CN111116504B

CN111116504B - Process method for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene

Info

Publication number: CN111116504B
Application number: CN201911323690.3A
Authority: CN
Inventors: 顾扬; 龙韬; 陈丕证; 邹增龙
Original assignee: SUZHOU BAILING WEICHAO FINE MATERIALS CO Ltd
Current assignee: SUZHOU BAILING WEICHAO FINE MATERIALS CO Ltd
Priority date: 2019-12-24
Filing date: 2019-12-24
Publication date: 2021-11-09
Anticipated expiration: 2039-12-24
Also published as: CN111116504A

Abstract

The invention discloses a process method for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene, which comprises the following steps: the method takes terephthalonitrile as a raw material, and reacts with acetophenone under the catalysis of a proper amount of acidic compounds, halides and oxidants to obtain the 1, 4-bis (5-phenyl-2-oxazolyl) benzene. The reaction steps are short and the danger is low.

Description

Process method for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene

Technical Field

The invention relates to the field of diagnostic reagents, in particular to a process method for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene.

Background

Scintillators are materials capable of emitting light after absorbing high-energy particles or rays, and play an important role in the field of radiation detection. In medicine, the scintillator is a core component of nuclear medicine imaging equipment, and can quickly diagnose the size and the position of pathological changes and tumor tissues of human organs.

1, 4-bis (5-phenyl-2-oxazolyl) benzene is an important organic scintillator, is mainly applied to liquid luminescence spectroscopy, and has wide application prospect in the fields of intelligent materials and life sciences.

1, 4-bis (5-phenyl-2-oxazolyl) benzene has been reported only in 1 synthetic route, which is reported in 1982 in Revue Roumaine de Chimie,27(11-12), 1125-9, 1982 as follows:

the route adopts a 4-step synthesis method, wherein terephthaloyl chloride is taken as an initial raw material, and is condensed with glycine, dehydrated and ring-closed with sulfuric acid, subjected to ring opening with benzene Friedel-crafts acylation, and dehydrated and ring-closed with sulfuric acid to obtain 1, 4-bis (5-phenyl-2-oxazolyl) benzene.

This method has two more serious problems: firstly, the reaction route is long, 4 steps of reaction are required, the ring is required to be closed and opened continuously in the whole process, and the synthesis efficiency is low; secondly, the reaction conditions are harsh, concentrated sulfuric acid with very high danger needs to be used in the ring closing of the second step and the fourth step, the reaction is heated to more than 100 ℃, and the reaction safety is very poor. These two problems make it very difficult to scale up the product to the kilogram level and ten kilograms.

In order to solve the problems of long synthesis steps, harsh reaction conditions and high reaction risk of the existing process route of the 1, 4-bis (5-phenyl-2-oxazolyl) benzene, the method for synthesizing the 1, 4-bis (5-phenyl-2-oxazolyl) benzene, which has reasonable route design, mild reaction conditions, safety and reliability, is found to have very important significance.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

FIG. 1 is a nuclear magnetic spectrum of example 1 of the present invention;

FIG. 2 is a nuclear magnetic spectrum of example 2 of the present invention.

Disclosure of Invention

In order to overcome the defects in the prior art, the embodiment of the invention provides a process method for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene, which has short reaction steps and low risk.

To achieve the above objects, the examples of the present application disclose a process for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene, comprising the steps of: taking terephthalonitrile as a raw material, and reacting the terephthalonitrile with acetophenone under the catalysis of a proper amount of an acidic compound, a halide and an oxidant to obtain 1, 4-bis (5-phenyl-2-oxazolyl) benzene;

preferably, the acidic compound is one or more of the following: methanesulfonic acid, glacial acetic acid, trifluoroacetic acid, benzoic acid, phosphoric acid, trifluoromethanesulfonic acid.

Preferably, the halide is one or more of the following: tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, potassium iodide, sodium iodide, potassium bromide, sodium bromide, benzyltriethylammonium iodide, benzyltrimethylammonium iodide, benzyltriethylammonium bromide, benzyltrimethylammonium bromide.

Preferably, the oxidant is one or more of the following: potassium peroxymonosulfonate, potassium hydrogen persulfate, hydrogen peroxide, m-chloroperoxybenzoic acid, sodium hypochlorite, calcium hypochlorite, urea hydrogen peroxide and sodium tungstate.

Preferably, the dosage of the acetophenone is as follows: 0.5 to 3.5 equivalents.

Preferably, the amount of the acidic compound is: 0.01 to 50 equivalents.

Preferably, the amount of the halide is: 0.01 to 2 equivalents.

Preferably, the amount of the oxidant is: 0.01 to 10 equivalents.

Preferably, the reaction temperature is-20 to 200 ℃.

The invention has the following beneficial effects:

1. the raw materials adopted by the invention are cheap and easily available, and the toxicity is low;

2. the synthetic route is short, only 1 step of reaction is needed, and the process is greatly simplified;

3. the process is simple, the reaction condition is mild, and extreme reaction conditions are not needed;

4. the reaction yield is high, the product purity is high, the production cost is greatly reduced, and the requirement of large-scale industrial production of the product can be fully met.

In order to make the aforementioned and other objects, features and advantages of the invention more comprehensible, preferred embodiments accompanied with figures are described in detail below.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

To achieve the above objects, the present invention provides a process for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene, comprising the steps of: taking terephthalonitrile as a raw material, and reacting the terephthalonitrile with acetophenone under the catalysis of a proper amount of an acidic compound, a halide and an oxidant to obtain 1, 4-bis (5-phenyl-2-oxazolyl) benzene;

in the present invention, the acidic compound is one or more of the following: methanesulfonic acid, glacial acetic acid, trifluoroacetic acid, benzoic acid, phosphoric acid, trifluoromethanesulfonic acid.

In the present invention, the halide is one or more of the following: tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, potassium iodide, sodium iodide, potassium bromide, sodium bromide, benzyltriethylammonium iodide, benzyltrimethylammonium iodide, benzyltriethylammonium bromide, benzyltrimethylammonium bromide.

In the present invention, the oxidizing agent is one or more of the following: potassium peroxymonosulfonate, potassium hydrogen persulfate, hydrogen peroxide, m-chloroperoxybenzoic acid, sodium hypochlorite, calcium hypochlorite, urea hydrogen peroxide and sodium tungstate.

In the invention, the dosage of the acetophenone is as follows: 1.8 to 2.5 equivalents.

In the present invention, the acidic compound is used in an amount of: 3 to 15 equivalents.

In the present invention, the amount of the halide is: 0.1 to 0.3 equivalent.

In the present invention, the amount of the oxidant is: 1 to 4 equivalents.

In the invention, the reaction temperature is 40-80 ℃.

Example 1

Under stirring at room temperature, 1.3Kg of terephthalonitrile, 2.6Kg of acetophenone, 10Kg of methanesulfonic acid and 0.4Kg of tetrabutylammonium iodide were sequentially added to a 50L glass reaction kettle, and stirred uniformly to obtain a reaction solution.

Further, 6.2Kg of potassium peroxymonosulfonate was added to the reaction mixture in divided portions, and stirred. After the addition, the reaction solution was heated to 60 ℃ and stirred to react for 8 hours, and the reaction was completed.

Further, the reaction solution was suction filtered under reduced pressure, and the filter cake was washed with 2Kg of methanesulfonic acid, and the filtrate was collected.

Further, the filtrate was subjected to distillation under reduced pressure to recover methanesulfonic acid.

Further, the residue was dissolved in 20L of toluene, and washed with a sodium sulfite solution, a sodium hydrogencarbonate solution, pure water and brine in this order.

Further, the residue was dried over anhydrous sodium sulfate, then filtered, and 10L of toluene was recovered from the filtrate by rotary evaporation.

Further, a proper amount of ethyl acetate was added to the residue, and the mixture was cooled in an ice salt bath and crystallized to obtain 3.8Kg of a crude product.

The crude product was dried in an oven under vacuum to yield 3.2Kg of pure product as a yellow solid powder in 87% yield.

HPLC purity of the product: 98.9 percent.

Melting point of the product: 236-238 ℃.

Nuclear magnetic data: 1H NMR (400MHz, DMSO-d 6): δ 8.27(s, 4H), 7.93(s, 2H), 7.90(d, 4H), 7.54(t, 4H), 7.43(t, 2H).

Nuclear magnetic spectrum diagram 1.

The raw materials adopted by the invention are cheap and easily available, and the toxicity is low; the synthetic route is short, only 1 step of reaction is needed, and the process is greatly simplified; the process is simple, the reaction condition is mild, and extreme reaction conditions are not needed; the reaction yield is high, the product purity is high, the production cost is greatly reduced, and the requirement of large-scale industrial production of the product can be fully met.

Example 2

Under stirring at room temperature, 2.6Kg of terephthalonitrile, 5.9Kg of acetophenone, 25Kg of trifluoroacetic acid and 0.7Kg of benzyltrimethylammonium iodide were sequentially added to a 50L glass reaction kettle, and stirred uniformly to obtain a reaction solution.

Further, 5.4Kg of sodium tungstate is added to the reaction solution in batches and stirred evenly. After the addition, the reaction solution was heated to 70 ℃ and stirred to react for 6 hours, and the reaction was completed.

Further, the reaction solution was suction filtered under reduced pressure, and the filter cake was washed with 3Kg of trifluoroacetic acid, and the filtrate was collected.

Further, the filtrate was distilled under reduced pressure to recover trifluoroacetic acid.

Further, the residue was dissolved in 30L of xylene, and washed with a sodium sulfite solution, a sodium hydrogencarbonate solution, pure water and brine in this order.

Furthermore, a proper amount of tert-butyl methyl ether is added into the residue, and the mixture is cooled in an ice salt bath and crystallized to obtain 8.1Kg of crude product.

The crude product was dried in an oven under vacuum to give 6.2Kg of a pure product as a yellow solid powder in 83% yield.

HPLC purity of the product: 99.2 percent.

Melting point of the product: 236-238 ℃.

The nuclear magnetic spectrum is shown in FIG. 1.

The principle and the implementation mode of the invention are explained by applying specific embodiments in the invention, and the description of the embodiments is only used for helping to understand the method and the core idea of the invention; meanwhile, for a person skilled in the art, according to the idea of the present invention, there may be variations in the specific embodiments and the application scope, and in summary, the content of the present specification should not be construed as a limitation to the present invention.

Claims

1. A process for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene, comprising:

taking terephthalonitrile as a raw material, and reacting the terephthalonitrile with acetophenone under the catalysis of a proper amount of an acidic compound, a halide and an oxidant to obtain 1, 4-bis (5-phenyl-2-oxazolyl) benzene;

the acidic compound is methanesulfonic acid or trifluoroacetic acid;

the halide is tetrabutylammonium iodide or benzyltrimethylammonium bromide;

the oxidant is potassium peroxymonosulfonate or sodium tungstate.

2. The process of claim 1, wherein the acetophenone is present in an amount of: 0.5 to 3.5 equivalents; the dosage of the acidic compound is as follows: 0.01 to 50 equivalents; the dosage of the halogenated substances is as follows: 0.01 to 2 equivalents; the dosage of the oxidant is as follows: 0.01 to 10 equivalents.

3. The process for preparing 1, 4-bis (5-phenyl-2-oxazolyl) benzene according to claim 1, wherein the reaction temperature is-20 to 200 ℃.