EP3362437A1

EP3362437A1 - Method for synthesising aromatic nitrones

Info

Publication number: EP3362437A1
Application number: EP16782219.6A
Authority: EP
Inventors: Jean-Luc Couturier; Etienne Fleury; Sergey Ivanov; Anne-Frédérique SALIT
Original assignee: Compagnie Generale des Etablissements Michelin SCA; Arkema France SA
Current assignee: Compagnie Generale des Etablissements Michelin SCA; Arkema France SA
Priority date: 2015-10-14
Filing date: 2016-10-14
Publication date: 2018-08-22
Also published as: FR3042499B1; WO2017064296A1; FR3042499A1

Abstract

The present invention concerns a method for synthesising a compound of formula (I) in which: - A is a carbon chain that can contain at least one group comprising one or more heteroatoms preferably chosen from O, N, Si, S and P; - R1 is a carbon group that can contain one or more heteroatoms; - Sp represents an atom or a group of atoms.

Description

Process for the synthesis of aromatic nitrones

The present invention relates to the field of molecules comprising a function capable of reacting with a polymer comprising unsaturations to form a covalent bond with said polymer.

More specifically, the present invention relates to aromatic nitrones. More specifically, the application relates to a process for synthesizing such molecules.

In the industrial field, polymer blends with fillers are often used. In order for such mixtures to have good properties, means are constantly sought to improve the dispersion of the fillers within the polymers. One of the means to achieve this result is the use of coupling agents capable of establishing interactions between the polymer and the filler.

Agents for coupling a polymer with a filler comprising nitrogen dipoles are described in the documents published under the numbers US71 86845B2 and JP2008208 1 63.

These documents describe the modification of polymers comprising diene units by nitrogenous dipolar compounds further comprising a heterocycle, said heterocycle comprising itself a nitrogen atom, and an oxygen and / or sulfur atom.

More particularly, the compounds described are nitrones carrying oxazoline and thiazoline functional groups, for example, ((2-oxazolyl) -phenyl-N-methylnitrone):

When diene polymers are reacted with such compounds, the resulting polymers will carry the oxazolines or thiazoline. These cycles present on the polymer are likely to react in turn, with charge surface functions, such as carbon black or silica, with which the polymers are mixed. This reaction leads to the establishment of covalent bonds between the polymer modi? Ed by the coupling agent and the filler due to the opening of the oxazoline or thiazoline ring. Indeed, as described in US7 1 86845B2, the oxazoline rings and / or thioazolines are likely to open in the presence of a nucleophile may for example be present on the surface of the charge.

The establishment of such covalent bonds nevertheless has drawbacks in the preparation of mixtures comprising these polymers modified with coupling agents with fillers. In particular, the existence of these early covalent bonds, between the polymer and the fillers, renders these mixtures very viscous in the uncrosslinked state, which makes difficult all the operations prior to the crosslinking (vulcanization) of the formulations based on of rubber, especially the preparation of mixtures of components, and their shaping. These disadvantages have a strong impact on industrial productivity.

It is therefore desirable to provide new molecules not having the above disadvantages, that is to say, molecules that are capable after reaction with a polymer and mixed with a filler, not to form covalent bonds. with the load and therefore not to cause an excessive increase in the viscosity of the mixture.

Thus, the patent application WO 2012/007684 relates to a compound comprising at least one group Q and at least one group A connected to each other by mo ins and preferably a Sp spacer group in which:

Q comprises a dipole containing at least and preferably a nitrogen atom;

- A comprises an associative group comprising at least one nitrogen atom; - Sp is an atom or a group of atoms forming a bond between Q and A.

When a polymer grafted with a compound as defined above is mixed with fillers, it only establishes labile bonds with the fillers, which makes it possible to ensure good polymer-filler interaction, which is beneficial for the final properties of the polymer, but without the disadvantages that too strong polymer - load interaction could cause.

An example of such a compound is (Z, E) -N- (4- (2- (2-oxoimidazolidin-1-yl) ethylcarbamoyl) benzylidene) aniline oxide:

This compound can be prepared from 4-formylbenzoic acid and 2-aminoethylimidazolidone (UDETA) according to the following synthetic scheme:

\ ^ UDETA

In this process, a hydroxylamine is used. However, hydroxylamines are characterized by their low commercial availability. The present invention aims to provide a solution to solve the problems mentioned above.

According to the invention, a process for synthesizing a compound of formula (I):

in which :

- A is a carbon chain which may contain at least one group comprising one or more heteroatoms chosen preferentially from O, N, Si, S and P;

Ri is a carbon group which may contain one or more heteroatoms;

- Sp represents an atom or a group of atoms,

comprises a reaction step (b) of a compound of formula

(II):

with a compound of formula (III): R 1 -NO ₂ (III);

in the presence:

at least one solvent;

at least one reducing agent;

at a temperature T ranging from -15 to 100 ° C.

For the purposes of the present invention, the term "carbon chain" or "carbon group" means a chain or a group comprising one or more carbon atoms.

Preferably, step (b) is followed by a step (c) of recovering the compound of formula (I).

It should be understood that the terms "from ... to ..." used in this specification should be understood to include each of the mentioned terminals. The process according to the invention makes it possible to access a large number of various structures, in particular thanks to the presence of the group A. Moreover, said process is an inexpensive process and which allows a very important production of the compound of formula (I ).

Other advantages and features of the invention will become more apparent upon examination of the detailed description.

The process according to the invention allows the synthesis of the compound of formula (I) mentioned above.

Advantageously, A is a carbon chain containing at least one group comprising one or more heteroatoms chosen preferentially from O, N, Si, S and P, more preferably from O, N, S and combinations thereof.

Preferably, A is a carbon chain C ₁ -C ₂₀ , more preferably d -C _{1 2} .

Preferably, A comprises a group selected from an associative group, an ester group, preferably a carboxylic acid ester group, and an ionomeric group.

When A is an associative group, it is meant that the groups A are capable of associating with each other by hydrogen bonds.

Thus, each associative group capable of associating with hydrogen bonds comprises at least one donor "site" and one acceptor site with respect to the hydrogen bonding so that two identical associative groups are self-complementary and can associate with each other forming at least two hydrogen bonds.

Preferably, A is an associative group chosen from an imidazo-lidinyl, thio-imidazo-lidinyl, triazoyl, trithioazoyl, ureyl, thioureyl, bis-ureyl, bis-thioureyl, ureido-pyrimidyl and thio-ureido group. pyrimidyl or a group corresponding to formula (IV): - C (OR ₂ ) = O (IV), in which R ₂ is a carbon group optionally comprising at least one heteroatom.

Advantageously, said carbon group R ₂ , optionally comprising at least one heteroatom, comprises from 1 to 20 carbon atoms, preferably from 1 to 12, more preferably from 1 to at 6, even more preferably from 1 to 3. Thus, said carbon group R ₂ may designate the methyl group or the ethyl group.

Preferably, when A is an associative group, it corresponds to one of the following formulas (V) to (IX):

HHHH (vil) ^HH (VIII)

or :

- R denotes a hydrocarbon group optionally comprising at least one heteroatom;

X denotes an oxygen atom, sulfur atom or an NH group, preferably an oxygen or sulfur atom.

Preferably, formula (V) represents a 5- or 6-membered, preferably diazotized, di or tri-nitrogen heterocycle comprising at least one carbonyl, thio carbonyl or imine functional group.

Preferentially, the group of formula (V) is the group of formula (Va):

(Goes), wherein X is selected from oxygen atom and sulfur atom.

The group Sp is a spacer group which makes it possible to connect the aromatic ring to the group A as the formula of the compound (I) indicates, and thus can be of any type known per se.

The group Sp is preferably a linear, branched or cyclic C1-C24 hydrocarbon-based chain which may contain one or more aromatic radicals and / or one or more heteroatoms. Said chain may optionally be substituted, provided that the substituents do not react with the group A and the nitrone function.

Advantageously, the group Sp is a straight or branched alkylene chain C1-C24, preferably C1-C10, more preferably Ci-C _6, said chain being optionally interrupted by one or more nitrogen atoms or oxygen atoms, and may include one or more carbonyl groups.

The term "interrupted by one or more nitrogen or oxygen atoms" in the sense of the present invention that a chain may comprise one or more nitrogen or oxygen atoms in the chain or at one end chain.

Preferably, the group Sp contains a unit selected from -

(CH ₂₎ _y i-, - [NH- (CH ₂₎ _y2] _x i- and - [0- (CH ₂₎ _{y 3]} _x2 -, y, y ₂ and y ₃ representing, independently, an integer from from 1 to 6, and xi and x ₂ independently represent an integer from 1 to 4.

According to a variant of the invention that can be applied to all the embodiments, the chain of the group Sp comprises an oxygen atom or a group chosen from OC (O), NHC (O), C (O) O and C (O) NH at the end of the chain, which end is not adjacent to group A.

As explained above, the process according to the invention comprises a step (b) of reaction of a compound of formula (II), as mentioned above, with a compound of formula (III): R 1 -NO ₂ (III) ), as mentioned above.

Preferably, Ri is a group selected from an alkyl group, preferably an alkyl group _Ci-2, more preferably C ₁ -C ₆ , still more preferably C ₁ -C 4; cycloalkyl, preferably cycloalkyl, C4-C12, more preferably C _O -CS; and an aryl group, preferably a C ₆ -C ₁₅ aryl group, Ri may contain one or more heteroatoms.

Preferably, the compound of formula (III) is chosen from nitromethane, nitrobenzene and 2-methyl-2-nitropropane.

Said step (b) of the process according to the invention is carried out in the presence of at least one solvent, and at least one reducing agent, at a temperature T ranging from -15 to 100 ° C.

Advantageously, the solvent is chosen from water, an alcohol solvent, an ether solvent, a nitrile solvent and their mixture.

According to a particular embodiment of the invention, the solvent is chosen from an alcohol solvent such as methanol, ethanol, propanol and isopropanol, water and their mixture.

Preferably, the compound of formula (II) represents from 5 to 50% by weight, preferably from 10 to 30% by weight, relative to the weight of the solvent.

Preferably, the reducing agent is chosen from zinc and hydrogen in the presence of a metal catalyst, preferably zinc.

According to a particular embodiment of the invention, the amount of reducing agent is from 1.5 to 6 equivalents, preferably from 2 to 5 equivalents, relative to the amount of compound of formula (II).

Advantageously, step (b) is carried out, when the reducing agent is zinc, in the presence of an acid chosen from an organic acid and a weak acid salt.

Preferably, step (b) is carried out, when the reducing agent is zinc, in the presence of ammonium chloride.

Particularly preferably, step (b) is carried out, when the reducing agent is zinc, both in the presence of an acid selected from an organic acid and a weak acid salt and ammonium chloride . Preferably, step (b) takes place at a temperature T ranging from 0 to 25 ° C.

Preferably, the process according to the invention comprises a step (c) of recovery, as mentioned above, of the compound of formula (I).

According to a particular embodiment of the invention, the process according to the invention comprises a step (a) of manufacturing the compound of formula (II), prior to step (b), by reacting a compound of formula (X):

wherein Z 1 is selected from OH, COOH, NH ₂ , COOR ₃ , wherein R ₃ is C ₁ -C ₄ alkyl, and COY, Y is halogen,

with a compound of formula (XI): Z ₂ -Sp'-A (XI), in which Z ₂ is selected from OH, NH ₂ , COOH and Cl, and Sp 'represents an atom or a group of atoms,

Being heard that :

if Z ₁ denotes OH, then Z ₂ is chosen from OH, COOH and Cl;

if Zi denotes COOH, then Z ₂ is chosen from OH and NH ₂ ;

if Z 1 denotes NH ₂ , then Z ₂ denotes COOH;

if Zi denotes COOR ₃ , then Z ₂ is chosen from OH and NH ₂ ;

if Zi denotes COY, then Z ₂ is chosen from OH and NH ₂ . Thus, when Z 1 denotes OH, step (a) is an etherification reaction (Z ₂ denotes OH or Cl) or esterification reaction (Z ₂ denotes COOH).

When Z 1 denotes COOH, step (a) is an esterification reaction (Z ₂ denotes OH) or amidification reaction (Z ₂ denotes NH ₂ ).

When Z 1 denotes NH ₂ , step (a) is an amidification reaction. When Z ₁ denotes COOR ₃ , step (a) is a transesterification reaction (Z ₂ denotes OH) or amidification reaction (Z ₂ denotes NH ₂ ).

When Z ₁ denotes COY, step (a) is an esterification reaction (Z ₂ denotes OH) or amidification reaction (Z ₂ denotes NH ₂ ).

Each of these reactions is a conventional reaction and well known to those skilled in the art.

The group Sp 'is a spacer group which makes it possible to connect the group Z ₂ to the group A as the formula of the compound (XI) indicates, and thus can be of any type known per se.

The group Sp 'is preferably a linear, branched or cyclic C1-C24 hydrocarbon-based chain which may contain one or more aromatic radicals and / or one or more heteroatoms. Said chain may optionally be substituted, provided that the substituents do not react with the group A and the nitrone function.

The present application also relates to the use of the compound of formula (I) obtained by the process according to the invention.

The present invention is further illustrated by the following non-limiting examples.

EXAMPLES

The structural analysis as well as the determination of the molar purities of the synthesis molecules are carried out by NMR analysis. The spectra are acquired on a BRUKER 500 MHz Avance spectrometer equipped with a BBIz-grad 5 mm wideband probe. The quantitative 1H NMR experiment uses a 30 ° single pulse sequence and a 3 second repetition time between each of the 64 acquisitions. The samples are solubilized in the deuterated dimethylsulfoxide (DMSO). This solvent is also used for the lock signal. Calibration is performed on the proton signal of DMSO deuterated at 2.44 ppm with respect to a TMS reference at 0 ppm. The 1 H NMR spectrum coupled to the 2D HSQC 'H / ¹³ C and HMBC' H / ¹³ C experiments allows the structural determination of the molecules. The molar quantifications are made from the quantitative 1H 1H NMR spectrum.

The mass spectrometry analysis is carried out by direct injection by an electrospray ionization mode (ID / ESI). The analyzes were performed on a Bruker HCT spectrometer (600 μί / ηιίη flow rate, 10 psi nebulizer gas pressure, 4 l / min nebulizer gas flow).

Example 1 Synthesis of (Z, E) -N- (4- (2- (2-oxoimidazolidin-1-yl) ethylcarbamoyl) benzylidene) aniline oxide

(1)

(Z, E) -N- (4- (2- (2-oxoimidazolidin-1-yl) ethylcarbamoyl) benzylidene) aniline oxide is synthesized from 4-formyl-benzoic acid, 2- aminoethylimidazolidone (UDETA) and nitrobenzene according to the following reaction scheme:

^ UDETA

The intermediate compound (Ia) can be obtained according to the protocol described in Example 4 of the patent application WO 2012/007684. This synthesis step corresponds to step (a) as described above.

The nitrone (1) is then obtained according to step (b) of the process according to the invention.

20 g of the compound (Ia) (77 mmol) and 200 g of a 50/50 ethanol / water mixture are introduced into a flask. It is cooled to 0 ° C. and then 9.5 g of nitrobenzene (77 mol) and 4.5 g of ammonium chloride (85 mmol) are added. Under vigorous stirring, 20.1 g of zinc powder (308 mmol) are gradually added. At the end of the addition, the reaction mixture is allowed to return to room temperature and the stirring is maintained for 6 hours. 200 ml of dichloromethane are added and filtered. The aqueous phase is extracted with dichloromethane. The organic phases are collected.

After evaporation, the nitrone (1) (33.9 g), in the form of a white solid, is obtained with a mass yield of 80%. Example 2 Synthesis of 1- [2- (2 - {(Z) - [oxido (phenyl) methyl} phenoxy) ethyl] imidazolidin-2-one

(2)

1- [2- (2 - {(Z) - [oxido (phenyl) -15-azanylidene] methyl} phenoxy) ethyl] imidazolidin-2-one is synthesized from salicylaldehyde, nitrobenzene and (1- (2-hydroxyethyl) imidazolidin-2-one) according to the following reaction scheme:

The 1- (2-chloroethyl) imidazolidin-2-one (compound (2a)) can be obtained according to the protocol described in Example 1 of the patent application WO 2012/007684.

25 g of sali-aldehyde (0.205 mol) and 250 g of isopropanol are introduced into a flask. 113 g of potassium carbonate are added (0.82 mol) and heated to reflux. 76.1 g of 1- (2-chloroethyl) imidazolidin-2-one (0.513 mol) are added in portions over a period of 5 hours. At the end of the addition, it is allowed to react at reflux for 2 hours. The isopropanol is then evaporated in half and 1 liter of water is added. The precipitate obtained is washed with ether and then dried under vacuum.

The derivative (2b) (39.3 g), in the form of a light yellow solid, is obtained with a mass yield of 82%. Thus, said derivative (2b) is obtained according to step (a) as described above.

The nitrone (2) is then obtained according to step (b) of the process according to the invention.

10 g of the derivative (2b) (43 mmol) and 200 g of a 50/50 mixture of water and ethyl ether are introduced into a flask. It is cooled to 0 ° C. and 5.3 g of nitrobenzene (43 mmol) and 2.5 g of ammonium chloride are added. Under vigorous stirring, 11.2 g of zinc powder (172 mmol) are gradually added. At the end of the addition, the reaction mixture is allowed to warm to room temperature and stirring is continued for 8 hours. 200 ml of dichloromethane are added and filtered. The aqueous phase is extracted with dichloromethane.

After evaporation, the nitrone (2) (10.5 g), in the form of a white solid, is obtained with a mass yield of 75%.

Example 3 Synthesis of 1- [2- (4 - {(Z) - [methyl (oxido) -15-azanylidene] methyl} phenoxy) ethyl] imidazolidin-2-one

O

1- [2- (4 - {(Z) - [methyl (oxido) -15-azanylidene] methyl} phenoxy) ethyl] imidazolidin-2-one is synthesized from 4-hydroxybenzaldehyde, nitrobenzene and l- (2- hydroxyethyl) imidazolidin-2-one) according to the following reaction scheme:

20 g of 4-hydroxybenzaldehyde (0.164 mol) and 130 g of dimethylformamide are introduced into a flask. 90 g of potassium carbonate (0.652 mol) are added and the mixture is heated to 100 ° C. 61 g of 1- (2-chloroethyl) imidazolidin-2-one (0.411 mol) are added portionwise over a period of 6 hours. At the end of the addition, it is allowed to react at reflux for 2 hours. The dimethylformamide is evaporated under vacuum. The residue is taken up in dichloromethane and then washed with water.

After evaporation, the derivative (3a) (39.3 g) is obtained with a mass yield of 88%. Thus, said derivative (3a) is obtained according to step (a) as described above.

The nitrone (3) is then obtained according to step (b) of the process according to the invention.

3.6 g of nitromethane (58 mmol), 3.7 g of ammonium chloride (70 mmol) and 100 ml of a 50/50 ethanol / water mixture are introduced into a flask. It is cooled to 0 ° C. and 9.5 g of zinc powder (145 mmol) are slowly added in portions. The mixture is stirred for 30 minutes and then 10 g of the derivative (3a) (42 mmol) and 50 ml of acetic acid are added. Allowed to warm to room temperature and stirring is maintained for 1 hour. The precipitate is filtered, washed with a saturated aqueous solution of sodium bicarbonate, then washed with water and with pentane.

After drying under vacuum, the nitrone (3) is obtained with a mass yield of 75%.

Example 4 Synthesis of 4 - {(Z) - [tert-butyl (oxido) -15-azanylidene] methyl} -N- [2- (2-thioxoimidazolidin-1-yl) ethylbenzamide

4 - {(Z) - [tert-butyl (oxido) -15-azanylidene] methyl} -N- [2- (2-thioxoimidazolidin-1-yl) ethylbenzamide is synthesized from 4-formylbenzoic acid, 2-methyl-2-nitropropane and 1- (2-aminoethyl) imidazolidine-2-thione according to the following reaction scheme:

The 1- (2-aminoethyl) imidazolidine-2-thione (compound 4a) can be obtained according to the protocol described in Example 4 of the patent application WO 2012/007684.

40 g of 4-formylbenzoic acid (0.266 mol) and 38.7 g of 1- (2-aminoethyl) imidazolidine-2-thione are introduced into a flask equipped with a Dean-Stark. The mixture is heated at 80 ° C for 30 minutes and then heated to 145 ° C to remove water in the Dean-Stark. The derivative (4b) is obtained. Thus, said derivative (4b) is obtained according to step (a) as described above.

The nitrone (4) is then obtained according to step (b) of the process according to the invention.

5 g of tert-nitrobutane (48 mmol), 2.8 g of ammonium chloride (32 mmol) and 50 g of water are introduced into a flask. It is cooled to 0 ° C., and with vigorous stirring, 8 g of zinc powder (122 mmol) are added slowly while keeping the temperature below 10 ° C. After stirring for 2 hours, the mixture is allowed to return to ambient temperature. 50 ml of acetic acid are added, followed by 11.5 g of derivative (4b) (43 mmol). Allowed to react for 8 hours. The reaction mixture is extracted with dichloromethane, and then the organic phase is washed with a saturated aqueous solution of sodium bicarbonate.

After evaporation of the dichloromethane, the nitrone (4) (8.2 g) is obtained with a mass yield of 55%.

Claims

1. Process for synthesizing a compound of formula (I):

in which :

Ri is a carbon group which may contain one or more heteroatoms;

- Sp represents an atom or a group of atoms,

comprising a step (b) of reacting a compound of formula

(II):

with a compound of formula (III): R 1 -NO ₂ (III);

in the presence:

at least one solvent;

at least one reducing agent;

at a temperature T ranging from -15 to 100 ° C.

The process according to claim 1, wherein A comprises a group selected from an associative group, an ester group, preferably a carboxylic acid ester group, and an ionomeric group.

3. Process according to any one of claims 1 to 2, in which A is an associative group chosen from an imidazolidinyl, thio-imidazolidinyl, triazoyl, trithioazoyl, ureyl, thioureyl, bis-ureyl and bis-thio group. -ureyl, ureido-pyrimidyl and thio-ureido-pyrimidyl or a group corresponding to formula (IV): C (OR ₂₎ = 0 (IV) wherein R ₂ is a carbon-based group optionally comprising at least one heteroatom.

4. The process according to claim 3, wherein said carbon group R ₂ comprises from 1 to 20 carbon atoms, preferably from 1 to 12, more preferably from 1 to 6, even more preferably from 1 to 3.

5. The method according to any of the preceding claims, wherein the group A, when associative, responds to

R denotes a hydrocarbon group optionally comprising at least one heteroatom;

6. Process according to the preceding claim, in which the group of formula (V) is the group of formula (Va):

wherein X is selected from oxygen atom and sulfur atom.

7. A method according to any preceding claim, wherein said group Sp is a straight or branched alkylene chain C1-C24, preferably C1-C10, more preferably Ci-C _6, said chain being optionally interrupted by one or more nitrogen or oxygen atoms, and may include one or more carbonyl groups.

8. Process according to any one of the preceding claims, in which the group R 1 is a group chosen from an alkyl group, preferentially a C 1 -C 12 alkyl group, more preferably a C ₁ -C ₆ alkyl group or even more preferably a C ₁ -C ₄ alkyl group. ; cycloalkyl, preferably cycloalkyl, C4-C12, more preferably C _O -CS; and an aryl group, preferably a C ₆ -C ₁₅ aryl group, Ri may contain one or more heteroatoms.

9. Process according to any one of the preceding claims, in which the compound of formula (III) is chosen from nitromethane, nitrobenzene and 2-methyl-2-nitropropane.

The process of any of the preceding claims, wherein the solvent is selected from water, an alcohol solvent, an ether solvent, a nitrile solvent, and mixtures thereof.

11. Method according to the preceding claim, wherein the solvent is selected from an alcohol solvent, preferably selected from methanol, ethanol, propanol and isopropanol, water and their mixture.

12. Process according to any one of the preceding claims, in which the compound of formula (II) represents from 5 to 50% by weight, preferably from 10 to 30% by weight, relative to the weight of the solvent.

13. Method according to any one of the preceding claims, wherein the reducing agent is selected from zinc and hydrogen in the presence of a metal catalyst, preferably zinc.

14. A process according to any one of the preceding claims, wherein the amount of reducing agent is 1.5 to 6 equivalents, preferably 2 to 5 equivalents, based on the amount of compound of formula (II).

The process according to any one of the preceding claims, wherein step (b) is carried out, when the reducing agent is zinc, in the presence of an acid selected from an organic acid and a weak acid salt. .

16. Process according to any one of the preceding claims, comprising a step (c) of recovering the compound of formula (I).

17. The process as claimed in any one of the preceding claims, wherein said process comprises a step (a) of manufacturing the compound of formula (II), prior to step (b), by reacting a compound of formula (X):

Being heard that :

if Z ₁ denotes OH, then Z ₂ is chosen from OH, COOH and Cl;

if Zi denotes COOH, then Z ₂ is chosen from OH and NH ₂ ;

if Z 1 denotes NH ₂ , then Z ₂ denotes COOH;

if Zi denotes COOR ₃ , then Z ₂ is chosen from OH and NH ₂ ;

if Zi denotes COY, then Z ₂ is chosen from OH and NH ₂ .

18. Use of the compound of formula (I) obtained by the process as defined in any one of the preceding claims.