Continuous flow process for preparing a nitrophenol-type compound

Abstract

The present invention relates to a process for preparing a nitrophenol-type compound, as described below, involving diazotization and hydrolysis reactions carried out in a single step in a continuous flow process from at least one nitroaniline compound, as defined below, and at least one diazotizing agent. The invention also relates to a continuous flow process for synthesizing a diazonium salt at a temperature of 80°C or higher from at least one nitroaniline compound and at least one diazotizing agent.

Description

Title of the invention: Process for the continuous flow preparation of a nitrophenol-type compound

[0001] The present invention relates to a process for preparing a nitrophenol-type compound, as described below, using diazotization and hydrolysis reactions carried out in a single step in continuous flow from at least one nitroaniline compound, as defined below, and at least one diazotization agent.

[0002] The invention also relates to a process for the continuous flow synthesis of a diazonium salt carried out at a temperature greater than or equal to 80°C from at least one nitroaniline compound and at least one diazotizing agent.

[0003] 2-Methyl-5-nitrophenol, belonging to the family of nitrophenol-type compounds, is a compound whose properties are generally of interest in the field of cosmetics, in particular for use as a colorant for keratin fibers, in particular human keratin fibers such as hair.

[0004] 2-Methyl-5-nitrophenol is generally prepared via two distinct steps, namely by carrying out a diazotization reaction between 2-methyl-5-nitroaniline, most often in solution or suspension in an aqueous solution of sulfuric acid, and a diazotization agent (also called a nitrosating agent), for example sodium nitrite, in order to generate a diazonium salt, as a reaction intermediate, then a subsequent reaction, for example of the hydrolysis, halogenation or azo coupling type, to convert the diazonium ion of the reaction intermediate into a phenol group.

[0005] The diazotization reaction is most often carried out cold, in particular at temperatures ranging from 0°C to 15°C, to minimize the risks of degradation of the diazonium salt which is a highly unstable species likely to decompose relatively easily under the action of a low heat input and to cause possible explosions.

[0006] Once the diazotization reaction is complete, the subsequent reaction of the hydrolysis, halogenation or azo coupling type is carried out hot at temperatures ranging from 70°C to 120°C.

[0007] In other words, the diazotization and hydrolysis reactions are carried out in two consecutive and distinct stages at different temperature ranges, in particular for reasons of instability of the diazonium salt.

[0008] However, such a process in a batch reactor presents in particular the major pitfall of causing an accumulation of the diazonium salt at the end of the diazotization step within a reactor, thus accentuating the safety problems.

[0009] Furthermore, the cold diazotization reaction carried out in an acid medium can lead to the formation of sodium sulfate, due to the presence of an excess of sulfuric acid compared to the diazotization agent, which requires carrying out one or more effluent washing operations at the reactor outlet. Such operations generate energy expenditure and additional costs.

[0010] In order to overcome these drawbacks and improve safety conditions, processes for preparing nitrophenol-type compounds, such as 2-methyl-5-nitrophenol, have been implemented in continuous flow.

[0011] By way of illustration, it has already been proposed to carry out in continuous flow a diazotization reaction in a temperature range from -15°C to 25°C followed by a halogenation reaction, in particular bromination, at higher temperatures which can in particular range from 45°C to 80°C.

[0012] Alternatively, it has also been proposed to carry out a process consecutively implementing a diazotization reaction, a reduction and an acid hydrolysis in continuous flow.

[0013] Furthermore, it has also been envisaged to implement a process alternating discontinuous and continuous reaction sequences. In particular, it has been proposed, in a first step, to react an aromatic amine and sulfuric acid to obtain a solution of aromatic amine sulfate, then, in a second step, to carry out a diazotization in continuous flow, at a temperature ranging from 10 to 50°C, followed by a separate reduction step at a temperature varying from 20 to 80°C, then a separate acid hydrolysis step at a temperature varying from 70°C to 120°C.

[0014] As a result, the processes conventionally implemented in the state of the art most of the time comprise at least two distinct steps carried out successively in different temperature ranges, in particular a diazotization reaction step carried out cold with temperatures which can possibly go up to 50°C, to minimize the risks of instability of the diazonium salt, and a subsequent reaction step of the hydrolysis, halogenation or azo coupling type carried out hot at higher temperatures, in particular which can vary from 70°C to 120°C.

[0015] However, such methods implemented in two stages have the disadvantage of involving tedious management of the flows of reactants, in particular in terms of stability of their flow rates, in a reactor and of requiring the use of connections within the reactor which may prove complex in certain cases, for example due to the number and type of pumps at the inlet and outlet of the reactor, the number of temperature and pressure sensors ensuring the control of the different temperature ranges depending on the reaction sequences, or the implementation of a flow of heat transfer fluid to maintain adequate temperatures during the diazotization reaction and the subsequent reaction.

[0016] In other words, the processes implemented in the state of the art involve an increasing number of parameters to be managed, resulting in the use of increasingly complex reactors, significant excess energy consumption and additional costs that may prove to be significant.

[0017] Furthermore, such processes may require the implementation of several additional washing operations impacting their yield.

[0018] In view of the above, one of the objectives of the present invention is to overcome the previously mentioned drawbacks, that is to say to propose a method for synthesizing a nitrophenol-type compound which is in particular simpler to implement than the methods conventionally described in the state of the art, for example in terms of the number of reagents, parameters and / or steps, while respecting safety conditions.

[0019] In other words, there is a real need to propose a process for preparing a nitrophenol-type compound during which the accumulation of the diazonium salt intermediate is minimized, thus ensuring enhanced safety conditions, while being relatively simple and efficient to implement.

[0020] The present invention therefore relates in particular to a process for the continuous flow preparation of a nitrophenol compound, comprising a diazotization and hydrolysis reaction step, at a temperature greater than or equal to 80°C, between at least one nitroaniline compound and at least one diazotization agent.

[0021] The process according to the invention therefore makes it possible to prepare a nitrophenol compound during which the diazotization and hydrolysis reactions are carried out in a single step in continuous flow, thus ensuring rapid, or even almost immediate, consumption of the diazonium salt intermediate.

[0022] In other words, the process according to the invention has the advantage of minimizing, or even eliminating, the accumulation of the diazonium salt reaction intermediate, resulting from the diazotization reaction, within a reactor, which makes it possible to significantly strengthen the safety conditions for obtaining a nitrophenol compound.

[0023] The process according to the invention thus has the advantage of carrying out the diazotization and hydrolysis reactions in a single step at the same temperature in a single reactor.

[0024] Thus, the implementation of the method according to the invention makes it possible to achieve a reduction in energy expenditure compared to the methods of the state of the art in which part of the energy expenditure is used to carry out the diazotization reaction cold, i.e. at so-called cold temperatures, and to maintain the diazonium salt in such conditions in order to minimize the risks of its decomposition. position.

[0025] The method according to the invention also has the advantage of being able to be implemented in simpler reaction systems, in particular in terms of structures and / or connections, than those used in the synthesis methods described in the state of the art.

[0026] The process can advantageously be implemented in miniaturized reactors.

[0027] Indeed, the method according to the invention makes it possible in particular to reduce the number of parameters to be managed during the diazotization and hydrolysis reactions, carried out in a single step, and can in particular be implemented in a reactor comprising two inlet orifices and one outlet orifice, which makes it possible to achieve energy savings and to reduce the costs associated with the synthesis of a nitrophenol-type compound.

[0028] In other words, the process according to the invention makes it possible to efficiently prepare a nitrophenol compound under improved safety conditions within simplified reaction systems.

[0029] In other words, the method according to the invention makes it possible to save time and resources without degrading safety conditions and while leading with an advantageous yield to a nitrophenol compound having an improved quality.

[0030] The process according to the invention also makes it possible to reduce the quantities of reagents used, to reduce the effluents at the reactor outlet and to limit any washing operations to recover the nitrophenol compound.

[0031] The method according to the invention also has a yield that may prove advantageous.

[0032] Furthermore, the nitrophenol compound obtained with the process according to the invention has a high purity.

[0033] The invention also relates to a process for the continuous flow preparation of a benzenediazonium compound comprising a diazotization reaction step at a temperature greater than or equal to 80°C between at least one nitroaniline compound and at least one diazotization agent.

[0034] The process according to the invention thus makes it possible to prepare a benzene-diazonium compound, in particular a benzenediazonium salt, at higher temperatures than those used in the processes of the prior art while respecting safety conditions.

[0035] Such a process advantageously makes it possible to carry out a single step of a diazotization and hydrolysis reaction in continuous flow to obtain a nitrophenol-type compound.

[0036] Other objects, characteristics, aspects and advantages of the invention will become apparent even more clearly when reading the description and the example that follows.

[0037] In what follows, and unless otherwise indicated, the limits of a domain of values ​​are included in this domain, in particular in the expressions “between” and “ranging from ... to ...”.

[0038] Furthermore, the expression “at least one” used in the present description is equivalent to the expression “one or more”.

[0039] Furthermore, the expression "at least" used in the present description is equivalent to the expression "greater than or equal to".

[0040] For the purposes of the present invention, the terms “diazonium salt” or “benzenediazonium salt” are used interchangeably.

[0041] Process for the preparation of a nitrophenol-type compound

[0042] As indicated above, the present invention relates in particular to a process for the continuous flow synthesis of a nitrophenol compound, implementing a single-step diazotization and hydrolysis reaction between at least one nitroaniline compound and at least one diazotization agent, at a temperature greater than or equal to 80°C.

[0043] By "continuous flow synthesis process" is meant within the meaning of the present invention that the nitroaniline compound and the diazotizing agent are conveyed, preferably in a fluid, and continuously pooled in the same reaction medium, preferably in the same reactor, in which the diazotization and hydrolysis reactions are carried out, without isolating a reaction intermediate between the two reactions, until the nitrophenol compound is obtained.

[0044] In accordance with the process according to the invention, the diazotization and hydrolysis reactions are carried out in a single step in continuous flow.

[0045] In accordance with the process according to the invention, the diazotization and hydrolysis reactions are carried out in a single step with almost immediate consumption of the diazonium salt.

[0046] In other words, the diazonium salt intermediate is not isolated between the diazotization and hydrolysis reactions.

[0047] For the purposes of the present invention, the term "nitrophenol compound or nitrophenol-type compound" means any type of nitrophenol compound, i.e. a compound comprising a benzene ring substituted by at least one hydroxyl group (-OH) and at least one nitro group (-NO2).

[0048] For the purposes of the present invention, the term "nitroaniline compound or nitroaniline-type compound" means any type of nitroaniline compound, i.e. a compound comprising a benzene ring substituted by at least one primary amine group (-NH2) and at least one nitro group (-NO2).

[0049] Preferably, the process according to the invention is a flow preparation process. continuous of a nitrophenol compound corresponding to the following formula (III): (III)

[0050] said process comprising a diazotization and hydrolysis reaction step, at a temperature greater than or equal to 80°C, between:

[0051] - at least one nitroaniline compound of formula (I): (I), And - at least one diazotizing agent;

[0052] Formula (III) in which: • Ri represents a hydrogen atom, a hydroxyl group (-OH) or a linear or branched alkyl group, C1-C10, • R2, R3, R4, and R5, identical or different, represent a hydroxyl group (-OH), a hydrogen atom, a linear or branched C i-C6 alkyl group, • provided that at least one of the radicals Rb R2, R3, R4, and R5 represents a hydroxyl group (-OH);

[0053] Formula (I) in which: • Rio represents a hydrogen atom, a primary amine group (-NH2) or a linear or branched alkyl group, C1-C10, • R20, R30, R40, and R50, identical or different, represent an amine group primary (-NH2), a hydrogen atom, a linear or branched alkyl group, C1-C6, provided that at least one of the radicals R10, R20, R30, R40, and R50 represents a primary amine group (-NH2).

[0054] Preferably, in formula (III), R1 or R5 represents a hydroxyl group (-OH), and, in formula (I), R10 or R50 represents a primary amine group (-NH2).

[0055] Preferably, in formula (III), R3 and R4 represent a hydrogen atom, and, in formula (I), R30 and R40 represent a hydrogen atom.

[0056] Preferably: in formula (III), R3 and R4 represent a hydrogen atom, R2 represents a hydrogen atom or a linear or branched alkyl group, C1-C6, preferably C1, in formula (I), R30 and R40 represent a hydrogen atom, R20 represents a hydrogen atom or a linear or branched alkyl group, C1-C6, preferably Cp

[0057] Preferably: in formula (III), R1 or R5 represents a hydroxyl group (-OH), R3 and R4 represent a hydrogen atom, R2 represents a hydrogen atom or a linear or branched alkyl group, C1-C6, preferably C1, in formula (I), R10 or R50 represents a primary amine group (-NH2), R30 and R40 represent a hydrogen atom, R20 represents a hydrogen atom or a linear or branched alkyl group, C1-C6, preferably C1

[0058] Preferably, in formula (III), R5 represents a hydroxyl group (-OH), and, in formula (I), R50 represents a primary amine group (-NH2).

[0059] Preferably, the process according to the invention is a process for the continuous flow preparation of a nitrophenol compound of the following formula (III'): Rt r3 'R2 NO (HD

[0060] said process comprising a diazotization and hydrolysis reaction step, at a temperature greater than or equal to 80°C, between:

[0061] - at least one nitroaniline compound of the following formula (I'):

[0062]

[0063]

[0064]

[0065]

[0066]

[0067]

[0068] (D, and - at least one diazotizing agent; Formula (III') in which: • Ri represents a hydrogen atom or a linear or branched alkyl group, CrCio, • R2, R3 and R4, identical or different, represent a hydrogen atom, a linear or branched alkyl group, C1-C6, preferably a hydrogen atom, Formula (F) in which: • Rio represents a hydrogen atom or a linear or branched alkyl group, C1-C10, • R2o, R30 and R40, identical or different, represent a hydrogen atom, a linear or branched alkyl group, C1-C6, preferably a hydrogen atom. Preferably, in formulas (I') and (III'), R1 and R10 represent a linear or branched alkyl group, C1-C4, preferably C1-C3, better still Cp Preferably, in formula (IH'), R2, R3 and R4, identical or different, represent a linear or branched C1-C4 alkyl group, or a hydrogen atom, and, in formula (I'), R20, R30 and R40, identical or different, represent a linear or branched C1-C4 alkyl group, or a hydrogen atom. Preferably, in formula (IH'), R2, R3 and R4 represent a hydrogen atom, and, in formula (I'), R20, R30 and R40 represent a hydrogen atom. Preferably, in formula (IH'), Ri represents a linear or branched alkyl group, C1-C4, preferably C1, and R2, R3 and R4 represent a hydrogen atom, and, in formula (I'), Rio represents a linear or branched alkyl group, C1-C4, preferably C1, and R20, R3o and R40 represent a hydrogen atom.

[0069] Advantageously, the compound of formula (I) or (!') corresponds to 2-methyl-5-nitroaniline.

[0070] Advantageously, the compound of formula (III) or (III') corresponds to 2-methyl-5-nitrophenol.

[0071] As indicated above, the temperature of the diazotization and hydrolysis reaction is greater than or equal to 80°C.

[0072] Advantageously, the temperature varies from 80°C to 150°C, preferably from 100°C to 140°C, more preferably from 100°C to 120°C.

[0073] The nitroaniline compound, preferably of formula (I) or (I'), may be present in a solution A at acidic pH, i.e. having a pH lower than 7, preferably a pH lower than 4, preferentially a pH lower than 3, in particular a pH lower than 1.

[0074] Preferably, solution A comprises at least one nitroaniline compound, preferably of formula (I) or (I'), and at least one acidifying agent, preferably organic and / or mineral, in particular mineral.

[0075] Among the acidifying agents, mention may be made, for example, of mineral or organic acids such as hydrochloric acid, orthophosphoric acid, sulfuric acid, carboxylic acids such as acetic acid, tartaric acid, citric acid, lactic acid, sulfonic acids, and mixtures thereof.

[0076] Preferably, the acidifying agents are chosen from the group consisting of mineral acids, more preferably sulfuric acid, hydrochloric acid and their mixtures, better still sulfuric acid.

[0077] Preferably, the acidifying agent is present in excess relative to the nitroaniline compound, preferably of formula (I) or (I'), in solution A.

[0078] Advantageously, the acidifying agent may be present in an amount ranging from 2 to 24 molar equivalents, preferably in an amount ranging from 10 to 14 molar equivalents, relative to the nitroaniline compound, preferably of formula (I) or (I'), in solution A.

[0079] Solution A is preferably prepared by mixing the nitroaniline compound, preferably of formula (I) or (I'), as described above, in an amount ranging from 2 to 24 molar equivalents, preferably in an amount ranging from 10 to 14 molar equivalents, of an acidifying agent as described above.

[0080] Solution A is preferably prepared at a temperature less than or equal to 50°C.

[0081] The diazotizing agent, also called nitrosating agent, can be chosen from the group consisting of nitrite salts, in particular inorganic nitrite salts.

[0082] The inorganic nitrite salts may be selected from the group consisting of alkali metal nitrite salts, alkaline earth metal nitrite salts and ammonium nitrite.

[0083] Preferably, the diazotizing agent is chosen from the group consisting of sodium nitrite, lithium nitrite, potassium nitrite, calcium nitrite, magnesium nitrite, ammonium nitrite and mixtures thereof, more preferably sodium nitrite.

[0084] The diazotizing agent may be present in an aqueous solution B in a content ranging from 1% to 50% by weight, preferably in a content ranging from 5 to 35% by weight, relative to the total weight of the aqueous solution B.

[0085] Aqueous solution B is liquid at a temperature ranging from 20 to 37°C.

[0086] In accordance with the process according to the invention, the nitroaniline compound, preferably of formula (I) or (!'), and the diazotizing agent are used in a continuous flow.

[0087] Thus when the nitroaniline compound, preferably of formula (I) or (!), is present in a solution A as described previously and the diazotizing agent is present in an aqueous solution B as described previously, solutions A and B are used at a constant flow rate.

[0088] Advantageously, the diazotizing agent and the nitroaniline compound, preferably of formula (I) or (!'), are used in the process according to the invention in a molar ratio ranging from 1.0 to 1.5, preferably in a molar ratio ranging from 1.05 to 1.2.

[0089] In particular, the flow rate of solution A and the flow rate of aqueous solution B are such that the molar ratio between the diazotizing agent and the nitroaniline compound, preferably of formula (I) or (!), advantageously varies from 1.0 to 1.5, preferably in a molar ratio ranging from 1.05 to 1.2.

[0090] The method according to the invention can be implemented in a reactor, preferably provided with two inlet ports and one outlet port.

[0091] Preferably, the inlet ports of the reactor are respectively supplied with the nitroaniline compound, preferably of formula (I) or (!'), preferably a solution A, as described above, comprising the nitroaniline compound, preferably of formula (I) or (!') as described above, and the diazotizing agent, preferably the aqueous solution B, as described above, comprising the diazotizing agent.

[0092] Preferably, solution A and aqueous solution B are each fed into the reactor via a feed pump.

[0093] Thus in the reactor, the diazotization and hydrolysis reactions take place in a single step at a temperature greater than or equal to 80°C, preferably at a temperature ranging from 80°C to 150°C, preferably from 100°C to 140°C, more preferably from 100°C to 120°C.

[0094] Preferably, the residence time in the reactor, preferably the microreactor, in particular the tubular microreactor, of the nitroaniline compound, preferably of formula (I) or (!'), and of the diazotizing agent, varies from 5 seconds to 5 minutes, preferably the residence time within the reactor is less than one minute.

[0095] The method according to the invention is notably implemented in a single reactor.

[0096] Advantageously, the reactor is a microreactor, preferably a tubular microreactor.

[0097] Preferably, the method according to the invention comprises a diazotization and hydrolysis reaction step carried out in a reactor, in particular a microreactor, in particular a tubular microreactor, in which the solution A as described previously and the aqueous solution B as described previously are conveyed and circulate in continuous flow.

[0098] Preferably, the nitrophenol compound, preferably of formula (III) or (III'), is recovered at the outlet of the reactor.

[0099] The nitrophenol-type compound, preferably of formula (III) or (III'), thus recovered may be in the form of a suspension.

[0100] The process according to the invention may further comprise a step of cooling the reaction medium, once the diazotization and hydrolysis reactions have been carried out in a single step, to a temperature which may range from 25°C to 90°C, preferably from 50°C to 85°C, before recovering the nitrophenol compound, preferably of formula (III) or (III').

[0101] In other words, the reaction medium can then be cooled in the reactor outlet line to a temperature ranging from 25°C to 90°C, preferably from 50°C to 85°C, before recovering the nitrophenol compound, preferably of formula (III) or (III'), at the reactor outlet orifice.

[0102] In other words, at the end of the diazotization and hydrolysis reactions carried out in a single step, the process according to the invention may further comprise a step of cooling the reaction medium to a temperature which may range from 25°C to 90°C, preferably from 50°C to 85°C.

[0103] The process according to the invention may also comprise a crystallization step and a filtration step of the nitrophenol compound, preferably of formula (III) or (in').

[0104] The nitrophenol compound, preferably of formula (III) or (III'), can then be hydrogenated in an autoclave reactor in a reaction medium comprising water and at least one C1-C4 alcohol, preferably ethanol, with a transition metal catalyst, in particular palladium, on a carbon support and under hydrogen pressure.

[0105] Advantageously, the process according to the invention is a process for the continuous flow preparation of a nitrophenol compound of the following formula (III'): no2 (IID

[0106] said process comprising a diazotization and hydrolysis reaction step, at a temperature ranging from 80°C to 150°C, preferably ranging from 100°C to 120°C, preferably in a microreactor, between:

[0107] - at least one solution A having an acidic pH, i.e. a pH lower than 7, and comprising at least one compound of the following formula (F): (D

[0108] , and - at least one aqueous solution B comprising at least one diazotizing agent, preferably chosen from the group consisting of nitrite salts, in particular inorganic nitrite salts;

[0109] Formula (III'), in which: • Ri represents a linear or branched alkyl group, C1-C4, preferably C1-C3, preferably C1, • R2, R3 and R4 represent a hydrogen atom;

[0110] Formula (F) in which: • Rio represents an alkyl group, linear or branched, in CrC4, preferably in Ci-C3, preferably in Ci, • R2o, R3o and R^ represent a hydrogen atom.

[0111] According to this embodiment advantageously, solution A comprises preferably at least one mineral acidifying agent, more preferably sulfuric acid.

[0112] According to this embodiment advantageously, solution B preferably comprises at least sodium nitrite.

[0113] According to this embodiment advantageously, the compound of formula (I) is 2-methyl-5-nitroaniline and the compound of formula (III) is 2-methyl-5-nitrophenol.

[0114] Process for the preparation of a benzenediazonium compound

[0115] As indicated previously, the process according to the invention also relates to a process for the continuous flow preparation of a benzenediazonium compound, and / or one of its salts, comprising a diazotization reaction step at a temperature greater than or equal to 80°C between at least one nitroaniline compound, as defined previously, and at least one diazotization agent, as described previously.

[0116] For the purposes of this document, the term “benzenediazonium or benzenediazonium-type compound” means a compound comprising a benzene ring substituted by at least one diazonium group (-AD = N)-

[0117] According to the method of synthesis of the benzenediazonium compound, the diazotization reaction takes place in continuous flow.

[0118] Preferably, the benzenediazonium compound corresponds to the following formula (II): R 5 R 3 2 (II)

[0119] Formula (II) in which: • R'i represents a hydrogen atom, a diazonium group, or a linear or branched alkyl group, C1-C10, • R'2, R'2, R\, and R'5, identical or different, represent a group diazonium, a hydrogen atom, a linear or branched C1-C6 alkyl group, • provided that at least one of the radicals R'b R'2, R'2, R'4, and R'5 represents a diazonium group (-A^ = N)-

[0120] Preferably, in formula (II), R' i or R'5 represents a diazonium group (-A / + = A / ), more preferably R'5 represents a diazonium group (-A^ = AD-

[0121] Preferably, the process according to the invention is a process for the continuous flow preparation of a benzenediazonium compound corresponding to the following formula (II):

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128] Rq R 4\^ 5 (ii) Formula (II) in which: • R'i represents a hydrogen atom, a diazonium group or a linear or branched alkyl group, C1-C10, • R'2, R'3, R'4, and R'5, identical or different, represent a group diazonium, a hydrogen atom, a linear or branched C1-C6 alkyl group, • provided that at least one of the radicals R'b R'2, R'3, R'4, and R'5 represents a diazonium group; said method comprising a diazotization reaction step at a temperature greater than or equal to 80°C between: - at least one nitroaniline compound, as defined above, and - at least one diazotizing agent as described above. Preferably, the process according to the invention is a process for the continuous flow preparation of a benzenediazonium compound, preferably corresponding to formula (II), as well as one of its salts, for example one of its acid salts, organic or mineral, preferably mineral. Preferably, in formula (II), R\ or R'5 represents a diazonium group, and, in formula (I), R10 or R50 represents a primary amine group (-NH2). Preferably, in formula (II), R'3 and R'4 represent a hydrogen atom, and, in formula (I), R30 and R40 represent a hydrogen atom. Preferably: - in formula (II), R'3 and R'4 represent a hydrogen atom, R'2 represent a hydrogen atom or a linear or branched alkyl group, C1-C6, preferably Cb and - in formula (I), R30 and R40 represent a hydrogen atom, R20 represent a hydrogen atom or a linear or branched alkyl group, C1-C6, preferably Cb Preferably, the process according to the invention is a process for the continuous flow preparation of a benzenediazonium compound corresponding to the following formula (II'): (ID

[0129] said method comprising a diazotization reaction step at a temperature greater than or equal to 80°C between: - at least one nitroaniline compound corresponding to the formula (!): - at least one diazotizing agent, as defined above;

[0130] Formula (II') in which: • R'i represents a linear or branched alkyl group, C1-C10, • R'2, R'3 and R'4, identical or different, represent a hydrogen atom, a linear or branched C1-C6 alkyl group, preferably a hydrogen atom;

[0131] Formula (F) in which R10, R2o, R30 and R40 have the same meanings as those indicated previously.

[0132] Preferably, the process according to the invention is a process for the continuous flow preparation of a benzenediazonium compound, preferably corresponding to the formula (IF), as well as one of its salts, for example one of its acid salts, organic or mineral, preferably mineral.

[0133] Preferably, in formulas (I') and (II'), R10 and R\ represent a linear or branched alkyl group, CrC4, preferably C1-C3, better still Cp

[0134] Preferably, in formula (I'), R20, R30 and R^ represent a hydrogen atom, and, in formula (IF), R'2, R'3 and R'4 represent a hydrogen atom.

[0135] Advantageously, in formulas (F), Rio represents a linear or branched alkyl group, C1-C4, preferably C1, and R2o, R30 and R40 represent a hydrogen atom, and in formula (IF), R\ represents a linear or branched alkyl group, C1-C4, preferably C1, and R'2, R'3 and R'4 represent a hydrogen atom.

[0136] Advantageously, the temperature varies from 80°C to 150°C, preferably from 100°C to 140°C, more preferably from 100°C to 120°C.

[0137] Preferably, the nitroaniline compound, preferably of formula (I) or (F), can be formulated in a solution A as described above.

[0138] Preferably, the diazotizing agent may be present in an aqueous solution B as described above.

[0139] The process for preparing the benzenediazonium compound can be prepared in a reactor as described above, preferably in a microreactor, even more preferably in a microtubular reactor.

[0140] The following examples serve to illustrate the invention without, however, being limiting in nature. Example I Preparation of solutions A and B

[0141] A solution A of 2-methyl-5-nitroaniline in 12 equivalents of sulfuric acid is prepared.

[0142] During the preparation of solution A, the temperature is preferably maintained at a temperature below 50°C. Once solution A has been prepared, the medium is liquid and cooled to room temperature.

[0143] In parallel, an aqueous solution B of sodium nitrite having a content of 5.5% by weight relative to the total weight of the solution is prepared. Process for the preparation of 2-methyl-5-nitrophenol

[0144] Solutions A and B are pumped through a tubular microreactor with an internal volume of 11 ml, heated to reach a temperature of 110°C (± 2°C) within the reaction medium.

[0145] The flow rate of solution A is set at 1.67 ml / min and that of aqueous solution B is set at 2.67 ml / min, ensuring a molar ratio of 1.1 between sodium nitrite and 2-methyl-5-nitroaniline.

[0146] The residence time within the reactor is approximately 19 seconds taking into account the volume of nitrogen generated during the reaction.

[0147] The reaction medium is cooled in the outlet line of the microreactor to reach 80°C.

[0148] By operating the system for a period of 30 minutes, 7.75 grams of 2-methyl-5-nitrophenol are recovered. The yield is approximately 81% and the purity of the product obtained is greater than 97%. Example II Preparation of solutions A and B

[0149] A solution A of 2-methyl-5-nitroaniline in 12 equivalents of sulfuric acid is prepared.

[0150] During the preparation of solution A, the temperature is preferably maintained at a temperature below 50°C. Once solution A has been prepared, the medium is liquid and cooled to room temperature.

[0151] In parallel, an aqueous solution B of sodium nitrite having a content of 33% by weight relative to the total weight of the solution is prepared. The solution obtained is liquid. Process for the preparation of 2-methyl-5-nitrophenol

[0152] Solutions A and B are pumped through a tubular microreactor with an internal volume of 11 ml, heated to reach a temperature of 100°C (± 2°C) within the reaction medium.

[0153] The flow rate of solution A is set at 4.00 ml / min and that of aqueous solution B is set at 1.12 ml / min, ensuring a molar ratio of 1.1 between sodium nitrite and 2-methyl-5-nitroaniline.

[0154] The residence time within the reactor is approximately 16 seconds taking into account the volume of nitrogen generated during the reaction.

[0155] The reaction medium is cooled in the outlet line of the microreactor to reach 80°C.

[0156] By operating the system for a period of 20 minutes, 13.3 grams of 2-methyl-5-nitrophenol are recovered. The yield is approximately 84% and the purity of the product obtained is greater than 93.2%.

Claims

1.

2. Claims Process for the continuous flow preparation of a nitrophenol compound, comprising a diazotization and hydrolysis reaction step, at a temperature greater than or equal to 80°C, between at least one nitroaniline compound and at least one diazotization agent. Method according to claim 1, characterized in that: - the nitrophenol compound corresponds to the following formula (III'): NO. (HD Formula (III') in which: • Ri represents a hydrogen atom or a linear or branched alkyl group, C1-C10, • R2, Ri and R4, identical or different, represent an atom hydrogen, a linear or branched C1-C6 alkyl group, preferably a hydrogen atom, the nitroaniline compound has the following formula (I'): (D Formula (!) in which: • Rio represents a hydrogen atom or a linear or branched alkyl group, in CrCio, • R2o, R30 and R40, identical or different, represent a hydrogen atom, a linear or branched alkyl group, in Ci-C6, preferably a hydrogen atom.

3. Method according to claim 1 or 2, characterized in that the temperature varies from 80°C to 150°C, preferably from 100°C to 140°C, more preferably from 100°C to 120°C.

4. Process according to claim 2 or 3, characterized in that, in the formulae (!') and (III'), R 1 and R 2 represent a linear or branched alkyl group, C 1 -C 4 , preferably C 1 -C 3 , in particular C

5. i- Process according to any one of claims 2 to 4, characterized in that, in formula (I'), R2o, R30 and R40 represent a hydrogen atom, and, in formula (III'), R2, R3 and R4 represent a hydrogen atom.

6. Process according to any one of the preceding claims, characterized in that the nitroaniline compound is present in a solution A having a pH less than 7, preferably a pH less than 4, preferentially a pH less than 3, in particular a pH less than 1.

7. Method according to claim 6, characterized in that solution A comprises at least one acidifying agent chosen from the group consisting of mineral acids, more preferably chosen from the group consisting of sulfuric acid, hydrochloric acid and their mixtures.

8. Method according to claim 6 or 7, characterized in that, in solution A, the acidifying agent is present in an amount ranging from 2 to 24 molar equivalents, preferably in an amount ranging from 10 to 14 molar equivalents, relative to the nitroaniline compound.

9. Method according to any one of the preceding claims, characterized in that the diazotizing agent is chosen from the group consisting of nitrite salts, in particular inorganic nitrite salts.

10. Method according to any one of the preceding claims, characterized in that the diazotizing agent is chosen from the group consisting of sodium nitrite, lithium nitrite, potassium, calcium nitrite, magnesium nitrite, ammonium nitrite and mixtures thereof, preferably sodium nitrite.

11. Process according to any one of the preceding claims, characterized in that the diazotizing agent and the nitroaniline compound are used in a molar ratio ranging from 1.0 to 1.5, preferably in a molar ratio ranging from 1.05 to 1.

2.

12. A method according to any one of the preceding claims, characterized in that the diazotization and hydrolysis reaction step is carried out in a microreactor, preferably a tubular microreactor.

13. Method according to claim 12, characterized in that the residence time of the nitroaniline compound and the diazotizing agent in the microreactor varies from 5 seconds to 5 minutes, preferably the residence time within the reactor is less than one minute.

14. Process according to any one of the preceding claims, characterized in that it further comprises, after the diazotization and hydrolysis reaction step, a step of cooling the reaction medium comprising the nitrophenol compound, preferably to a temperature ranging from 25°C to 95°C, more preferably to a temperature ranging from 50 to 85°C.

15. Process for the continuous flow preparation of a benzene-diazonium compound comprising a diazotization reaction step at a temperature greater than or equal to 80°C between at least one nitroaniline compound and at least one diazotization agent.

16. Process according to claim 15, characterized in that: - the benzenediazonium compound corresponds to the following formula (II'): (II')

17. Formula (II') in which: • R' i represents a linear or branched alkyl group, C1-C10, • R'2, R'3 and R'4, identical or different, represent an atom hydrogen, a linear or branched C1-C6 alkyl group, preferably a hydrogen atom; - the nitroaniline compound corresponds to the formula (!) as defined according to any one of claims 2 to 5. Process according to claim 16, characterized in that, in formula (I'), Rio represents a linear or branched alkyl group, C1-C4, preferably C1, and R20, R30 and R40 represent a hydrogen atom, and, in formula (II'), R\ represents a linear or branched alkyl group, C1-C4, preferably C1, and R'2, R'3 and R'4 represent a hydrogen atom.