CN110590750B - Preparation method and application of novel tetrazine imidazole ylide - Google Patents

Preparation method and application of novel tetrazine imidazole ylide Download PDF

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CN110590750B
CN110590750B CN201910913974.1A CN201910913974A CN110590750B CN 110590750 B CN110590750 B CN 110590750B CN 201910913974 A CN201910913974 A CN 201910913974A CN 110590750 B CN110590750 B CN 110590750B
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王健春
耿延雪
孙伟君
李聪
宗颖
涂顺棋
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Abstract

The invention relates to a preparation method and application of a novel tetrazine imidazole ylide, in particular to a preparation method and application of a novel 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide. The synthesis method is that 3, 6-dichloro-1, 2,4,5-tetrazine reacts with 1 ', 2', 4 ', 5' -substituted imidazole to generate intramolecular salt with a plurality of functional groups such as carbonyl, carbon-carbon double bond, nitrogen-nitrogen double bond, carbon-nitrogen double bond and the like, namely nitrogen ylide. The synthesis method has the characteristics of mild reaction conditions, simple operation, easy product separation, no need of adding a catalyst and the like, and has the advantages that the substituent of the imidazole 1 ', 2', 4 ', 5' -substitution position in the 1 ', 2', 4 ', 5' -substitution-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide can be changed, and the like. The compound is insensitive to water and oxygen and is stable at room temperature. The derivatives can be used for the aspects of ion and small molecule recognition and the like.

Description

Preparation method and application of novel tetrazine imidazole ylide
Technical Field
The invention belongs to the field of fine chemical product synthesis, and particularly relates to a preparation method and application of a novel tetrazine imidazole ylide, in particular to a preparation method and application of a novel 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide.
Background
The synthesis of tetrazine has been in the history for a century, and the derivative thereof has wide application in the fields of organic synthesis, energetic materials, life sciences, pesticides, ion recognition and the like. One of the most studied isomers is 1,2,4,5-tetrazine, which is an electron deficient aromatic system possessing four nitrogen atoms (formula III). Wherein, R, R' can be H, halogen, alkyl, alkoxy, alkyl mercapto, alkyl amino, alkynyl, aryl, heteroaryl, etc. Because of the strong electron-withdrawing effect of nitrogen atoms in the conjugated rings, two carbon atoms at the 3 and 6 positions in the tetrazine rings lack electrons and are easily attacked by nucleophilic reagents.
Figure BDA0002215531830000011
The earliest tetrazine syntheses were the Pinner synthesis (Gilles, c.; Pierre, a., s-Tetrazines as building Blocks for New Functional Molecules and molecular materials, chem. rev.2010,110,3299-3314.), by reaction of hydrazine with nitrile derivatives to form 1, 2-dihydrotetrazines, followed by oxidation to form the Tetrazines. The method has narrow substrate range, is only suitable for synthesizing aromatic tetrazine, and has very low yield of fatty tetrazine.
Figure BDA0002215531830000021
Although the synthesis of tetrazines is improved and even with the addition of sulfur as a catalyst to accelerate the reaction and thus increase the yield (Abdel-Rahman, M.O.; Kira, M.A.; Tolba, M.N., A direct synthesis of hydrotetrazines Tetrahedron Lett 1968,35, 3871-. Until 1998, the work of the Hiskey group opened a new route to the preparation of a large number of symmetric and asymmetric tetrazines. The process can be carried out from very cheap and readily available raw materials: guanidine, hydrazine and 2, 4-pentanedione were reacted to give Bis (3, 5-dimethylpyrazole) -1,2,4,5-tetrazine (BDT) (Wang, B.Z.; Lai, W.P.; Liu, Q.; Lian, P.; Xue, Y.Q., Synthesis, Characteriza and Quantum Chemistry Study on 3,6-Bis (1H-1,2,3,4-tetrazol-5-yl-amino) -1,2,4,5-tetrazine. Chinese J.org. chem.2008,28(3), 422-427.). The pyrazolyl group of BDT acts as a better leaving group, allowing the introduction of a variety of heterocyclic substituents. Thereafter, Hiskey et al have discovered that if bis (hydrazino) -s-tetrazine is treated with chlorine, it can be converted to a variety of nucleophiles (e.g., NH)3Morpholine, pyrrolidine, hydrazine, alcohols, thiols, carbanions, etc.), thereby opening up a method for synthesizing various symmetric and asymmetric tetrazines (Chavez, d.e.; hiskey, m.a.,1,2,4,5-tetrazine based cementitious materials.j.energ.mater.1999,17(4),357-377.Chavez, d.e.; hiskey, m.a.; gilardi, R.D.,3, 3' -Azobis (6-amino-1,2,4,5-tetrazine) A Novel High-Nitrogen Energetic Material, Angew.chem., int.Ed.2000,39(10), 1791-1793).
Figure BDA0002215531830000031
The synthesis of tetrazines has been greatly developed in recent years. In 2012, the subject group of Neal k. Devaraj found that 1,2,4,5-tetrazine (Yang, j.; Karver, m.r.; Li, w.; Sahu, s.; Devaraj, n.k., Metal-catalyzed one-potyntheses of tetrazines direct free aliphatic nitriles and hydrazines. angelchem Int Ed Engl 2012,51(21), 5222) could be synthesized in one pot starting from nitriles and using Metal salts (e.g., nickel and zinc triflate, etc.) as catalysts. In 2018, the Pierre Audebert project group discovered a simple, efficient and Metal-Free method for synthesizing 3-Monosubstituted asymmetric 1,2,4,5-Tetrazines (Qu, Y.; Sauvage, F.X.; Clavier, G.; Miomandre, F.; Audebert, P., Metal-Free Synthetic Approach to 3-monosubustulated asymmetric 1,2,4,5-Tetrazines Useful for bioirthololreaction, Angel Chem Int Engl 2018,57(37), 12057-12061.). They found that methylene chloride is a new formamidine replacement reagent. It can exhibit excellent reactivity and selectivity during the formation of the tetrazine ring, resulting in mild synthesis conditions and high yield. In 2019, Haying Wu project group discovered a new organic catalytic method for synthesizing asymmetric tetrazine (Mao, W.; Shi, W.; Li, J.; Su, D.; Wang, X.; Zhang, L.; Pan, L.; Wu, X.; Wu H.; organic and Scalable Syntheses of unmesymmetrical 1,2,4,5-Tetrazines byThiol-containment promoters, Angew Chem Int Engl 2019,58(4), 1106-1109.). They have found that tetrazines can be readily prepared in the presence of thiol-containing organic catalysts such as 3-mercaptopropionic acid and glutathione.
Tetrazinone free radicals (verazyl radicals) are an important class of free radicals (formula IV), and their derivatives are all stable in air (Ratera, I.; Veciana, J., Playing with organic building blocks for functional molecular materials. chem. Soc Rev 2012,41(1), 303-349.). The compounds have wide application prospects in the fields of biochemistry, catalysis, organic magnetic materials, molecular devices and the like.
Figure BDA0002215531830000041
The synthesis of such Organic radicals is subject to a multi-step reaction, the key step of which is the condensation cyclization with an aldehyde followed by oxidation to give a radical (Train, c.; Norel, l.; Baumgarten, m., Organic radicals, electrochemical processes oriented mechanical molecule-based materials, co. d. chem. rev.2009,253(19-20), 2342-.
Figure BDA0002215531830000042
At present, tetrazinone compounds with imidazole attached are very rare, and only one tetrazinone derivative with quinoid structure is prepared by reacting azacarbene with BDT (Bostai, B.; Novak, Z.; Benyei, A.C.; Kotschy, A., Quinoidaltetrazines: formation of a fasconing composite class, org Lett 2007,9(17), 3437-. Furthermore, since the imidazole ring is bonded to the tetrazine ring at the 2-position carbon atom, no compound in which imidazole is bonded to tetrazine ketone at the nitrogen atom has been reported.
Figure BDA0002215531830000051
The structure of the compound has distinct characteristics. 1. The tetrazone ketone is connected with nitrogen atoms on imidazole, and X-ray diffraction analysis proves that the dihedral angle of imidazole ring and the tetrazone ketone is 0 degree, and the two rings are in the same plane and are completely conjugated; 2. the compound belongs to organic inner salt, namely nitrogen atoms connected with imidazole and tetrazinone have positive charges, and the No. 2 carbon of the imidazole has negative charges, namely nitrogen ylide; 3. one of the compounds is 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is p-B4O7 2-The ions have high selectivity; 4. the synthesis method of the compound only needs one-step reaction to obtain the product.
Disclosure of Invention
The invention aims to provide a 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazin-3-ketone) -1H imidazole ylide derivative. The 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide with the structural general formula I has double bonds of nitrogen 1 and nitrogen 2 in the tetrazine ring, carbon 6 and nitrogen 3 'in the imidazole ring are connected by the double bonds, nitrogen 4 and nitrogen 5 are double bonds, carbon 3 has carbonyl, the imidazole ring carbon 2' and nitrogen 3 'are in the ylide form, so that the nitrogen 3' in the imidazole ring exists in the 4-valence state and has a positive charge, carbon 2 has a negative charge, namely the nitrogen ylide structure, and carbon 4 'and carbon 5' are double bonds.
Figure BDA0002215531830000061
Another object of the present invention is to provide a process for preparing 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide.
The invention provides a method for preparing a 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide derivative shown as a structural general formula I, which comprises the following steps: in an inert atmosphere, 3, 6-dichloro-1, 2,4,5-tetrazine and 1,2,4, 5-substituted imidazole are subjected to substitution reaction in an organic solvent in the absence of a catalyst, and after the reaction is finished, the 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide derivative with the structural general formula of the formula I is obtained.
In the structural general formula of the formula I, R1Any one selected from the following groups: methyl, ethyl, propyl, butyl, hexyl, isopropyl, vinyl, allyl, acetonitrile, trityl, benzyl, 3-aminopropyl, 2-aminoethyl, aminomethyl, chloromethyl, hydroxymethyl, and the like. R2Any one selected from the following groups: hydrogen, methyl, ethyl, isopropyl, butyl, vinyl, allyl, acetonitrile, aminomethyl, hydroxymethyl. R3Any one selected from the following groups: hydrogen, methyl, ethyl, propyl, isopropyl, phenyl, acetonitrile, hydroxymethyl. R4Any one selected from the following groups: hydrogen, methyl, ethyl, amino, hydroxymethyl and nitro.
The preparation method of the 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide can be carried out without a catalyst.
The preparation method of the 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide comprises the step of preparing the 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide by using tetrahydrofuran, water or dichloromethane as an organic solvent.
The preparation method of the 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide comprises the following steps of: alkyl imidazole, alkenyl imidazole, aryl imidazole, amino imidazole, hydroxyalkyl imidazole, haloalkyl imidazole, nitro imidazole.
The preparation method of the 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is characterized in that the reaction temperature is 5-50 ℃, preferably 25 ℃; the reaction time is 1 to 4hr, preferably 1 to 2 hr.
Another object of the present invention is to provide the use of 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide. The derivative 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide (formula II) has the characteristic of identifying borate ions.
Figure BDA0002215531830000071
The invention has the beneficial effects that: the synthesis method has the advantages of mild reaction conditions, simple operation, easy product separation, no need of adding a catalyst and the like, and the alkane at the 1 ', 2', 4 ', 5' -substitution position in the 1 ', 2', 4 ', 5' -substitution-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide can be changed and the like, and the compound is stable at room temperature. The derivatives can be used in the aspects of ion and small molecule recognition.
Drawings
FIG. 1-1 shows the compound 1' -methyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide compound (formula I) obtained in example 1 of the present invention1H-NMR data chart.
FIG. 1-2 shows the ylidation of 1' -methyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole, which is the compound obtained in example 1 of the present inventionOf the formula I13C-NMR data chart.
FIGS. 1 to 3 are HRMS data of 1' -methyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide compound (formula I) obtained in example 1 of the present invention.
FIGS. 1 to 4 are crystal structures of 1' -methyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide compound (formula I) obtained in example 1 of the present invention.
FIG. 2-1 shows the synthesis of 1' -ethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide compound obtained in example 3 of the present invention1H-NMR data chart.
FIG. 2-2 shows the reaction product of 1' -ethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide compound obtained in example 3 of the present invention13C-NMR data chart.
FIGS. 2 to 3 are graphs of HRMS data of 1' -ethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide compound obtained in example 3 of the present invention.
FIG. 3-1 is a drawing showing the results of example 2 of the present invention for the ylide compound of formula 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole (formula II)1H-NMR data chart.
FIG. 3-2 shows the compound of formula 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide (formula II) obtained in example 2 of the present invention13C-NMR data chart.
FIGS. 3-3 are graphs of HRMS data for the ylide compound of formula 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole (formula II) obtained in example 2 of the present invention.
FIGS. 3 to 4 are UV-VIS absorption spectra of the compound of formula 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide (formula II) obtained in example 2 of the present invention for different anions.
FIGS. 3 to 5 are graphs of the color of the ylide compound of formula 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole (formula II) obtained in example 2 according to the invention after interaction with different anions.
FIGS. 3 to 6 are UV-VIS absorption spectra of 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide compounds of formula (formula II) obtained in example 2 of the present invention after exposure to borate ions of various concentrations.
FIGS. 3-7 are color charts of the ylide compound of formula 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole (formula II) obtained in example 2 of the present invention after exposure to different concentrations of borate ion.
FIGS. 3 to 8 are graphs showing the measurement of the minimum detection limit of the ylide compound of the formula 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole (formula II) obtained in example 2 of the present invention with borate ion.
Detailed Description
The present invention will be further described with reference to the following examples, which are intended to be illustrative only and not to be limiting of the invention in any way, and any person skilled in the art can modify the present invention by applying the teachings disclosed above and applying them to equivalent embodiments with equivalent modifications. Any simple modification or equivalent changes made to the following embodiments according to the technical essence of the present invention, without departing from the technical spirit of the present invention, fall within the scope of the present invention.
Example 1
Under the protection of nitrogen, dissolving 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine in 20mL of tetrahydrofuran solution, stirring at room temperature for 10min, dropwise adding 0.3mL (1mmol) of 1-methylimidazole to precipitate orange-red solid, stirring for 2h, filtering, washing with tetrahydrofuran, and purifying by column chromatography, wherein a developing agent is V (ethyl acetate): and (3) collecting a second layer of orange-red spectral band, and removing the solvent by rotary evaporation to obtain an orange-red powdery solid, wherein the yield of the target product 1' -methyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 78%. FIGS. 1-1, 1-2, 1-3 and 1-4 are the structures of hydrogen, carbon, high resolution mass and X-ray single crystal of the product prepared in this example, respectively, and it can be seen that the structure of the compound is correct.
Example 2
Under the protection of nitrogen, dissolving 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine in 20mL of tetrahydrofuran solution, stirring at room temperature for 10min, dropwise adding 120mg (1.25mmol) of 1, 2-dimethylimidazole in 5mL of tetrahydrofuran, separating out orange-red solid, stirring for 2h, performing suction filtration, washing with tetrahydrofuran, and purifying by column chromatography, wherein a developing agent is V (ethyl acetate): and (3) collecting a second layer of orange-red spectral band, and removing the solvent by rotary evaporation to obtain an orange-red powdery solid, wherein the yield of the target product 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 75%. FIG. 3-1, FIG. 3-2, and FIG. 3-3 are the NMR spectra, carbon spectra, and high-resolution mass spectra of the product prepared in this example, respectively, which show that the compound has a correct structure.
Example 3
Under the protection of nitrogen, 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine is dissolved in 20mL of tetrahydrofuran solution, stirred for 10min at room temperature, 0.15mL (1.5mmol) of 1-ethylimidazole is added dropwise to precipitate orange-red solid, stirred for 2h and then filtered, washed with tetrahydrofuran and purified by column chromatography, and a developing agent is V (ethyl acetate): and (3) collecting a second layer of orange-red spectral band, and removing the solvent by rotary evaporation to obtain an orange-red powdery solid, wherein the yield of the target product 1' -ethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 70%. FIG. 2-1, FIG. 2-2, and FIG. 2-3 show the NMR spectra, carbon spectra, and high-resolution mass spectra of the product obtained in this example, respectively, which show that the compound has a correct structure.
Example 4
Under the protection of nitrogen, 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine is dissolved in 20mL of tetrahydrofuran solution, stirred at room temperature for 10min, 0.16mL (1.5mmol) of 1-propylimidazole is added dropwise to precipitate orange-red solid, stirred for 2h, filtered by suction, washed with tetrahydrofuran, and purified by column chromatography, wherein a developing agent is V (ethyl acetate): and (3) collecting a second layer of orange red spectral band, and removing the solvent by rotary evaporation to obtain an orange red powdery solid, wherein the yield of the target product 1' -propyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 72%.
Example 5
Under the protection of nitrogen, 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine is dissolved in 20mL of tetrahydrofuran solution, stirred at room temperature for 10min, 0.2mL (1.5mmol) of 1-butylimidazole is added dropwise to precipitate a mauve solid, stirred for 2h and then filtered, washed with tetrahydrofuran, and purified by column chromatography, wherein a developing solvent is V (ethyl acetate): and (3) collecting a second layer of brick red spectral band, and removing the solvent by rotary evaporation to obtain a purple powdery solid, wherein the yield of the target product 1' -butyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 68%.
Example 6
Under the protection of nitrogen, dissolving 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine in 20mL of tetrahydrofuran solution, stirring at room temperature for 10min, dropwise adding 0.24mL (2mmol) of 1-vinyl imidazole to precipitate a mauve solid, stirring for 2h, filtering, washing with tetrahydrofuran, and purifying by column chromatography with a developing solvent V (ethyl acetate): and (3) collecting a second layer of brick red spectral band, and removing the solvent by rotary evaporation to obtain a purple powdery solid, wherein the yield of the target product 1' -vinyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 66%.
Example 7
Under the protection of nitrogen, 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine is dissolved in 20mL of tetrahydrofuran solution, stirred at room temperature for 10min, 0.16mL (1.5mmol) of 1-allylimidazole is added dropwise to precipitate a mauve solid, stirred for 2h and then filtered, washed with tetrahydrofuran, and purified by column chromatography, wherein a developing agent is V (ethyl acetate): and (3) collecting a second layer of brick red color band, and removing the solvent by rotary evaporation to obtain a purple red powdery solid, wherein the yield of the target product 1' -allyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 66%.
Example 8
Under the protection of nitrogen, dissolving 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine in 20mL of tetrahydrofuran solution, stirring at room temperature for 10min, dropwise adding (1-imidazolyl) acetonitrile 214mg (2mmol) in 5mL of tetrahydrofuran solvent to precipitate a mauve solid, stirring for 2h, suction filtering, washing with tetrahydrofuran, and purifying by column chromatography, wherein a developing solvent is V (ethyl acetate): and (3) collecting a second layer of brick red spectral band, and removing the solvent by rotary evaporation to obtain a purple powdery solid, wherein the yield of the target product 1' -acetonitrile-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 64%.
Example 9
Under the protection of nitrogen, dissolving 150mg (1mmol) of 3, 6-dichloro-1, 2,4,5-tetrazine in 20mL of tetrahydrofuran solution, stirring at room temperature for 10min, dropwise adding 1-benzyl imidazole 237mg (1.5mmol), dissolving in 5mL of tetrahydrofuran solvent, precipitating a mauve solid, stirring for 2h, performing suction filtration, washing with tetrahydrofuran, and purifying by column chromatography, wherein a developing agent is V (ethyl acetate): and (3) collecting a second layer of brick red spectral band, and removing the solvent by rotary evaporation to obtain a purple powdery solid, wherein the yield of the target product 1' -benzyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is 62%.
Example 10
One of the uses of the 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylides of the invention is described below in connection with the specific examples for B4O7 2-Identification of (1).
Preparing a sample solution of the parent formula II1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide, namely dissolving 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide shown in the formula II in a beaker by using dimethyl sulfoxide (DMSO), transferring the sample solution into a 100mL volumetric flask, and fixing the volume by using the DMSO to prepare the sample solution with the concentration of 1 × 10-3mol/L of sample solution.
Preparation of various ionic solutions: weighing the various anions (F) in sequence-、Cl-、Br-、I-、OH-、CO3 2-、HCO3 -、SO4 2-、HSO4 -、SO3 2-、HSO3 -、NO3 -、NO2 -、PO4 3-、HPO4 2-、H2PO4 -、CH3COO-、B4O7 3-) Dissolving salt in distilled water in a beaker, transferring into a 50mL volumetric flask to constant volume, and preparing into a solution with a concentration of 1 × 10-2mol/L of ionic solution.
Measuring the UV-visible spectrum of the sample with different anions by measuring 2ml of each of the ylide solution of formula II1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H-imidazole and the anion solution in a 10m cuvette, metering the volume with DMSO to obtain a concentration of 2 × 10 in the cuvette of formula II1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H-imidazole-4mol/L of various ionsThe concentration is 2 × 10-3mol/L。
As shown in FIG. 3-4, the maximum absorption peak of 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide in the visible light region is 372.4nm, and B is added4O7 2-The latter maximum absorption peak was shifted to 441.8 nm. The results are shown in FIGS. 3-5, where the color of the solution in the cuvette with borate ions added changed from pink to yellow. "naked eye" recognition can be performed, blank in fig. 3-5 indicating null, as can other figures.
The visible-ultraviolet spectra of the samples were measured for their interaction with borate ions at different concentrations:
prepared as DMSO solution of formula II1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide with concentration of 1 × 10-3Respectively preparing the concentrations of 0 and 2 × 10-4、4×10-4、6×10-4、8×10-4、1.0×10-3、1.2×10-3、1.4×10-3、1.6×10-3、1.8×10-3、2.0×10-3、2.2×10-3、2.4×10-3A mol/L aqueous solution of borate ions.
Measuring ultraviolet spectrum, respectively measuring 2ml of borate solution with different concentrations and the ylide solution of formula II1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole, adding into 10ml colorimetric tube, adding DMSO to constant volume, and measuring the volume to obtain the final solution of formula II1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole with concentration of 2 × 10-4And the concentration of borate ion is 0, 4 × 10-5、8×10-5、1.2×10-4、1.6×10-4、2×10-4、2.4×10-4、2.8×10-4、3.2×10-4、3.6×10-4、4×10-4、4.4×10-4、4.8×10-4A series of solutions of mol/L.
As shown in FIGS. 3 to 6, the UV-Vis spectrum absorption peak was gradually increased at 441.8nm with the increase of the borate ion concentration. The color change is as in figures 3-7.
1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide borate ion shown in formula IIThe identification experiment shows that 1 ', 2' -dimethyl-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide is 2 × 10-4The dilute solution of mol/L can identify borate ions, has obvious color change in a visible light region, changes from pink to brown, and can be identified by naked eyes. The lowest detection limit of the method for borate ions was 1.4685mol/L (FIGS. 3-8).

Claims (9)

1. A preparation method of 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide is characterized by comprising the following steps: in an inert environment, 3, 6-dichloro-1, 2,4,5-tetrazine and different substituted imidazoles are subjected to substitution reaction in an organic solvent without adding a catalyst to obtain a 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide derivative with a structural general formula I,
Figure FDA0002652062590000011
in the structural general formula of the formula I, R1Any one selected from the following groups: methyl, ethyl, propyl, butyl, hexyl, isopropyl, vinyl, allyl, acetonitrile, trityl, benzyl, 3-aminopropyl, 2-aminoethyl, aminomethyl, chloromethyl, hydroxymethyl, and the like. R2Any one selected from the following groups: hydrogen, methyl, ethyl, isopropyl, butyl, vinyl, allyl, acetonitrile, aminomethyl, hydroxymethyl. R3Any one selected from the following groups: hydrogen, methyl, ethyl, propyl, isopropyl, phenyl, acetonitrile, hydroxymethyl. R4Any one selected from the following groups: hydrogen, methyl, ethyl, amino, hydroxymethyl and nitro.
2. The method for preparing 1,2,4, 5-substituted-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide according to claim 1, wherein: the tetrazine ring and the imidazole ring of the 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide with the structural general formula of the formula I are connected by a carbon-nitrogen double bond, the dihedral angle of the two rings is zero degree, and the whole molecule is of a plane conjugated structure. The nitrogen 3' in the imidazole ring exists in a 4-valence state and carries a positive charge, and the carbon 2 carries a negative charge, namely, a nitrogen ylide structure.
3. The method for preparing 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide according to claim 1, wherein: the solvent is tetrahydrofuran or dichloromethane.
4. The method for preparing 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide according to claim 1, wherein: the reaction temperature is 5-50 ℃, and the reaction time is 1-4 h.
5. The method for preparing 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide according to claim 1, wherein: the reaction temperature is 25 ℃, and the reaction time is 1-2 h.
6. The method for preparing 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide according to claim 1, wherein: the reaction molar ratio of the 3, 6-dichloro-1, 2,4,5-tetrazine to the 1 ', 2', 4 ', 5' -substituted imidazole is 1: 1-1: 2.
7. Use of the 1 ', 2', 4 ', 5' -substituted-6- (1,2,4, 5-tetrazin-3-one) -1H imidazole ylide derivative according to claim 1 for identifying borate ions in a mixed solvent, characterized in that: the derivative is 1, 2-dimethyl-6- (1,2,4, 5-tetrazine-3-ketone) -1H imidazole ylide, and the structural formula is shown as a formula II.
Figure FDA0002652062590000021
8. Use according to claim 7, characterized in that: the solvent is dimethyl sulfoxide and water, and/or the detection temperature is room temperature (24-25 ℃), and the response time is within 0.5 second.
9. Use according to claim 7, characterized in that: the concentration of formula II required to detect different concentrations of borate is fixed, and the greater the borate concentration, the more obvious the change in color from purple to pale yellow.
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