CN112480071B - Isolongifolane ratio type fluorescent probe for detecting hydrazine and preparation method thereof - Google Patents
Isolongifolane ratio type fluorescent probe for detecting hydrazine and preparation method thereof Download PDFInfo
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention discloses an isolongifolane ratio type fluorescent probe for detecting hydrazine and a preparation method and application thereof. The fluorescent probe is as follows: 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzoquinazolin-4-yl) pyridine bromide. The invention uses 6,6,10, 10-tetramethyl-4- (pyridine-4-yl) -6,7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzoquinazoline-2-amine as a raw material to carry out quaternization reaction with 4- (bromomethyl) phenol acetate to obtain 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzoquinazoline-4-yl) pyridine bromide. The compound can specifically perform hydrolysis reaction with hydrazine, and the fluorescence of the solution changes from orange to bright blue under the irradiation of 365nm ultraviolet light, so that the compound can be used as a ratiometric fluorescent probe for detecting hydrazine, and the detection limit reaches 4.8 multiplied by 10‑8And M, the response time is less than 40s, so that the method has a good application prospect.
Description
Technical Field
The invention belongs to the technical field of fine organic synthesis, and relates to an isolongifolane ratio type fluorescent probe for detecting hydrazine and a preparation method thereof.
Background
Hydrazine is an important chemical reagent, can be used as a strong reducing agent and high-activity alkali, and is widely applied to the fields of medicines, textiles, catalysts, pesticides, aviation and the like. Meanwhile, hydrazine is a highly toxic chemical, and can be absorbed by human body through skin, oral cavity, nasal cavity and other ways, thereby causing damage to kidney, lung, liver and central nervous system. Therefore, it is very important to develop an assay method capable of detecting hydrazine sensitively and efficiently.
Compared with the traditional detection method, the fluorescent probe gradually becomes an important analysis and detection means due to the advantages of good selectivity, high sensitivity, simple and convenient operation, low cost, rapid response, real-time monitoring and the like. A novel ratiometric fluorescent probe for detecting hydrazine is synthesized by using 6,6,10, 10-tetramethyl-4- (pyridine-4-yl) -6,7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazoline-2-amine and 4- (bromomethyl) phenol acetate as raw materials, and related reports are not reported temporarily.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide an isolongifolane ratio type fluorescent probe for detecting hydrazine, which can meet the use requirement. The invention aims to solve another technical problem and provides a preparation method of 1- (4-acetoxy benzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
an isolongifolane ratio type fluorescent probe for detecting hydrazine is 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide, and the structural formula of the probe is as follows:
the preparation method of the isolongifolane ratio type fluorescent probe for detecting hydrazine comprises the following steps: 6,6,10, 10-tetramethyl-4- (pyridin-4-yl) -6,7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-2-amine is quaternized with 4- (bromomethyl) phenol acetate to give 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide; the reaction formula is as follows:
the preparation method of the isolongifolane ratio type fluorescent probe for detecting hydrazine comprises the following steps of carrying out quaternization reaction on 6,6,10, 10-tetramethyl-4- (pyridine-4-yl) -6,7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenz [ H ] quinazoline-2-amine and 4- (bromomethyl) phenol acetate in acetonitrile to obtain 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10 alpha-hexahydro-5H-6 alpha, 9-methanobenz [ H ] quinazolin-4-yl) pyridine bromide, wherein the specific preparation method comprises the following steps:
(1) sequentially adding 0.12mol of 6,6,10, 10-tetramethyl-4- (pyridine-4-yl) -6,7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazoline-2-amine, 0.12-0.20 mol of 4- (bromomethyl) phenol acetate and 0.5-1.0L of anhydrous acetonitrile into a three-neck flask with a stirrer, and carrying out reflux reaction at 80-90 ℃ for 10-12H under the protection of nitrogen;
(2) distilling the reaction liquid to recover the solvent to obtain a crude product of 1- (4-acetoxy benzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide;
(3) the crude product of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide is chromatographed on silica gel chromatography column (dichloromethane: methanol ═ 15:1) and recrystallized from methanol to obtain 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide as light yellow powder.
The 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide is applied to the detection of hydrazine.
The 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide is applied to the preparation of isolongifolane ratio type fluorescent probes.
The 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide is applied to the detection of hydrazine as an isolongifolane ratio type fluorescent probe.
Has the advantages that: compared with the prior art, the invention utilizes 6,6,10, 10-tetramethyl-4- (pyridine-4-yl) -6,7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ]]Quinazoline-2-amine as raw material to prepare novel 1- (4-acetoxy benzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ]]Quinazoline-4-yl) pyridine bromide can specifically identify hydrazine in a solution, the fluorescence of the solution changes from orange to bright blue under the irradiation of 365nm ultraviolet light, and the ratiometric fluorescent probe for detecting the hydrazine has the advantages of simple synthesis method, wide raw material source, good selectivity, high sensitivity, high response speed (the response time is less than 40s) and detection limit reaching 4.8 multiplied by 10-8M and the like, and has good application value.
Drawings
FIG. 1 is a graph of the fluorescence spectrum of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide with different concentrations of hydrazine;
FIG. 2 is a graph of the fluorescence spectra of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide with different metal ions, anions, amino acids and amines;
FIG. 3 is a graph of the fluorescence spectra of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide reacted with hydrazine at various times.
Detailed Description
The present invention will be further described with reference to the following specific examples.
Example 1
Preparation of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide, reaction formula:
the specific process is as follows:
1.2mmol of 6,6,10, 10-tetramethyl-4- (pyridin-4-yl) -6,7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ]]Quinazoline-2-amine, 1.6mmol 4- (bromomethyl) phenol acetate and 18mL anhydrous acetonitrile are put into a three-neck flask which is sequentially provided with a stirrer and are refluxed for reaction for 11 hours at 85 ℃ under the protection of nitrogen. Distilling the reaction liquid to recover the solvent to obtain the 1- (4-acetoxy benzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ]]The crude product of quinazoline-4-yl) pyridine bromide is subjected to silica gel chromatography (dichloromethane: methanol 15:1) and methanol recrystallization to obtain light yellow powder 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] of 1- (4-acetoxybenzyl) -4]Quinazolin-4-yl) pyridine bromide. The yield was 27.3%, the purity was 99.6%, and the melting point was 187.2-187.7 ℃.1H NMR(400MHz,DMSO-d6)δ:9.29(d,J＝4Hz,2H),8.36(d,J＝4Hz,2H),7.66(d,J＝4Hz,2H),7.45(d,J＝4Hz,1H),7.25(d,J＝8Hz,2H),6.84(d,J＝8Hz,1H),5.91(s,2H),2.90-2.94(m,1H),2.27(s,3H),2.24(s,1H),1.99-2.02(m,1H),1.80(d,J＝8Hz,2H),1.73(d,J＝4Hz,1H),1.60-1.64(m,1H),1.48-1.52(m,1H),1.33(s,3H),1.19-1.23(m,2H),0.95(s,3H),0.75(s,3H),0.60(s,3H)；13C NMR(100MHz,CDCl3)δ:169.44,159.60,153.99,151.72,144.88,131.50,130.59,128.42,128.23,122.83,121.64,116.98,62.97,58,56.48,57.47,55.31,50.54,48.06,47.25,44.83,44.65,38.86,37.27,32.81,29.85,28.33,26.00,25.29,24.75,22.91,22.10；HRMS(m/z):[M-Br]+calcd for C31H37N4O2,497.2911；found,497.2916。
Example 2
1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ]]Quinazoline-4-yl) pyridine bromide is dissolved in PBS buffer solution to prepare 1 × 10-5M solution, hydrazine is dissolved in PBS buffer solution to make the concentration 0, 0.5X 10-5,1×10-5,1.5×10-5,2×10-5,2.5×10-5,3×10-5,3.5×10-5,4×10-5,4.5×10-5,5×10-5,6×10-5,7×10-5,8×10-5,9×10-5,1×10-4A solution of M. Hydrazine p-1- (4-acetoxy benzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] with different concentrations is measured on a fluorescence spectrophotometer by adopting a fluorescence spectrum titration method]Quinazolin-4-yl) pyridine bromide, as shown in FIG. 1. The results show that the fluorescence intensity of the probe at 595nm gradually decreases and the fluorescence intensity at 447nm gradually increases with increasing hydrazine concentration in the solution. Furthermore, according to the formula LOD-3 σbiM, combined with experimentally obtained data (. sigma.)bi＝1.29×10-9M, M ═ 0.0798) was calculated to give a hydrazine detection Limit (LOD) of 4.8 × 10 for this probe-8And M. Thus, the compound can be used as a ratiometric fluorescent probe for sensitively detecting hydrazine.
Example 3
1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ]]Quinazoline-4-yl) pyridine bromide is dissolved in PBS buffer solution to prepare 1 × 10-5M solution, different metal ions, anions, amino acids and amines are dissolved in PBS buffer solution to prepare 1 in the same way10-4A solution of M. Measuring different metal ions, anions, amino acids and amine pair 1- (4-acetoxy benzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] H on a fluorescence spectrophotometer by adopting a fluorescence spectrum titration method]Quinazolin-4-yl) pyridine bromide, as shown in FIG. 2. The results show that the addition of hydrazine can eliminate orange fluorescence of the solution and enhance blue fluorescence, while the addition of metal ions (Ag)+,Mg2+,Pb2+,Zn2+,Al3+,Hg2+,Na+,Ca2+,Fe3+,Fe2+,Ni2+,Cd2+) An anion (F)-,Br-,I-,NO3 -,CO3 2-,HCO3 -,SO4 2-,SO3 2-,ACO-,PO4 3-,H2PO4 -,SCN-,HS-) The fluorescence spectrum of the solution does not change significantly according to comparative observation of amino acids (alanine, arginine, glutamic acid, valine, cysteine, homocysteine, lysine, tryptophan, serine, histidine, leucine, glutathione) and other amines (ammonia, methylamine, laurylamine, ethylenediamine, hydroxylamine, diisopropylethylamine, triethylamine, urea, thiourea, piperidine, n-butylamine, aniline). Thus, the compound can be used as a fluorescent probe for specifically recognizing hydrazine.
Example 4
1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ]]Quinazoline-4-yl) pyridine bromide is dissolved in PBS buffer solution to prepare 1 × 10-5M, then adding hydrazine to the solution at a concentration of 1X 10-4M in PBS buffer. Measuring 1- (4-acetoxy benzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] by a fluorescence spectrum titration method on a fluorescence spectrophotometer]Quinazolin-4-yl) pyridine bromide and hydrazine in the presence of 0,15,30,45,60,75,90,105,120,135,150,165,180,200,225,250,275,300,350,400,450s fluorescenceLight emission spectrum, as shown in FIG. 3. The results showed that the fluorescence intensity ratio value (F) of the probe was increased with the reaction time after hydrazine was added to the probe solution447nm/F595nm) Rises rapidly and reaches a plateau within 40 s. Thus, the compound can be used as a ratiometric fluorescent probe for rapidly detecting hydrazine.
Claims (6)
1. An isolongifolane ratio type fluorescent probe for detecting hydrazine is characterized in that the structural formula is as follows:
2. the method for preparing an isolongifolane ratio-type fluorescent probe for detecting hydrazine as set forth in claim 1, wherein: 6,6,10, 10-tetramethyl-4- (pyridin-4-yl) -6,7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-2-amine is quaternized with 4- (bromomethyl) phenol acetate to give 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide, of the formula:
3. the method of claim 2, wherein 6,6,10, 10-tetramethyl-4- (pyridin-4-yl) -6,7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-2-amine is quaternized with 4- (bromomethyl) phenol acetate in acetonitrile to obtain 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide, the preparation method comprises the following steps:
(1) sequentially adding 0.12mol of 6,6,10, 10-tetramethyl-4- (pyridine-4-yl) -6,7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazoline-2-amine, 0.12-0.20 mol of 4- (bromomethyl) phenol acetate and 0.5-1.0L of anhydrous acetonitrile into a three-neck flask with a stirrer, and carrying out reflux reaction at 80-90 ℃ for 10-12H under the protection of nitrogen;
(2) distilling the reaction liquid to recover the solvent to obtain a crude product of 1- (4-acetoxy benzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide;
(3) the crude product of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide is subjected to silica gel chromatography, dichloromethane and methanol are respectively 15:1, and the crude product is recrystallized by methanol to obtain 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10 alpha-hexahydro-5H-6 alpha, 9-methanobenzo quinazolin-4-yl) pyridine bromide as light yellow powder.
4. Use of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide according to claim 1 for the detection of hydrazine.
5. Use of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide according to claim 1 for the preparation of isolongifolanyl ratio type fluorescent probes.
6. Use of 1- (4-acetoxybenzyl) -4- (2-amino-6, 6,10, 10-tetramethyl-6, 7,8,9,10,10 α -hexahydro-5H-6 α, 9-methanobenzo [ H ] quinazolin-4-yl) pyridine bromide according to claim 1 as isolongifolane ratio type fluorescent probe for the detection of hydrazine.
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