阅读说明：本技术 樟脑合成喹唑啉类化合物用作次氯酸检测用荧光探针 (Camphor synthesized quinazoline compound used as fluorescent probe for hypochlorous acid detection ) 是由 杨益琴 王忠龙 徐徐 王石发 张燕 李明新 谷文 徐海军 卞天岑 于 2018-07-26 设计创作，主要内容包括：本发明公开了樟脑合成喹唑啉类化合物用作次氯酸检测用荧光探针。本发明利用天然可再生资源樟脑为原料,与水杨醛缩合生成3-(2′-羟基苯亚甲基)樟脑；3-(2′-羟基苯亚甲基)樟脑再与盐酸胍进行缩合环化得到2-氨基-4-(2′-羟苯基)-8,9,9-三甲基-5,6,7,8-四氢-5,8-桥亚甲基喹唑啉。该化合物能能专一性的被次氯酸氧化,在365nm紫外光照射下产生绿色荧光,因此该化合物可作为检测次氯酸的荧光探针,具有良好的应用前景。(The invention discloses a quinazoline compound synthesized by camphor and used as a fluorescent probe for hypochlorous acid detection. The method utilizes natural renewable resources camphor as raw materials, and the raw materials are condensed with salicylaldehyde to generate 3- (2' -hydroxybenzene methylene) camphor; and carrying out condensation cyclization on the 3- (2 '-hydroxybenzylidene) camphor and guanidine hydrochloride to obtain the 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline. The compound can be specifically oxidized by hypochlorous acid and generates green fluorescence under the irradiation of 365nm ultraviolet light, so that the compound can be used as a fluorescent probe for detecting the hypochlorous acid and has good application prospect.)

1. The method for synthesizing the quinazoline compound from the camphor serving as the fluorescent probe for detecting the hypochloric acid is characterized in that the quinazoline compound has a structural formula as follows:

2. the method for synthesizing the quinazoline compound as claimed in claim 1, which comprises the steps of:

1) and performing aldol condensation on the camphor and salicylaldehyde to obtain the 3- (2' -hydroxybenzylidene) camphor.

2)3- (2 '-hydroxybenzylidene) camphor and guanidine hydrochloride are subjected to condensation reaction to obtain 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline.

3. The method for synthesizing quinazoline compounds according to claim 2, wherein in the step 1), camphor and salicylaldehyde are subjected to aldol condensation to obtain 3- (2' -hydroxybenzylidene) camphor, and the specific preparation method comprises the following steps:

(1) 0.1mol of camphor, 0.1-0.15 mol of salicylaldehyde, 0.2-0.3 mol of potassium tert-butoxide and 0.1-0.3L of tert-butanol are sequentially added into a three-neck flask provided with a stirrer, a thermometer and a reflux condenser, and the reaction is carried out at the temperature of 0-100 ℃ under the protection of nitrogen.

(2) Extracting the reactant with 0.3-0.5L ethyl acetate for 3 times, combining organic phases, then washing with saturated saline solution to be neutral, drying the organic phase with anhydrous sodium sulfate, filtering, concentrating and recovering the solvent to obtain a crude product of the 3- (2' -hydroxybenzylidene) camphor.

(3) Recrystallizing the crude product of the 3- (2 '-hydroxybenzylidene) camphor with methanol-ethyl acetate to obtain the 3- (2' -hydroxybenzylidene) camphor.

4. The method for synthesizing quinazoline compounds according to claim 2, wherein in the step 2), 3- (2 '-hydroxybenzylidene) camphor reacts with guanidine hydrochloride under the action of potassium tert-butoxide to obtain 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methanoquinazoline, and the specific preparation method comprises the following steps:

(1) 0.1mol of 3- (2' -hydroxybenzylidene) camphor, 0.4-0.6 mol of guanidine hydrochloride, 0.4-1.0 mol of potassium tert-butoxide and 0.2-0.4L of tert-butanol are sequentially added into a three-neck flask provided with a stirrer, a thermometer and a reflux condenser, heated and refluxed for 18h under the protection of nitrogen, and the reaction is followed and detected by GC.

(2) Extracting the reaction solution for 3 times by using 0.4-0.8L ethyl acetate, combining organic phases, washing the organic phases to be neutral by using saturated saline solution, drying the organic phases by using anhydrous sodium sulfate, filtering, concentrating and recovering a solvent to obtain a crude product of the 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methanoquinazoline.

(3) Recrystallizing the crude product of the 2-amino-4- (2 '-hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline by methanol-ethyl acetate to obtain white blocky crystals of the 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline.

5. The quinazoline compound 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methanoquinazoline of claim 1, which is useful as a fluorescent probe for hypochlorous acid detection.

Technical Field

The invention belongs to the technical field of fine organic synthesis, and relates to a method for synthesizing quinazoline compounds by using camphor as a raw material and using the quinazoline compounds as fluorescent probes for hypochlorous acid detection.

The invention discloses a quinazoline compound synthesized by camphor and used as a fluorescent probe for hypochlorous acid detection. The method utilizes natural renewable resources camphor as raw materials, and the raw materials are condensed with salicylaldehyde to generate 3- (2' -hydroxybenzene methylene) camphor; and carrying out condensation cyclization on the 3- (2 '-hydroxybenzylidene) camphor and guanidine hydrochloride to obtain the 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline. The compound can be specifically oxidized by hypochlorous acid and generates green fluorescence under the irradiation of 365nm ultraviolet light, so that the compound can be used as a fluorescent probe for detecting the hypochlorous acid and has good application prospect.

Background

Hypochlorous acid (HClO) is a commonly used disinfectant and bleaching agent in our lives and plays a very critical role in the human immune system. However, in humans, hypochlorous acid levels above normal levels can induce a number of inflammation-related disorders, such as arteriosclerosis, rheumatoid arthritis, pneumonia, cardiovascular and renal diseases. Therefore, the development of an assay for detecting hypochlorous acid is of great interest for the clinical diagnosis and treatment of these diseases.

Compared with the traditional analysis method, the small-molecule fluorescent probe attracts more and more researchers with the advantages of high selectivity, high sensitivity, simplicity and the like. The natural renewable resource camphor is used as a raw material to synthesize a novel fluorescent probe for detecting hypochlorous acid.

Disclosure of Invention

The purpose of the invention is as follows: aiming at the defects in the prior art, the invention aims to provide a quinazoline compound fluorescent probe which is synthesized by taking camphor as a raw material and is used for detecting hypochlorous acid.

The technical scheme is as follows: in order to achieve the purpose, the invention adopts the technical scheme that:

the quinazoline compound is 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline, and the structural formula is as follows:

the synthetic method of the quinazoline compound comprises the following steps:

1) and performing aldol condensation on the camphor and salicylaldehyde to obtain the 3- (2' -hydroxybenzylidene) camphor.

2)3- (2 '-hydroxybenzylidene) camphor and guanidine hydrochloride are subjected to condensation reaction to obtain 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline.

In the step 1), camphor and salicylaldehyde are subjected to aldol condensation to obtain 3- (2' -hydroxybenzylidene) camphor, and the specific preparation method comprises the following steps:

(1) 0.1mol of camphor, 0.1-0.15 mol of salicylaldehyde, 0.2-0.3 mol of potassium tert-butoxide and 0.1-0.3L of tert-butanol are sequentially added into a three-neck flask provided with a stirrer, a thermometer and a reflux condenser, and the reaction is carried out at the temperature of 0-100 ℃ under the protection of nitrogen.

(2) Extracting the reaction solution with 0.3-0.5L ethyl acetate for 3 times, combining organic phases, washing with saturated saline water to neutrality, drying the organic phase with anhydrous sodium sulfate, filtering, concentrating and recovering the solvent to obtain a crude product of the 3- (2' -hydroxybenzylidene) camphor.

(3) Recrystallizing the crude product of the 3- (2 '-hydroxybenzylidene) camphor with methanol-ethyl acetate to obtain a pure product of the 3- (2' -hydroxybenzylidene) camphor.

In the step 2), 3- (2 '-hydroxybenzylidene) camphor reacts with guanidine hydrochloride under the action of potassium tert-butoxide to obtain 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methanoquinazoline, and the specific preparation method comprises the following steps:

(1) sequentially adding 0.1mol of 3- (2 '-hydroxybenzylidene) camphor, 0.4-0.6 mol of guanidine hydrochloride, 0.4-1.0 mol of potassium tert-butoxide and 0.2-0.4L of tert-butanol into a three-neck flask provided with a stirrer, a thermometer and a reflux condenser, heating and refluxing for 18 hours under the protection of nitrogen, and terminating the reaction until the conversion rate of the 3- (2' -hydroxybenzylidene) camphor reaches 95% by GC tracking detection.

(2) Extracting the reaction liquid for 3 times by using 0.4-0.8L ethyl acetate, combining organic phases, washing the organic phases to be neutral by using saturated salt water, drying the organic phases by using anhydrous sodium sulfate, filtering, concentrating and recovering a solvent to obtain a crude product of the 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methanoquinazoline.

(3) Recrystallizing the crude product of the 2-amino-4- (2 '-hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline with ethanol-ethyl acetate to obtain white blocky crystals of the 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline.

The 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methanoquinazoline is used as a fluorescent probe for detecting hypochlorous acid.

The invention uses natural renewable resources camphor as raw materials, and the natural renewable resources camphor and salicylaldehyde are condensed to generate 3- (2' -hydroxybenzylidene) camphor; condensing and cyclizing 3- (2 '-hydroxybenzylidene) camphor and guanidine hydrochloride to obtain 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methano quinazoline; the compound can specifically recognize hypochlorous acid and can be used as a fluorescent probe for detecting hypochlorous acid.

Has the advantages that: compared with the prior art, the quinazoline compound prepared by using natural renewable resource camphor as a raw material can specifically identify hypochlorous acid, can be specifically oxidized by the hypochlorous acid to generate green fluorescence, and therefore, the compound can be used as a fluorescent probe for detecting the hypochlorous acid and has good practical value.

Drawings

FIG. 1 is a graph showing the effect of hypochlorous acid concentration on the fluorescence spectrum of 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methanoquinazoline;

FIG. 2 is a graph showing the effect of different ions on the fluorescence spectrum of 2-amino-4- (2' -hydroxyphenyl) -8, 9, 9-trimethyl-5, 6, 7, 8-tetrahydro-5, 8-methanoquinazoline;

Detailed Description

The present invention will be further described with reference to the following specific examples.