600; Acta Chem. Scand. 1996, 50, 954-957); 2-(4’-ethylbenzoyl)benzoic acid has beensynthesized in 5 equivalents ethylbenzene (cf. CN111747839; CN 115368227) and 2-(4’- amylbenzoyl)benzoic acid has been synthesized in 6 equivalents tert-amylbenzene (cf. CN 101602660). However, a large excess is required to compensate for the low solubility of phthalic anhydride in (alkyl)benzenes. As the (alkyl)benzene is typically the most expensive reagent of these Friedel-Crafts reactions, a large excess of (alkyl)benzene is not a good alternative for using halogenated solvents.

[0008] The excess (alkyl)benzene can be significantly reduced by changing the mixing method from stirring a solution to mechanical mixing of the reagents in the absence of a solvent. For example, Ind. Eng. Chem. vol. 22(6) pp 620-625 (1930) discloses the synthesis of 2-(4'-phenyl-benzoyl) benzoic acid by reacting biphenyl with phthalic anhydride using AICI3 in a rotating iron mill. For example, mixing phthalic anhydride, aluminum chloride and benzene in a tumbler ball mill reduced the required excess of benzene from 7-10 equivalents to 2-3 equivalents for the synthesis of 2-benzoylbenzoic acid (cf. US1656575; US2496894). However, due to the low rotating speed of the tumbler ball mill, the reaction took several hours to reach full conversion. For 2-(4’-methylbenzoyl)benzoic acid, mixing phthalic anhydride, aluminum chloride and toluene in a vibrational ball mill reduced the excess benzene from 3-11 equivalents to 1 equivalent (cf. Beilstein J. Org. Chem. 2019, 15, 1313- 1320). Due to the high vibrational frequency, the reaction in the vibrational ball mill was much faster and was complete within 1 hour. However, the vibrational ball mill procedure was only used on a very small (milligram) scale. A similar solventless synthesis of 2-(4’- ethylbenzoyl)benzoic acid and 2-(4’-amylbenzoyl)benzoic acid has not been described.

[0009] Thus, there remains a desire to produce 2-(4’-C2-C10-alkylbenzoyl)benzoic acids, such as 2-(4’-ethylbenzoyl)benzoic acid and 2-(4’-amylbenzoyl)benzoic acid, by Friedel- Crafts acylation of the corresponding C2-C10-alkylbenzene, such as ethylbenzene or amylbenzene, with phthalic anhydride in the presence of a Lewis acid in a manner that avoids or minimizes the use of hazardous or noxious solvents, especially, halogenated solvents, such as dichloromethane, or solvents that are expensive or difficult to handle, or the use of large excesses of the alkylbenzene serving as reaction medium. It is also desirable to use the thus produced 2-(4’-C2-C10-alkylbenzoyl)benzoic acid to produce 2-(C2- C10-alkyl)-9,10-anthraquinone, which can in turn be used in the production of hydrogen peroxide.SUMMARY OF THE INVENTION

[0010] The problem to be solved by the invention is to provide a process for the manufacture of 2-(4’-C2-C10-alkylbenzoyl)benzoic acids by Friedel-Crafts acylation of the corresponding C2-C10-alkylbenzene with phthalic anhydride in the presence of a Lewis acid that avoids the disadvantages of known such processes.

[0011] In particular, the process is to avoid or minimizes the use of hazardous or noxious (e.g. carcinogenic, mutagenic or toxic for reproduction) solvents such as halogenated solvents (especially, dichloromethane, 1,2-dichloroethane, p-dichlorobenzene), nitrobenzene, or other solvents which are difficult to prepare or expensive; the process is also to avoid the use of large excesses of the alkylbenzene serving as reaction medium.

[0012] Furthermore, the process is to provide the target 2-(4’-C2-C10-alkylbenzoyl)benzoic acid in high yield and purity and to suppress unwanted side reactions. In particular, the ratio of the mass of isolated target product (2-(4’-C2-C10-alkylbenzoyl)benzoic acid) over the sum of the mass of all the reagents and additives introduced in the reaction (“process mass efficiency”) should be high.

[0013] The invention also aims to provide a process for the manufacture of 2-(C2-C10-alkyl)- 9,10-anthraquinones, for which the aforementioned 2-(4’-C2-C10-alkylbenzoyl)benzoic acids are starting materials, and a process for the manufacture of hydrogen peroxide that uses the 2-(C2-C10-alkyl)-9,10-anthraquinones obtained thereby.

[0014] In order to solve the above problems, the invention provides a process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, said process comprising causing a C2-C10-alkylbenzene and phthalic anhydride to undergo a mechanochemical Friedel-Crafts acylation in the presence of a Lewis acid to obtain a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, wherein no solvent at all is used, wherein C2-C10-alkylbenzene and, if present, nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, are not considered as solvents, and wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 1.1 : 1 to 4.8 : 1.Further, the invention provides process for the manufacture of a 2-(4’-C2-C10- alkylbenzoyl)benzoic acid, said process comprising causing a C2-C10-alkylbenzene and phthalic anhydride to undergo a mechanochemical Friedel-Crafts acylation in the presence of a Lewis acid to obtain a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, wherein the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid is 2-(4’-ethylbenzoyl)benzoic acid and the C2-C10-al kyl benzene is ethylbenzene, or the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid is 2-(4’-amylbenzoyl)benzoicacid and the C2-C10-alkylbenzene is tert-amyl benzene, wherein no solvent at all is used, wherein ethylbenzene and tert-amylbenzene and, if present, 1 -nitropropane are not considered as solvents, and wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 1.1 : 1 to 2.5 : 1.Preferably, the invention provides a process for the manufacture of a 2-(4’-C2-C10- alkylbenzoyl)benzoic acid, said process comprising causing a C2-C10-alkylbenzene and phthalic anhydride to undergo a mechanochemical Friedel-Crafts acylation in the presence of a Lewis acid to obtain a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, wherein the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid is 2-(4’-ethylbenzoyl)benzoic acid and the C2-C10-al kyl benzene is ethylbenzene, or the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid is 2-(4’-amylbenzoyl)benzoic acid and the C2-C10-alkylbenzene is tert-amylbenzene, wherein no solvent at all is used, wherein C2-C10-alkylbenzene and, if present, nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group - in particular, wherein the nitrohydrocarbon compound of formula R-NO2 comprises 1 -nitropropane - are not considered as solvents, and wherein the molar ratio of the C2-C 10-al kyl benzene to the phthalic anhydride used in the process is 1.1 : 1 to 2.5 : 1.

[0015] In the process according to the invention, the C2-C10-alkylbenzene may be ethylbenzene, in which case the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid produced is 2-(4’- ethylbenzoyl)benzoic acid.

[0016] In the process according to the invention, the C2-C10-alkylbenzene may be tert- amylbenzene, in which case the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid is 2-(4’- amylbenzoyl)benzoic acid.

[0017] In one embodiment, the process according to the invention does not comprise a step of pre-mixing the phthalic anhydride and the Lewis acid in the absence of the C2-C10- alkylbenzene.

[0018] In another embodiment, the process according to the invention comprises (A) first pre-mixing the phthalic anhydride and the Lewis acid to obtain a powdery mixture and (B) then mixing the powdery mixture with the C2-C10-alkylbenzene to effect the mechanochemical Friedel-Crafts acylation to obtain the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid.

[0019] In the process according to the invention, the C2-C 10-al kyl benzene and phthalic anhydride may be caused to undergo the mechanochemical Friedel-Crafts acylation in thefurther presence of a nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, for example R may be n-propyl.

[0020] In the process according to the invention, if the C2-C10-alkylbenzene and phthalic anhydride are caused to undergo the mechanochemical Friedel-Crafts acylation in the further presence of a nitrohydrocarbon compound, the process may comprise: (A) first pre-mixing the phthalic anhydride and the Lewis acid to obtain a powdery mixture and (B) then mixing the powdery mixture with the C2-C10-al kyl benzene and the nitrohydrocarbon compound to effect the mechanochemical Friedel-Crafts acylation to obtain the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid.

[0021] In the process according to the invention, if the C2-C10-alkylbenzene and phthalic anhydride are caused to undergo the mechanochemical Friedel-Crafts acylation in the further presence of a nitrohydrocarbon compound, the C2-C10-alkylbenzene may be a C3-C10- alkylbenzene having a branched alkyl group.

[0022] In the process according to the invention, the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process may be 1.0 : 1 to 2.5 : 1. Preferably, the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is at least 1.2, possibly at least 1.5 or at least 2.0. Preferably, the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is at most 3.6, possibly at most 3.0 or at most 2.4. Preferably, the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 1.2 : 1 to 2.4 : 1. Alternatively, when the reaction is carried out in a reactive extruder, a preferred molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process can be 2.0 : 1 to 3.0 : 1.

[0023] In the process according to the invention, the molar ratio of the nitrohydrocarbon compound, if used, to the phthalic anhydride used in the process may be 0.1 : 1 to 0.5 : 1.

[0024] In the process according to the invention, the reactants may be mixed in a planetary ball mill, a vibrational ball mill, a tumbler ball mill, a kneader or an attritor.

[0025] In any of the processes according to the invention, the reaction may be carried out in a reactive extruder. Preferably, the extruder is a single screw extruder, a multiple screw extruder, a twin-screw extruder or a planetary extruder. More preferably, the extruder is a twin-screw extruder. Preferably, when the reaction is carried out in a reactive extruder, the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 2.0 : 1 to 3.0 : 1.

[0026] The invention further provides a process for the manufacture of a 2-(C2-C10-alkyl)- 9,10-anthraquinone, said process comprising the following steps: (i) manufacturing a 2-(4’- C2-C10-alkylbenzoyl)benzoic acid by the aforementioned process according to the invention; (ii) causing the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid to react with a dehydrating agent, to obtain the 2-(C2-C10-alkyl)-9,10-anthraquinone.

[0027] Furthermore, the invention also provides a process for the manufacture of hydrogen peroxide, said process comprising: (a) manufacturing a 2-(C2-C10-alkyl)-9,10-anthraquinone by the process described in the preceding paragraph; (b) hydrogenating a solution which comprises the 2-(C2-C10-alkyl)-9,10-anthraquinone to produce a hydrogenated working solution containing a 2-(C2-C10-alkyl)-9,10-anthrahydroquinone; (c) oxidizing the 2-(C2-C10- alkyl)-9,10-anthrahydroquinone contained in the hydrogenated working solution to produce an oxidized working solution comprising hydrogen peroxide and 2-(C2-C10-alkyl)-9,10- anthraquinone; (d) isolating the hydrogen peroxide from the oxidized working solution.DETAILED DESCRIPTION OF THE INVENTION

[0028] The invention provides a process for the manufacture of a 2-(4’-C2-C10- alkylbenzoyl)benzoic acid, said process comprising causing a C2-C10-alkylbenzene and phthalic anhydride to undergo a mechanochemical Friedel-Crafts acylation in the presence of a Lewis acid to obtain a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, wherein no solvent at all is used, wherein C2-C10-alkylbenzene and, if present, nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, are not considered as solvents, and wherein the molar ratio of the C2-C10-al kyl benzene to the phthalic anhydride used in the process is 1.1 : 1 to 4.8 : 1.Further, the invention provides process for the manufacture of a 2-(4’-C2-C10- alkylbenzoyl)benzoic acid, said process comprising causing a C2-C10-alkylbenzene and phthalic anhydride to undergo a mechanochemical Friedel-Crafts acylation in the presence of a Lewis acid to obtain a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, wherein the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid is 2-(4’-ethylbenzoyl)benzoic acid and the C2-C 10-al kyl benzene is ethylbenzene, or the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid is 2-(4’-amylbenzoyl)benzoic acid and the C2-C10-alkylbenzene is tert-amyl benzene, wherein no solvent at all is used, wherein ethylbenzene and tert-amylbenzene and, if present, 1 -nitropropane are not considered as solvents, and wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 1.1 : 1 to 2.5 : 1.

[0029] In the context of the present invention, “C2-C10-alkyl”, alone or in combinations such as “C2-C10-alkylbenzene” and “2-(4’-C2-C10-alkylbenzoyl)benzoic acid”, means an alkyl group having 2 to 10 carbon atoms. Hence “C2-C10” means “having 2 to 10 carbon atoms”. C2-C10 alkyl groups may be, for example, ethyl, propyl, n-propyl, / so-propyl, butyl, n-butyl, sec-butyl, / so-butyl, tert-butyl, pentyl (amyl), n-pentyl, sec-pentyl, 3-pentyl, / so-pentyl, sec- / so-pentyl, tert-pentyl, neo-pentyl, hexyl, heptyl, octyl, nonyl, or decyl.

[0030] Hence, the C2-C10-alkylbenzene used in the process may be ethylbenzene, propylbenzene, n-propylbenzene, / so-propylbenzene, butylbenzene, n-butylbenzene, secbutylbenzene, / so-butylbenzene, tert-butylbenzene, pentylbenzene (amylbenzene), n- pentylbenzene, sec-pentylbenzene, 3-pentylbenzene, / so-pentylbenzene, sec- / so- pentylbenzene, tert-pentylbenzene, neo-pentylbenzene, hexylbenzene, heptylbenzene, octylbenzene, nonylbenzene, or decylbenzene, in which case the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid produced in the process is, respectively, 2-(4’- ethylbenzoyl)benzoic acid, 2-(4’-propylbenzoyl)benzoic acid, 2-(4’-n-propylbenzoyl)benzoic acid, 2-(4’- / so-propylbenzoyl)benzoic acid, 2-(4’-butylbenzoyl)benzoic acid, 2-(4’-n- butylbenzoyl)benzoic acid, 2-(4’-sec-butylbenzoyl)benzoic acid, 2-(4’- / so- butylbenzoyl)benzoic acid, 2-(4’-tert-butylbenzoyl)benzoic acid, 2-(4’-pentylbenzoyl)benzoic acid (2-(4’-amylbenzoyl)benzoic acid), 2-(4’-n-pentylbenzoyl)benzoic acid, 2-(4’-sec- pentylbenzoyl)benzoic acid, 2-(4’-3-pentylbenzoyl)benzoic acid, 2-(4’- / so- pentylbenzoyl)benzoic acid, 2-(4’-sec- / so-pentylbenzoyl)benzoic acid, 2-(4’-tert- pentylbenzoyl)benzoic acid, 2-(4’-neo-pentylbenzoyl)benzoic acid, 2-(4’- hexylbenzoyl)benzoic acid, 2-(4’-heptylbenzoyl)benzoic acid, 2-(4’-octylbenzoyl)benzoic acid, 2-(4’-nonylbenzoyl)benzoic acid, or 2-(4’-decylbenzoyl)benzoic acid. The latter 2-(4’-C2-C 10- alkylbenzoyl)benzoic acids may be used to produce the corresponding 2-(C2-C10-alkyl)-9.10-anthraquinones, i.e. 2-ethyl-9,10-anthraquinone, 2-propyl-9,10-anthraquinone, 2-n- propyl-9,10-anthraquinone, 2- / so-propyl-9,10-anthraquinone, 2-butyl-9,10-anthraquinone, 2- n-butyl-9, 10-anthraquinone, 2-sec-butyl-9, 10-anthraquinone, 2- / so-butyl-9, 10-anthraquinone, 2-tert-butyl-9,10-anthraquinone, 2-pentyl-9,10-anthraquinone (2-amyl-9,10-anthraquinone), 2-n-pentyl-9, 10-anthraquinone, 2-sec-pentyl-9, 10-anthraquinone, 2-3-pentyl-9, 10- anthraquinone, 2- / so-pentyl-9,10-anthraquinone, 2-sec- / so-pentyl-9,10-anthraquinone, 2-tert- pentyl-9,10-anthraquinone, 2-neo-pentyl-9,10-anthraquinone, 2-hexyl-9,10-anthraquinone, 2- heptyl-9,10-anthraquinone, 2-octyl-9,10-anthraquinone, 2-nonyl-9,10-anthraquinone, 2-decyl-9.10-anthraquinone

[0031] The alkyl group in the C2-C10-al kyl benzene may have 3 to 10 carbon atoms, in which case the C2-C 10-al kyl benzene used in the process according to the invention is a C3-C10-alkylbenzene and the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid produced in the process is a 2- (4’-C3-C10-alkylbenzoyl)benzoic acid; the 2-(C2-C10-alkyl)-9,10-anthraquinone manufactured therefrom is a 2-(C3-C10-alkyl)-9,10-anthraquinone.

[0032] The alkyl group in the C2-C10-alkylbenzene may have 2 to 8 carbon atoms, in which case the C2-C10-al kyl benzene used in the process according to the invention is a C2-C8- alkylbenzene and the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid produced in the process is a 2- (4’-C2-C8-alkylbenzoyl)benzoic acid; the 2-(C2-C10-alkyl)-9,10-anthraquinone manufactured therefrom is a 2-(C2-C8-alkyl)-9,10-anthraquinone.

[0033] The alkyl group in the C2-C10-alkylbenzene may have 2 to 6 carbon atoms, in which case the C2-C 10-al kyl benzene used in the process according to the invention is a C2-C6- alkylbenzene and the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid produced in the process is a 2- (4’-C2-C6-alkylbenzoyl)benzoic acid; the 2-(C2-C10-alkyl)-9,10-anthraquinone manufactured therefrom is a 2-(C2-C6-alkyl)-9,10-anthraquinone.

[0034] The alkyl group in the C2-C10-alkylbenzene may have 3 to 6 carbon atoms, in which case the C2-C 10-al kyl benzene used in the process according to the invention is a C3-C6- alkylbenzene and the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid produced in the process is a 2- (4’-C3-C6-alkylbenzoyl)benzoic acid; the 2-(C2-C10-alkyl)-9,10-anthraquinone manufactured therefrom is a 2-(C3-C6-alkyl)-9,10-anthraquinone.

[0035] The alkyl group in the C2-C10-alkylbenzene may have 4 to 6 carbon atoms, in which case the C2-C 10-al kyl benzene used in the process according to the invention is a C4-C6- alkylbenzene and the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid produced in the process is a 2- (4’-C4-C6-alkylbenzoyl)benzoic acid; the 2-(C2-C10-alkyl)-9,10-anthraquinone manufactured therefrom is a 2-(C4-C6-alkyl)-9,10-anthraquinone.

[0036] The alkyl group in the C2-C 10-al kyl benzene may have 5 carbon atoms, in which case the C2-C 10-al kyl benzene used in the process according to the invention is a C5- alkylbenzene and the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid produced in the process is a 2- (4’-C5-alkylbenzoyl)benzoic acid; the 2-(C2-C10-alkyl)-9,10-anthraquinone manufactured therefrom is a 2-(C5-alkyl)-9,10-anthraquinone.

[0037] In the process according to the invention, the C2-C10-alkylbenzene may be ethylbenzene, in which case the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid produced is 2-(4’- ethylbenzoyl)benzoic acid; the 2-(C2-C10-alkyl)-9,10-anthraquinone manufactured from the latter is 2-ethyl-9,10-anthraquinone.

[0038] In the process according to the invention, the C2-C10-alkylbenzene may be tert- amylbenzene, in which case the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid is 2-(4’- amylbenzoyl)benzoic acid; the 2-(C2-C10-alkyl)-9,10-anthraquinone manufactured from the latter is 2-amyl-9,10-anthraquinone.

[0039] The process according to the invention is a mechanochemical process. Mechanochemistry or mechanochemical reaction refers to chemical reactions induced by the direct absorption of mechanical energy (IIIPAC Compendium of Chemical Terminology, 3rd ed. International Union of Pure and Applied Chemistry; 2006. Online version 3.0.1, 2019. https: / / doi.org / 10.1351 / goldbook).

[0040] That is, in accordance with the invention, a mixture of the C2-C10-alkylbenzene, phthalic anhydride and Lewis acid is subjected to a mechanical stress at least sufficient to bring about a mechanochemical reaction between the C2-C10-al kyl benzene and phthalic anhydride.

[0041] In the process according to the invention, the mechanical stress employed advantageously produces sufficient mechanical energy to bring about the mechanochemical synthesis of the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid.

[0042] The magnitude of the mechanical energy necessary will depend on various parameters, in particular on the reactants brought together, on the Lewis acid, on the respective particle sizes of the solid materials of the mixture, on the pressure and temperature at which the process is carried out and on the equipment used in this stage. The minimum and optimum magnitudes of this mechanical energy must consequently be determined in each specific case by a person skilled in the art.

[0043] Devices which can be used in the process according to the invention comprise ball mills, such as planetary ball mills, vibrational ball mills and tumbler ball mills, extruders such a reactive extruder, preferably a single screw extruder, a multiple screw extruder, for example a twin-screw extruder or a planetary extruder, kneaders and attritors.

[0044] The process according to the invention advantageously starts at standard atmospheric pressure. The temperature is advantageously suitable for the C2-C10- alkylbenzene to react with the phthalic anhydride in the presence of the Lewis acid.

[0045] The optimum temperature will depend on various parameters, including the selection of the materials participating in the reaction and their physical state. The temperature is preferably less than or equal to 100 °C and of greater than or equal to 0 °C and particularlypreferably the temperature is less than or equal to 80 °C and greater than or equal to 10 °C. Very particularly preferably, the starting temperature is the room temperature and the latter naturally rises during the reaction to reach values of the order of 50 °C maximum.

[0046] In general, in the process according to the invention, the duration of the process advantageously varies between a few minutes and a few hours depending on the nature and the physical state of the reactants. In general, the duration is preferably at least 5 minutes, particularly preferably at least 10 minutes and very particularly preferably at least 15 minutes. In general, the duration is preferably at most 10 hours, particularly preferably at most 5 hours and very particularly preferably at most 2 hours.

[0047] However, in particular embodiments wherein the reaction is carried out in a reactive extruder the duration of the process advantageously varies between 30 seconds and 1 hour depending on various parameters including the nature and the physical state of the reactants. In general, the duration is preferably at least 30 seconds, particularly preferably at least 1 minute and very particularly preferably at least 2 minutes. In general, the duration is preferably at most 1 hour, particularly preferably at most 20 minutes and very particularly preferably at most 5 minutes. In general, durations of between 2 minute and 4 minutes are highly suitable.

[0048] The process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid according to the invention can be carried out as a one-step process which does not comprise a step of pre-mixing the phthalic anhydride and the Lewis acid in the absence of the C2-C10- alkylbenzene. In this case, a mixture prepared by adding C2-C10-alkylbenzene, for example tert-amylbenzene, and optionally a nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, for example 1 -nitropropane, to a not pre-milled mixture of phthalic anhydride and Lewis acid, for example anhydrous AICI3, may be mixed, for example with a planetary ball mill or a vibrational ball mill or in a batch kneader or in a reactive extruder. Such a process may be carried out with an excess of at least 2 equivalents of C2- C10-alkylbenzene, for example tert-amylbenzene, and varying amounts of nitrohydrocarbon compound, for example, nitropropane. 1 -Nitropropane may be used in combination with nitromethane.

[0049] More specifically, phthalic anhydride (for example 1 eq), anhydrous AICI3 (for example 2.2 eq), C2-C10-alkylbenzene, for example tert-amylbenzene (for example 2 eq), and optionally 1 -nitropropane, may be placed in a container and ball milled with a planetary ball mill. The reaction mixture may then be contacted with aqueous HCI solution, and the target 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, for example 2-(4’-amylbenzoyl)benzoic acid,may be isolated by means known to the person skilled in the art.

[0050] Similarly, phthalic anhydride (for example 1 eq), anhydrous AlCh (for example 2.2 eq), C2-C10-alkylbenzene, for example tert-amylbenzene (for example 2 eq), and optionally 1 -nitropropane, may be milled in a kneader or attritor. The reaction mixture may then be contacted with aqueous HCI solution, and the target 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, for example 2-(4’-amylbenzoyl)benzoic acid, may be isolated by means known to the person skilled in the art. For instance, phthalic anhydride (for example 1 eq), AICI3 (for example 2.4 eq), C2-C10-alkylbenzene, for example tert-amylbenzene (for example 3 eq) and 1- nitropropane (for example 0.5 eq) may be milled in a batch kneader. The reaction mixture may then be contacted with aqueous HCI solution, and the target 2-(4’-C2-C10- alkylbenzoyl)benzoic acid, for example 2-(4’-amylbenzoyl)benzoic acid, may be isolated by means known to the person skilled in the art.

[0051] Similarly, the process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid according to the invention can be carried out as a one-step process by adding phthalic anhydride, C2-C10-alkylbenzene, for example ethylbenzene, and Lewis acid, for example AICI3, to the inlet of a reactive extruder, for example a twin-screw extruder, and mixing the reaction mixture therein. For example, phthalic anhydride (for example 1 eq), C2-C10- alkylbenzene, for example tert-amylbenzene (for example 2.0 to 3.0 eq), and anhydrous AICI3 (for example 2.6 eq), optionally nitromethane and optionally 1 -nitropropane, may be mixed in a twin-screw extruder.

[0052] The process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid according to the invention can also be carried out as a two-step process which comprises a first step (A) of first pre-mixing the phthalic anhydride and the Lewis acid to obtain a powdery mixture and a second step (B) of then mixing the powdery mixture with the C2-C10- alkylbenzene, and optionally a nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, for example 1 -nitropropane, to effect the mechanochemical Friedel-Crafts acylation to obtain the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid. In this case, the mixing may be carried out with a ball mill, for example a planetary ball mill.

[0053] More specifically, in the first step, the powders of phthalic anhydride and Lewis acid, for example aluminum chloride, may be mixed, for example at a molar ratio of about 1 : 2. The resulting mixture may then be ball milled with C2-C10-alkylbenzene, for example ethylbenzene (in varying stoichiometric excess) to provide, after work-up, the target 2-(4’-C2- C10-alkylbenzoyl)benzoic acid, for example 2-(4’-ethylbenzoyl)benzoic acid. The work-up may be effected by contacting the reaction mixture with aqueous HCI solution and isolatingthe target 2-(4’-C2-C10-alkylbenzoyl)benzoic acid by means known to the person skilled in the art.

[0054] Similarly, the process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid according to the invention can be carried out as a two-step process by effecting solventless Friedel-Crafts acylation between phthalic anhydride, Lewis acid, for example aluminum chloride, and C2-C10-alkylbenzene, for example tert-amylbenzene, and optionally a nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, for example 1 -nitropropane, in two steps, for example with a planetary ball mill. In the case of using tert-amylbenzene, as with the conventional Friedel-Crafts acylation in solution, isomerization of the tert-amyl function to sec- / so-amyl and the dealkylation to 2- benzoylbenzoic acid may occur.

[0055] More specifically, phthalic anhydride (1 eq) and Lewis acid, for example anhydrous AlCh (about 2.2 eq) may be placed in a container and ball milled, for example with a planetary or vibrational ball mill. C2-C10-alkylbenzene, for example tert-amylbenzene, and optionally a nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, for example 1 -nitropropane, may be added and the mixture may be ball milled further. The reaction mixture may then be contacted with an aqueous HCI solution and the target 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, for example containing 2 isomers of 2-(4’- amylbenzoyl)benzoic acid together with a small amount of 2-benzoylbenzoic acid, may be isolated by means known to the person skilled in the art.

[0056] In the process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid according to the invention, the molar ratio of the phthalic anhydride to the Lewis acid used in the process may be at least 1 : 1.9, preferably at least 1 : 2.0, in particular, this ratio may be 1 : 1.9 to 1 : 5.0, preferably 1 : 1.9 to 1 : 2.5, more preferably 1 : 2.0 to 1 : 2.5.

[0057] In the process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid according to the invention, the molar ratio of the C2-C10-al kyl benzene to the phthalic anhydride used in the process may be 1.0 : 1 to 2.5 : 1 ; preferably, this ratio may be 1.1 : 1 to 2.5 : 1 , more preferably 1.2 : 1 to 2.4 : 1 , particularly preferably 1.2 : 1 to 2.0 : 1 , 1.2 : 1 to 1.5 : 1 , or 1.5 : 1 to 2.0 : 1. Alternatively, when the reaction is carried out in a reactive extruder, preferably a twin-screw extruder, the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process can be 2.0 : 1 to 3.0 : 1.

[0058] In the process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid according to the invention, the molar ratio of the nitrohydrocarbon compound, if used, to thephthalic anhydride used in the process may be 0.1 : 1 to 0.5 : 1 ; preferably this ratio may be 0.1 : 1 to 0.4 : 1 , more preferably 0.1 : 1 to 0.3 : 1 , particularly preferably 0.2 : 1 to 0.5 : 1 , 0.3 : 1 to 0.5 : 1 , or 0.2 : 1 to 0.4 : 1.

[0059] In the process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid according to the invention, the Lewis acid can be any Lewis acid that is conventionally used in Friedel-Crafts reactions, such as aluminum halides (AIX3, where X is F, Cl or Br, preferably Cl, in particular aluminum chloride, AICI3), alkylaluminum halides (RnAIX3-n, where X is F, Cl or Br, preferably Cl, and R is a C1-C10 alkyl group), titanium tetrachloride (TiCL), zinc dichloride (ZnCh), boron trifluoride (BF3), phosphorus pentafluoride (PF5), antimony pentafluoride (SbFs), tin dichloride (SnCh) or tin tetrachloride (SnCL).

[0060] The process according to the invention allows the synthesis of 2-(4’-(C2-C10)- alkylbenzoyl)benzoic acids, especially 2-(4’-ethylbenzoyl)benzoic acid, 2-(4’-tert- butylbenzoyl)benzoic acid or 2-(4’-amylbenzoyl)benzoic acid, without requiring the use of halogenated or other hazardous and / or expensive solvents.

[0061] In fact, the process according to the invention is solventless, i.e. no solvent at all is used in the process. The term “no solvent at all” encompasses “essentially no solvent”. Naturally, the materials employed in the inventive process can contain solvent impurities, in particular impurities inevitably resulting from the production thereof or from incomplete drying of equipment. The term “no solvent at all” or “essentially no solvent” means that minor amounts of solvent impurities can be present, namely those not materially affecting the essential characteristics of the employed materials and the process. Thus, as used herein, “no solvent at all” means that in the process, no amounts of solvents are present which materially affect the essential characteristics of the process. In other words, the process according to the invention can be realized with nearly no solvent, i.e. in the absence of a substantial amount of solvent. That is, all or at least some of reactants, reagents and any additives used in the process are solid at room temperature. Ethylbenzene and tert- amylbenzene, which may be starting materials in the process, are liquid at room temperature; 1 -nitropropane, which may be used as a mediator in the process, is also liquid at room temperature. However, in the context of the present invention these compounds, that is to say ethylbenzene, tert-amylbenzene and 1 -nitropropane, are not considered as solvents. More generally, in the context of the present invention, C2-C10-al kyl benzene and, if present, nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, are advantageously not considered as solvents.

[0062] By mechanical mixing of the solventless system, the required excess of the C2-C10- alkylbenzene can be minimized to 2 equivalents (or even slightly less), resulting in an almost doubling of the ratio of the mass of isolated target product (2-(4’-C2-C10- alkylbenzoyl)benzoic acid) over the sum of the mass of all the reagents and additives introduced in the reaction (“process mass efficiency”, PME).

[0063] Moreover, the solventless reaction in the process according to the invention is much faster than both the conventional synthesis using halogenated solvents and previously described tumbler ball mill synthesis of 2-benzoylbenzoic acid.

[0064] In the case of manufacturing 2-(4’-amylbenzoyl)benzoic acid, more dealkylation to the undesired 2-benzoylbenzoic acid may occur in solventless conditions than in a conventional synthesis in solution. However, it was found that such dealkylation may be effectively reduced by the addition of a substoichiometric amount (0.2 to 0.5 equivalents) of a nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, preferably 1 -nitropropane, as mediator which reduces dealkylation to a similar level as for the conventional reaction in solution.

[0065] The invention further provides a process for the manufacture of a 2-(C2-C10-alkyl)- 9,10-anthraquinone, said process comprising the following steps: (i) manufacturing a 2-(4’- C2-C10-alkylbenzoyl)benzoic acid by the aforementioned process according to the invention; (ii) causing the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid to react with a dehydrating agent, to obtain the 2-(C2-C10-alkyl)-9,10-anthraquinone.

[0066] Such processes are generally known to the person skilled in the art and described, for example, in W020103118 and WO22104763.

[0067] Suitable dehydrating agents are concentrated sulfuric acid, oleum, which may be used in large excess and at elevated temperatures. Zeolites (or zeolite catalysts), resins and carbon materials may also be used as dehydrating materials. The zeolite catalyst is not particularly limited. All the zeolites having catalytic activity towards the reaction can be used. Notably, the zeolite catalyst can be MOR, BEA, MFI, FAU or FER framework. MOR, MFI, BEA, FAU and FER framework are all the framework type codes assigned by International Zeolite Association (IZA) structure commission, which is authorized by IUPAC. The zeolite catalyst may be H-MOR, H-BEA, H-MFI, H-FAU or H-FER; it preferably is H-MOR or H-BEA. The zeolite catalyst may also be a zeolitic material which is obtained by modifying a H-type parent zeolite and wherein the ratio of the total amount of acid sites of the zeolitic material to the total amount of acid sites of the H-type parent zeolite is in the range of 0.3: 1 to 0.99: 1,wherein the total amount of acid sites is defined as the total molar amount of desorbed ammonia per mass of the zeolitic material or the H-type parent zeolite determined according to the temperature programmed desorption of ammonia. Preferably, the weight ratio of the 2- (4’-C2-C10-alkylbenzoyl)benzoic acid to zeolite may be 10 : 1 to 1 : 1 , preferably 5 : 1 to 2 : 1.

[0068] Furthermore, the invention also provides a process for the manufacture of hydrogen peroxide, said process comprising: (a) manufacturing a 2-(C2-C10-alkyl)-9,10-anthraquinone by the process described in the preceding paragraph; (b) hydrogenating a solution which comprises the 2-(C2-C10-alkyl)-9,10-anthraquinone to produce a hydrogenated working solution containing a 2-(C2-C10-alkyl)-9,10-anthrahydroquinone; (c) oxidizing the 2-(C2-C10- alkyl)-9,10-anthrahydroquinone contained in the hydrogenated working solution to produce an oxidized working solution comprising hydrogen peroxide and 2-(C2-C10-alkyl)-9,10- anthraquinone; (d) isolating the hydrogen peroxide from the oxidized working solution.

[0069] Such processes are generally known to the person skilled in the art and described, for example, in WO2024100221 and US 2014 / 0234202.

[0070] The process for the manufacture of a 2-(C2-C10-alkyl)-9,10-anthraquinone and the process for the manufacture of hydrogen peroxide according to the invention are particularly advantageous in that they allow the manufacture of 2-(C2-C10-alkyl)-9,10-anthraquinone and hydrogen peroxide, respectively, in integrated processes that avoid the use of hazardous or noxious solvents, especially, halogenated solvents, such as dichloromethane, or solvents that are expensive or difficult to handle, or the use of large excesses of the alkylbenzene serving as reaction medium.Examples

[0071] The invention is further described and illustrated by the following non-limiting examples.

[0072] In the examples, the mechanochemical synthesis of 2-(4’-C2-C10- alkylbenzoyl)benzoic acids by solventless Friedel-Crafts acylation between phthalic anhydride and a C2-C10-alkylbenzene was carried out according to the invention.

[0073] Unless otherwise stated, all experiments were started at room temperature. Crude products, aqueous and organic phases were analyzed by standard HPLC methods.

[0074] The abbreviations used have the following meanings:BOB: 2-benzoylbenzoic acidEBOB: 2-(4’-ethylbenzoyl)benzoic acidABOB: 2-(4’-amylbenzoyl)benzoic acidSABOB: 2-(4’-sec- / so-amylbenzoyl)benzoic acidTABOB: 2-(4’-tert-amylbenzoyl)benzoic acid o-DCB: ortho-dichlorobenzene (= 1,2-dichlorobenzene)PME: process mass efficiency n / d: not determined

[0075] In order to compare the process according to the invention with the conventional process of Friedel-Crafts acylation in a solvent, the “process mass efficiency” (PME) is used, which is defined as the ratio of the mass of product over the sum of the mass of all the reagents and additives introduced in the reaction:

[0076] In this definition, mproduct is the mass of the desired product (namely 2-(4’-C2-C10- alkylbenzoyl)benzoic acid) in the crude product; mreagents is the total mass of the reagents used (namely phthalic anhydride [PAH], aluminum chloride and C2-C10-al kyl benzene); and madciitives is the total mass of any additives used.

[0077] Furthermore, for quantitative assessment of the yield and selectivity of the process in the production of 2-(4’-ethylbenzoyl)benzoic acid and in the production of 2-(4’- amylbenzoyl)benzoic acid, EBOB yield, ABOB yield, BOB yield and %TABOB are defined as follows:

[0078] OPAH, initial is the amount (mol) of phthalic anhydride introduced in the reaction mixture and OEBOB, product, HTABOB, roduct, HSABOB, product and OBOB, product are the amounts (mol) of EBOB, TABOB, SABOB and BOB measured in the crude product by HPLC analysis.

[0079] The “phthalic anhydride conversion rate” is defined as:Phthalic anhydride conversion ratewith npAH, product and HPA, product being the amount (mol) of phthalic anhydride and phthalic acid measured in the crude product by HPLC analysis and npAH,aqand npA,aqbeing the amount (mol) of phthalic anhydride and phthalic acid measured in the aqueous phase by HPLC analysis.Example 1 : Synthesis of 2-(4’-ethylbenzoyl)benzoic acid (2-step process; planetary ball mill)

[0080] In a series of experiments, solventless Friedel-Crafts acylation was effected in two steps with a planetary ball mill. The first step involved the mixing of the powders of phthalic anhydride and aluminum chloride at a fixed molar ratio (1 : 2). The resulting mixture was then ball milled with ethylbenzene (in varying stoichiometric excess) to provide, after work-up, 2- (4’-ethylbenzoyl)benzoic acid in a high yield.

[0081] The general procedure was as follows: Phthalic anhydride (1 eq) and anhydrous AlCh (2 eq) were placed at room temperature in a 25 mL glass flask together with 50 glass balls (5 mm). After the sealing of the flask, the mixture was ball milled for 1 hour at 500 rpm with a planetary ball mill. Ethylbenzene was then added and the mixture was ball milled for 1 hour at 500 rpm with a planetary ball mill. The reaction mixture was poured into a stirred 50 mL 3.57 M HCI solution, extracted with dichloromethane (2 x 50 mL) and evaporated to dryness to give 2-(4’-ethylbenzoyl)benzoic acid as a white solid crude product.

[0082] The reaction conditions may be summarized as follows:1) Phthalic anhydride (1 eq), AlCh (2 eq), 500 rpm, 1 h;2) Ethylbenzene, 500 rpm, 1 h

[0083] The amounts of reagents used and the results obtained are summarized in Table 1 below:Table 1. Effect of ethylbenzene excess on EBOB yield and PME

[0084] These results show that reducing the excess of ethylbenzene from 10 eq to 2.2 eq reduces the chemical yield slightly, but greatly improves the PME (Examples 1a, 1b and 1c). However, reducing the ethylbenzene excess further to 1.1 eq results in a low chemical yield (and lower PME) due to difficulties in mixing the resulting sticky mixture (Example 1d).Example 2: Synthesis of 2-(4’-amylbenzoyl)benzoic acid (2-step process; planetary ball mill)

[0085] In a series of experiments, solventless Friedel-Crafts acylation between phthalic anhydride, aluminum chloride and tert-amylbenzene was effected in two steps with a planetary ball mill. The molar ratio of phthalic anhydride and aluminum chloride was kept constant (at 1 : 2.2), while the stoichiometric excess of tert-amylbenzene was varied. The reaction provides, after work-up, 2-(4’-amylbenzoyl)benzoic acid in a good yield. Just as with the conventional Friedel-Crafts acylation in solution, isomerization of the tert-amyl function to sec- / so-amyl and the dealkylation to 2-benzoylbenzoic acid occur under these conditions.

[0086] The general procedure was as follows: Phthalic anhydride (1 eq) and anhydrous AlCh (2.2 eq) were placed at room temperature in a 25 mL glass flask together with 30 glass balls (5 mm). After the sealing of the flask, the mixture was ball milled for 1 hour at 500 rpm with a planetary ball mill. tert-Amylbenzene was then added and the mixture was ball milled for 1 hour at 500 rpm with a planetary ball mill. The reaction mixture was poured into a stirred 50 mL 3.57 M HCI solution, extracted with dichloromethane (2 x 50 mL) and evaporated to dryness to give a white solid crude product containing 2 isomers of 2-(4’- amylbenzoyl)benzoic acid together with a small amount of 2-benzoylbenzoic acid.

[0087] The reaction conditions may be summarized as follows:1) Phthalic anhydride (1 eq), AlCh (2.2 eq), 500 rpm, 1h;2) tert-amylbenzene, 500 rpm, 1h

[0088] The amounts of reagents used and the results obtained are summarized in Table 2 below:Table 2. Effect of tert-amylbenzene excess on ABOB yield and PME

[0089] These results show that reducing the excess of tert-amylbenzene from 20 eq to 2 eq reduces the chemical yield, but it greatly improves the PME. Reducing the excess of tert- amylbenzene also increases the amount of isomerization and decreases the yield of 2- benzoylbenzoic acid. Results in a planetary ball mill are better than with conventional mixing in tert-amylbenzene in terms of ABOB yield and PME (compare Example 2a with Comparative Example 1, below, and Example 2d with Comparative Example 2, below).Example 3: Synthesis of 2-(4’-amylbenzoyl)benzoic acid using 1 -nitropropane as mediator (2-step process, planetary ball mill)

[0090] In a series of experiments, solventless Friedel-Crafts acylation was effected in two steps with a planetary ball mill. The first step involved the mixing of the powders of phthalic anhydride and aluminum chloride at a fixed molar ratio (1 : 2.2). The resulting mixture was then ball milled with tert-amylbenzene (in varying stoichiometric excess) and varying amounts of nitropropane to provide, after work-up, 2-(4’-amylbenzoyl)benzoic acid.

[0091] The general procedure was as follows: Phthalic anhydride (1 eq) and anhydrous AlCh (2.2 eq) were placed at room temperature in a 25 mL glass flask together with 30 glass balls (5 mm). After the sealing of the flask, the mixture was ball milled for 1 hour at 500 rpm with a planetary ball mill. 1 -Nitropropane and tert-amylbenzene were then added and the mixture was ball milled for 1 hour at 500 rpm with a planetary ball mill. The reaction mixture was poured into a stirred 50 mL 3.57 M HCI solution, extracted with dichloromethane (2 x 50 mL) and evaporated to dryness to give a white solid crude product containing 2 isomers of 2-(4’- amylbenzoyl)benzoic acid together with a small amount of 2-benzoylbenzoic acid.

[0092] The reaction conditions may be summarized as follows:1) Phthalic anhydride (1 eq), AICI3 (2.2 eq), 500 rpm, 1h;2) 1 -nitropropane, tert-amylbenzene, 500 rpm, 1h

[0093] The amounts of reagents used and the results obtained are summarized in Table 3 below:Table 3. Effect of 1 -nitropropane on ABOB yield and PMEExample 4: Synthesis of 2-(4’-amylbenzoyl)benzoic acid using 1 -nitropropane as mediator (1 -step process; planetary ball mill)

[0094] In a series of experiments, solventless Friedel-Crafts acylation was effected in one step with a planetary ball mill by mixing a mixture prepared by adding 1 -nitropropane and tert-amylbenzene to, not pre-milled, phthalic anhydride and anhydrous AICI3. The reaction was conducted with an excess of 2 equivalents tert-amylbenzene and varying amounts of nitropropane.

[0095] The general procedure was as follows: Phthalic anhydride (1 eq), anhydrous AICI3 (2.2 eq), 1 -nitropropane and tert-amylbenzene (2 eq) were placed at room temperature in a 25 mL glass flask together with 60 glass balls (5 mm). After the sealing of the flask, the mixture was ball milled with a planetary ball mill first for 0.5 hours at 500 rpm and then at 750 rpm for the remaining time. The reaction mixture was poured into a stirred 50 mL 3.57 M HCI solution, extracted with dichloromethane (2 x 50 mL) and evaporated to dryness to give awhite solid crude product containing 2 isomers of 2-(4’-amylbenzoyl)benzoic acid together with a small amount of 2-benzoylbenzoic acid.

[0096] The reaction conditions may be summarized as follows:1) Phthalic anhydride (1 eq), AlCh (2.2 eq), 1 -nitropropane, tert-amylbenzene (2 eq), 500-750 rpm

[0097] The amounts of reagents used and the results obtained are summarized in Table 4 below:Table 4. Effect of 1 -nitropropane and milling time on ABOB yield and PME using 1-step process

[0098] In comparison to Examples 3, these results show that the reaction afforded a higher 2-(4’-amylbenzoyl)benzoic acid yield while minimizing the 2-benzoylbenzoic acid side product and maintaining the same level of TABOB isomerization and PME (compare Examples 4c, 4d and 4b). The results also show that a longer milling time improved the ABOB yield (compare Examples 4a to 4b and 4d to 4e). In comparison to the 2-step process, the ABOB yield was improved (compare Examples 4b, 4c, 4d to Examples 3k, 3i, 3h of Table 3).Example 5: Syntheses of 2-(4’-amylbenzoyl)benzoic acid using 1 -nitropropane as mediator (1-step process; vibrational ball mill)

[0099] In a series of experiments, solventless Friedel-Crafts acylation was effected in one step with a vibrational ball mill by mixing a mixture prepared by adding 1 -nitropropane and tert-amylbenzene to, not pre-milled, phthalic anhydride and anhydrous AlCh. The reaction was conducted with an excess of 1.5 or 3 equivalents of tert-amylbenzene.

[0100] The general procedure was as follows: Phthalic anhydride (1 eq), anhydrous AlCh (2.5 eq), 1 -nitropropane (0.5 eq) and tert-amylbenzene were equally divided at roomtemperature over two 80 mL zirconium oxide coated metallic vessels together with 50 mL of zirconium oxide balls (5 mm). After the closure of the vessels, the mixture was ball milled with a vibrational ball mill at 30 Hz. The reaction mixture was poured into a stirred 50 mL 3.57 M HCI solution, extracted with dichloromethane (2 x 50 mL) and evaporated to dryness to give a white solid crude product containing 2 isomers of 2-(4’-amylbenzoyl)benzoic acid together with a small amount of 2-benzoylbenzoic acid.

[0101] The reaction conditions may be summarized as follows:1) Phthalic anhydride (1 eq), AlCh (2.5 eq), 1 -nitropropane (0.5 eq), tert- amylbenzene, 30 Hz

[0102] The amounts of reagents used and the results obtained are summarized in Table 5 below:Table 5. Effect of tert-amylbenzene excess and milling time on ABOB yield and PME using 1-step process in a vibrational ball mill

[0103] These results show: A longer milling time improved the ABOB yield (compare Examples 5d, 5e and 5f). And a larger excess of tert-amylbenzene lowered the undesired BOB content and increased the amount of TABOB (compare Examples 5c and 5f).Example 6: Synthesis of 2-(4’-ethylbenzoyl)benzoic acid (1-step process; twin-screw micro compounder)

[0104] The reaction was done in a micro compounder equipped by a pair of stainless steel 1.4122 conical screws and a high performance plastic mold steel (M340) barrel. The general procedure was as follows: 14 mmol phthalic anhydride, 28 mmol ethylbenzene and 34 mmol AlCh were sequentially added to the inlet of a twin-screw micro compounder with a screw rotation speed of 150 rpm at 70 °C. The reaction mixture was mixed in the microcompounder at 150 rpm for 30 min at 70 °C. Afterwards, part of the reaction mixture was discharged into a 3.57 M HCI solution which was extracted with dichloromethane. The organic phase was collected and evaporated to dryness to give a solid containing 2-(4’- ethylbenzoyl)benzoic acid (73 wt% based on the HPLC of the sample).Example 7: Synthesis of 2-(4’-amylbenzoyl)benzoic acid (1-step process; twin-screw micro compounder)

[0105] The reaction was done in a micro compounder equipped by a pair of stainless steel 1.4122 conical screws and a high performance plastic mold steel (M340) barrel. The general procedure was as follows: 11 mmol phthalic anhydride, 24 mmol tert-amylbenzene and 29 mmol AlCh were sequentially added to the inlet of a twin-screw micro compounder with a screw rotation speed of 150 rpm at 30 °C. The reaction mixture was mixed in the micro compounder at 150 rpm for 10 min at 30 °C. Afterwards, the temperature was increased to 100 °C over 2 min and part of the reaction mixture was discharged into a 3.57 M HCI solution which was extracted with dichloromethane. The organic phase was collected and evaporated to dryness to give a gel containing 2-(4’-amylbenzoyl)benzoic acid (45 wt% based on the HPLC of the sample) with an tert-amyl : sec- / so-amyl ratio of 38 : 62 together with 2- benzoylbenzoic acid (ABOB / BOB = 5 as calculated from HPLC of the sample).Example 8: Synthesis of 2-(4’-amylbenzoyl)benzoic acid using 1 -nitropropane as mediator (1-step process, twin-screw micro compounder)

[0106] The reaction was done in a micro compounder equipped by a pair of stainless steel 1.4122 conical screws and a high performance plastic mold steel (M340) barrel. The general procedure was as follows: 11 mmol phthalic anhydride, 24 mmol tert-amylbenzene, 11 mmol 1 -nitropropane and 29 mmol AICI3 were sequentially added to the inlet of a twin-screw micro compounder with a screw rotation speed of 150 rpm at 30 °C. The reaction mixture was mixed in the micro compounder at 150 rpm for 10 min at 30 °C. Afterwards, the temperature was increased to 100 °C over 2 min and part of the reaction mixture was discharged into a 3.57 M HCI solution which was extracted with dichloromethane. The organic phase was collected and evaporated to dryness to give a gel containing 2-(4’-amylbenzoyl)benzoic acid (48 wt% based on the HPLC of the sample) with an tert-amyl : sec- / so-amyl ratio of 47 : 53 together with 2-benzoylbenzoic acid (ABOB / BOB = 41 as calculated from HPLC of the sample).Example 9: Synthesis of 2-(4’-amylbenzoyl)benzoic acid (1-step process; batch kneader)The reaction was done in a sigma-blade kneader with a volume of 2 L and equipped with double stainless steel SS 316L sigma-shaped blades for kneading and an extrusion screw for emptying the equipment. The general procedure was as follows: phthalic anhydride (1 eq), anhydrous AlCh (2.4 eq), 1 -nitropropane (0.5 eq) and tert-amylbenzene were sequentially added to the inlet of the kneader. The reaction mixture was mixed in the kneader at 38 rpm for 2 hours at room temperature. Afterwards, the reaction mixture was discharged using the extrusion screw at the bottom of the kneader into a 5 wt% HCI solution which was extracted with dichloromethane. The organic phase was collected and evaporated to dryness to give a white solid crude product containing 2 isomers of 2-(4’-amylbenzoyl)benzoic acid together with a small amount of 2-benzoylbenzoic acid.The reaction conditions may be summarized as follows:1) Phthalic anhydride (1 eq), AlCh (2.4 eq), 1 -nitropropane (0.5 eq), tert- amylbenzene, 38 rpm, 2hThe amounts of reagents used and the results obtained are summarized in Table 6 below:Table 6. Effect of tert-amylbenzene excess on ABOB yield and PME using 1-step process in a batch kneaderThese results show: Using a sigma-blade kneader, an excess tert-amylbenzene of more than 2 equivalents is required to reach a good phthalic anhydride conversion rate, and hence a good ABOB yield and a high PME.Example 10: Synthesis of 2-(4’-amylbenzoyl)benzoic acid (1-step process; twin-screw extruder)The reaction was done in a twin-screw extruder equipped with a pair of stainless steel AISI 430 screws with an outer screw diameter of 26 mm and 21 barrels in series which are cooled to room temperature. The general procedure was as follows: phthalic anhydride (0.75 kg / h) and anhydrous AlCh (1.75 kg / h, 2.6 eq) were continuously added to the inlet of barrel 1. Amixture of nitromethane, 1 -nitropropane and tert-amylbenzene was continuously added to the inlet of barrel 2. The reaction mixture at the outlet of barrel 21 was collected and poured into a 5 wt% HCI solution which was extracted with dichloromethane. The organic phase was collected and evaporated to dryness to give a white solid crude product containing 2 isomers of 2-(4’-amylbenzoyl)benzoic acid together with a small amount of 2-benzoylbenzoic acid.The reaction conditions may be summarized as follows:1) Phthalic anhydride (1 eq), AlCh (2.6 eq), nitromethane, 1 -nitropropane, tert- amylbenzeneThe amounts of reagents used and the results obtained are summarized in Table 7 below:Table 7. Effect of tert-amylbenzene excess and rotation speed on ABOB yield and PME using 1-step process in a twin-screw extruderThese results show: Using a twin-screw extruder, an excess of tert-amylbenzene below 2 equivalents resulted in an incomplete phthalic anhydride conversion which could be partially offset by increasing the screw rotation speed.Comparative Examples

[0107] For comparison, conventional Friedel-Crafts acylation of phthalic anhydride and tert- amylbenzene using a large excess tert-amylbenzene as reaction medium was carried out in the following comparative examples:Comparative Example 1 :

[0108] 0.15 mol phthalic anhydride in 3.55 mol tert-amylbenzene under nitrogen was cooled to 0 °C, 0.31 mol anhydrous AlCh was added over 4 min. The reaction cooling was turned off and the reaction mixture was stirred without cooling for 6 hours. Afterwards, the reaction mixture was added to a stirred 200 mL 0.71 M HCI solution and stirred for 5 min. The organic phase was collected and the aqueous phase was extracted with dichloromethane (2 x 100 mL). The organic phases were combined, washed with water (2 x 100 mL) and evaporated to dryness to give a yellow oil with a white precipitate which was filtered off to give a white solid crude product containing 2-(4’-amylbenzoyl)benzoic acid (yield = 53%, PME = 4%) with an tert-amyl : sec- / so-amyl ratio of 70 : 30 together with 2-benzoylbenzoic acid (yield = 0.3%).Comparative Example 2:

[0109] 0.47 mol phthalic anhydride in 1.42 mol tert-amylbenzene under nitrogen was cooled to 0 °C, 1.04 mol anhydrous AlCh was added over 2 min. The reaction cooling was turned off and the reaction mixture was stirred without cooling for 4 hours. Afterwards, the reaction was quenched with 500 mL 0.71 M HCI solution and the mixture was stirred for 40 min. The reaction mixture was extracted with dichloromethane (500 mL) and the aqueous phase was extracted with dichloromethane (100 mL). The organic phases were combined, washed with 0.18 M NaOH solution (275 mL) and evaporated to dryness to give a gray-brown sludge crude product containing 2-(4’-amylbenzoyl)benzoic acid (yield = 21%, PME = 7%) with an tert-amyl : sec- / so-amyl ratio of 49 : 51 together with 2-benzoylbenzoic acid (yield = 3.5%).Comparative Example 3:

[0110] 0.47 mol phthalic anhydride in 1.40 mol tert-amylbenzene under nitrogen was cooled to 0 °C, 1.02 mol anhydrous AlCh was added over 2 min. The reaction heating was started and the reaction was stirred at 65 °C for 3 hours. Afterwards, the reaction was quenched with 500 mL 0.71 M HCI solution and the mixture was stirred for 40 min. The reaction mixture was extracted with dichloromethane (3 x 250 mL) and the aqueous phase was extracted with dichloromethane (200 mL). The organic phases were combined, washed with 0.18 M NaOH solution (275 mL) and evaporated to dryness to give a gray-brown solid crude productcontaining 2-(4’-amylbenzoyl)benzoic acid (yield = 61%, PME = 21%) with an tert-amyl : sec- / so-amyl ratio of 33 : 67 together with 2-benzoylbenzoic acid (yield = 2.4%).Conclusion

[0111] The above examples and comparative examples show that the process according to the invention (using a planetary or vibrational ball mill) results in a higher yield and a significantly higher process mass efficiency (PME) than conventional Friedel-Crafts acylation of tert-amylbenzene with phthalic anhydride in a large excess of tert-amylbenzene as reaction medium.Industrial Applicability

[0112] The invention provides an improved process for the production of 2-(4’-C2-C10- alkylbenzoyl)benzoic acids such as 2-(4’-ethylbenzoyl)benzoic acid and 2-(4’- amylbenzoyl)benzoic acid. Such compounds are precursors for commonly used “carriers”, such as 2-ethyl-9,10-anthraquinone and 2-amyl-9,10-anthraquinone, in the working solution of hydrogen peroxides plants. Thus, the invention is industrially applicable in the production of hydrogen peroxide.

Claims

CLAIMS1 . A process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, said process comprising causing a C2-C10-al kyl benzene and phthalic anhydride to undergo a mechanochemical Friedel-Crafts acylation in the presence of a Lewis acid to obtain a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, wherein no solvent at all is used, wherein C2-C 10-al kyl benzene and, if present, nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group, are not considered as solvents, and wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 1.1 : 1 to 4.8 : 1.

2. The process according to claim 1 , wherein the C2-C 10-al kyl benzene is ethylbenzene and the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid is 2-(4’-ethylbenzoyl)benzoic acid, or wherein the C2-C 10-al kyl benzene is tert-amylbenzene and the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid is 2-(4’-amylbenzoyl)benzoic acid.

3. A process for the manufacture of a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, said process comprising causing a C2-C10-alkylbenzene and phthalic anhydride to undergo a mechanochemical Friedel-Crafts acylation in the presence of a Lewis acid to obtain a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid, wherein the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid is 2-(4’-ethylbenzoyl)benzoic acid and the C2-C10-alkylbenzene is ethylbenzene, or the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid is 2-(4’-amylbenzoyl)benzoic acid and the C2-C10- alkylbenzene is tert-amylbenzene, wherein no solvent at all is used, wherein ethylbenzene and tert-amylbenzene and, if present, 1 -nitropropane are not considered as solvents, and wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 1.1 : 1 to 2.5 : 1.

4. The process according to any one of the preceding claims, wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is at least 1.2, possibly at least 1 .5 or at least 2.0.

5. The process according to any one of the preceding claims, wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is at most 3.6, possibly at most 3.0 or at most 2.4.

6. The process according to any one of the preceding claims, wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 1.2 : 1 to 2.4 : 1.

7. The process according to any one of the preceding claims, which does not comprise a step of pre-mixing the phthalic anhydride and the Lewis acid in the absence of the C2-C10-alkyl benzene.

8. The process according to any one of claims 1 to 6, which comprises(A) first pre-mixing the phthalic anhydride and the Lewis acid to obtain a powdery mixture and(B) then mixing the powdery mixture with the C2-C10-alkylbenzene to effect the mechanochemical Friedel-Crafts acylation to obtain the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid.

9. The process according to any one of the preceding claims, wherein the C2-C10- alkylbenzene and phthalic anhydride are caused to undergo the mechanochemical Friedel-Crafts acylation in the further presence of a nitrohydrocarbon compound of formula R-NO2, wherein R is a C1-C20 hydrocarbyl group.

10. The process according to claim 9, wherein R is n-propyl.11 . The process according to claim 9 or 10, which comprises(A) first pre-mixing the phthalic anhydride and the Lewis acid to obtain a powdery mixture and(B) then mixing the powdery mixture with the C2-C10-alkylbenzene and the nitrohydrocarbon compoundto effect the mechanochemical Friedel-Crafts acylation to obtain the 2-(4’-C2-C10- alkylbenzoyl)benzoic acid.

12. The process according to any one of claims 9 to 11 , wherein the C2-C10- alkylbenzene is a C3-C10-alkylbenzene having a branched alkyl group.

13. The process according to any one of claims 9 to 12, wherein the molar ratio of the nitrohydrocarbon compound to the phthalic anhydride used in the process is 0.1 : 1 to 0.5 : 1.

14. The process according to any one of the preceding claims, wherein the reactants are mixed in a planetary ball mill, vibrational ball mill, tumbler ball mill, kneader or attritor.

15. The process according to claim 3, wherein the reaction is carried out in a reactive extruder.

16. The process according to any one of the preceding claims but claim 3 and 14, wherein the reaction is carried out in a reactive extruder.

17. The process according to claim 15 or 16, wherein the extruder is a single screw extruder, a multiple screw extruder, a twin-screw extruder or a planetary extruder.

18. The process according to claim 17, wherein the extruder is a twin-screw extruder.

19. The process according to any one of claims 16 to 18 wherein the molar ratio of the C2-C10-alkylbenzene to the phthalic anhydride used in the process is 2.0 : 1 to 3.0 : 1.

20. A process for the manufacture of a 2-(C2-C10-al ky l)-9 , 10-anthraquinone, said process comprising the following steps:(i) manufacturing a 2-(4’-C2-C10-alkylbenzoyl)benzoic acid by the process according to any one of the preceding claims;(ii) causing the 2-(4’-C2-C10-alkylbenzoyl)benzoic acid to react with a dehydrating agent, to obtain the 2-(C2-C10-alkyl)-9,10-anthraquinone.

21. A process for the manufacture of hydrogen peroxide, said process comprising:(a) manufacturing a 2-(C2-C10-alkyl)-9,10-anthraquinone by the process according to claim 20;(b) hydrogenating a solution which comprises the 2-(C2-C10-alkyl)-9,10- anthraquinone to produce a hydrogenated working solution containing a 2- (C2-C10-al ky l)-9 , 10-anthrahydroquinone;(c) oxidizing the 2-(C2-C10-alkyl)-9,10-anthrahydroquinone contained in the hydrogenated working solution to produce an oxidized solution comprising hydrogen peroxide and 2-(C2-C10-alkyl)-9,10-anthraquinone;(d) isolating the hydrogen peroxide from the oxidized solution.

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