CN109705051B - 2, 4, 5-trisubstituted oxazole and synthesis method thereof - Google Patents

2, 4, 5-trisubstituted oxazole and synthesis method thereof Download PDF

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CN109705051B
CN109705051B CN201910077793.XA CN201910077793A CN109705051B CN 109705051 B CN109705051 B CN 109705051B CN 201910077793 A CN201910077793 A CN 201910077793A CN 109705051 B CN109705051 B CN 109705051B
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刘赛文
张劲
张令君
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Hunan City University
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Abstract

The application relates to a 2, 4, 5-trisubstituted oxazole compound and a synthesis method thereof, which adopts a technical scheme that a non-metallic iodine simple substance is used as a catalyst, air or oxygen is used as an oxidant, pyridine, quinoline, triethylamine, NMP, DMA, DMSO, 1, 4-dioxane, toluene and the like are used as organic solvents, and alpha, beta-diketone compounds, ketone and ammonium salt are converted into the 2, 4, 5-trisubstituted oxazole and derivatives thereof. The method overcomes the difficulties that the existing synthesis method of the 2, 4, 5-trisubstituted oxazole compound has complex synthesis steps, can be completed by adopting a multi-step synthesis process, and also needs to use a metal catalyst, a chemical equivalent oxidant and the like. It is suitable for being used as a plurality of functional materials; is particularly suitable for preparing important raw materials of the antidiabetic AD-5061.

Description

2, 4, 5-trisubstituted oxazole and synthesis method thereof
Technical Field
The invention relates to the field of organic synthesis, in particular to 2, 4, 5-trisubstituted oxazole and a synthesis method thereof.
Background
The oxazole compounds are important heterocyclic compounds, and a plurality of compounds containing oxazole rings have certain biological activity and have very wide application in the fields of natural products, medicines, pesticides and the like. Hantzsch identified this heterocyclic structure as oxazole in 1887, after which a number of oxazoles were extracted from marine invertebrates and microorganisms. With the development of organic chemistry, more and more chemically synthesized oxazole compounds are now available, and many tri-substituted oxazoles show biological activity in the field of treating diabetes, breast cancer, pancreatic cancer and other diseases. The synthesis methods of the compounds are rarely disclosed, and most methods in the published documents need multi-step synthesis or have complicated raw materials. Such as org.lett., 2015, 17, 4070-; commun., 2013, 49, 10266-; tetrahedron lett, 2015, 56, 3872-; methods for synthesizing such materials have been reported in WO2010/141696 (2010). Some of the methods have complex raw materials, some methods are completed by adopting a multi-step synthesis process, and some methods need to use a metal catalyst.
Disclosure of Invention
In view of the above circumstances, the present invention aims to provide a 2, 4, 5-trisubstituted oxazole and its derivatives, which have stable molecular structure and excellent chemical properties, are important molecular fragments, and are compound fragments containing physiological activity and pharmacological activity.
The invention also aims to provide a method for preparing the 2, 4, 5-trisubstituted oxazole and the derivative, which has the advantages of scientific and reasonable process, easy operation, few reaction steps, simple required equipment, cheap and easily obtained raw materials, no need of using a metal catalyst, a metal oxidant or peroxide in the reaction, capability of greatly keeping atom economy, low input and high output, and easy industrial production and popularization.
The technical scheme adopted by the invention for solving the technical problems is as follows:
a2, 4, 5-trisubstituted oxazole and derivatives having the general formula I:
Figure BSA0000178392140000011
wherein
R 1 Is selected from C 1 -C 10 Linear, branched, cyclic alkyl of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 The straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen group, nitro group and amino group;
R 2 is selected from C 1 -C 10 Linear, branched, cyclic alkyl groups of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 The straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen group, nitro group and amino group;
R 3 is selected from C 1 -C 10 Linear, branched, cyclic alkyl of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 Straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen, nitro and amino.
Under the action of catalytic amount of iodide and oxidant, alpha, beta-diketone compound, ketone, ammonium salt and organic solvent are mixed and reacted and purified to obtain the product.
Preferably, in the synthesis method of the present invention, the iodide is selected from the group consisting of Kl, Nal, Cul, Znl 2 、Agl、NH 4 l、l 2 One or more of N-iodosuccinimide, 2-iodosylbenzoic acid, tetrabutylammonium iodide, tetramethylammonium iodide, iodine chloride and trimethyl sulfoxide iodide; the oxidant is air or oxygen; the organic solvent is pyridine, quinoline, triethylamine, NMP, DMA, DMF, DMSO, 1, 4-dioxane, toluene and anisole.
Preferably, in the synthesis method, the molar ratio of the monoketone, the alpha, beta-diketone compound and the ammonium salt is 1: 0.6-3: 1.1-10, and the reaction temperature is 20-200 ℃.
Preferably, in the synthesis method of the present invention, the ketone compound is selected from C 4 -C 30 The chain ketone of (4), having the following general formula:
formula II:
Figure BSA0000178392140000021
wherein
R 2 Is selected from C 1 -C 10 Linear, branched, cyclic alkyl groups of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 The straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen group, nitro group and amino group;
R 3 is selected from C 1 -C 10 Linear, branched, cyclic alkyl groups of (a); substituted or unsubstituted C 6 -C 20 An aryl group; substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atom; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 Straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen, nitro and amino.
Preferably, in the synthesis method of the present invention, the chain ketone in formula II is selected from α - (4-nitrophenyl) acetophenone, α - (4-nitrophenyl) -2-chloroacetophenone, α - (4-nitrophenyl) -3-chloroacetophenone, α - (4-nitrophenyl) -4-chloroacetophenone, α - (4-nitrophenyl) -3-bromoacetophenone, α - (4-nitrophenyl) -4-methylacetophenone, α - (4-nitrophenyl) -4-tert-butylacetophenone, α - (4-nitrophenyl) -4-isobutylacetophenone, 2-pentanone, 2-hexanone, 4-methyl-2-pentanone, 2-heptanone, 2-octanone, 2-nonanone, 2-decanone, 2-eicosanone, 3-pentanone, 4-heptanone, 5-nonanone, 8-pentadecanone, propiophenone, p-methylpropiophenone, p-chloropropiophenone, p-nitroacetophenone, 1, 2-diphenylethanone, 1, 2-bis (4-isopropylphenyl) ethanone, 1, 2-bis (4-bromophenyl) ethanone, 1, 2-bis (4-aminophenyl) ethanone.
When the above-mentioned chain ketone is selected, R 2 The phenyl group is 4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-aminophenyl, 4-chlorophenyl, 2-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 4-pyridyl, 2-furyl, 2-thienyl, methyl, isopropyl, cyclohexyl, phenyl.
Preferably, in the synthesis method of the present invention, the α, β -diketones have the following general formula:
formula III
Figure BSA0000178392140000022
Wherein
R 1 Is selected from C 1 -C 10 Linear, branched, cyclic alkyl groups of (a); substituted or unsubstituted C 6 -C 20 An aryl group; substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atom; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 Linear alkyl, branched alkyl, cyclic alkyl, halogen, nitro, amino.
Preferably, in the synthesis method of the present invention, the α, β -diketone compound is selected from benzil, 2 ' -dimethoxybenzil, 4 ' -difluorobenzil, furoyl, 3 ' -dimethoxybenzil, 4 ' -dimethylbenzoyl, 4 ' -dichlorobenzil, 4 ' -bisdimethylaminobenzoyl, 4 ' -dibromobenzil, 2, 3-butanedione, 3, 4-hexanedione, 4, 5-octanedione, and 5, 6-decanedione.
When the above-mentioned alpha, beta-diketones are selected, R 1 The specific compound is 4-nitrophenyl, 4-methylphenyl, 4-bis-dimethylaminophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-methoxyphenyl, 3-methoxyphenyl, 4-bromophenyl, 4-pyridyl, 2-furyl, 2-thienyl, methyl, isopropyl, propyl, cyclopropyl, phenyl.
Preferably, in the synthesis method of the present invention, the ammonium salt has the following general formula:
formula IV:
Figure BSA0000178392140000031
wherein
n, m and p are integers of 1 to 3,
Y (m-) is an anion, is - 、Br - 、Cl - 、PF 6 - 、BF 4 - 、HCO 3 - 、NO 3 - 、OAc - 、CrO 4 2- 、S 2 O 3 2- 、SO 4 2- 。
Preferably, in the synthesis method of the present invention, the ammonium salt is selected from NH 4 l、NH 4 Br、NH 4 Cl、NH 4 PF 6 、NH 4 BF 4 、NH 4 HCO 3 、NH 4 NO 3 、NH 4 OAc、(NH 4 ) 2 CrO 4 、(NH 4 ) 2 S 2 O 3 、(NH 4 ) 2 SO 4 。
The invention has the beneficial effects that:
compared with the prior art, the invention has the following beneficial effects:
(I) the invention adopts the technical scheme that alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof by taking air or oxygen as an oxidant and ammonium salt as a nitrogen source under the catalysis of elemental iodine for the first time, so as to prepare products with stable molecular structures and excellent chemical properties and additional products thereof;
the invention (II) adopts the technical scheme that under the catalytic action of elemental iodine, air or oxygen is used as an oxidant for the first time, ammonium salt is directly used as a nitrogen source, and alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof, so that reaction raw materials are cheap and easy to obtain, stable and easy to store, and the atom economy of the reaction is high;
the invention (III) adopts the technical scheme that under the catalytic action of elemental iodine, air or oxygen is used as an oxidant for the first time, ammonium salt is used as a nitrogen source, and alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof, the reaction does not need to use a metal catalyst, a metal oxidant or peroxide, only catalytic amounts of elemental iodine and green oxidant air or oxygen are needed, the post-treatment is simple, the environmental pollution is reduced, the raw materials are saved, and the reaction cost is reduced;
(IV) the invention adopts the technical scheme that alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof by taking air or oxygen as an oxidant and ammonium salt as a nitrogen source under the catalysis of elemental iodine for the first time, and the product is directly synthesized by adopting a two-component one-pot method with high yield, thereby overcoming the difficulty of huge waste of people, property and materials caused by the existing multi-step synthesis method, and saving a large amount of development time and production period;
the invention adopts the technical scheme that alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof by using air or oxygen as an oxidant and ammonium salt as a nitrogen source under the catalytic action of elemental iodine for the first time, thereby overcoming the difficulty of higher product implementation cost caused by the existing multistep synthesis method, greatly advancing the practical application of the product and creating basic conditions for the advanced industrial production;
(VI) the invention adopts the technical scheme that under the catalytic action of elemental iodine, air or oxygen is used as an oxidant for the first time, ammonium salt is used as a nitrogen source, and alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof, the temperature required by the reaction is greatly lower than the temperature required by the conventional multistep synthesis method, and a large amount of energy consumption is saved;
(VII) the invention adopts the technical scheme that under the catalytic action of elemental iodine, air or oxygen is used as an oxidant for the first time, ammonium salt is used as a nitrogen source, and alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof, the process is scientific and reasonable, the operation is easy, the reaction steps are few, and the required equipment is few;
the invention (VIII) adopts the technical scheme that alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof by using air or oxygen as an oxidant and ammonium salt as a nitrogen source under the catalysis of elemental iodine for the first time, and the preparation method has the advantages of wide raw materials, low investment, high yield and easy mass production and popularization;
the Invention (IX) adopts the technical scheme that under the catalytic action of elemental iodine, air or oxygen is used as an oxidant for the first time, ammonium salt is used as a nitrogen source, and alpha, beta-diketone compounds and ketone are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof.
The invention is suitable for being used as raw materials of various functional materials; is particularly suitable for preparing important raw materials of the antidiabetic AD-5061.
Drawings
The technical solution of the present application is further explained below with reference to the drawings and the embodiments.
FIG. 1 is a scheme for the synthesis of compounds of the invention.
FIG. 2-1 nuclear magnetic hydrogen spectrum of the product of example 1.
FIG. 2-2 nuclear magnetic carbon spectrum of the product of example 1.
FIG. 3-1 nuclear magnetic hydrogen spectrum of the product of example 2.
Figure 3-2 nuclear magnetic carbon spectrum of the product of example 2.
Detailed Description
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict.
In combination with the synthetic route of the compound of the invention, the 2, 4, 5-trisubstituted oxazole compound and the synthetic principle thereof are shown in the attached figure 1: the method comprises the following steps of adopting a technical scheme that an alpha, beta-diketone compound, ketone and ammonium salt are converted into 2, 4, 5-trisubstituted oxazole and derivatives thereof for the first time by using air or oxygen as an oxidant and pyridine, quinoline, triethylamine, NMP, DMA, DMF, DMSO, 1, 4-dioxane, toluene, anisole and the like as organic solvents under the action of a catalytic amount of a simple substance iodine without using a metal catalyst; the method overcomes the difficulties that the existing synthesis method of the 2, 4, 5-trisubstituted oxazole compound has complex synthesis steps, can be completed by adopting a multi-step synthesis process, and also needs a metal catalyst and a metal oxidant or peroxide with chemical equivalent; it maintains atom economy to the utmost extent; it has stable molecular structure, excellent chemical property, molecular blocks and compound segments containing rich contents of biological activity and pharmacological activity; the method also has the characteristics of simple reaction system, mild reaction conditions, less reaction equipment, simple and convenient experimental operation, wide material sources, easy expansion of application, higher product utilization value, prospective market commercialization prospect and the like.
With reference to the attached drawing, a 2, 4, 5-trisubstituted oxazole and a derivative thereof have a general formula I:
Figure BSA0000178392140000041
wherein
R 1 Is selected from C 1 -C 10 Linear, branched, cyclic alkyl of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 The straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen group, nitro group and amino group;
R 2 is selected from C 1 -C 10 Linear, branched, cyclic alkyl groups of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 Straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen, nitro, amino;
R 3 is selected from C 1 -C 10 Linear, branched, cyclic alkyl groups of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 Linear alkyl, branched alkyl, cyclic alkyl, halogen, nitro, amino.
In order to realize the method for synthesizing the 2, 4, 5-trisubstituted oxazole and the derivatives thereof, under the action of an iodine-containing compound and an oxidant, an alpha, beta-diketone compound, ketone, ammonium salt and an organic solvent are mixed for reaction and purification to obtain a product.
In order to improve the comprehensive performance of the invention and realize the optimization of structure and effect, the invention has the further measures that:
the catalyst containing iodine is selected from KI, NaI, CuI and ZnI 2 、AgI、NH 4 I、I 2 N-iodobutanedioic acidOne or more of imide, 2-iodoxybenzoic acid, tetrabutylammonium iodide, tetramethylammonium iodide, iodine chloride and trimethyl sulfoxide iodide; the catalyst containing iodine is I 2 . The oxidant is air or oxygen. The organic solvent is pyridine, quinoline, triethylamine, NMP, DMA, DMF, DMSO, 1, 4-dioxane, toluene and anisole. The molar ratio of the monoketone, the alpha, beta-diketone compound and the ammonium salt is 1: 0.6-3: 1.1-10, and the reaction temperature is 20-200 ℃.
The monoketone compound is selected from C 4 -C 30 The chain ketone of (1), having the general formula of formula II:
Figure BSA0000178392140000051
wherein
R 2 Is selected from C 1 -C 10 Linear, branched, cyclic alkyl of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 The straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen group, nitro group and amino group;
R 3 is selected from C 1 -C 10 Linear, branched, cyclic alkyl of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 Linear alkyl, branched alkyl, cyclic alkyl, halogen, nitro, amino.
The chain ketone in formula II is further selected from the group consisting of α - (4-nitrophenyl) acetophenone, α - (4-nitrophenyl) -2-chloroacetophenone, α - (4-nitrophenyl) -3-chloroacetophenone, α - (4-nitrophenyl) -4-chloroacetophenone, α - (4-nitrophenyl) -3-bromoacetophenone, α - (4-nitrophenyl) -4-methylacetophenone, α - (4-nitrophenyl) -4-tert-butylbenzophenone, α - (4-nitrophenyl) -4-isobutylacetophenone, 2-pentanone, 2-hexanone, 4-methyl-2-pentanone, 2-heptanone, 2-octanone, 2-nonanone, 2-decanone, 2-eicosanone, 3-pentanone, 4-heptanone, 5-nonanone, 8-pentadecanone, propiophenone, p-methylpropiophenone, p-chloropropiophenone, p-nitroacetophenone, 1, 2-diphenylethanone, 1, 2-bis (4-isopropylphenyl) ethanone, 1, 2-bis (4-bromophenyl) ethanone, 1, 2-bis (4-aminophenyl) ethanone.
The general formula of the alpha, beta-diketone compound is shown as the formula III:
Figure BSA0000178392140000052
wherein
R 1 Is selected from C 1 -C 10 Linear, branched, cyclic alkyl groups of (a); substituted or unsubstituted C 6 -C 20 An aryl group; a substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein the substituents of the aryl or heterocyclic group are selected from C 1 -C 10 Straight-chain alkyl, branched-chain alkyl, cyclic alkyl, halogen, nitro and amino.
The alpha, beta-diketone compound is further selected from benzil, 2 ' -dimethoxybenzil, 4 ' -difluorobenzil, furobioyl, 3 ' -dimethoxybenzil, 4 ' -dimethylbenzoyl, 4 ' -dichlorobenzil, 4 ' -bisdimethylaminobenzoyl, 4 ' -dibromobenzil, 2, 3-butanedione, 3, 4-hexanedione, 4, 5-octanedione and 5, 6-decanedione.
The general formula of the ammonium salt is formula IV:
Figure BSA0000178392140000053
wherein
n, m and p are integers of 1 to 3,
Y (m-) is an anion of - 、Br - 、Cl - 、PF 6 - 、BF 4 - 、HCO 3 - 、NO 3 - 、OAc - 、CrO 4 2- 、S 2 O 3 2- 、SO 4 2- 。
Said ammonium salt is further selected from NH 4 I、NH 4 Br、NH 4 Cl、NH 4 PF 6 、NH 4 BF 4 、NH 4 HCO 3 、NH 4 NO 3 、NH 4 OAc、(NH 4 ) 2 CrO 4 、(NH 4 ) 2 S 2 O 3 、(NH 4 ) 2 SO 4 。
The general formula of the reaction system of the invention is synthesized by 2, 4, 5-trisubstituted oxazole and derivatives thereof which are formed by formulas I, II, III and IV, as follows:
Figure BSA0000178392140000054
comprises the following steps
(1) Adding iodide, alpha, beta-diketone, monoketone and organic solvent;
(2) fully mixing the reactants, filling an oxidant, and heating for reaction;
(3) purifying to obtain a product;
wherein the organic solvent is pyridine, quinoline, triethylamine, NMP, DMA, DMF, DMSO, 1, 4-dioxane, toluene and anisole;
preferably 1, 4-dioxane;
the oxidant is air or oxygen;
preferably oxygen, the oxidant is 1atm of oxygen;
in order to achieve better synthesis effect, the mol ratio of the monoketone, the alpha, beta-diketone compound and the ammonium salt is preferably 1: 0.6-3: 1.1-10, and the optimal scheme is preferably 1: 0.8: 3;
the catalyst containing iodine is KI, Nal, CuI, ZnI 2 、AgI、NH 4 I、I 2 N-iodosuccinimide, 2-iodoxybenzoic acid, tetrabutylammonium iodide, tetramethylammonium iodide, iodine chloride, trimethyliodonium iodideOne or more of a sulfone;
particularly preferred is I 2 ；
The reaction temperature is preferably 20-200 ℃;
more preferably 80 deg.c.
The 2, 4, 5-trisubstituted oxazole and derivatives thereof can be obtained from the process of the synthesis reaction system of the compound of the invention, and the mono-ketone, the alpha, beta-diketone compound and the ammonium salt are reacted and converted into the 2, 4, 5-trisubstituted oxazole by using air or oxygen as an oxidant in the presence of catalytic amount of iodide without using a metal catalyst for the first time.
The compound of the formula I is taken as an important molecular fragment, has stable molecular structure and excellent chemical property, has certain physiological activity, can further synthesize a plurality of compound fragments containing oxazole structures by converting functional groups, and has strong physiological activity and pharmacological activity; for example, an oxazole derivative AD-5061 is an insulin sensitizer with good anti-diabetic activity.
AD-5061 structural formula
Figure BSA0000178392140000061
In conclusion, the compound has the advantages that the reaction raw materials are cheap and easy to obtain; the reaction does not need to use a metal oxidant or peroxide; only non-metallic iodine simple substance is used as a catalyst, and the used oxidant is green and cheap air or oxygen; the reaction is directly synthesized in one pot, and the like; the method solves the problems of higher cost and the like caused by the conventional multi-step synthesis method; the reaction condition is mild, and the temperature required by the reaction is greatly lower than the reaction temperature of the previous multi-step synthesis; a series of synthesized 2, 4, 5-trisubstituted oxazole compounds have quite high potential application value.
Examples 1 to 17 are as follows:
EXAMPLE 12 Synthesis of 4, 4-Diphenyl-5- (4-nitrophenyl) oxazole
Figure BSA0000178392140000062
A reaction tube was taken and added with alpha- (4-nitrophenyl) acetophenone (0.2mmol, 48.2mg), benzil (0.16mmol, 33.6mg), ammonium acetate (46.2mg, 0.6mmol), I 2 (5.1mg, 0.01mmol), 1, 4-dioxane (0.5mL), one atmosphere of oxygen at 80 ℃ for 24 h, and conventional treatment gave pure red-brown solid, 51.3mg, 75% yield.
The nuclear magnetic spectrum data of the product of example 1 are as follows:
1 H NMR(400MHz，CDCl 3 ，ppm)δ8.23(d，J＝8.4Hz，2H)，8.18(d，J＝3.2Hz，2H)，7.84(d，J＝8.4Hz，2H)，7.69(d，J＝6.4Hz，2H)，7.52-7.41(m，6H)； 13 C NMR(100MHz，CDCl 3 ，ppm)δ161.4，146.9，143.2，140.3，134.8，131.8，131.0，129.2，129.0，128.9，128.4，126.7，126.2，124.1.
EXAMPLE 22 Synthesis of diphenyl-4- (3-chlorophenyl) -5- (4-nitrophenyl) oxazole
Figure BSA0000178392140000071
Adding alpha- (4-nitrophenyl) -3-chloroacetophenone (0.2mmol, 55.0mg), benzil (0.16mmol, 33.6mg), ammonium acetate (46.2mg, 0.6mmol), I 2 (5.1mg, 0.01mmol), 1, 4-dioxane (0.5mL), one atmosphere of oxygen at 80 ℃ for 24 h, and conventional treatment gave a pure brownish red solid, 45.2mg, 60% yield.
The nuclear magnetic spectrum data of the product of example 2 are as follows:
1 H NMR(400MHz，CDCl 3 ，ppm)δ8.26(d，J＝8.4Hz，2H)，8.16(d，J＝2.4Hz，2H)，7.84(d，J＝8.8Hz，2H)，7.73(m，1H)，7.68(s，1H)，7.56-7.48(m，5H)； 13 C NMR(100MHz，CDCl 3 ，ppm)δ161.5.147.1，143.7，138.7，135.0，134.4，131.2，130.2，129.2，128.9，128.5，128.0，126.7，126.5，126.3，124.2，124.0.
following the procedure described in example 1, the present invention synthesizes the following compounds:
Figure BSA0000178392140000072
Figure BSA0000178392140000081
Figure BSA0000178392140000091
Figure BSA0000178392140000101
Figure BSA0000178392140000111
Figure BSA0000178392140000121
Figure BSA0000178392140000131
Figure BSA0000178392140000141
Figure BSA0000178392140000151
Figure BSA0000178392140000161
Figure BSA0000178392140000171
in light of the foregoing description of the preferred embodiments according to the present application, it is to be understood that various changes and modifications may be made by those skilled in the art without departing from the scope of the invention as defined by the appended claims. The technical scope of the present application is not limited to the contents of the specification, and must be determined according to the scope of the claims.

Claims (1)

1. A method for synthesizing 2, 4, 5-trisubstituted oxazole and its derivative, characterized by that, under the influence of catalyst iodide and oxidizing agent, mix alpha, beta-diketone compound, ketone, ammonium salt and organic solvent to react, purify and get the product;
the iodide is selected from KI, NaI, CuI and ZnI 2 、AgI、NH 4 I、I 2 One or more of N-iodosuccinimide, 2-iodosylbenzoic acid, tetrabutylammonium iodide, tetramethylammonium iodide, sulfochloride and trimethyl sulfoxide iodide;
the oxidant is air or oxygen;
the organic solvent is pyridine, quinoline, triethylamine, NMP, DMA, DMF, DMSO, 1, 4-dioxane, toluene and anisole;
the molar ratio of the ketone, the alpha, beta-diketone compound and the ammonium salt is 1: 0.6-3: 1.1-10, and the reaction temperature is 20-200 ℃;
the ketone is selected from:
Figure FSB0000199972160000011
the alpha, beta-diketone compound is selected from the group consisting of:
Figure FSB0000199972160000012
Figure FSB0000199972160000021
the ammonium salt is selected from: NH (NH) 4 I、NH 4 Br、NH 4 Cl、NH 4 PF 6 、NH 4 BF 4 、NH 4 HCO 3 、NH 4 NO 3 、NH 4 OAc、(NH 4 ) 2 CrO 4 、(NH 4 ) 2 S 2 O 3 、(NH 4 ) 2 SO 4 ；
The structural formula of the 2, 4, 5-trisubstituted oxazole and the derivative is as follows:
Figure FSB0000199972160000022
Figure FSB0000199972160000031
Figure FSB0000199972160000041
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