Colorimeter detection system for the detection of chemical compounds using a color indicator from the hydrozone family

Description

TECHNICAL FIELD

[0001] The present invention relates to a new colorimetric detection system usable for the detection of chemical compounds, in particular toxic warfare compounds, by means of a colored indicator from the hydrazone family and to a method for detecting the presence or absence of chemical compounds implementing this colorimetric detection system.

[0002] In particular, the present invention can find application for the detection of toxic chemical compounds, such as toxic warfare compounds and, in particular, organophosphate compounds; toxic industrial chemical compounds (known as TICs), pesticides.

[0003] In general, organophosphate compounds are organic compounds with proven toxicity to the human body. Indeed, these compounds can be involved in the inhibition of serine proteases, and in particular, acetylcholinesterase, which plays a role in synaptic junctions and whose dysregulation can prevent muscle relaxation and thus cause death by asphyxiation.

[0004] These compounds may be included in the formulation of insecticides, pesticides, or chemical warfare agents (such as G-series organophosphate compounds, like sarin (GB, CAS No. 107-44-8) or V-series organophosphate compounds, like VX (CAS No. 50782-69-9)). Due to the high lethality of these compounds and their proliferation, it is important to have systems for preliminary detection and identification.

[0005] Some detection systems used to date are based on technologies involving physical measurement methods, such as ion mobility spectroscopy, flame photometry, IR and Raman spectroscopies, with the difficulties that these systems require expensive and complex equipment and are not necessarily suitable for all intervention environments in terms of mass and size, in addition to the expertise of the operator to be taken into account.

[0006] In view of what exists, the authors of the present invention have turned to the design of a detection system usable for the detection of chemical compounds, such as organophosphorus compounds, from a specific colored indicator. DESCRIPTION OF THE INVENTION

[0007] Thus, the invention relates to a colorimetric detection system usable for the detection of a chemical compound comprising a support including a colored indicator of said chemical compound to be detected, characterized in that the colored indicator is a conjugated hydrazone compound. The detection system of the present invention is defined in claim 1.

[0008] A colored indicator (also called a colorimetric detection indicator) is classically understood to be a chemical substance that takes on at least one characteristic color in the presence of a chemical compound, or, in other words, a chemical substance that exhibits at least two colored states: one colored state existing when the chemical substance is not in the presence of the chemical compound to be detected, and at least one other colored state when the chemical substance is in the presence of the chemical compound to be detected.

[0009] The constitutive support of the detection system may be, in particular, a support comprising glass fibers or is a paper support (for example, chromatography paper), with a preference for the support comprising glass fibers, or is a support comprising a powder (for example, silica powder, polyethylene powder) it being understood that this support must be suitable for impregnating the conjugated hydrazone compound.

[0010] By conjugated hydrazone, we mean a compound comprising a hydrazone function of formula -NH-N=C-, whose double bond is conjugated to another double bond, that is, in other words, that the carbon atom bearing the double bond of the hydrazone function is bonded to another carbon atom bearing a double bond, which can be schematically represented by the following formula (I):

[0011] X denotes a carbon atom or heteroatom, the curly braces indicating that atoms are bonded to other atoms to achieve their valence, this formula also covering tautomeric forms. Further, when reference is made to the nitrogen atom of the hydrazone function, it refers to the nitrogen atom not bearing the double bond, this nitrogen atom being the one shown on the left side of formula (I). It is also understood that when X is a carbon atom, it will have an additional valence compared to what is shown in formula (I).

[0012] More specifically, the other carbon bearing a double bond may belong to an aromatic group, possibly heteroaromatic, or may belong to an ethylenic group.

[0013] According to a first embodiment, the conjugated hydrazone compound comprises at least one cyclic group bonded to the carbon atom bearing the double bond of the hydrazone function and further comprises an aromatic group bearing at least one electron-withdrawing group (such as NO2), bonded to the nitrogen atom of the hydrazone function.

[0014] Hydrazone compounds meeting the specifics of this first embodiment may be compounds in which the cyclic group(s) linked to the carbon atom bearing the double bond of the hydrazone function are carbon cyclic groups (i.e., in which the atoms of the ring are all carbon atoms, which does not exclude that these carbon atoms may be linked to groups bearing one or more heteroatoms), for example carbon aromatic groups and, even more specifically, hydrazone compounds in which the cyclic group(s) linked to the carbon atom bearing the double bond of the hydrazone function are carbon cyclic groups (for example carbon aromatic groups) and the aromatic group bearing at least one electron-withdrawing group is an aromatic group bearing at least one NO2 group.

[0015] Hydrazone compounds meeting these criteria may correspond to one of the following formulas (II), (III), (IV), (V), (VI) and (VI'): for which: for formula (II), R 1< represents -N(CH 3 ) 2 , -CH 3 , -OCH 3 , -OH, -SCH 3 or -NO 2 ; R 2< represents -H or -OCH 3 ; R 3< represents -H or -CH 3 ; for formula (III), R 1< and R 2< represent, independently of each other, -H, -N(CH 3 ) 2 , -OCH 3 or -NO 2 ; for formula (IV), R 1< and R 2< represent, independently of each other, -CH 3 or -CH 2 -CH 3 .

[0016] More specifically, particular compounds included in the definition of compounds of formula (II) are as follows: the compound for which R1< represents -N(CH3)2, R2< represents -H and R3< represents H (hereafter referred to as compound 1a); the compound for which R1< represents -CH3, R2< represents H and R3< represents H (hereafter referred to as compound 1b); the compound for which R1< represents -OCH3, R2< represents -H and R3< represents H (hereafter referred to as compound 1c); the compound for which R1< represents -OH, R2< represents -OCH3 and R3< represents H (hereafter referred to as compound 1d); the compound for which R1< represents -SCH3, R2< represents -H and R3< represents H (hereafter referred to as compound 1e); and the compound for which R 1< represents -NO 2 , R 2< represents -H and R 3< represents -CH 3 (hereafter referred to as "compound 1f").

[0017] More specifically, particular compounds included in the definition of formula (III) compounds are as follows: the compound for which R 1< represents -H and R 2< represents -H (hereafter referred to as "compound 3a"); the compound for which R 1< represents -N(CH 3 ) 2 , R 2< represents - N(CH 3 ) 2 (hereafter referred to as "compound 3b"); and the compound for which R 1< represents -OCH 3 and R 2< represents - OCH 3 (hereafter referred to as "compound 3c").

[0018] More specifically, particular compounds falling within the definition of formula (IV) compounds are as follows: the compound for which R 1< represents -CH 3 and R 2< represents - CH 3 (hereafter referred to as "compound 5a"); and the compound for which R 1< represents -CH 2 -CH 3 , R 2< represents -CH 2 -CH 3 (hereafter referred to as "compound 5b").

[0019] Hydrazone compounds meeting the specifics of the first embodiment may also be compounds in which the cyclic group(s) linked to the carbon atom bearing the double bond of the hydrazone function are heteroaromatic groups (i.e. a group in which at least one atom of the ring(s) is a heteroatom, such as O, N, S) and, more specifically, hydrazone compounds in which the cyclic group(s) linked to the carbon atom bearing the double bond of the hydrazone function are heteroaromatic groups and the aromatic group bearing at least one electron-withdrawing group is an aromatic group bearing at least one NO2 group.

[0020] Hydrazone compounds meeting these criteria may correspond to one of the following formulas (VII), (VIII), (IX), (X) and (XI): for which: for formula (VII), R 1< represents -H or -OH; for formula (VIII), R 1< represents -H or -OH.

[0021] More specifically, particular compounds falling within the definition of compounds of formula (VII) or (VIII) are as follows: the compound for which R 1< represents -H (hereafter referred to as "compound 2a"); the compound for which R 1< represents -OH (hereafter referred to as "compound 2b").

[0022] According to a second embodiment, the conjugated hydrazone compound comprises at least one ethylenic group bonded to the carbon atom bearing the double bond of the hydrazone function and further comprising an aromatic group bearing at least one electron-withdrawing group (such as NO2 or a heteroaromatic group) bonded to the nitrogen atom of the hydrazone function, particular compounds meeting this specificity corresponding to one of the following formulas (XII) or (XIII):

[0023] According to a third embodiment, the conjugated hydrazone compound comprises at least one aromatic group bearing an -OH group bonded to the nitrogen atom of the hydrazone function or to the carbon atom bearing the double bond of the hydrazone function, particular compounds meeting this specificity corresponding to one of the following formulas (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) and (XX):

[0024] According to a fourth embodiment, the conjugated hydrazone compound comprises a heteroaromatic group linked, optionally via a spacer group (such as a -CO- group), to the nitrogen atom of the hydrazone function and another heteroaromatic group linked to the carbon atom bearing the double bond of the hydrazone function, or comprises a diazoaromatic group linked to the nitrogen atom of the hydrazone function and a heteroaromatic group encompassing the carbon atom bearing the double bond of the hydrazone function, particular compounds meeting this specificity corresponding to one of the following formulas (XXI), (XXII), (XXIII) and (XXIV):

[0025] Among the aforementioned hydrazone compounds, some are novel and are the subject of the invention, these compounds corresponding to one of the following formulas (5a), (5b) and (X):

[0026] These compounds can be classically obtained by a condensation reaction between a carbonyl compound (e.g., a ketone or an aldehyde) and a compound containing a hydrazine function.

[0027] Detection systems according to the invention can be prepared by a process comprising a step of depositing the colored indicator onto the support by projecting an ink comprising the colored indicator onto it.

[0028] Regarding the possible deposition techniques, these could include micropipette deposition, printing (for example, via a Dimatix printer), from a warehouse via particles impregnated with the appropriate color indicator or a screen-printed deposit.

[0029] Finally, the invention also relates to a method for detecting the presence or absence of a chemical compound comprising the following steps: a step of bringing into contact the medium(s), whose presence or absence we want to detect, with the detection system as defined above; a step of deduction, based on the possible color changes observed, of the presence or absence of said chemical compound.

[0030] This contact step may consist of depositing on the surface of the detection system one or more separate drops of each medium whose absence or presence of a chemical compound we want to analyze.

[0031] It is understood that the colorimetric detection system to be used in the aforementioned process must be capable of detecting the chemical compound whose absence or presence is to be determined.

[0032] Between the contact stage and the deduction stage, a waiting period may be provided so that, if necessary, the color change can take place.

[0033] Regarding the deduction step, the operator can rely on a colorimetric scale associated with the detection system, which will define, for all chemical compounds likely to be detected by the system, the corresponding color change. This colorimetric scale can be determined, through preliminary tests, for each of the systems and the chemical compounds intended to be detected by said systems. The deduction can be made by visual inspection or, if necessary, via opto-electronic means.

[0034] The compounds that can be detected by the process of the invention may be toxic warfare compounds; toxic industrial compounds, pesticides and, more specifically, may be organophosphate compounds and, even more specifically, toxic organophosphate compounds corresponding to one of the following formulas (XXV) and (XXVI): in which: R 1< represents H or an alkyl group, possibly cyclic, which may include up to 10 carbon atoms; R 2< and R 3< represent, independently of each other, an alkyl group, possibly cyclic, which may include up to 10 carbon atoms; R 4< represents H, an alkyl group, possibly cyclic, which may include up to 10 carbon atoms or an amino group.

[0035] In particular, detection systems, especially when the support is made of glass fibers and the colored indicator is a hydrazone compound 1b, 1d, 1f, 2a, 2b or 3c as defined above or a compound of formula (IX) as defined above, are particularly suited to the selective detection of toxic organophosphate compounds corresponding to one of the following formulas (XXV) and (XXVI): in which: R 1< represents H or an alkyl group, possibly cyclic, which may include up to 10 carbon atoms; R 2< and R 3< represent, independently of each other, an alkyl group, possibly cyclic, which may include up to 10 carbon atoms; R 4< represents H, an alkyl group, possibly cyclic, which may include up to 10 carbon atoms or an amino group.

[0036] Specific organophosphorus compounds falling into this category are specific compounds corresponding to one of the following formulas (XXVII), (XXVIII), (XXIX) and (XXX):

[0037] The invention also relates to a colorimetric detection kit usable for the detection of a chemical compound comprising the following elements: a detection system according to the invention and as defined above; and a colorimetric scale enabling the correspondence between the observed color change and the detected chemical compound.

[0038] Other features and advantages of the invention will become clearer upon reading the following supplementary description, which relates to an example of preparing a detection system according to the invention.

[0039] Of course, the following example is given only as an illustration of the object of the invention and in no way constitutes a limitation of that object. DETAILED DESCRIPTION OF SPECIFIC METHODS OF IMPLEMENTATION EXAMPLE 1

[0040] This example illustrates the preparation of various specific conjugated hydrazone compounds usable as a colored indicator within the framework of the invention, this preparation being carried out by condensation of the hydrazine function carried by 2,4-dinitrophenylhydrazine with the carbonyl function -C=O carried by a carbonyl reagent.

[0041] The general protocol for preparing these hydrazone compounds is as follows.

[0042] Initially, 2,4-Dinitrophenylhydrazine (1.3 eq) is solubilized at 50°C to 0.1 M in ethanol in the presence of concentrated sulfuric acid (3 eq). An ethanolic solution containing the carbonyl reagent (1 eq) is then added dropwise to the 2,4-dinitrophenylhydrazine solution. The reaction mixture is then refluxed until complete conversion of the reagents. In the case of aldehyde-derived reagents, the reaction is almost instantaneous, and addition at 50°C is sufficient. The hydrazone formed is only partially soluble in ethanol and forms as a byproduct suspension in the reaction medium. After cooling to room temperature, the reaction mixture is evaporated to three-quarters. The residue is then partially dissolved in a volume of deionized water and treated with a basic 1 M NaOH solution.Hydrazone precipitates and is then filtered and rinsed with deionized water at least twice. The crude solid is then washed with a suitable solvent, usually ethanol. It is subsequently dried in an oven (80°C) and then under vacuum using a rotary vane pump.

[0043] Certain modalities were carried out according to the selected carbonyl derivatives and are described more precisely for each of the hydrazones. has) Precise preparation methods for compound 1a

[0044] The paragraph below illustrates the precise preparation methods for compound 1a, which corresponds to the following formula:

[0045] 2,4-Dinitrophenylhydrazine (estimated purity 68%, 4.74 mmol, 1.382 g, 1.3 eq) is reacted according to the general synthesis protocol with 4-dimethylaminobenzaldehyde (3.64 mmol, 549.1 mg, 1 eq). The reaction mixture is stirred at 50°C for 15 min. The hydrazone compound (1a) is obtained as a black powder (0.98 g, 98%).

[0046] The results of IR spectroscopy and 1< H NMR are shown below.

[0047] IR: 3302 (NH), 3135 to 2979 (Ar-H), 1604 (C=N), 1583, 1406, 1333, 1281, 1125, 1062, and 698 cm-1; 1< H NMR (DMSO-d 6, 400 MHz): δ 11.57 (s, 1H, NH), 8.872 (s, 1H, ArDNPH-H), 8.553 (s, 1H, ArDNPH-H), 8.346 (d, 1H, ArDNPH-H), 8.045 (d, 1H, N=CH), 7.623 (d, 2H, Arcarbonyl-H), 6.787 (d, 2H, Arcarbonyl-H), 3.010 (s, 6H, N-CH 3 ). b) Precise preparation methods for compound 1b

[0048] The paragraph below illustrates the precise preparation methods for compound 1b, which corresponds to the following formula:

[0049] p-Tolualdehyde (0.333 mmol, 0.04 mL, 1 eq) in liquid form is directly added while hot to 2,4-dinitrophenylhydrazine (0.43 mmol, 126.3 mg, 1.3 eq). The reaction mixture is stirred at 50°C for 15 min. The hydrazone compound (1b) is obtained as an orange-colored powder (86.9 mg, 86.9%).

[0050] The results of 1< H NMR spectroscopy are shown below.

[0051] 1< H NMR (CDCl 3, 400 MHz): δ 11.57 (s, 1H, NH), 9.149 (d, 1H, ArDNPH-H), 8.35 (dd, 1H, ArDNPH-H), 8.08 (s, 1H, ArDNPH-H), 8.04 (s, 1H, N=CH), 7.667 (d, 2H, Arcarbonyl-H), 7.282 (s, 1H, Ar-H), 2.422 (s, 3H, Ar-CH 3 ). c) Precise preparation instructions for compound 1c

[0052] The paragraph below illustrates the precise preparation methods for compound 1c, which corresponds to the following formula:

[0053] Anisaldehyde (0.32 mmol, 0.038 mL, 1 eq) in liquid form is directly added while hot to 2,4-dinitrophenylhydrazine (0.41 mmol, 119.9 mg, 1.3 eq). The reaction mixture is stirred at 50°C for 15 min. The hydrazone compound (1c) is obtained as an orange-red powder (73.4 mg, 73.4%).

[0054] The results of 1< H NMR spectroscopy are shown below.

[0055] 1< H NMR (CDCl 3, 400 MHz): δ 11.57 (s, 1H, NH), 9.151 (d, 1H, ArDNPH-H), 8.342 (dd, 1H, ArDNPH-H), 8.0615 (s, 1H, ArDNPH-H), 8.04 (s, 1H, N=CH), 7.724 (d, 2H, Arcarbonyl-H), 6.984 (d, 2H, Arcarbonyl-H), 3.882 (s, 3H, Ar-OCH 3 ) d) Precise preparation methods for compound 1d

[0056] The paragraph below illustrates the precise preparation methods for compound 1d, which corresponds to the following formula:

[0057] 2,4-Dinitrophenylhydrazine (0.452 mmol, 131.8 mg, 1 eq) is reacted with vanillin (0.452 mmol, 69.4 mg, 1 eq) according to the general synthesis protocol. The reaction mixture is stirred at 50°C for 1 h. No basic treatment is performed for this hydrazone. The product is only rinsed with ethanol. The hydrazone compound (1d) is obtained as a red powder (146.5 mg, 97.5%).

[0058] The results of IR spectroscopy and 1< H NMR are shown below.

[0059] IR (cm -1< ) ​​v: 3385 (OH), 3278 (NH), 1622 (C=N), 1515 (NO2), 1418, 1334, 1268 (CO), 1134, 1062 and 865 1< H NMR (DMSO-d 6, 500 MHz) δ (ppm): 11.59 (s, 1H, NH), 9.694 (s, 1H, OH), 8.88 (s, 1H), 8.584 (s, 1H, N=CH), 8.35 (d, 1H, Ar-H), 8.10 (d, J = 9.66 Hz, 1H), 7.40 (s, 1H), 7.18 (d, 1H), 6.88 (d, J = 8.1 Hz, 1H), 3.875 (s, 3H, OCH 3 ) e) Precise preparation methods for compound 1e

[0060] The paragraph below illustrates the precise preparation methods for compound 1e, which corresponds to the following formula:

[0061] 4-Methylthiobenzaldehyde (0.602 mmol, 82.51 µL, 1 eq) in liquid form is directly added while hot to 2,4-dinitrophenylhydrazine (0.783 mmol, 0.228 g, 1.3 eq). The reaction mixture is stirred at 50°C for 2 h. The hydrazone compound (1e) is obtained as an orange-red powder (168 mg, 84%).

[0062] The results of 1< H NMR spectroscopy are shown below.

[0063] 1< H NMR (CDCl 3, 500 MHz): δ 11.306 (s, 1H, NH), 9.155 (s, 1H), 8.353 (ddd, 1H), 8.080 (t, 2H), 7.682 (d, 2H), 7.30 (d, 2H), 3.541 (s, 3H) f) Precise preparation methods for compound 1f

[0064] The paragraph below illustrates the precise preparation methods for compound 1f, which corresponds to the following formula:

[0065] 2,4-Dinitrophenylhydrazine (0.75 mmol, 219.7 mg, 1.3 eq) is reacted according to the general synthesis protocol with 4-nitroacetophenone (0.58 mmol, 96.6 mg, 1 eq). The reaction mixture is stirred at 50°C for 1 h. The hydrazone compound (1f) is obtained as an orange-yellow powder (162 mg, 81%).

[0066] 1< H NMR (CDCl 3, 500 MHz): δ 11.59 (s, 1H, NH), 9.195 (s, 1H), 8.43 (dd, 1H), 8.315 (d, 2H), 8.142 (d, 1H), 8.02 (d, 2H), 2.518 (s, 3H) g) Precise preparation methods for compound 2a

[0067] The paragraph below illustrates the precise preparation methods for compound 2a, which corresponds to the following formula:

[0068] 2,4-Dinitrophenylhydrazine (0.964 mmol, 281.2 mg, 1.3 eq) is reacted according to the general procedure with 4-quinoline carboxaldehyde (0.741 mmol, 120.1 mg, 1 eq). The reaction mixture is stirred at 50°C for 4 h. The hydrazone compound (2a) is obtained as a yellow powder (255 mg, 100%). h) Precise preparation methods for compound 2b

[0069] The paragraph below illustrates the precise preparation methods for compound 2b, which corresponds to the following formula:

[0070] 2,4-Dinitrophenylhydrazine (1.104 mmol, 322.1 mg, 1.3 eq) is reacted according to the general procedure with 8-hydroxy-2-quinoline carboxaldehyde (0.849 mmol, 151.5 mg, 1 eq). The reaction mixture is stirred at 50°C for 2 h. The hydrazone compound (2b) is obtained as a yellow powder (234.56 mg, 78.2%). i) Precise preparation methods for compound 3a

[0071] The paragraph below illustrates the precise preparation methods for compound 3a, which corresponds to the following formula:

[0072] 2,4-Dinitrophenylhydrazine (4.414 mmol, 1.21 g, 1.3 eq) was reacted with benzophenone (2.76 mmol, 0.508 g, 1 eq) according to the general synthesis protocol. The reaction mixture was refluxed for 1 h and monitored by TLC (toluene: THF 99:1, Rf=0.67). The hydrazone compound (3a) was obtained as an orange powder (0.98 g, 98%).

[0073] The results of IR spectroscopy and 1< H NMR are shown below.

[0074] IR: 3302 (NH), 3135 to 2979 (Ar-H), 1604 (C=N), 1583, 1406, 1333, 1281, 1125, 1062, and 698 cm -1< 1< H NMR (DMSO-d 6, 400 MHz): δ (ppm) 11.25 (1H, s, NH), 8.829 (s, 1H, ArDNPH-H), 8.472 to 8.2531 (dd, 2H, ArDNPH-H), 7.69 (m, 5H, Ar-H), 7.49 (s, 5H, Ar-H) j) Precise preparation methods for compound 3b

[0075] The paragraph below illustrates the precise preparation methods for compound 3b, which corresponds to the following formula:

[0076] 2,4-Dinitrophenylhydrazine (0.58 mmol, 169.2 mg, 1.3 eq) is reacted in methanol according to the general synthesis protocol with 4,4'-bisdimethylaminobenzophenone (0.45 mmol, 120.9 mg, 1 eq). The reaction mixture is refluxed for 4 h and monitored by TLC (toluene: THF 98:2, Rf = 0.3). The hydrazone compound (3b) is obtained as a very dark purple powder (162.8 mg, 81.4%).

[0077] The results of IR spectroscopy and 1< H NMR are shown below.

[0078] IR: 3275 (NH), 3000 to 2800 (Ar-H), 1607 (C=N), 1590, 1512, 1328, 1132, 1083, 827 and 741 cm -1< 1< H NMR (DMSO-d 6, 400 MHz): δ (ppm) 11.29 (s, 1H, NH), 8.81 (s, 1H), 8.35 (d, 1H), 8.12 (d, 1H), 7.36 (dd, 2H), 7.05 (dd, 2H), 6.78 (dd, 2H), 6.59 (dd, 2H) k) Precise preparation instructions for compound 3 c

[0079] The paragraph below illustrates the precise preparation methods for compound 3c, which corresponds to the following formula:

[0080] 2,4-Dinitrophenylhydrazine (0.58 mmol, 168.9 mg, 1.3 eq) was reacted in methanol according to the general protocol with 4,4'-Dimethoxybenzophenone (0.45 mmol, 110.6 mg, 1 eq). The reaction mixture was refluxed for 1 h and monitored by TLC (Cyclohexane:AcOEt 70:30, Rf = 0.62). The hydrazone compound (3c) was obtained as a slightly flecked red powder (162 mg, 81%).

[0081] The results of IR spectroscopy and 1< H NMR are shown below. IR: 3273 (NH), 3000 to 2800 (Ar-H), 1614 (C=N), 1587, 1503, 1334, 1251, 1136, 1025, 1083 and 840 cm -1< 1< H NMR (DMSO-d 6, 400 MHz): δ (ppm) 11.56 (s, 1H, NH), 8.828 (s, 1H, ArDNPH-H), 8.435 (dd, 1H, ArDNPH-H), 8.21 (d, 1H, ArDNPH-H), 7.59 (d, 2H, Ar-H), 7.405 (d, 2H, Ar-H), 7.24 (d, 2H, Ar-H), 7.02 (d, 2H, Ar-H), 3.896 (s, 3H, OCH 3 ), 3.818 (s, 3H, OCH 3 ) I) Precise preparation methods for compound 4

[0082] The paragraph below illustrates the precise preparation methods for compound 4, which corresponds to the following formula:

[0083] Trans-cinnamaldehyde (0.32 mmol, 0.041 mL, 1 eq) in liquid form is directly added while hot to 2,4-dinitrophenylhydrazine (0.416 mmol, 121.5 mg, 1.3 eq). The reaction mixture is stirred at 50°C for 15 min. Hydrazone (1c) is obtained as a red powder (88.5 mg, 88.5%).

[0084] The results of IR spectroscopy, 1< H NMR and 13< C NMR are shown below.

[0085] IR: 3302 (NH), 3135 to 2979 (Ar-H), 1604 (C=N), 1583, 1406, 1333, 1281, 1125, 1062, and 698 cm -1< 1< H NMR (CDCl 3, 400 MHz): δ (ppm) 11.5 (s, 1H, NH), 9.0143 (s, 1H, ArDNPH-H), 8.356 to 8.326 (dd, 1H, ArDNPH-H), 8.006 to 7.982 (d, 1H, ArDNPH-H), 7.946 (d, 1H, N=CH), 7.52 (d, 2H), 7.425 to 7.36 (m, 3H, Ar-H), 7.03 (m, 2H, C=CH) 13< C NMR (CDCl 3, 400 MHz): δ (ppm) 149.84 (HC=N), 141.18 (CAr-NHN), 130.04, 129.49, 128.86, 127.33, 124.07, 123.51, 116.77 m) Precise preparation methods for compound 5a

[0086] The paragraph below illustrates the precise preparation methods for compound 5a, which corresponds to the following formula:

[0087] 2,4-Dinitrophenylhydrazine (0.97 mmol, 257 mg, 1.3 eq) is reacted according to the general procedure with 4-(4-dimethylamino)phenylazo)acetophenone (0.75 mmol, 200 mg, 1 eq) in the presence of 4 equivalents of sulfuric acid. The reaction mixture is refluxed for 2 h. The hydrazone compound (5a) is obtained as a brick-red powder (267.7 mg, 80%). n) Precise preparation methods for compound 5b

[0088] The paragraph below illustrates the precise preparation methods for compound 5b, which corresponds to the following formula:

[0089] 2,4-Dinitrophenylhydrazine (0.04 mmol, 12.9 mg, 1.3 eq) is reacted according to the general procedure with 4-(4-diethylamino)phenylazo)acetophenone (0.03 mmol, 10 mg, 1 eq) dissolved to 0.025 M in ethanol. The reaction mixture is refluxed for 2 h. The hydrazone compound (5b) is obtained as a brick-red powder (12.3 mg, 76.4%). o) Precise preparation methods for compound 6

[0090] The paragraph below illustrates the precise preparation methods for compound 6, which corresponds to the following formula:

[0091] 2,4-Dinitrophenylhydrazine (0.769 mmol, 224.5 mg, 1.3 eq) is reacted according to the general procedure with 5-(methylthio)thiophene-2-carbaldehyde (0.592 mmol, 96.4 mg, 1 eq). The reaction mixture is stirred at 50°C for 2.5 hours. The hydrazone compound (6) is obtained as a brick-red powder (175.14 mg, 87.6%).

[0092] The results of 1< H NMR spectroscopy are shown below.

[0093] 1< H NMR (CDCl 3, 400 MHz): δ 11.26 (s, 1H, NH), 9.137 (d, 1H), 8.3314 to 8.3615 (dd, 1H), 8.1696 (s, 1H), 7.997 to 7.973 (d, 1H), 7.189 (d, 1H), 6.959 (d, 1H), 2.608 (s, 3H) p) Precise preparation methods for compound 7

[0094] The paragraph below illustrates the precise preparation methods for compound 7, which corresponds to the following formula:

[0095] 2,4-Dinitrophenylhydrazine (0.797 mmol, 231.7 mg, 1.3 eq) is reacted according to the general procedure with 7-azaindole-3-carboxaldehyde (0.613 mmol, 92.4 mg, 1 eq). The reaction mixture is stirred at 50°C for 15 minutes. The hydrazone compound (7) is obtained as a brick-red powder (152.78 mg, 76.4%).

[0096] The results of 1< H NMR spectroscopy are shown below.

[0097] 1< H NMR (DMSO-d 6, 400 MHz): δ 12.311 (s, 1H, NH), 11.632 (s, 1H, NH), 8.882 (s, 1H), 8.338 (s, 1H), 8.585 (d, 1H), 8.385 (m, 2H), 8.08 (s, 1H), 8.06 (s, 1H), 7.30 (m, 1H). EXAMPLE 2

[0098] In this example, compounds 1d, 1f, 3c, 1b, 2a, 2b, and 6, whose preparation is described in Example 1 above, are deposited, respectively, via a solution of the given compound (10 mM) in dimethyl sulfoxide, onto separate glass fiber supports. The supports are then naturally dried to evaporate the dimethyl sulfoxide and subsequently scanned to serve as controls prior to exposure to chemical compounds.

[0099] Each substrate is then exposed to 13 toxic compounds, each deposited at a rate of 1.6 µL via a multichannel electronic pipette into individual wells on the substrate. Each substrate is then scanned after 5 minutes and again after 1 hour of exposure to the toxic compounds.

[0100] The 13 toxic compounds are organophosphate compounds of the G series (Sarin, Soman and Tabun (GA, CAS No. 77-81-6), an organophosphate compound of the V series (VX), vesicants (sulfur mustard gas (HD, CAS No. 505-60-2), nitrogen mustard gas (HN-3, CAS No. 555-71-1), lewisite (L1, CAS No. 541-25-3), arsenic compounds (diphenylchlorarsine, known as "C1", and diphenylcyanoarsine, known as "C2") and the organophosphate compounds corresponding to the following formulas (XXVII), (XXVIII), (XXIX) and (XXX):

[0101] For each of the supports, exposure to organophosphorus compounds of formulas (XXVII), (XXVIII), (XXIX) and (XXX) causes a color change from yellow or orange to purple, blue or brown instantaneously, whereas there is no change for the other compounds.

[0102] This example thus demonstrates the specificity of detection of organophosphorus compounds of formulas (XXVII), (XXVIII), (XXIX) and (XXX) by the hydrazone compounds mentioned above. EXAMPLE 3

[0103] In this example, compounds 1f, 1b, 3a, 5a, whose preparation is shown in example 1 above, and compounds of the following formulas (V) and (XI): The compounds are deposited, respectively, via a solution comprising the given compound (10 mM) in dimethyl sulfoxide, onto separate glass fiber substrates. The substrates are then naturally dried to evaporate the dimethyl sulfoxide and subsequently scanned to serve as controls prior to exposure to chemical compounds.

[0104] Each of the supports is then subjected to 4 toxic compounds, each deposited at a rate of 1.6 µL viaA multichannel electronic pipette is used, with individual wells provided on the support. Each support is then scanned after 5 minutes and then after 1 hour of exposure to the toxic compounds.

[0105] The 4 toxic compounds correspond to the following formulas (XXVII), (XXVIII), (XXIX) and (XXX):

[0106] The contact of the 4 aforementioned organophosphorus neurotoxic agents with the glass fiber supports, on which the aforementioned hydrazone compounds have been deposited, causes a color change in the latter, thus attesting to the effectiveness of the supports according to the invention for the detection of this specific type of organophosphorus compounds. EXAMPLE 4

[0107] In this example, compounds 1a, 1b, 1c, 1d, 1e, 1f, 2a, 2b, 3a, 3b, 3c, 4, 5a, 5b and 6, the preparation of which is shown in Example 1 above, compounds of formulas (V) and (XI) as defined above, and compounds of the following formulas: The compounds are deposited, respectively, via a solution comprising the given compound (10 mM) in dimethyl sulfoxide, onto separate glass fiber substrates. The substrates are then naturally dried to evaporate the dimethyl sulfoxide and subsequently scanned to serve as controls prior to exposure to chemical compounds.

[0108] Each of the supports is then subjected to 4 toxic compounds, each deposited at a rate of 1.6 µL viaA multichannel electronic pipette is used, with samples placed in individual wells on the support. Each support is then scanned after 5 minutes and again after 1 hour of exposure to the toxic compounds. The four toxic compounds are those defined in Example 3 below.

[0109] The contact of the 4 aforementioned organophosphorus neurotoxic agents with the glass fiber supports, on which the aforementioned hydrazone compounds have been deposited, causes a color change in the latter, thus attesting to the effectiveness of the supports according to the invention for the detection of this specific type of organophosphorus compounds. EXAMPLE 5

[0110] In this example, the compounds 1a, 1c, 1e, 1f, 2a, 2b, 3b, 4, whose preparation is shown in example 1 above, the compounds of formulas (XXI), (VI), (XIX) whose formulas are defined in example 4 above and the compound of formula (XX) following: are deposited respectively on separate chromatography paper supports, said supports being subjected to the four organophosphorus neurotoxic agents as defined in Example 3 above.

[0111] The contact of the 4 aforementioned organophosphorus neurotoxic agents with the chromatography paper supports, on which the aforementioned hydrazone compounds have been deposited, causes a color change in the latter, thus attesting to the effectiveness of the supports according to the invention for the detection of this specific type of organophosphorus compounds.

Claims

1. Colorimetric detection system usable for detecting a chemical compound comprising a carrier comprising a coloured indicator of said chemical compound to be detected, characterised in that the coloured indicator is a conjugated hydrazone compound chosen from: a) conjugated hydrazone compounds comprising at least one cyclic group bonded to the carbon atom carrying the double bond of the hydrazone function and comprising an aromatic group carrying at least one electro-attractive group bonded to the nitrogen atom of the hydrazone function; b) conjugated hydrazone compounds comprising at least one ethylene group bonded to the carbon atom carrying the double bond of the hydrazone function and further comprising an aromatic group carrying at least one electro-attractive group; c) conjugated hydrazone compounds comprising at least one aromatic group carrying an -OH group bonded to the nitrogen atom of the hydrazone function or to the carbon atom carrying the double bond of the hydrazone function; d) the conjugated hydrazone compounds comprising a heteroaromatic group bonded to the nitrogen atom of the hydrazone function and another heteroaromatic group bonded to the carbon atom carrying the double bond of the hydrazone function or comprises a diazoaromatic group bonded to the nitrogen atom of the hydrazone function and a heteroaromatic group including the carbon atom carrying the double bond of the hydrazone function.

2. Colorimetric detection system according to claim 1, wherein, when the conjugated hydrazone compound is a compound of category a), the cyclic group(s) bonded to the carbon atom carrying the double bond of the hydrazone function are carbon-containing cyclic groups and the aromatic group carrying at least one electro-attractive group is an aromatic group carrying at least one NO2 group.

3. Colorimetric detection system according to either of the preceding claims, wherein the conjugated hydrazone compound meets one of the following formulae (II), (III), (IV), (V), (VI) and (VI'): where: - for the formula (II), R1 represents -N(CH3)2, -CH3, -OCH3, -OH, -SCH3 or - NO2; R2 represents -H or -OCH3 and R3 represents -H or -CH3; - for the formula (III), R1 and R2 represent, independently of one another, - H, -N(CH3)2, -OCH3 or -NO2; - for the formula (IV), R1 and R2 represent, independently of one another, - CH3 or -CH2 -CH3.

4. Colorimetric detection system according to claim 3, wherein, when the conjugated hydrazone compound is a compound of formula (II), it is: - the compound for which R1 represents -N(CH3)2, R2 represents -H and R3 represents H; - the compound for which R1 represents -CH3, R2 represents H and R3 represents H; - the compound for which R1 represents -OCH3, R2 represents -H and R3 represents H; - the compound for which R1 represents -OH, R2 represents -OCH3 and R3 represents H; - the compound for which R1 represents -SCH3, R2 represents -H, and R3 represents H; or - the compound for which R1 represents -NO2, R2 represents -H and R3 represents -CH3.

5. Colorimetric detection system according to claim 3, wherein, when the conjugated hydrazone compound is a compound of formula (III), it is: - the compound for which R1 represents -H and R2 represents -H; - the compound for which R1 represents -N(CH3)2 and R2 represents -N(CH3)2; or - the compound for which R1 represents -OCH3 and R2 represents OCH3.

6. Colorimetric detection system according to claim 3, wherein, when the conjugated hydrazone compound is a compound of formula (IV), it is: - the compound for which R1 represents -CH3 and R2 represents -CH3; or - the compound for which R1 represents -CH2-CH3 and R2 represents -CH2-CH3.

7. Colorimetric detection system according to claim 1, wherein, when the conjugated hydrazone compound is a compound of category a), the cyclic group(s) bonded to the carbon atom carrying the double bond of the hydrazone function are heteroaromatic groups and the aromatic group carrying at least one electro-attractive group is an aromatic group carrying at least one NO2 group.

8. Colorimetric detection system according to claim 7, wherein the conjugated hydrazone compound meets one of the following formulae (VII), (VIII), (IX), (X) and (XI): where: - for formula (VII), R1 represents -H or -OH; - for formula (VIII), R1 represents -H or -OH.

9. Colorimetric detection system according to claim 1, wherein, when the conjugated hydrazone compound is a compound of category b), it meets one of the following formulae (XII) or (XIII):

10. Colorimetric detection system according to claim 1, wherein, when the conjugated hydrazone compound is a compound of category c), it meets one of the following formulae (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) and (XX):

11. Colorimetric detection system according to claim 1, wherein, when the conjugated hydrazone compound is a compound of category d), it meets one of the following formulae (XXI), (XXII), (XXIII) and (XXIV):

12. Colorimetric detection system according to any one of the preceding claims, wherein the carrier comprises glass fibres or is a paper carrier, preferably comprising glass fibres.

13. Hydrazone compound meeting one of the following formulae (5a), (5b) and (X):

14. Method for detecting the presence or absence of a chemical compound comprising the following steps: - a step of placing in contact the medium / media in which it is desired to detect the presence or absence of said chemical compound(s) with the detection system as defined according to any one of claims 1 to 12; - a step of deducing, according to any chromatic curve(s) observed, the presence or absence of said chemical compound.

15. Method according to claim 14, which is a method for detecting the presence or absence of a chemical compound selected from toxic warfare compounds, toxic industrial compounds, pesticides.

16. Method according to claim 15, which is a method for detecting the presence or absence of a chemical compound meeting one of the following formulae (XXV) and (XXVI): where: - R1 represents H or an alkyl group, optionally cyclic, which may comprise up to 10 carbon atoms; - R2 and R3 represent, independently of each other, an alkyl group, optionally cyclic, which may comprise up to 10 carbon atoms; - R4 represents H, an alkyl group, optionally cyclic, which may comprise up to 10 carbon atoms or an amino group.

17. Colorimetric detection kit usable for the detection of a chemical compound comprising the following elements: - a detection system as defined according to any one of claims 1 to 12; and - a colorimetric scale making it possible to make a connection between the observed chromatic curve and the chemical compound detected.