RU2723243C1 - Use of monosubstituted pyrazines containing triphenylamine substitute, as monomolecular sensors for detecting nitroaromatic compounds - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to use of 2-monosubstituted pyrazines containing a triphenylamine substitute of general formula (I) as monomolecular sensors for detecting nitroaromatic compounds.

EFFECT: technical result is use of compounds of general formula (I), which show high sensitivity and selectivity for visual detection of a wide range of nitroaromatic compounds.

1 cl, 2 ex, 3 tbl

Description

The use of monosubstituted pyrazines containing a triphenylamine substituent as monomolecular sensors for the detection of nitroaromatic compounds.

FIELD OF THE INVENTION

The present invention relates to the field of organic synthesis of sensor materials and relates to 2-monosubstituted pyrazines having sensory properties and intended to detect the presence of nitroaromatic compounds on surfaces, in solutions of non-polar solvents, water and in air in ultra-low concentrations based on changes in optical properties - quenching of photoluminescence designated sensor in contact with molecules of nitroaromatic compounds. The invention can be used to create sensors for nitroaromatic compounds, which can be used in law enforcement agencies (army, police, security companies, etc.), customs services, research laboratories, as well as in everyday life and agriculture.

The prior art:

Methods of preparing a compound of formula Ia based on cross-coupling reactions under various conditions (except for the use of activation under the influence of microwave radiation)

, as well as its spectral characteristics are described in the literature [C. Liu, Q. Ni. Method for synthesizing 4-diphenylamino-biaryl compounds by Suzuki cross coupling reaction in aqueous phase. // Patent CN 101948366 A, 2011; C. Liu, Q. Ni, J. Qiu. Very Fast, Ligand-Free and Aerobic Protocol for the Synthesis of 4-Aryl-Substituted Triphenylamine Derivatives. // European Journal of Organic Chemistry 2011, Issue 16, P. 3009-3015; C. Liu, Y. Wu, N. Han, J. Qiu. Efficient synthesis of 4-heteroaryl-substituted triphenylamine derivatives via a ligand-free Suzuki reaction. // Applied Organometallic Chemistry 2011, Vol. 25, Issue 12, P. 862-866; C. Liu, X. Rao, X. Song, J. Qiu, Z. Jin. Palladium-catalyzed ligand-free and aqueous Suzuki reaction for the construction of (hetero) aryl-substituted triphenylamine derivatives. // RSC Advances 2013, Vol. 3, Issue 2, P. 526-531; C. Liu, X. Song. Metal ligand-platinum complex and manufacture. // Patent CN 103145763 A, 2013; K. Hoffert, R. J. Durand, S. Gauthier, F. Robin-le Guen, S. Achelle. Synthesis and Photophysical Properties of a Series of Pyrazine-Based Push-Pull Chromophores. // European Journal of Organic Chemistry 2017, Issue 3, P. 523-529].

Information on the method of synthesis, physico-chemical properties and scope of 2- [5- (4-diphenylaminophenyl) thiopheni-2-yl] pyrazine (Ib) is not available in the scientific, technical and patent literature.

The closest in structure to compound Ia is compound 1 - 5- [4- (diphenylamino) phenyl] -2-pyrazinecarboxylic acid, and compound Ib is compound 2 - 5- {5- [4- (diphenylamino) phenyl] thiophene- 2-yl} -2-pyrazinecarboxylic acid, in the structure of which there is no additional carboxyl group [H. Aihara, T. Shono. Preparation of pyrazine carboxylic acid compounds useful for dye-sensitized solar cells. // Patent JP 2015140319 A, 2015].

There is data in the literature on the use of compounds 1 and 2 as a dye – sensitizer for color-sensitized solar cells [H. Aihara, T. Shono. Preparation of pyrazine carboxylic acid compounds useful for dye-sensitized solar cells. // Patent JP 2015140319 A, 2015].

Information on other properties and applications of monosubstituted pyrazines containing a triphenylamine substituent of the general formula (I) is absent.

A method for preparing compound (2) is described in the literature, which is based on the use of the Suzuki cross coupling reaction of 5- (5-bromothiophen-2-yl) -pyrazine-2-carboxylic acid (3) with 4- (diphenylamino pinacone ester ) phenylboronic acid (4) in 1,4-dioxane in the presence of tetrakis (tripheniphosphine) palladium (0) and potassium phosphate in the form of a 2M aqueous solution at 100 ° C for 24 h [H. Aihara, T. Shono. Preparation of pyrazine carboxylic acid compounds useful for dye-sensitized solar cells. // Patent JP 2015140319 A, 2015].

Compounds Ia and Ib were prepared in a similar manner using a microwave-promoted Suzuki cross coupling reaction of 2-chloropyrazine (5) [or 2- (5-bromothiophen-2-yl) pyrazine (6)] (1.0 mmol) and pinacone ester 4- (diphenylamino) phenylboronic acid (4) (1.2 mmol) in 1,4-dioxane at 160 ° C for 30 minutes.

A time of 30 minutes is enough for the reaction to take place; an increase in time does not significantly increase the yield of 2- (4-diphenylaminophenyl) pyrazine (Ia) [or 2- [5- (4-diphenylaminophenyl) thiophen-2-yl] pyrazine (Ib) ], while a decrease in time of less than 30 minutes leads to a decrease in the yield of product (I).

Isolation of product (I) is carried out by chromatographic separation on silica gel with an ethyl acetate-hexane ratio of 1: 4 in the eluent. An increase in this ratio in favor of hexane will lead to an unreasonable consumption of solvent, whereas with an increase in the proportion of ethyl acetate in the eluent, the target product of the general formula (I) is not selectively separated from by-products.

The analysis of intermediate and target compounds is carried out using NMR spectroscopy ( ¹ H and ¹³ C NMR spectra were measured on a Bruker AVANCE ^III -500 spectrometer (500 and 126 MHz) in a DMSO-d ₆ solution, internal TMS standard) and high resolution mass spectra registered on a Bruker maXis Impact HD spectrometer (electrospray ionization). Melting points are determined on Boetius combi tables.

Example 1

2-Chlorpyrazine (5) 115 mg (1.0 mmol) is mixed with 4- (diphenylamino) phenylboronic acid pinaconic ester (4) 446 mg (1.2 mmol), tetrakis (tripheniphosphine) palladium (0) 58 mg (0.05 mmol) and K ₃ PO ₄ 530 mg (2.5 mmol). The resulting mixture was dissolved in 15 ml of degassed 1,4-dioxane. The resulting mixture was irradiated with microwave at 160 ° C (250 W) for 30 minutes. After this, the solvent was distilled off on a rotary evaporator under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate-hexane, 1: 4). The result is 2- (4-diphenylaminophenyl) pyrazine (Ia) as a yellow powder. Yield 259 mg (80%).

Mp 74–76 ° C.

¹ H NMR spectrum (500 MHz, DMSO-d ₆ ) δ (ppm): 9.17 (d, J = 1.5 Hz, 1H), 8.65 (dd, J = 2.5, 1.5 Hz, 1H), 8.52 (d , J = 2.5 Hz, 1H), 8.07–8.04 (m, 2H), 7.39–7.34 (m, 4H), 7.16–7.10 (m, 6H), 7.05–7.01 (m, 2H).

¹³ C NMR spectrum (126 MHz, DMSO-d ₆ ) δ (ppm): 151.1, 148.9, 146.5, 144.1, 142.4, 141.4, 129.7, 128.8, 127.8, 124.9, 124.0, 121.6.

Found, m / z: 324.1502 [M + H] ⁺ . C ₂₂ H ₁₈ N ₃ . Calculated, m / z: 324.1495.

Example 2

2- (5-Bromothiophen-2-yl) pyrazine 241 mg (1.0 mmol) (6) is mixed with 4- (diphenylamino) phenylboronic acid pinacone ester (4) 446 mg (1.2 mmol), tetrakis (tripheniphosphine) palladium (0) 58 mg (0.05 mmol) and K ₃ PO ₄ 530 mg (2.5 mmol). The resulting mixture was dissolved in 15 ml of degassed 1,4-dioxane. The resulting mixture was irradiated with microwave at 160 ° C (250 W) for 30 minutes. After this, the solvent was distilled off on a rotary evaporator under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate-hexane, 1: 4). The result is 2- [5- (4-diphenylaminophenyl) thiophen-2-yl] pyrazine (Ib) as a yellow powder. Yield 251 mg (81%).

Mp 133–134 ° C.

¹ H NMR spectrum (500 MHz, DMSO-d ₆ ) δ (ppm): 9.24 (d, J = 1.5 Hz, 1H), 8.57 (dd, J = 2.6, 1.5 Hz, 1H), 8.48 (d , J = 2.6 Hz, 1H), 7.97 (d, J = 3.9 Hz, 1H), 7.67–7.62 (m, 2H), 7.51 (d, J = 3.9 Hz, 1H), 7.37–7.31 (m, 4H) , 7.13–7.06 (m, 6H), 7.01–6.97 (m, 2H).

¹³ C NMR spectrum (126 MHz, DMSO-d ₆ ) δ (ppm): 147.6, 147.4, 146.7, 146.5, 144.0, 142.4, 140.4, 139.2, 129.6, 128.0, 127.0, 126.6, 124.5, 124.1, 123.6 , 122.6.

Found, m / z: 406.1370 [M + H] ⁺ . C ₂₆ H ₂₀ N ₃ S. Calculated, m / z: 406.1372.

Information confirming the possibility of carrying out the invention.

Visual detection of nitroaromatic compounds using the claimed compound (I).

To visually detect nitroaromatic compounds using 2- (4-diphenylaminophenyl) pyrazine (Ia) and 2- [5- (4-diphenylaminophenyl) thiophen-2-yl] pyrazine (Ib), the interaction of the compound of general formula I with nitroaromatic compounds was studied (Table 1), which is carried out in a solution of dry dichloromethane in a sensor concentration of 5 × 10 ^-7 M.

As a comparison compound, N, N-diphenyl-4- [5- (pyrimidin-4-yl) thiophen-2-yl] aniline (II) is used

,

,

which has optical characteristics (maximum fluorescence excitation - Ex and maximum fluorescence emission - Em) close to compound I (Table 2) and for which it is described the use as a monomolecular optical sensor for detecting the presence of nitroaromatic compounds [E.V. Verbitskiy, A.A. Baranova, K.I. Lugovik, M.Z. Shafikov, K.O. Khokhlov, E.M. Cheprakova, G.L. Rusinov, O.N. Chupakhin, V.N. Charushin. Detection of nitroaromatic explosives by new D – π – A sensing fluorophores on the basis of the pyrimidine scaffold. // Analytical and Bioanalytical Chemistry, 2016, Vol. 408, Issue 15, P. 4093-4101; Verbitsky E.V., Cheprakova E.M., Baranova A.A., Khokhlov K.O., Rusinov G.L., Charushin V.N. The use of 4- (5-R-thiophen-2-yl) pyrimidine as a monomolecular optical sensor for the detection of nitroaromatic compounds. // RF patent 2616296 C1, Bulletin of inventions No. 11, 2017 dated 04/14/2017].

Table 1. List of nitroaromatic compounds that can be detected using a sensor based on compound I.

Fluorescence titration is carried out using solutions of nitroaromatic compounds listed in Table 1, in concentrations from 5 × 10 ^-7 M to 1 × 10 ^-3 M.

To assess the effectiveness of the proposed compound I determine the value of the Stern-Volmer constant (Stern-Volmer) - K _sv and the detection limits of nitroaromatic compounds (detection limit) - DT.

The Stern-Volmer constant is a quenching constant, it is also the association constant of the obtained complex of the proposed compound with a nitroaromatic compound, is expressed by the equation:

I ₀ / I = 1 + K _sv [Q],

where I ₀ and I - the fluorescence intensity before and after the addition of nitroaromatic compounds (quencher);

Q is the concentration of nitroaromatic compounds, mol / l;

K _sv - constant value, l / mol.

The detection limit of a nitroaromatic compound in an acetonitrile solution is determined and calculated in accordance with the following formulas:

where S _b is the standard deviation by measuring the intensity of the solutions of compound I or the comparison compound, in the absence of a nitroaromatic compound, more than 10 times;

x _i is the fluorescence intensity (in each case) for solutions of compound I or a comparison compound, in the absence of a nitroaromatic compound;

- средняя интенсивность флуоресценции растворов соединения I или соединения сравнения, в отсутствие нитроароматического соединения;

- the average fluorescence intensity of the solutions of compound I or the comparison compound, in the absence of a nitroaromatic compound;

S is a value characterizing the change in fluorescence intensity for solutions of compound I or a comparison compound, in the absence of a nitroaromatic compound and in the presence of a solution of a nitroaromatic compound with a maximum concentration.

ΔI is the difference in fluorescence intensity for solutions of compound I or a comparison compound in the absence of a nitroaromatic compound and in the presence of a solution of a nitroaromatic compound with a maximum concentration.

Δc is the difference in the concentrations of solutions of compound I or the comparison compound in the absence of a nitroaromatic compound and in the presence of a solution of a nitroaromatic compound with a maximum concentration.

The proposed compounds Ia and Ib are superior to Compound II both in terms of detection limit and in terms of the Stern-Volmer constant (Table 2).

Thus, the detection limit of 2,4,6-trinitrotoluene (TNT) when using compounds Ia and Ib as a sensor exceeds the corresponding detection limit for the comparison compound by 2 times. The value of the Stern-Volmer constants for the proposed compounds Ia and Ib also exceeds the corresponding values of the Stern-Volmer constants for the comparison compound in most cases by several tens of times. In addition, compounds Ia and Ib have a significantly larger range of detectable nitro compounds - 18 compounds (Table 3), while for Compound II, only 6 nitroaromatic compounds are described.

Thus, the results obtained for the proposed compounds of General formula (I) show high sensitivity and selectivity for the visual detection of a wide range of nitroaromatic compounds.

Table 2. The values of the fluorescence quenching constants (Stern-Volmer constants) and the detection limits of various nitroaromatic compounds for compound Ia, Ib and comparison compound N, N-diphenyl-4- [5- (pyrimidin-4-yl) thiophen-2- il] aniline (II).

The photophysical properties were measured for compounds Ia and Ib in dichloromethane, for the comparison compound N, N-diphenyl-4- [5- (pyrimidin-4-yl) thiophen-2-yl] aniline (II), the measurements were carried out in an acetonitrile solution.

Ex - Maximum excitation of fluorescence;

Em - Maximum fluorescence emission;

φ - Relative quantum output. A solution of quinine sulfate (φ = 0.55) in 0.1 N H ₂ SO _{4 was} used as a standard for measuring the relative quantum yield. The method of determining the relative quantum is performed according to the procedure described in the literature [AM Brouwer. Standards for photoluminescence quantum yield measurements in solution (IUPAC Technical Report). // Pure Appl. Chem. 2011, 83, 2213-2228].

Table 3. Values of the fluorescence quenching constants (Stern-Volmer constants) and the detection limits of various nitroaromatic compounds for compounds Ia and Ib.

Claims (3)

The use of 2-monosubstituted pyrazines containing triphenylamine Deputy, General formula (I)

as a monomolecular optical sensor for detecting nitroaromatic compounds.