Use of p-aminobenzoic acid in the preparation of compounds of interest

Abstract

The present invention relates to the use of p-aminobenzoic acid in a method for preparing a compound selected from p-toluidine, p-chlorobenzonitrile, benzoic acid, aniline, and hydroxybenzomorpholine. In particular, the p-aminobenzoic acid is produced or obtained from a microorganism.

Description

[0001] USE OF p-AMINOBENZOIC ACID IN THE PREPARATION OF COMPOUNDS OF INTEREST

[0002] SUBJECT OF THE INVENTION

[0003] The present invention relates to the synthesis of compounds or molecules of interest in various fields, mainly in the field of dyes and pigments, from a common precursor, para-aminobenzoic acid (p-aminobenzoic acid, PABA).

[0004] BACKGROUND OF THE INVENTION

[0005] For decades, numerous products have been developed for use as precursors or reaction intermediates in the industrial-scale synthesis of dyes and pigments. Among these products or compounds are para-toluidine (p-toluidine), para-chlorobenzonitrile (p-chlorobenzonitrile), benzoic acid, aniline, and hydroxybenzomorpholine.

[0006] Generally, from an industrial perspective, the synthesis of p-toluidine is carried out by nitration of toluene followed by hydrogenation, but requires separation of the different isomers. The synthesis of p-chlorobenzonitrile from p-chlorotoluene requires the use of vanadium and chromium catalysts and very high temperatures (> 350 °C), and also requires isomeric separation of chlorotoluene. The synthesis of benzoic acid is carried out by oxidation of toluene and requires the use of vanadate catalysts and temperatures around 200 °C. The synthesis of aniline from benzene requires a nitration step and a hydrogenation step in the presence of iron. Finally, the synthesis of hydroxybenzomorpholine requires, firstly, the preparation of 2,5-dimethoxyaniline in six steps from benzene, including a nitration step, before providing hydroxybenzomorpholine with two additional steps.

[0007] The industrial synthesis of these five compounds thus presents significant constraints that are not always suitable for industrial scale. More specifically, they use fossil fuels, often toxic and carcinogenic, such as benzene and toluene, and some require reactions that demand numerous precautions, particularly nitration steps that can prove dangerous at industrial scales. Certain steps in these syntheses also require working at very high temperatures and include purification steps that must be avoided for reasons of cost and industrial feasibility.

[0008] There therefore remains a real need to develop and make available improved processes for preparing these compounds that are simple, efficient, ecological, safe, and well suited to industrial scale.

[0009] SUMMARY OF THE INVENTION

[0010] In this context, the inventors proposed various industrially suitable preparation processes for the five compounds of interest, namely p-toluidine, p-chlorobenzonitrile, benzoic acid, aniline, and hydroxybenzomorpholine, from a single precursor, p-aminobenzoic acid.

[0011] Thus, the present invention relates to the use of p-aminobenzoic acid in a process for preparing a compound selected from p-toluidine, p-chlorobenzonitrile, benzoic acid, aniline, and hydroxybenzomorpholine.

[0012] One aspect of the invention is the use of p-aminobenzoic acid in a process for preparing p-toluidine.

[0013] According to this aspect, the process includes the following steps: a1) reacting p-aminobenzoic acid with a catalyst, preferably a metallic catalyst, in a solvent, optionally under a hydrogen atmosphere; and a2) recovering p-toluidine.

[0014] In particular, step a1) includes reacting p-aminobenzoic acid with tin dioxide in a mixture of 2-propanol and decane at a temperature between 250 and 400 °C, preferably about 330 °C for 30 minutes to 10 hours, preferably about 1 hour.

[0015] Another aspect of the invention is the use of p-aminobenzoic acid in a process for preparing p-chlorobenzonitrile.

[0016] According to this aspect, the process includes the following steps: b1) reacting p-aminobenzoic acid with potassium nitrate and hydrochloric acid in a solvent to obtain p-chlorobenzoic acid; b2) reacting p-chlorobenzoic acid with an aqueous solution of ammonia under reflux to obtain p-chlorobenzamide; b3) reacting p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C; and b4) recovering p-chlorobenzonitrile.

[0017] In particular, step bl) includes reacting p-aminobenzoic acid with potassium nitrate and hydrochloric acid in dimethyl sulfoxide at a temperature between 20 and 50 °C, preferably about 35 °C, for 2 to 6 hours, preferably about 4 hours.

[0018] Another aspect of the invention is the use of p-aminobenzoic acid in a process for preparing benzoic acid.

[0019] According to this aspect, the process includes the following steps: c1) reacting p-aminobenzoic acid with sodium nitrite and acetic acid in a solvent; and c2) recovering benzoic acid.

[0020] In particular, step cl) includes reacting an equimolar aqueous solution of p-aminobenzoic acid chloroform and sodium nitrite in a solution of acetic acid and water at a temperature between 15 and 35 °C, preferably about 25 °C, for 15 to 60 minutes, preferably about 30 minutes.

[0021] Another aspect of the invention is the use of p-aminobenzoic acid in a process for preparing aniline.

[0022] According to this aspect, the process includes the following steps: d1) the reaction of p-aminobenzoic acid at a temperature between 50 and 200 °C, in particular between 50 and 190 °C; and d2) the recovery of aniline.

[0023] In particular, step dl) comprises reacting p-aminobenzoic acid at a temperature of approximately 150 °C for 1 to 5 hours, preferably for approximately 3 hours. Another aspect of the invention is the use of p-aminobenzoic acid in a process for preparing hydroxybenzomorpholine.

[0024] According to this aspect, the process comprises the following steps: e1) reacting p-aminobenzoic acid with a solution of sodium bromate and potassium bromide to obtain 4-amino-3-bromobenzoic acid; e2) reacting 4-amino-3-bromobenzoic acid with sodium nitrite and N-(2-hydroxyethyl)acetamide in a solvent to obtain 4-(2-acetamidoethoxy)-3-bromobenzoic acid; e3) reacting 4-(2-acetamidoethoxy)-3-bromobenzoic acid with copper sulfate and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine to obtain 3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylic acid; e4) the reaction of 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid with an iron complex, preferably [Fe n (BPMEN)(CH3CN)2](C104)2, and hydrogen peroxide; and e5) the recovery of hydroxybenzomorpholine.

[0025] In particular, step el) includes reacting a solution of p-aminobenzoic acid in acetic acid with a solution of sodium bromate and potassium bromide in water at room temperature followed by the addition of hydrochloric acid and maintaining the reaction at room temperature for 10 to 60 minutes, preferably for about 30 minutes.

[0026] In particular, step e2) includes the following substeps: e2a) reacting a solution of 4-amino-3-bromobenzoic acid in sulfuric acid with sodium nitrite at room temperature for 30 to 120 minutes, preferably for about 60 minutes, and e2b) reacting the reaction medium of step e2a) in a solution of N-(2-hydroxyethyl)acetamide in methoxycyclopentane at room temperature for 30 to 120 minutes, preferably for about 60 minutes.

[0027] In particular, step e3) includes the following substeps: e3a) reacting 4-(2-acetamidoethoxy)-3-bromobenzoic acid and sodium carbonate with copper sulfate and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine at a temperature between 75 and 125 °C, preferably about 100 °C for 10 to 16 hours, and e3b) treating the reaction medium of step e3a) with sodium hydroxide at a temperature between 75 and 125 °C, preferably about 100 °C for 2 to 6 hours, preferably about 4 hours.

[0028] In particular, step e4) comprises the following substeps: e4a) the reaction of 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid with [Fe n(BPMEN)(CH3CN)2](C104)2 and hydrogen peroxide in acetonitrile at room temperature for 10 to 60 minutes, preferably for about 30 minutes, and e4b) treatment of the reaction medium from step e4a) with an aqueous solution of Na2EDTA.

[0029] According to this aspect, another embodiment relates to a process comprising the following steps: f1) reacting p-aminobenzoic acid with a sodium nitrite solution in water to obtain 4-hydroxybenzoic acid; f2) reacting 4-hydroxybenzoic acid with acetic anhydride to obtain 4-acetoxybenzoic acid; f3) reacting 4-acetoxybenzoic acid with thionyl chloride and a palladium-based catalyst under a hydrogen atmosphere to obtain 4-hydrobenzaldehyde; f4) reacting 4-hydrobenzaldehyde with sodium hydroxide and a hydrogen peroxide solution to obtain hydroquinone; f5) reacting hydroquinone with copper acetate and a hydrogen peroxide solution to obtain benzoquinone; f6) the reaction of benzoquinone with acetic acid and ethylenediamine to obtain 2-((2-aminoethyl)amino)benzene-l,4-diol;f7) and the reaction of 2-((2-aminoethyl)amino)benzene-1,4-diol with sulfuric acid and sodium nitrite; and f8) the recovery of the orphan hydroxybenzom.

[0030] According to a particular embodiment of the invention, p-aminobenzoic acid is produced from a microorganism, in particular a bacterium, preferably of the species Escherichia coli.

[0031] An additional object of the invention relates to a compound selected from p-toluidine, p-chlorobenzonitrile, benzoic acid, and aniline, wherein said compound comprises a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

[0032] Another additional object of the invention relates to hydroxybenzomorpholine comprising a percentage of modern carbon equal to or greater than 60%, preferably equal to or greater than 74%, and even more preferably equal to or greater than 99%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

[0033] DETAILED DESCRIPTION

[0034] In this application, the term "approximately" associated with a value is a term well known to those skilled in the art and means that said value may vary to some extent depending on the context in which the term is used. If some uses of this term are not clear to those skilled in the art depending on the context, then "approximately" means plus or minus 30%, plus or minus 20%, preferably plus or minus 10% of said associated value.

[0035] Unless otherwise stated, when a range is expressed using the phrase "between", the limit values ​​are included within the range described.

[0036] According to the invention, the terms "includes" or "comprising" can be interpreted generally as meaning that all specifically mentioned features and all optional, additional, and unspecified features are included. They can also be interpreted more specifically, as with the expressions "consists of" or "consisting of," when only the specified features are included, unless otherwise indicated.

[0037] As used here, the term "microorganism" is a unicellular organism that may be a bacterium, such as Escherichia coli or Corynebacterium glutamicum, a filamentous fungus, or a yeast, such as Saccharomyces cerevisiae. In a particular mode, the term "microorganism" also includes a "recombinant microorganism." By "recombinant microorganism," we mean a microorganism that is not found in nature and that contains a modified genome resulting from the insertion, modification, or deletion of one or more genetic elements. This term also includes any offspring of said microorganism that are not identical to the parent microorganism due to mutations that occur during replication. In a preferred mode, the microorganism is a bacterium, specifically E. coli.

[0038] The present invention relates to the use of p-aminobenzoic acid in a process for preparing a compound selected from p-toluidine, p-chlorobenzonitrile, benzoic acid, aniline, and hydroxybenzomorpholine. It therefore concerns a process for preparing these five compounds using p-aminobenzoic acid, particularly as a starting material in reaction syntheses.

[0039] p-Aminobenzoic acid (PABA) or 4-aminobenzoic acid is an organic compound with the following formula:

[0040] PABA is an intermediate involved in several metabolic pathways, such as the synthesis of folic acid by many bacteria, yeasts, and plants. PABA and its derivatives (salts, aldehydes, and salicylaldehydes) exhibit antibacterial and anti-inflammatory activities, cytotoxic effects, and an anticoagulant effect. In agriculture, it can play a role in plant growth and resistance to bacterial or viral agents. In cosmetics, it can be used as a sunscreen agent.

[0041] No application or use of PABA in the field of dyes and pigments has been reported to date, particularly in the synthesis of compounds of interest such as p-toluidine, p-chlorobenzonitrile, benzoic acid, aniline, and hydroxybenzomorpholine.

[0042] In the context of the invention, PABA can be obtained from multiple sources. It can easily be chemically synthesized by a person skilled in the art and possessing general knowledge, or simply purchased from various suppliers. Alternatively, it can be obtained through biological processes from microorganisms that are far more environmentally friendly. According to this alternative, PABA has a 100% bio-based carbon content.

[0043] The determination of the bio-based carbon content of a compound or molecule can be determined by any method known to a person skilled in the art from the measurement of the carbon content 14 ( 14 C) In particular, it can be determined by accelerator mass spectrometry (AMS) according to standard NF EN 16640 published on April 15, 2017. The unit is the percentage of modern carbon (pMC). The pMC represents the ratio between the concentration of carbon-14 ( 14C) in the analyzed molecule and the concentration of carbon 14 ( 14 C) in standardized modern carbon. The pMC thus corresponds to the percentage of bio-based carbon derived from biomass relative to fossil carbon (derived from petrochemicals). Therefore, a compound with 100% bio-based carbon content has a pMC of 100%. Conversely, a compound entirely of fossil origin, i.e., with 0% bio-based carbon content, has a pMC of 0%. A value between 0 and 100% indicates a mixture of bio-based and fossil carbon.

[0044] Annex E of standard NF EN 16640 describes a procedure for determining the content of 14C by SMA in carbonate solutions obtained from the combustion of bio-based product samples in a bomb calorimeter, tube furnace, or laboratory combustion device. More specifically, this procedure includes the following steps: a) Transfer the carbonate solution to the extraction bottle. b) Attach the HCl dosing device. c) Vacuum the bottle and dosing device (degassing, removing dissolved N2 and FO2 from the air). d) Add HCl to the carbonate solution. e) Remove water vapor using a trap filled with acetone and dry ice. f) Collect the CO2 formed in a trap immersed in liquid N2. g) Take a small sample to determine the 13 C at this stage. h) Transfer the CO2 to the graphitization system.

[0045] The gaseous sample must be introduced into the system either via a quartz tube or trapped in liquid nitrogen and then heated. Next, convert the gas to graphite using an iron catalyst according to the following formulas: co2 + H2H2O + co → co + H2H2O + ci. Remove the water produced by this reaction to ensure complete reduction to graphite. This step is particularly important to avoid any fractionation. j) Compress the graphite into a target and mount it on a wheel before loading it into the accelerator mass spectrometer. In the ion source, a high-intensity beam of cesium ions (Cs) is directed. +) is focused on the target. This operation releases negatively charged target atoms, producing a 36 keV beam of C' ions. The targets are kept 10 mm apart to prevent mutual contamination and moved during sputtering to avoid crater formation, which causes fractionation. The negative ion beam is then focused by a lens in a recombiner. In the recombiner, a series of magnets removes ions other than carbon ions from the beam and separates the three carbon isotopes ( 12 C, 13 This 14 C) Next, the chopper wheel physically blocks most of the 12 C, which allows the recombination of a very reduced carbon ion beam for simultaneous injection into the accelerator. k) In the tandem accelerator, the C' ions are accelerated to the terminal (to +2.5 MeV), then changed into C ions 3+by collision with Ar atoms in the degasser. These positive ions are accelerated to 10 MeV. A 3+ charge state is chosen because the mass / charge ratio of the 14 C 3+ is truly unique, which allows for its precise separation in the high-energy mass spectrometer. l) Measure the beams of 12 C and of 13 C in Faraday ionization chambers (typical currents of 250 nA). m) Purify the ions 14 C 3+ by an electrostatic deflector and a 90° magnet. They are measured in an ionization chamber filled with isobutene, isolated from the accelerator vacuum by a thin metal sheet. Generally, a sample is counted for one hour.

[0046] The isotopic ratios of 14 C / 12 This 13 C / 12C are determined relative to the appropriate primary reference material. All percentage modern carbon (pMC) values ​​obtained from radiocarbon analysis measurements must be corrected for isotopic fractionation using stable isotope data (ratios 13 C / 12 C) obtained on CO2 from the combustion of the sample.

[0047] The SMA system allows the measurement of carbon isotopes 12 C, 13 This 14 C of a carbon sample during the same sample analysis cycle. A sample lot must also contain samples of the reference material. The measured quantity of 14 C (= isotope concentration) 14 C) in a sample is calculated based on the measured quantity (average) of 14C. Reference material samples in the same lot. If the reference material is the primary reference standard, oxalic acid II (HOx-II, SRM 4990c), which is commonly used for this purpose, the standardized amount of 14 C in the sample, , Or

[0048] 14 Sample C represents the measured value of 14 C (in pMC) of the CO2 sample studied,

[0049] 14 A sample represents the measured signal of the 14 C (isotopic concentration or activity) of the sample,

[0050] 14 Ab g represents the measured signal of the 14 C (isotopic concentration or activity) of the reference sample / control sample, measured in the same batch as the sample and representing the background noise signal of the 14 C of the measured samples,

[0051] 14 AOX2 represents the measured (average) signal of the 14C (concentration or isotopic activity) of the reference standard samples, oxalic acid (HOx-II, SRM 4990c), measured in the same batch as the unknown samples,

[0052] 14 A b g ox2 represents the measured (average) signal of the 14 C (concentration or isotopic activity) of the reference samples, which represents the background noise signal of the measured reference standard, oxalic acid (HOx-II, SRM 4990c), measured in the same batch as the oxalic acid samples, î]measurement represents the measurement efficiency of the measurement technique used, l 3 ô \- represents the standardized value of isotopic fractionation: l3 ô \- = - 0.025 (relative to VPDB),

[0053] "sample" represents the measured value of the isotopic fractionation of the sample. It is obtained by measuring the ratio 13 C / 12 C of the sample as a function of the ratio 13 C / 12C measured from a reference standard having a known isotopic fractionation value associated with VPDB, and

[0054] 13 ùo. 2 represents the standardized value of the isotopic fractionation of the reference standard, oxalic acid (HOx-II, SRM 4990c): 13c>c 2 = 0.0176 (relative to VPDB). Preferably, p-aminobenzoic acid is produced from a microorganism, in particular a bacterium, preferably of the species Escherichia coli. According to a particular method, the PABA produced from a microorganism, in particular a bacterium, preferably of the species Escherichia coli, has a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640 as described above. In other words, the PABA produced from a microorganism, in particular a bacterium, preferably of the species Escherichia coli, has a bio-based carbon content equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%.

[0055] According to one aspect of the invention, p-aminobenzoic acid is used in a process for preparing p-toluidine. Preferably, p-aminobenzoic acid is used in a process for preparing p-toluidine as described in this application.

[0056] Specifically, PABA can be converted to p-toluidine via a single hydrogenation reaction step in the presence of a catalyst in a solvent. Such a catalyst can be a metallic catalyst, for example, tin dioxide, or catalysts based on palladium, platinum, or nickel. Depending on the nature of the metallic catalyst, the reaction proceeds either in the absence or presence of a hydrogen atmosphere. For example, the use of tin dioxide does not require a hydrogen atmosphere, unlike metallic catalysts based on palladium, platinum, or nickel. Examples of solvents include polar and / or nonpolar solvents. Polar solvents include alcohols, for example, methanol, ethanol, propanol, isopropanol (2-propanol), and butanol. Nonpolar solvents include aliphatic hydrocarbon solvents, for example, hexane, heptane, and decane.A solvent can also be a mixture of a polar solvent and a nonpolar solvent such as, for example, a mixture of 2-propanol and decane.

[0057] One object of the invention relates to a process or method for preparing p-toluidine comprising the following steps: a) reacting p-aminobenzoic acid with a catalyst, preferably a metallic catalyst, in a solvent, optionally under a hydrogen atmosphere; and a2) recovering the p-toluidine. Another object of the invention also relates to a process or method for preparing p-toluidine consisting of the following steps: a) reacting p-aminobenzoic acid with a catalyst, preferably a metallic catalyst, in a solvent, optionally under a hydrogen atmosphere; and a2) recovering the p-toluidine.

[0058] Specifically, the metallic catalyst is chosen from tin dioxide, or from catalysts based on palladium, platinum, or nickel. Preferably, the metallic catalyst is tin dioxide.

[0059] According to a particular embodiment, step a1) includes reacting p-aminobenzoic acid with tin dioxide in a mixture of 2-propanol and decane at a temperature between 250 and 400 °C, preferably about 330 °C for 30 minutes to 10 hours, preferably about 1 hour.

[0060] An object is therefore a process or method for preparing p-toluidine comprising or consisting of the following steps: a1) reacting p-aminobenzoic acid with tin dioxide in a mixture of 2-propanol and decane at a temperature between 250 and 400 °C, preferably about 330 °C for 30 minutes to 10 hours, preferably about 1 hour; and a2) recovering p-toluidine.

[0061] In particular, p-aminobenzoic acid is produced or obtained by a biological process from a microorganism, in particular a bacterium, preferably of the species Escherichia coli.

[0062] A particular object of the invention is therefore a process or method for preparing p-toluidine comprising or consisting of the following steps: a) the culture of a microorganism as described in this application to produce p-aminobenzoic acid; and steps a1) and a2) as described in this application.

[0063] A particular object of the invention is also a process or method for preparing p-toluidine comprising or consisting of the following steps: a0) culturing a microorganism as described in this application, in particular of the species E. coli, to produce p-aminobenzoic acid; a1) reacting the p-aminobenzoic acid obtained in step a0) with a catalyst, preferably a metallic catalyst, and even more preferably tin dioxide in a solvent, preferably a mixture of 2-propanol and decane, at a temperature between 250 and 400 °C, preferably about 330 °C, for 30 minutes to 10 hours, preferably about 1 hour; and a2) recovering the p-toluidine.

[0064] p-Toluidine, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640. Also, p-Toluidine, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a bio-based carbon content equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%.

[0065] An object of the invention therefore relates to p-Toluidine comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

[0066] An object of the invention also relates to p-Toluidine comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640 obtained by a process or method of preparation comprising or consisting of the following steps: a1) the culture of a microorganism, in particular of the species E. Coli, to produce p-aminobenzoic acid; a2) the reaction of p-aminobenzoic acid with a catalyst, preferably a metallic catalyst, in a solvent, optionally under a hydrogen atmosphere; and a3) the recovery of p-toluidine.Another object of the invention also relates to p-Toluidine comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640 obtained by a process or method comprising or consisting of the following steps: aO) the culture of a microorganism, in particular of the species E. Coli, to produce p-aminobenzoic acid; ai) the reaction of the p-aminobenzoic acid obtained in step aO) with a catalyst, preferably a metallic catalyst, and even more preferably tin dioxide in a solvent, preferably a mixture of 2-propanol and decane, at a temperature between 250 and 400 °C, preferably about 330 °C, for 30 minutes to 10 hours, preferably about 1 hour; and a2) the recovery of p-toluidine.

[0067] According to another aspect of the invention, p-aminobenzoic acid is used in a process for preparing p-chlorobenzonitrile. Preferably, p-aminobenzoic acid is used in a process for preparing p-chlorobenzonitrile as described in this application.

[0068] More specifically, PABA can be converted to p-chlorobenzonitrile via the chlorination of a diazonium salt previously formed to give p-chlorobenzoic acid. The diazonium salt's carboxylic acid group is then converted to an amide group to give p-chlorobenzamide, and then to a nitrile group to give p-chlorobenzonitrile. p-Chlorobenzoic acid can be obtained by forming the corresponding diazonium salt of PABA with potassium nitrate in a solvent, such as DMSO, and hydrochloric acid at a temperature between 20 and 50 °C for 2 to 6 hours. p-Chlorobenzamide can then be obtained by refluxing p-chlorobenzoic acid with aqueous ammonia. Finally, p-Chlorobenzonitrile can be obtained by reacting p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C.

[0069] An object of the invention therefore relates to a process or method for preparing p-chlorobenzonitrile comprising the following steps: b1) reacting p-aminobenzoic acid with potassium nitrate and hydrochloric acid in a solvent to obtain p-chlorobenzoic acid; b2) reacting p-chlorobenzoic acid with an aqueous solution of ammonia under reflux to obtain p-chlorobenzamide; b3) reacting p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C; and b4) recovering p-chlorobenzonitrile.

[0070] An object of the invention also relates to a process or method for preparing p-chlorobenzonitrile consisting of the following steps: b1) reacting p-aminobenzoic acid with potassium nitrate and hydrochloric acid in a solvent to obtain p-chlorobenzoic acid; b2) reacting p-chlorobenzoic acid with an aqueous solution of ammonia under reflux to obtain p-chlorobenzamide; b3) reacting p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C; and b4) recovering p-chlorobenzonitrile.

[0071] According to a particular embodiment, step b 1) includes reacting p-aminobenzoic acid with potassium nitrate and hydrochloric acid in dimethyl sulfoxide at a temperature between 20 and 50 °C, preferably about 35 °C, for 2 to 6 hours, preferably about 4 hours.

[0072] An object is therefore a process or method for preparing p-chlorobenzonitrile comprising or consisting of the following steps: b1) reacting p-aminobenzoic acid with potassium nitrate and hydrochloric acid in dimethyl sulfoxide at a temperature between 20 and 50 °C, preferably about 35 °C, for 2 to 6 hours, preferably about 4 hours, to obtain p-chlorobenzoic acid; b2) reacting p-chlorobenzoic acid with an aqueous solution of ammonia under reflux to obtain p-chlorobenzamide; b3) reacting p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C; and b4) recovering p-chlorobenzonitrile. In particular, p-aminobenzoic acid is produced or obtained by a biological process from a microorganism, in particular a bacterium, preferably of the species Escherichia coli.

[0073] A particular object of the invention is therefore a process or method for preparing p-chlorobenzonitrile comprising or consisting of the following steps: b1) the culture of a microorganism as described in this application to produce p-aminobenzoic acid; and steps b1), b2), b3), and b4) as described in this application.

[0074] A particular object of the invention is also a process or method for preparing p-chlorobenzonitrile comprising or consisting of the following steps: b0) the culture of a microorganism as described in this application, in particular of species E.E. coli, to produce p-aminobenzoic acid; b1) the reaction of p-aminobenzoic acid with potassium nitrate and hydrochloric acid in a solvent, preferably dimethyl sulfoxide, to obtain p-chlorobenzoic acid, preferably at a temperature between 20 and 50 °C, and even more preferably about 35 °C, preferably for 2 to 6 hours, and even more preferably for about 4 hours; b2) the reaction of p-chlorobenzoic acid with an aqueous solution of ammonia under reflux to obtain p-chlorobenzamide; b3) the reaction of p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C; and b4) the recovery of p-chlorobenzonitrile.

[0075] p-Chlorobenzonitrile, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640. Also, p-Chlorobenzonitrile, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a bio-based carbon content equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%.An object of the invention therefore relates to p-chlorobenzonitrile comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

[0076] Another object of the invention also relates to p-chlorobenzonitrile comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640 obtained by a process or method comprising or consisting of the following steps: b0) the culture of a microorganism, in particular of species E.Coli, to produce p-aminobenzoic acid; b1) the reaction of p-aminobenzoic acid with potassium nitrate and hydrochloric acid in a solvent to obtain p-chlorobenzoic acid; b2) the reaction of p-chlorobenzoic acid with an aqueous solution of ammonia under reflux to obtain p-chlorobenzamide; b3) the reaction of p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C; and b4) the recovery of p-chlorobenzonitrile.

[0077] According to another aspect of the invention, p-aminobenzoic acid is used in a process for preparing benzoic acid. Preferably, p-aminobenzoic acid is used in a process for preparing benzoic acid as described in this application.

[0078] More specifically, p-aminobenzoic acid can be converted to benzoic acid in a single step by nitrous deamination, which includes the production of the corresponding diazonium salt in aqueous media with sodium nitrite and acetic acid, followed by hydrogenation in a solvent. Examples of solvents include polar and / or nonpolar solvents. Polar solvents include water and alcohols, for example, methanol, ethanol, propanol, isopropanol (2-propanol), and butanol. Nonpolar solvents include halogenated solvents, for example, chloroform and dichloromethane. A solvent can also be a mixture of a polar solvent and a nonpolar solvent, such as a mixture of water and chloroform.An object of the invention therefore relates to a process or method for preparing benzoic acid comprising the following steps: c1) reacting p-aminobenzoic acid with sodium nitrite and acetic acid in a solvent; and c2) recovering benzoic acid.

[0079] An object of the invention also relates to a process or method for preparing benzoic acid consisting of the following steps: c1) reacting p-aminobenzoic acid with sodium nitrite and acetic acid in a solvent; and c2) recovering the benzoic acid.

[0080] According to a particular embodiment, step cl) includes reacting an equimolar aqueous solution of p-aminobenzoic acid chloroform, sodium nitrite in a solution of acetic acid and water at a temperature between 15 and 35 °C, preferably about 25 °C, for 15 to 60 minutes, preferably about 30 minutes.

[0081] An object is therefore a process or method for preparing benzoic acid comprising or consisting of the following steps: c1) reacting an equimolar aqueous solution of p-aminobenzoic acid and sodium nitrite in chloroform with a solution of acetic acid and water at a temperature between 15 and 35 °C, preferably about 25 °C, for 15 to 60 minutes, preferably about 30 minutes; and c2) recovering the benzoic acid.

[0082] In particular, p-aminobenzoic acid is produced or obtained by a biological process from a microorganism, in particular a bacterium, preferably of the species Escherichia coli.

[0083] A particular object of the invention is therefore a process or method for preparing benzoic acid comprising or consisting of the following steps: c1) the cultivation of a microorganism as described in this application for producing p-aminobenzoic acid; and steps c2) and c3) as described in this application. A particular object of the invention is also a process or method for preparing benzoic acid comprising or consisting of the following steps: c1) the cultivation of a microorganism as described in this application, in particular of species E.Coli to produce p-aminobenzoic acid; c1) reacting p-aminobenzoic acid with sodium nitrite and acetic acid in a solvent, preferably an equimolar aqueous solution of p-aminobenzoic acid and sodium nitrite in chloroform in a solution of acetic acid and water at a temperature between 15 and 35 °C, preferably about 25 °C, for 15 to 60 minutes, preferably about 30 minutes; and c2) recovering benzoic acid.

[0084] Benzoic acid, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640. Also, benzoic acid, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a bio-based carbon content equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%.

[0085] An object of the invention therefore relates to benzoic acid comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

[0086] Another object of the invention also relates to benzoic acid comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640 obtained by a process or method comprising or consisting of the following steps: c1) the culture of a microorganism, in particular of the species E. Coli, to produce p-aminobenzoic acid; c2) the reaction of p-aminobenzoic acid with sodium nitrite and acetic acid in a solvent; and c3) the recovery of benzoic acid.

[0087] According to another aspect of the invention, p-aminobenzoic acid is used in a process for preparing aniline. Preferably, p-aminobenzoic acid is used in a process for preparing aniline as described in this application.

[0088] In particular, p-aminobenzoic acid can be converted to aniline by a decarboxylation reaction upon heating at temperatures between 50 and 200 °C. Advantageously, no solvent is used in this process. More specifically, the reaction can be carried out at temperatures between 50 and 200 °C, especially between 50 and 190 °C, between 60 and 190 °C, between 70 and 180 °C, between 80 and 180 °C, between 90 and 180 °C, between 100 and 180 °C, between 110 and 180 °C, between 120 and 180 °C, between 130 and 170 °C, between 140 and 160 °C, and preferably around 150 °C.

[0089] An object of the invention therefore relates to a process or method for preparing aniline comprising the following steps: d1) reacting p-aminobenzoic acid at a temperature between 50 and 200 °C, in particular between 50 and 190 °C; and d2) recovering the aniline.

[0090] An object of the invention therefore relates to a process or method for preparing aniline consisting of the following steps: d1) reacting p-aminobenzoic acid at a temperature between 50 and 200 °C, in particular between 50 and 190 °C; and d2) recovering the aniline.

[0091] According to a particular embodiment, step dl) includes reacting p-aminobenzoic acid at a temperature of about 150 °C for 1 to 5 hours, preferably for about 3 hours.

[0092] An object is therefore a process or method for preparing aniline comprising or consisting of the following steps: d1) reacting p-aminobenzoic acid at a temperature of about 150 °C for 1 to 5 hours, preferably for about 3 hours; and d2) recovering the aniline. In particular, the p-aminobenzoic acid is produced or obtained by a biological process from a microorganism, in particular a bacterium, preferably of the species Escherichia coli.

[0093] A particular object of the invention is therefore a process or method for preparing aniline comprising or consisting of the following steps: d1) the culture of a microorganism as described in this application to produce p-aminobenzoic acid; and steps d1) and d2) as described in this application.

[0094] A particular object of the invention is also a process or method for preparing aniline comprising or consisting of the following steps: d1) culturing a microorganism as described in this application to produce p-aminobenzoic acid; d2) reacting p-aminobenzoic acid at a temperature between 50 and 200 °C, in particular between 50 and 190 °C, preferably about 150 °C, for 1 to 5 hours, preferably about 3 hours; and d3) recovering the aniline.

[0095] Aniline, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640. Also, aniline, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a bio-based carbon content equal to or greater than 90%, preferably equal to or greater than 99%, and even more preferably 100%.

[0096] An object of the invention therefore relates to aniline comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

[0097] An object of the invention also relates to aniline comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640 obtained by a process or method of preparation comprising or consisting of the following steps: d1) the culture of a microorganism, in particular of the species E. Coli, to produce p-aminobenzoic acid; d1) the reaction of p-aminobenzoic acid at a temperature between 50 and 200 °C, in particular between 50 and 190 °C; and d2) the recovery of the aniline.

[0098] According to another aspect of the invention, p-aminobenzoic acid is used in a process for preparing hydroxybenzomorpholine. Preferably, p-aminobenzoic acid is used in a process for preparing hydroxybenzomorpholine as described in this application.

[0099] More specifically, PABA can be converted to hydroxybenzomorpholine in four successive reaction steps, including a PABA bromination step followed by a step to form 4-(2-avetamidoethoxy)-3-bromobenzoic acid. This latter product is then cyclized to form 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid, and a reduction step using an iron complex yields hydroxybenzomorpholine.

[0100] An object of the invention therefore relates to a process or method for preparing hydroxybenzomorpholine comprising the following steps: e1) reacting p-aminobenzoic acid with a solution of sodium bromate and potassium bromide to obtain 4-amino-3-bromobenzoic acid; e2) reacting 4-amino-3-bromobenzoic acid with sodium nitrite and N-(2-hydroxyethyl)acetamide in a solvent to obtain 4-(2-acetamidoethoxy)-3-bromobenzoic acid; e3) reacting 4-(2-acetamidoethoxy)-3-bromobenzoic acid with copper sulfate and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine to obtain 3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylic acid; e4) the reaction of 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid with an iron complex, preferably [Fe n (BPMEN)(CH3CN)2](C104)2, and hydrogen peroxide; and e5) the recovery of hydroxybenzomorpholine.

[0101] An object of the invention also relates to a process or method for preparing hydroxybenzomorpholine consisting of the following steps: e1) reacting p-aminobenzoic acid with a solution of sodium bromate and potassium bromide to obtain 4-amino-3-bromobenzoic acid; e2) reacting 4-amino-3-bromobenzoic acid with sodium nitrite and N-(2-hydroxyethyl)acetamide in a solvent to obtain 4-(2-acetamidoethoxy)-3-bromobenzoic acid; e3) the reaction of 4-(2-acetamidoethoxy)-3-bromobenzoic acid with copper sulfate and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine to obtain 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid; e4) the reaction of 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid with an iron complex, preferably [Fe n (BPMEN)(CH3CN)2](C104)2, and hydrogen peroxide; and e5) the recovery of hydroxybenzomorpholine.

[0102] According to a particular embodiment, step e1) includes reacting a solution of p-aminobenzoic acid in acetic acid with a solution of sodium bromate and potassium bromide in water at room temperature followed by the addition of hydrochloric acid and maintaining the reaction at room temperature for 10 to 60 minutes, preferably for about 30 minutes.

[0103] According to a particular embodiment, step e2) comprises the following substeps: e2a) reacting a solution of 4-amino-3-bromobenzoic acid in sulfuric acid with sodium nitrite at room temperature for 30 minutes to 120 minutes, preferably for about 60 minutes, and e2b) reacting the reaction medium of step e2a) in a solution of N-(2-hydroxyethyljacetamide in methoxycyclopentane at room temperature for 30 minutes to 120 minutes, preferably for about 60 minutes.

[0104] According to a particular embodiment, step e3) comprises the following substeps: e3a) reacting 4-(2-acetamidoethoxy)-3-bromobenzoic acid and sodium carbonate with copper sulfate and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine at a temperature between 75 and 125 °C, preferably about 100 °C for 10 to 16 hours, and e3b) treating the reaction medium of step e3a) with sodium hydroxide at a temperature between 75 and 125 °C, preferably about 100 °C for 2 to 6 hours, preferably for about 4 hours.

[0105] According to a particular embodiment, step e4) comprises the following substeps: e4a) reacting 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid with an iron complex, preferably [Fe n(BPMEN)(CH3CN)2](C104)2 and hydrogen peroxide in acetonitrile at room temperature for 10 to 60 minutes, preferably for about 30 minutes, and e4b) treatment of the reaction medium from step e4a) with an aqueous solution of Na2EDTA. An object is therefore a process or method for preparing the orphan hydroxybenzom comprising or consisting of the following steps e1), e2a), e2b), e3a), e3b), e4a), e4b), and e5) as described above.

[0106] In particular, p-aminobenzoic acid is produced or obtained by a biological process from a microorganism, in particular a bacterium, preferably of the species Escherichia coli.

[0107] A particular object of the invention is therefore a process or method for preparing hydroxybenzomorpholine comprising or consisting of the following steps: e1) the culture of a microorganism as described in this application to produce p-aminobenzoic acid; and steps e1), e2), e3), e4), and e5) as described in this application.

[0108] A particular object of the invention is also a process or method for preparing hydroxybenzomorpholine comprising or consisting of the following steps: e0) the culture of a microorganism as described in this application to produce p-aminobenzoic acid; and steps e1), e2a), e2b), e3a), e3b), e4a), e4b), and e5) as described in this application.

[0109] According to another aspect, PABA can be converted to hydroxybenzomorpholine in seven successive reaction steps, including the conversion of PABA to 4-hydroxybenzoic acid followed by a protection step to form 4-acetoxybenzoic acid. The latter is then converted to 4-hydrobenzaldehyde, and reaction with hydrogen peroxide in a basic medium yields the intermediate hydroquinone. This intermediate undergoes an oxidation reaction to give benzoquinone, which is then reacted in a slightly acidic medium with ethylenediamine to form 2-((2-aminoethyl)amino)benzene-1,4-diol. This last product is then cyclized to give the orphan hydroxybenzom.

[0110] An object of the invention therefore relates to a process or method for preparing hydroxybenzomorpholine comprising the following steps: f1) reacting p-aminobenzoic acid with a sodium nitrite solution in water to obtain 4-hydroxybenzoic acid; f2) reacting 4-hydroxybenzoic acid with acetic anhydride to obtain 4-acetoxybenzoic acid; f1) reacting 4-acetoxybenzoic acid with thionyl chloride and a palladium-based catalyst under a hydrogen atmosphere to obtain 4-hydrobenzaldehyde; f4) reacting 4-hydrobenzaldehyde with sodium hydroxide and a hydrogen peroxide solution to obtain hydroquinone; f5) reacting hydroquinone with copper acetate and a hydrogen peroxide solution to obtain benzoquinone;f6) the reaction of benzoquinone with acetic acid and ethylenediamine to obtain 2-((2-aminoethyl)amino)benzene-l,4-diol; f7) and the reaction of 2-((2-aminoethyl)amino)benzene-l,4-diol with sulfuric acid and sodium nitrite; and f8) the recovery of hydroxybenzomorpholine.

[0111] An object of the invention also relates to a process or method for preparing hydroxybenzomorpholine consisting of the following steps: f1) reacting p-aminobenzoic acid with a sodium nitrite solution in water to obtain 4-hydroxybenzoic acid; f2) reacting 4-hydroxybenzoic acid with acetic anhydride to obtain 4-acetoxybenzoic acid; f1) reacting 4-acetoxybenzoic acid with thionyl chloride and a palladium-based catalyst under a hydrogen atmosphere to obtain 4-hydrobenzaldehyde; f4) reacting 4-hydrobenzaldehyde with sodium hydroxide and a hydrogen peroxide solution to obtain hydroquinone; f5) reacting hydroquinone with copper acetate and a hydrogen peroxide solution to obtain benzoquinone;f6) the reaction of benzoquinone with acetic acid and ethylenediamine to obtain 2-((2-aminoethyl)amino)benzene-1,4-diol; f7) and the reaction of 2-((2-aminoethyl)amino)benzene-1,4-diol with sulfuric acid and sodium nitrite; and f8) the recovery of the orphan hydroxybenzom.

[0112] According to one particular embodiment, step fl) comprises the solubilization of p-aminobenzoic acid in a water / sulfuric acid mixture followed by the addition of methoxycyclopentane (CPME) and a sodium nitrite solution in water. Preferably, the reaction mixture is stirred under reflux (approximately 110 °C) for 30 min to 4 hours, preferably for approximately 2 hours.

[0113] According to a particular embodiment, step f2) includes reacting 4-hydroxybenzoic acid with acetic anhydride in a solvent, preferably a toluene / tetrahydrofuran mixture, in the presence of pyridine, at room temperature.

[0114] According to a particular embodiment, step f3) comprises the following substeps: f3a) reacting 4-acetoxybenzoic acid in tetrahydrofuran with thionyl chloride at room temperature particularly for 2 to 6 hours, preferably about 4 hours, f3b) adding palladium supported on barium sulfate and hydrogen, then maintaining the reaction at a temperature between 50 and 100 °C, preferably about 70 °C, for a few hours, preferably about 16 hours, and f3c) filtering the palladium supported on barium sulfate and adding a sodium hydroxide solution, then maintaining the reaction under reflux, particularly for 1 to 6 hours, preferably about 3 hours.

[0115] According to a particular embodiment, step f4) includes reacting 4-hydrobenzaldehyde and sodium hydroxide in water with a hydrogen peroxide solution at a temperature between 50 and 90 °C, preferably about 85 °C, and particularly for 8 to 48 hours, preferably about 24 hours.

[0116] According to a particular embodiment, step f5) includes adding a hydrogen peroxide solution to an aqueous solution comprising hydroquinone and copper acetate, and then maintaining the reaction at room temperature, particularly for 20 minutes to 2 hours, preferably for about 1 hour.

[0117] According to a particular embodiment, step f6) includes reacting benzoquinone with acetic acid and ethylenediamine at room temperature, particularly for 2 to 6 hours, preferably for about 4 hours.

[0118] According to a particular embodiment, step f7) comprises the following substeps: f7a) suspending 2-((2-aminoethyl)amino)benzene-1,4-diol in water to which sulfuric acid and an aqueous solution of sodium nitrite are added, then maintaining the reaction at room temperature, particularly for 30 minutes to 4 hours, preferably for about 2 hours, and f7b) heating the reaction medium under reflux for 1 to 6 hours, preferably for 4 hours.

[0119] In particular, p-aminobenzoic acid is produced or obtained by a biological process from a microorganism, in particular a bacterium, preferably of the species Escherichia coli.

[0120] A particular object of the invention is therefore a process or method for preparing hydroxybenzomorpholine comprising or consisting of the following steps: (f1)) the culture of a microorganism as described in this application to produce p-aminobenzoic acid; and steps (f1), (f2), (f3), (f4), (f5), (f6), (f7) and (f8) as described in this application.

[0121] A particular object of the invention is also a process or method for preparing hydroxybenzomorpholine comprising or consisting of the following steps: (f1) culturing a microorganism as described in this application to produce p-aminobenzoic acid; and steps (f2), (f3), (f4), (f5), (f6), (f7a), (f7b), and (f8) as described in this application. Hydroxybenzomorpholine, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a percentage of modern carbon equal to or greater than 60%, preferably equal to or greater than 74%, in particular between 74% and 76%, for example 75%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.Hydroxybenzomorpholine, obtained by such processes using PABA produced or obtained by a biological process from a microorganism, may comprise a bio-based carbon content of 60% or more, preferably 74% or more, in particular between 74% and 76%, for example 75%. If the additional carbons in hydroxybenzomorpholine, i.e., those not originating from PABA, come from a bio-based carbon source, the hydroxybenzomorpholine may comprise a percentage of modern carbon of 99% or more, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640, or a bio-based carbon content of 99% or more.

[0122] An object of the invention therefore relates to hydroxybenzomorpholine comprising a percentage of modern carbon equal to or greater than 60%, preferably equal to or greater than 74%, even more preferably equal to or greater than 99%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

[0123] Another object of the invention also relates to hydroxybenzomorpholine comprising a percentage of modern carbon equal to or greater than 60%, preferably equal to or greater than 74%, even more preferably equal to or greater than 99%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640, obtained by a process or method comprising or consisting of the following steps: eO) the culture of a microorganism, in particular of species E.E. coli, to produce p-aminobenzoic acid; e1) the reaction of p-aminobenzoic acid with a solution of sodium bromate and potassium bromide to obtain 4-amino-3-bromobenzoic acid; e2) the reaction of 4-amino-3-bromobenzoic acid with sodium nitrite and N-(2-hydroxyethyl)acetamide in a solvent to obtain 4-(2-acetamidoethoxy)-3-bromobenzoic acid; e3) the reaction of 4-(2-acetamidoethoxy)-3-bromobenzoic acid with copper sulfate and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine to obtain 3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylic acid; e4) the reaction of 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid with an iron complex, preferably [Fe. n (BPMEN)(CH3CN)2](C104)2, and hydrogen peroxide; and e5) the recovery of hydroxybenzomorpholine.

[0124] Another object of the invention also relates to hydroxybenzomorpholine comprising a percentage of modern carbon equal to or greater than 60%, preferably equal to or greater than 74%, even more preferably equal to or greater than 99%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640, obtained by a process or method comprising or consisting of the following steps:

[0125] FO) the culture of a microorganism, in particular of the species E. coli, to produce p-aminobenzoic acid; fl) the reaction of p-aminobenzoic acid with a sodium nitrite solution in water to obtain 4-hydroxybenzoic acid; f2) the reaction of 4-hydroxybenzoic acid with acetic anhydride to obtain 4-acetoxybenzoic acid; f3) the reaction of 4-acetoxybenzoic acid with thionyl chloride and a palladium-based catalyst under a hydrogen atmosphere to obtain 4-hydrobenzaldehyde; f4) the reaction of 4-hydrobenzaldehyde with sodium hydroxide and a hydrogen peroxide solution to obtain F-hydroquinone; f5) the reaction of F-hydroquinone with copper acetate and a hydrogen peroxide solution to obtain benzoquinone; f6) the reaction of benzoquinone with acetic acid and ethylenediamine to obtain 2-((2-aminoethyl)amino)benzene-l,4-diol;f7) and the reaction of 2-((2-aminoethyl)amino)benzene-1,4-diol with sulfuric acid and sodium nitrite; and f8) the recovery of hydroxybenzomorpholine.

[0126] The processes or methods for preparing the five compounds of interest described above all include a final step of recovering the compound of interest. It is understood that a person skilled in the art knows how to recover the compound of interest after a reaction step, thanks to their general knowledge as an organic chemist. These recovery steps may include one or more treatment steps of the reaction mixture and one or more isolation and / or purification steps. For example, isolation and purification steps include distillation, evaporation, concentration, filtration, and / or drying.

[0127] The invention will be better understood in light of the following examples, which are given purely for illustrative purposes and are not intended to limit the scope of the invention as defined by the attached claims.

[0128] EXAMPLES

[0129] Example 1. Process for preparing p-toluidine

[0130] 1. Industrial synthesis

[0131] Scheme IA below illustrates the common industrial synthesis of p-toluidine by nitration and vapor-phase reduction of toluene by hydrogenation (Bowers, JS (2000), Toluidines, Ullmann's Encyclopedia of Industrial Chemistry). A mixture of ortho, meta, and para isomers of nitrotoluene in a ratio of 15:1:9 is obtained after the nitration reaction, which necessitates a separation step to obtain p-nitrotoluene. A maximum of 9 / 25 = 36% of p-toluidine is thus produced from one equivalent of toluene, which is a petroleum product.

[0132] AI diagram:

[0133] 2. Synthesis according to the invention

[0134] The process for synthesizing p-toluidine from PABA according to the invention is illustrated by Scheme IB below. Scheme IB:

[0135] 2 g of S11O2.H2O catalyst were placed in a fixed-bed reactor. A mixture of PABA, 2-propanol, and decane was injected at a total flow rate of 5 cm⁻¹ 3 . h' 1 at 330 °C. The concentration of PABA in 2-propanol was 0.2 M. The products were analyzed by gas chromatography. After a reaction time of one hour, the conversion was 90% and the yield of the isolated compound was 80% after distillation (1.37 g of p-toluidine).

[0136] 'H NMR (400 MHz, DMSO-d6) ô (ppm): 7.08 (d, J= 8.48 Hz, 2H), 6.70 (d, J= 8.36 Hz, 2H), 3.59 (br s, 2H), 2.36 (s, 3H).

[0137] Compared to the commonly used industrial synthesis, the process for synthesizing p-toluidine from PABA according to the invention is industrially attractive insofar as it does not require any nitration step from fossil carbon (Toluene) and it allows the para isomer to be produced selectively.

[0138] Example 2. Process for preparing p-chlorobenzonitrile

[0139] 1. Industrial synthesis

[0140] Scheme 2A below illustrates the routine industrial synthesis of p-chlorobenzonitrile from p-chlorotoluene using a vanadium-chromium catalyst (CN109847772). The reaction is carried out at 380 °C with a p-chlorotoluene / ammonia / air ratio of 1:3:30 in a fixed-bed reactor with an air stream.

[0141] Diagram 2A:

[0142] This synthetic route requires the preparation of p-chlorotoluene by direct chlorination of toluene with chlorine gas under moderate or atmospheric pressure. However, this reaction produces a mixture of chlorination isomers at positions 2 and 4, which must therefore be separated by distillation before reacting the p-chlorotoluene (Beck, U. & Loser, E. (2011), Chlorinated benzene and other nucleous-chlorinated aromatic hydrocarbons, Ullmann's Encyclopedia of Industrial Chemistry).

[0143] 2. Synthesis according to the invention

[0144] The process for synthesizing p-chlorobenzonitrile from PABA according to the invention is illustrated by Scheme 2B below. It consists of the chlorination of the diazonium salt derived from PABA, followed by the conversion of the carboxylic acid to an amide and then its dehydration.

[0145] Diagram 2B:

[0146] One mole of PABA was added to a DMSO solution containing one mole of potassium nitrate. After stirring for one hour, one mole of HCl(aq) was added, and the mixture was stirred at 35 °C for four hours. The crude product was concentrated and then resuspended in five volumes of aqueous ammonia solution, and the mixture was heated under reflux for two hours. The pH was adjusted to 3.5, and the product was filtered and then dissolved in five volumes of pyridine. One mole of diphenylchlorophosphate was added, and the mixture was heated at 60 °C for two hours. The reaction mixture was concentrated, and the precipitated product was isolated by simple filtration (96 g, 70%).

[0147] 'H NMR (400 MHz, DMSO-d6) ô (ppm): 7.87 (d, J= 8.4 Hz, 2H), 7.66 (d, J= 8.4 Hz, 2H).

[0148] Compared to the commonly used industrial synthesis, the process for synthesizing p-chlorobenzonitrile from PABA according to the invention is industrially attractive because it is carried out at temperatures more suitable for industrial scale and does not require any purification and isomer separation steps.

[0149] Example 3. Process for preparing benzoic acid

[0150] 1. Industrial Synthesis Scheme 3A below illustrates the common industrial synthesis of benzoic acid by gas-phase oxidation of toluene using vanadate catalysts (Benzoic acids, Ullmann's Encyclopedia of Industrial Chemistry). The reaction takes place at 200 °C.

[0151] Diagram 3A:

[0152] 2. Synthesis according to the invention

[0153] The process for synthesizing benzoic acid from PABA according to the invention is illustrated by diagram 3B below. It consists of the nitrous deamination of PABA in a single step (production of the diazonium salt in aqueous media and hydrogenation by chloroform in a biphasic medium).

[0154] Diagram 3B:

[0155] An equimolar aqueous solution of sodium nitrite and PABA (in 10 volumes of chloroform) was mixed with 10 volumes of water and 2 volumes of acetic acid, and the mixture was stirred at 25 °C for 30 minutes. The aqueous phase was discarded, and the organic phase was concentrated under reduced pressure. The precipitate was recovered by filtration and dried (712 mg, 80%).

[0156] 'H NMR (400 MHz, DMSO-d6) ô (ppm): 12.93 (s, 1H), 7.96-7.94 (m, 2H), 7.63-7.60 (m, 1H), 7.51-7.48 (m, 2H).

[0157] Compared to the commonly used industrial synthesis, the process for synthesizing benzoic acid from PABA according to the invention is industrially attractive because it consumes little energy since it takes place in water and at room temperature.

[0158] Example 4. Aniline preparation process 1. Industrial synthesis

[0159] Scheme 4A below illustrates the common industrial synthesis of aniline by nitration of benzene followed by hydrogenation in the presence of iron in acidic medium (Anilines, Ullmann's Encyclopedia of Industrial Chemistry).

[0160] Diagram 4A:

[0161] 2. Synthesis according to T invention

[0162] The process for synthesizing aniline from PABA according to the invention is illustrated by Scheme 4B below. It consists of the decarboxylation of PABA in a single step without the use of a solvent. Scheme 4B:

[0163] In a round-bottom flask, 1 gram of PABA was placed under stirring and the mixture was gradually heated to 150 °C, with the temperature maintained for 3 hours. The mixture became liquid, and the residual compound was purified by distillation (0.5 g, 70%).

[0164] 'H NMR (400 MHz, DMSO-d6) ô (ppm): 7.02-6.97 (m, 2H), 6.55 (d, J= 7.9 Hz, 2H), 6.48 (t, J= 7.3 Hz, 2H), 4.99 (s, 2H).

[0165] Compared to the commonly used industrial synthesis, the process for synthesizing aniline from PABA according to the invention is industrially attractive insofar as it does not use nitric acid or sulfuric acid, it comprises a single reaction step and a purification step by simple distillation.

[0166] Example 5. Process for preparing hydroxybenzomorpholine

[0167] 1. Industrial Synthesis Schemes 5A1 and 5A2 below illustrate the common industrial synthesis of hydroxybenzomorpholine via the intermediate 2,5-dimethoxyaniline.

[0168] The synthetic route for the orphan hydroxybenzom precursor, 2,5-dimethoxyaniline, comprises six steps illustrated in Scheme 5 Al. It uses a fossil-based and carcinogenic starting substrate, benzene, employs a methylation reaction involving DMS, a carcinogenic compound, and also uses a nitration step involving significant acidic effluents and low regioselectivity. The yield of this route is around 35%. (Phenol, Ullmann's Encyclopedia of Industrial Chemistry).

[0169] Diagram 5A1:

[0170] Two further synthesis steps, illustrated in Scheme 5A2, are required to finalize the production of hydroxybenzomorpholine: alkylation with bromoethanol and cyclization in the presence of a catalyst. The yield of each step is 48% and 57%, respectively (BE737265A).

[0171] Diagram 5A2:

[0172] The complete sequence comprising 8 reaction steps has a yield of approximately 10%.

[0173] 2. Synthesis according to the invention (bromination route) The process for the synthesis of orphan hydroxybenzom from PABA according to the invention is illustrated by diagram 5B below and comprises 4 steps.

[0174] Diagram 5B:

[0175] Step 1:

[0176] Yield 81%

[0177] A solution of 4-aminobenzoic acid (1.00 g, 7.29 mmol) in AcOH (5 mL, 5 vol) was combined with a solution of sodium bromate (0.44 g, 2.92 mmol, 0.4 equiv.) and potassium bromide (1.74 g, 14.58 mmol, 2 equiv.) in water (7 mL, 7 vol). The mixture was stirred at room temperature for 5 minutes. Then, 6 N HCl (6 mL, 6 vol) was added to the reaction mixture. After thorough stirring, the reaction mixture was left at room temperature for 30 minutes. The reaction mixture was then added to ice-cold water with continuous stirring. The precipitate was filtered, washed with cold water, and dried to give 4-amino-3-bromobenzoic acid (1.28 g) in 81% yield.

[0178] 'HNMR (300 MHz, DMSO-d6) ô (ppm): 12.42 (s, 1H), 7.86 (d, J= 1.9 Hz, 1H), 7.62 (dd, J= 8.4, 1.9 Hz, 1H), 6.78 (d, J= 8.5 Hz, 1H), 6.09 (s, 2H).

[0179] Step 2: To a solution of 4-amino-3-bromobenzoic acid (0.20 g, 0.93 mmol) in H₂SO₄ (1.5 mL, 26.85 mmol, 29 equiv.) at 5 °C, sodium nitrite (0.070 g, 1.02 mmol, 1.1 equiv.) was added. The solution was stirred at room temperature for 1 hour. The solution was then added to a solution of N-(2-hydroxyethyl)acetamide (2.0 mL, 22.22 mmol, 24 equiv.) in CPME (6.5 mL, 32.5 vol). The mixture was stirred at room temperature for 1 hour. The mixture was extracted with AcOEt and washed with a 2 M HCl solution. The organic phase was dried with Na2SO4 and concentrated under reduced pressure to give 4-(2-acetamidoethoxy)-3-bromobenzoic acid with a yield of 90%.

[0180] Step 3:

[0181] 4-(2-acetamidoethoxy)-3-bromobenzoic acid (200 mg, 0.66 mmol) was dissolved in water (660 pL, 1 M) with Na₂CO₃ (105 mg, 0.99 mmol, 1.5 equiv.). The heterogeneous mixture was stirred at 75 °C until completely dissolved under Ar. A solution of copper sulfate pentahydrate (1.6 mg, 0.007 mmol, 1 mol%) and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine (2.1 pL, 0.013 mmol, 2 mol%) in water (326 pL) was added to the mixture and heated at 100 °C overnight. The medium was treated with 4 equivalents of NaOH and heated to 100 °C for 4 hours, then acidified to pH 3 with 2 M HCl and extracted with ethyl acetate. The organic phase was dried with MgSCU and the solvent was evaporated under vacuum to give the light brown solid 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid (105 mg, 90% yield).

[0182] 'H NMR (400 MHz, DMSO-d6) ô (ppm): 12,30 (s, 1H), 7,19 (d, J= 2,0 Hz, 1H), 7,10 (dd, J= 8,3, 2,0 Hz, 1H), 6,70 (d, J= 8,3 Hz, 1H), 6,02 (s, 1H), 4,17 (t, J= 4,3 Hz, 2H), 3,28 (t, J= 4,3 Hz, 2H)

[0183] Étape 4 :

[0184] Yield 90%

[0185] Du [Fe n(BPMEN)(CH3CN)2][C1O4)2 (72 mg, 0.12 mmol, 50 mol%) was dissolved in acetonitrile (20 mL) under an argon atmosphere, and 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid (43 mg, 0.24 mmol) was added. A supplement of H2O2 (35% in water, 0.30 mmol, 20 pL, 1.5 equiv.) was added to the prepared mixture. The solution was stirred for 30 minutes at room temperature. The complex was then decomposed by treatment with an aqueous solution of Na2EDTA (20 mL, 5% solution). The pH was adjusted to 7 with an IM NaOH solution. The organic products were extracted with ethyl acetate and the organic extract was dried over MgSO-r before evaporating the solvent under vacuum to give hydroxybenzomorpholine (32 mg) with a yield of 90%.

[0186] 'H NMR (400 MHz, DMSO-d6) ô (ppm): 8.50 (s, 1H), 6.39 (d, J = 8.5 Hz, 1H), 5.99 (d, J = 2.8 Hz, 1H), 5.85 (dd, J = 8.5, 2.8 Hz, 1H), 5.62 (t, J = 2.5 Hz, 1H), 4.02-3.95 (m, 2H), 3.23-3.18 (m, 2H).

[0187] Compared to the commonly used industrial synthesis, the process of synthesizing hydroxybenzomorpholine from PABA according to the invention via a bromination reaction is industrially attractive insofar as it does not use nitric acid or sulfuric acid, it does not use carcinogenic compounds, and it is shorter (fewer steps) than the industrial process from benzene.

[0188] 3. Synthesis according to the invention (route via hydroquinone)

[0189] The process for the synthesis of hydroxybenzomorpholine from PABA via the hydroquinone intermediate according to the invention is illustrated by the 5C diagram below and comprises 7 steps.

[0190] Diagram 5C: Step 1: 4-Hydroxybenzoic acid

[0191] 4-Aminobenzoic acid (1.0 g, 7.29 mmol) was dissolved in a mixture of water (5 mL, 5 vol) and sulfuric acid (818 qL, 14.58 mmol, 2 eq) at room temperature. The mixture was stirred for 20 min at this temperature. CPME (5 mL, 5 vol) was then added, followed by a sodium nitrite solution (553 mg, 8.02 mmol, 1.1 eq) in water (5 mL, 5 vol) added dropwise over 10 min. The mixture was stirred for 2 h under reflux (110°C) before taking an aliquot to verify the complete conversion of the starting reagent (CTL CyHex / AcOEt 50 / 50). The mixture was cooled to 35°C before being extracted with 2 x 50 mL of ethyl acetate. The organic phase was dried with sodium sulfate and the solvent was evaporated under vacuum. 4-Hydroxybenzoic acid was obtained as an orange powder (1.01 g, 6.18 mmol, purity 85%, yield 85%).

[0192] 'H NMR (400 MHz, DMSO-t / 6) ô (ppm): 12.42 (s, 1H), 10.21 (s, 1H), 7.82 - 7.75 (m, 2H), 6.84 - 6.79 (m, 2H).

[0193] Step 2: 4-Acetoxybenzoic acid

[0194] Pyridine (1.17 mL, 14.48 mmol, 2 eq.) was slowly added at 0°C to a solution of 4-hydroxybenzoic acid (1.0 g, 7.24 mmol) in a mixture of toluene (38 mL, 38 vol) and THF (8 mL, 8 vol). Acetic anhydride (684 qL, 7.24 mmol, 1 eq.) was also slowly added at 0°C. The mixture was stirred at room temperature for 16 h. TLC (CyHex / EtOAc 50 / 50) of an aliquot showed complete conversion of the limiting reagent. The solvent was evaporated under vacuum. 4-Acetoxybenzoic acid was obtained as a white powder (1.52 g, 6.67 mmol, 79% purity, 92% yield).

[0195] 'H NMR (400 MHz, DMSO-t / 6) ô (ppm): 10.34 (s, 1H), 7.83 - 7.78 (m, 2H), 6.86 - 6.81 (m, 2H), 3.78 (s, 3H).

[0196] Step 3: 4-hydroxybenzaldehyde

[0197] 4-Acetoxybenzoic acid (1.0 g, 5.55 mmol) was dissolved in anhydrous THF (0.5 M) under nitrogen. Thionyl chloride (1.5 eq, 8.33 mmol, 605 pL) was added dropwise at room temperature. The reaction was stirred at room temperature for 4 h. Palladium supported on barium sulfate (5% Pd@BaS₄) (591 mg, 0.28 mmol, 5 mol%) was added to the reaction mixture. Hydrogen was bubbled into the mixture, and the hydrogen pressure was set at 3 bar. The mixture was heated to 70°C for 16 h, then cooled and purged with nitrogen. The catalyst was filtered through Celite, and the cake was rinsed with THF. A 2 M sodium hydroxide solution (10 mL) was added to the mixture, and the mixture was heated under reflux for 3 hours. The mixture was extracted with ethyl acetate. The organic phase was dried with magnesium sulfate, and the solvent was evaporated under vacuum. The aldehyde was obtained as a beige powder (576 mg, 4.72 mmol, 85% yield).

[0198] 'H NMR (400 MHz, DMSO-t / 6) ô (ppm): 10.60 (s, 1H), 9.79 (s, 1H), 7.79 - 7.73 (m, 2H), 6.95 - 6.90 (m, 2H).

[0199] 4-Hydrobenzaldehyde (200 mg, 1.64 mmol) was dissolved in water (0.1 M), to which sodium hydroxide (71 mg, 1.8 mmol, 1.1 eq) and a 35% hydrogen peroxide solution (243 pL, 3.61 mmol, 2.2 eq) were subsequently added. The reaction mixture was heated at 85°C for 24 h. After verifying complete conversion of the limiting reagent by TLC, the mixture was cooled to room temperature. The pH of the aqueous solution was adjusted to pH 7, and the mixture was then extracted with ethyl acetate. The organic phase was dried with magnesium sulfate, and the solvent was evaporated under vacuum. Hydroquinone was obtained as a brown powder (104 mg, 0.89 mmol, 94% purity, 55% yield). HNMR (400 MHz, DMSO-t / 6) ô (ppm): 8.1 (s, 2H), 6.55 (s, 4H).

[0200] Hydroquinone (1.0 g, 9.08 mmol) was dissolved in water (0.2 M), and copper acetate (445 mg, 2.45 mmol, 27 mol%) was added. A 35% hydrogen peroxide solution (2.34 mL, 27.24 mmol, 3 eq.) was also added. The mixture was stirred at room temperature for 1 h. The mixture was then extracted with ethyl acetate. The organic phase was dried with magnesium sulfate, and the solvent was evaporated under vacuum. A yellow powder was obtained, corresponding to benzoquinone (942 mg, 8.72 mmol, 96% yield) at NMR (400 MHz, DMSO-t / 6) and β (ppm): 6.87 (s, 4H).

[0201] Step 6: 2-((2-aminoethyl)amino)benzene-l,4-diol

[0202] Benzoquinone (1.0 g, 9.25 mmol) was dissolved in ethanol (5 mL, 5 vol). The reactor was purged with nitrogen. Acetic acid (529 pL, 9.25 mmol, 1 eq) was added to the medium, followed by ethylenediamine (618 pL, 9.25 mmol, 1 eq) dropwise. The medium was stirred at room temperature for 4 h. The medium was evaporated under vacuum, yielding a pale pink solid (1.49 g, 8.79 mmol, 95% yield).

[0203] Step 7: Hydroxybenzomorpholine 2-((2-aminoethyl)amino)benzene-1,4-diol (1.0 g, 5.95 mmol) was suspended in water (10 mL, 10 vol). Sulfuric acid (3 eq.) was added to the mixture at room temperature. An aqueous solution (5 mL) of sodium nitrite (1.05 eq.) was added dropwise. The reaction was stirred for 2 h at room temperature. The reaction was then heated under reflux for 4 h. The mixture was cooled to room temperature and the pH was adjusted to 8.1 with IM sodium hydroxide solution. The mixture was extracted with ethyl acetate. The organic phase was dried with magnesium sulfate and the solvent was evaporated under vacuum, yielding a brown powder (719 mg, 4.76 mmol, 80% yield).

[0204] 'H NMR (400 MHz, DMSO-t / 6) ô (ppm): 8.50 (s, 1H), 6.39 (d, J = 8.5 Hz, 1H), 5.99 (d, J = 2.8 Hz, 1H), 5.85 (dd, J = 8.5, 2.8 Hz, 1H), 5.62 (t, J = 2.5 Hz, 1H), 4.02 - 3.95 (m, 2H), 3.23 -

[0205] 3.18 (m, 2H).

[0206] Compared to the commonly used industrial synthesis, the process of synthesizing hydroxybenzomorpholine from PABA according to the invention via the hydroquinone intermediate is industrially attractive insofar as it does not use nitric acid and does not require any nitration step.

Claims

DEMANDS 1. Use of p-aminobenzoic acid in a process for preparing a compound selected from p-toluidine, p-chlorobenzonitrile, benzoic acid, aniline, and hydroxybenzomorpholine.

2. Use according to claim 1 in a process for the preparation of p-toluidine, characterized in that said process comprises the following steps: a1) reacting p-aminobenzoic acid with a catalyst, preferably a metallic catalyst, in a solvent, optionally under a hydrogen atmosphere; and a2) recovering p-toluidine.

3. Use according to claim 2, wherein step a1a) comprises reacting p-aminobenzoic acid with tin dioxide in a mixture of 2-propanol and decane at a temperature between 250 and 400 °C, preferably about 330 °C for 30 minutes to 10 hours, preferably about 1 hour.

4. Use according to claim 1 in a process for preparing p-chlorobenzonitrile, characterized in that said process comprises the following steps: b1) reacting p-aminobenzoic acid with potassium nitrate and hydrochloric acid in a solvent to obtain p-chlorobenzoic acid; b2) reacting p-chlorobenzoic acid with an aqueous solution of ammonia under reflux to obtain p-chlorobenzamide; b3) reacting p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C; and b4) recovering p-chlorobenzonitrile.

5. Use according to claim 4, wherein step bl) comprises reacting p-aminobenzoic acid with potassium nitrate and hydrochloric acid in dimethyl sulfoxide at a temperature between 20 and 50 °C, preferably about 35 °C, for 2 to 6 hours, preferably about 4 hours.

6. Use according to claim 1 in a process for the preparation of benzoic acid, characterized in that said process comprises the following steps: c1) the reaction of p-aminobenzoic acid with sodium nitrite and acetic acid in a solvent; and c2) the recovery of benzoic acid.

7. Use according to claim 6, wherein step cl) comprises reacting an equimolar aqueous solution of p-aminobenzoic acid chloroform and sodium nitrite in a solution of acetic acid and water at a temperature between 15 and 35 °C, preferably about 25 °C, for 15 to 60 minutes, preferably about 30 minutes.

8. Use according to claim 1 in a process for the preparation of aniline, characterized in that said process comprises the following steps: d1) the reaction of p-aminobenzoic acid at a temperature between 50 and 200 °C, in particular between 50 and 190 °C; and d2) the recovery of aniline.

9. Use according to claim 8, wherein step dl) comprises reacting p-aminobenzoic acid at a temperature of about 150 °C for 1 to 5 hours, preferably for about 3 hours.

10. Use according to claim 1 in a process for preparing hydroxybenzomorpholine, characterized in that said process comprises the following steps: e1) reacting p-aminobenzoic acid with a solution of sodium bromate and potassium bromide to obtain 4-amino-3-bromobenzoic acid; e2) reacting 4-amino-3-bromobenzoic acid with sodium nitrite and N-(2-hydroxyethyl)acetamide in a solvent to obtain 4-(2-acetamidoethoxy)-3-bromobenzoic acid; e3) the reaction of 4-(2-acetamidoethoxy)-3-bromobenzoic acid with copper sulfate and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine to obtain 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid; e4) the reaction of 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid with an iron complex, preferably [Fe n(BPMEN)(CH3CN)2](C104)2, and hydrogen peroxide; and e5) the recovery of hydroxybenzomorpholine.

11. Use according to claim 1 in a process for preparing hydroxybenzomorpholine, characterized in that said process comprises the following steps: f1) reacting p-aminobenzoic acid with a sodium nitrite solution in water to obtain 4-hydroxybenzoic acid; f2) reacting 4-hydroxybenzoic acid with acetic anhydride to obtain 4-acetoxybenzoic acid; f1) reacting 4-acetoxybenzoic acid with thionyl chloride and a palladium-based catalyst under a hydrogen atmosphere to obtain 4-hydrobenzaldehyde; f4) reacting 4-hydrobenzaldehyde with sodium hydroxide and a hydrogen peroxide solution to obtain hydroquinone; f5) reacting hydroquinone with copper acetate and a hydrogen peroxide solution to obtain benzoquinone;f6) the reaction of benzoquinone with acetic acid and ethylenediamine to obtain 2-((2-aminoethyl)amino)benzene-l,4-diol; f7) and the reaction of 2-((2-aminoethyl)amino)benzene-l,4-diol with sulfuric acid and sodium nitrite; and f8) the recovery of hydroxybenzomorpholine.

12. Use according to any one of claims 1 to 11, wherein p-aminobenzoic acid is produced from a microorganism, in particular a bacterium, preferably of the species Escherichia coli.

13. p-Toluidine comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

14. p-Toluidine according to claim 13 obtained by a process or method comprising or consisting of the following steps: a1) the culture of a microorganism, in particular of the species E. coli, to produce p-aminobenzoic acid; a2) the reaction of p-aminobenzoic acid with a catalyst, preferably a metallic catalyst, in a solvent, optionally under a hydrogen atmosphere; and a3) the recovery of p-toluidine.

15. p-Chlorobenzonitrile comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

16. p-Chlorobenzonitrile according to claim 15 obtained by a process or method comprising or consisting of the following steps: b1) the culture of a microorganism, in particular of the species E. coli, to produce p-aminobenzoic acid; b2) the reaction of p-aminobenzoic acid with potassium nitrate and hydrochloric acid in a solvent to obtain p-chlorobenzoic acid; b3) the reaction of p-chlorobenzoic acid with an aqueous solution of ammonia under reflux to obtain p-chlorobenzamide; b4) the reaction of p-chlorobenzamide with diphenylchlorophosphonate in pyridine at a temperature between 40 and 80 °C; and b5) the recovery of p-chlorobenzonitrile.

17. Benzoic acid comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

18. Benzoic acid according to claim 17 obtained by a process or method comprising or consisting of the following steps: c1) the culture of a microorganism, in particular of the species E. coli, to produce p-aminobenzoic acid; c2) the reaction of p-aminobenzoic acid with sodium nitrite and acetic acid in a solvent; and c3) the recovery of benzoic acid.

19. Aniline comprising a percentage of modern carbon equal to or greater than 90%, preferably equal to or greater than 99%, even more preferably 100%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

20. Aniline according to claim 19 obtained by a process or method comprising or consisting of the following steps: d1) the culture of a microorganism, in particular of the species E. coli, to produce p-aminobenzoic acid; d1) the reaction of p-aminobenzoic acid at a temperature between 50 and 200 °C, in particular between 50 and 190 °C; and d2) the recovery of the aniline.

21. Orphan hydroxybenzom comprising a percentage of modern carbon equal to or greater than 60%, preferably equal to or greater than 74%, and even more preferably equal to or greater than 99%, the percentage of modern carbon being determined by accelerator mass spectrometry according to standard NF EN 16640.

22. Hydroxybenzomorpholine according to claim 21 obtained by a process or method comprising or consisting of the following steps: e1) the culture of a microorganism, in particular of the species E. coli, to produce p-aminobenzoic acid; e2) the reaction of p-aminobenzoic acid with a solution of sodium bromate and potassium bromide to obtain 4-amino-3-bromobenzoic acid; e3) the reaction of 4-amino-3-bromobenzoic acid with sodium nitrite and N-(2-hydroxyethyl)acetamide in a solvent to obtain 4-(2-acetamidoethoxy)-3-bromobenzoic acid; e3) the reaction of 4-(2-acetamidoethoxy)-3-bromobenzoic acid with copper sulfate and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine to obtain 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid; e4) the reaction of 3,4-dihydro-2H-benzo[b][l,4]oxazine-6-carboxylic acid with an iron complex, preferably [Fe n(BPMEN)(CH3CN)2](C104)2, and hydrogen peroxide; and e5) the recovery of hydroxybenzomorpholine.

23. Hydroxybenzomorpholine according to claim 21 obtained by a process or method comprising or consisting of the following steps: fi)) the culture of a microorganism, in particular of the species E. coli, to produce p-aminobenzoic acid; f1) the reaction of p-aminobenzoic acid with a sodium nitrite solution in water to obtain 4-hydroxybenzoic acid; f2) the reaction of 4-hydroxybenzoic acid with acetic anhydride to obtain 4-acetoxybenzoic acid; f1) the reaction of 4-acetoxybenzoic acid with thionyl chloride and a palladium-based catalyst under a hydrogen atmosphere to obtain 4-hydrobenzaldehyde; f4) the reaction of 4-hydrobenzaldehyde with sodium hydroxide and a hydrogen peroxide solution to obtain hydroquinone; f5) the reaction of hydroquinone with copper acetate and a hydrogen peroxide solution to obtain benzoquinone; f6) the reaction of benzoquinone with acetic acid and ethylenediamine to obtain 2-((2-aminoethyl)amino)benzene-l,4-diol;f7) and the reaction of 2-((2-aminoethyl)amino)benzene-1,4-diol with sulfuric acid and sodium nitrite; and f8) the recovery of the orphan hydroxybenzom.

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