CN114790179B - Sulfur-containing 2,4, 5-trisubstituted oxazole compound and preparation method and application thereof - Google Patents
Sulfur-containing 2,4, 5-trisubstituted oxazole compound and preparation method and application thereof Download PDFInfo
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- CN114790179B CN114790179B CN202210297499.1A CN202210297499A CN114790179B CN 114790179 B CN114790179 B CN 114790179B CN 202210297499 A CN202210297499 A CN 202210297499A CN 114790179 B CN114790179 B CN 114790179B
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- -1 2,4, 5-trisubstituted oxazole compound Chemical class 0.000 title claims abstract description 38
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 239000011593 sulfur Substances 0.000 title claims abstract description 24
- 229910052717 sulfur Inorganic materials 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 143
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 144
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 108
- 238000003756 stirring Methods 0.000 claims description 47
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 42
- 238000004440 column chromatography Methods 0.000 claims description 40
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 36
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 28
- 239000003153 chemical reaction reagent Substances 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 22
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 claims description 18
- 239000012363 selectfluor Substances 0.000 claims description 18
- 239000000758 substrate Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 2
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical group [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 13
- 125000001424 substituent group Chemical group 0.000 abstract description 10
- 239000002243 precursor Substances 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 abstract description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 abstract description 2
- 125000005842 heteroatom Chemical group 0.000 abstract description 2
- 125000001624 naphthyl group Chemical group 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 abstract description 2
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical group C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 abstract 1
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract 1
- 229920002554 vinyl polymer Polymers 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 116
- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- 238000012512 characterization method Methods 0.000 description 33
- 239000000047 product Substances 0.000 description 27
- 239000007787 solid Substances 0.000 description 26
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 125000001153 fluoro group Chemical group F* 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 239000007788 liquid Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 150000002825 nitriles Chemical class 0.000 description 7
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 5
- 150000002916 oxazoles Chemical class 0.000 description 5
- 125000002971 oxazolyl group Chemical group 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- 125000003963 dichloro group Chemical group Cl* 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- PMBXCGGQNSVESQ-UHFFFAOYSA-N 1-Hexanethiol Chemical compound CCCCCCS PMBXCGGQNSVESQ-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
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- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 2
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- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
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- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 2
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- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
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- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007978 oxazole derivatives Chemical class 0.000 description 1
- 238000005691 oxidative coupling reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/46—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a sulfur-containing 2,4, 5-trisubstituted oxazole compound, which is characterized by having a structure shown in a formula I: Wherein R 1 is selected from naphthalene ring, aryl hetero group, C 1‑4 alkyl, phenyl or benzene ring containing ring substituent; r 2 is selected from: cyclohexyl, benzyl, phenyl or a benzene ring containing a substituent on the ring; r 3 is selected from: c 1‑4 hydrocarbyl, vinyl, cyclopentyl, benzyl phenyl, or a benzene ring containing a ring substituent. The invention also provides a corresponding preparation method and application. Overcomes the defects of complex precursor synthesis, complex reaction system, multiple byproducts and the like in the traditional synthesis method.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a sulfur-containing 2,4, 5-trisubstituted oxazole compound, and a preparation method and application thereof.
Background
Oxazole is a five-membered heterocyclic compound containing one oxygen atom and one nitrogen atom, which occupy the 1-and 3-positions, respectively. Oxazole is a liquid with a similar smell to pyridine, and has a boiling point of 69-70 ℃, is easy to oxidize and not easy to hydrogenate, and the substituent group on the ring can have a certain influence on the stability of the ring.
In the last 80 s of the century, natural products with oxazole rings were isolated from marine organisms, and these oxazoles were derived from post-translational modification of peptides, from which studies on oxazoles began. Nowadays, the oxazole compounds are widely applied in the field of medicines, and the oxazole drugs are marketed and clinically shown in the fields of nervous system diseases, infectious diseases, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases and the like. In other fields such as tumor, respiratory system, etc., some of the drugs under investigation of oxazoles are also in the leading position. In addition, the oxazole compound can be used for fluorescent dye and polymer, and can also be used as a ligand for transition metal catalysis. Therefore, it is important to develop a method for efficiently constructing an oxazole ring.
At present, three main methods exist for synthesizing oxazole compounds, in particular 2,4, 5-trisubstituted oxazole compounds:
1) Starting from non-cyclized oxazole ring precursors, the oxazole ring is constructed by an intermolecular cyclization reaction, such as classical Robinson-Gabriel synthesis. The disadvantage of this type of process is that the preparation of acyclic precursors is cumbersome.
2) Functionalization modifications are made to the existing oxazole ring. The disadvantage of this type of process is that the selectivity of the reaction site is difficult to control, and that multiple steps of reaction are inevitably required to obtain the target compound.
3) Starting from alkyne, amide, enamine or other precursors, the target product is constructed through direct cyclization under the catalysis of transition metal or the mediation of iodine oxidizing agent (containing high-valence iodine reagent). Most of the methods require expensive transition metal catalysts or additional oxidants, and the application range of the substrate is limited.
Thus, there is a need to develop a simple and efficient method for synthesizing 2,4, 5-trisubstituted oxazole derivatives.
Disclosure of Invention
The invention aims to overcome the defects of the process for synthesizing the 2,4, 5-trisubstituted oxazole compounds in the prior art and provides a simple and efficient method for synthesizing oxazole molecules.
The invention provides a2, 4, 5-trisubstituted oxazole compound, which has a structure shown in a general formula I.
A sulfur-containing 2,4, 5-trisubstituted oxazole compound having a structure as shown in formula I:
Wherein,
R 1 is selected from naphthalene ring, aryl hetero group, C 1-4 alkyl, phenyl or benzene ring containing ring substituent;
R 2 is selected from: cyclohexyl, benzyl, phenyl or a benzene ring containing a substituent on the ring;
R 3 is selected from: a C 1-4 hydrocarbon group, a vinyl group, a cyclopentyl group, a benzyl phenyl group, or a benzene ring containing a substituent on the ring;
Preferably, the R 1 is selected from: phenyl or a benzene ring containing a ring substituent; the R 2 is selected from: phenyl (containing ring substituents).
In one embodiment according to the invention, any one selected from the following compounds:
the invention also provides a preparation method of the sulfur-containing 2,4, 5-trisubstituted oxazole compound, which is characterized by comprising the following steps of:
1) Using alkene II or alpha-halogenated ketone III containing R 1 substituent as initial substrate, and carrying out oxidative coupling reaction with thiol substrate thiol or thiophenol IV containing R 2 group to obtain beta-carbonyl sulfoxide V containing R 1 and R 2 groups;
2) And (3) reacting the obtained beta-carbonyl sulfoxide V with an organic nitrile VI containing an R 3 group to obtain the sulfur-containing 2,4, 5-trisubstituted oxazole compound I.
In one embodiment according to the invention, the olefin I is styrene; the sulfhydryl substrate IV is 4-chlorophenylthiol; the organic nitrile VI is selected from any one of acetonitrile, butyronitrile, benzonitrile or benzyl cyanide.
In one embodiment according to the invention, step 1) comprises:
Uniformly mixing styrene II, a fluorine reagent Selectfluor and a solvent methanol in a reaction container, slowly dripping a methanol solution of 4-chlorophenylthiol IV, maintaining the temperature at 0-30 ℃ after dripping, stirring and reacting until the reaction is complete, and performing post-treatment to obtain beta-carbonyl sulfoxide V; preferably, the reaction temperature is 10 to 20 ℃.
Wherein, the proportion of the solution of the styrene II, the fluorine reagent Selectfluor, the solvent methanol, the thiophenol IV and the methanol is 1:2:10:1.5:10.
In one embodiment according to the invention, step 2) comprises:
Adding beta-carbonyl sulfoxide V and organic nitrile VI into a reaction container filled with methylene dichloride, adding trifluoroacetic anhydride or trifluoromethanesulfonic anhydride or acetic anhydride, maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, and carrying out post-treatment to obtain a target product I, wherein the ratio of methylene dichloride, beta-carbonyl sulfoxide V, organic nitrile VI and anhydride is 10 in terms of ml: mmol: mmol: mmol: 1:6:1.1.
The invention also provides application of the sulfur-containing 2,4, 5-trisubstituted oxazole compound serving as an intermediate in preparation of medicines.
The invention also provides a method for preparing the novel sulfone compound by taking the sulfur-containing 2,4, 5-trisubstituted oxazole compound as an intermediate, which comprises the steps of mixing methylene dichloride, the sulfur-containing 2,4, 5-trisubstituted oxazole compound 1 and m-chloroperoxybenzoic acid in a reaction container, maintaining the temperature between 0 and 30 ℃ and stirring for reaction until the reaction is complete, thus preparing a target product 1a; wherein, in terms of ml: mmol, the ratio of dichloromethane, sulfur-containing 2,4, 5-trisubstituted oxazole compound 1 and m-chloroperoxybenzoic acid is 10:1:2.
The invention also provides a method for preparing a pharmaceutical compound by taking the sulfur-containing 2,4, 5-trisubstituted oxazole compound as an intermediate, which comprises the following steps:
Under the protection of nitrogen, uniformly mixing sulfur-containing 2,4, 5-trisubstituted oxazole compounds 1 and Ni (dppp) Cl 2 in a reaction vessel, then adding anhydrous tetrahydrofuran, then slowly dropwise adding a methyl magnesium chloride format reagent into the reaction system, and controlling the dropwise adding time to be about 5 min; maintaining the temperature at 0-30 ℃ and stirring for reaction for 10min, heating and refluxing for 10h until the reaction is complete, and performing post-treatment to obtain a target product 1b;
Wherein, the mol ratio of the sulfur-containing 2,4, 5-trisubstituted oxazole compound 1, ni (dppp) Cl 2, anhydrous tetrahydrofuran and methyl magnesium chloride format reagent is 10 in mmol: ml: 1:100:3.
The technical scheme of the invention has the following beneficial effects:
1) Firstly, synthesizing a beta-carbonyl sulfoxide intermediate from a simple and easily obtained olefin and methyl ketone substrate, and further reacting with organic nitrile under an acid catalytic system to synthesize the sulfur-containing 2, 4, 5-trisubstituted oxazole compound. The method is the biggest difference from the traditional method in that the target molecule is constructed through intermolecular cyclization reaction of the beta-carbonyl sulfoxide intermediate and the organic nitrile. The core of the method is that Lewis acid is introduced to efficiently convert the beta-carbonyl sulfoxide intermediate into alpha-carbonyl carbonium ion, and then the alpha-carbonyl carbonium ion is attacked by organic nitrile, and the target product is obtained through serial cyclization.
2) The synthesis yield of the invention is high, particularly the conversion rate of the step 2) is close to 100%, and almost no by-products are found, so that the invention has wide universality. Realizes the efficient and simple synthesis of the sulfur-containing 2, 4, 5-trisubstituted oxazole compounds. Overcomes the defects of complex precursor synthesis, complex reaction system, multiple byproducts and the like in the traditional synthesis method.
The 2,4, 5-trisubstituted oxazole compound provided by the invention is a novel functional material molecule with aggregation-induced emission (AIE) effect, and the fluorescence quantum yield can reach 72%.
Detailed Description
In order to make the technical problems, technical solutions and advantages to be solved by the present invention more apparent, the following detailed description will be made with reference to specific embodiments.
EXAMPLE 1 Synthesis of Compound 1
Step 1) to a 100ml round bottom flask was added p-chlorostyrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, the temperature is maintained at 10-20 ℃ after the dropwise addition, the reaction is stirred until the reaction is complete, the mixture is subjected to aftertreatment by ethyl acetate and saturated saline solution, and the beta-carbonyl sulfoxide 1' is separated by column chromatography, so that the yield is 62%. Characterization of data: white solid (m.p.128-129℃);1H NMR(400MHz,Chloroform-d)δ 7.82(d,J＝8.0Hz,2H),7.61(d,J＝8.0Hz,2H),7.48(d, J＝8.0Hz,2H),7.43(d,J＝8.0Hz,2H),4.38(dd,J＝14.4 Hz,75.2Hz,2H);13C{1H}NMR(100MHz,Chloroform-d)δ190.3, 141.6,141.2,138.2,134.5,130.4,129.9,129.4,125.9,65.8; IR(KBr):νmax 2945,1675,1385,1204,1047(S＝O),821,741, 495;HRMS(ESI,m/z)calcd.for C14H10Cl2NaO2S+[M+Na]+ 334.9671, found,334.9670.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 1' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring to react for about 30 minutes to completely react, performing aftertreatment by using ethyl acetate and saturated saline, and separating by column chromatography to obtain the target product 1 with the yield of 63%.
Characterization of data: white solid (m.p.88-92℃);1H NMR(400MHz,CDCl3) δ7.92(d,J＝8.0Hz,2H),7.39(d,J＝8.0Hz,2H),7.22-7.20(m,4H),2.54(s,3H);13C NMR(101MHz,CDCl3)δ161.1,151.3, 135.0,133.4,132.7,129.6,129.5,129.2,127.2,126.0,125.8, 14.3.IR(KBr):νmax 2922,1584,1738,1477,1089,810,477cm-1 HRMS(ESI,m/z)calcd.for C16H11Cl2NNaOS+[M+Na]+ 357.9831,found, 357.9832.
EXAMPLE 2 Synthesis of Compound 3
Step 1) to a 100ml round bottom flask was added 2-naphthalene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, the temperature is maintained at 10-20 ℃ after the dropwise addition, the reaction is stirred until the reaction is complete, ethyl acetate and saturated saline solution are used for post-treatment, and the corresponding beta-carbonyl sulfoxide 3' is separated through column chromatography, and the yield is 81%. Characterization of data: white solid (m.p.116-117℃);1H NMR(400MHz,Chloroform-d)δ 8.36(s,1H),7.93(t,J＝8.0Hz,2H),7.87(d,J＝8.0Hz,2H),7.67-7.55(m,4H),7.47(d,J＝8.0Hz,2H),4.57(dd,J ＝14.4Hz,104Hz,2H);13C{1H}NMR(100MHz,Chloroform-d)δ 191.2,141.9,138.1,136.2,133.4,132.4,131.6,130.0,129.8,129.5,129.1,128.1,127.4,126.0,123.7,66.2;IR(KBr):νmax 3057,1651,1469,1292,1047(S＝O),789,732,470;HRMS(ESI, m/z)calcd.for C18H13ClNaO2S+[M+Na]+351.0217,found,351.0218.
Step 2): to the dried reaction tube was added beta-carbonyl sulfoxide 3' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 3 by column chromatography, wherein the yield is 89%.
Characterization of data: white solid (m.p.118-120℃);1H NMR(400MHz,CDCl3) δ8.43(s,1H),8.13(d,J＝8.0Hz,1H),7.89-7.83(m,3H),7.52-7.51(m,2H),7.28(d,J＝8.0Hz,2H),7.23(d,J＝8.0 Hz,2H),2.59(s,3H);13C NMR(101MHz,CDCl3)δ161.1,152.5, 133.8,133.4,133.2,132.7,129.8,129.5,128.7,128.7,127.9,127.1,125.9,125.6,124.8,123.2,14.3.IR(KBr):νmax 3055, 2922,1580,1477,1089,815,738,469;HRMS(ESI,m/z)calcd. for C20H14ClNNaOS+[M+Na]+ 374.0377,found 374.0379.
EXAMPLE 3 Synthesis of Compound 4
Step 1) to a 100ml round bottom flask was added 4-methylstyrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, the temperature is maintained at 10-20 ℃ after the dropwise addition, the reaction is stirred until the reaction is complete, ethyl acetate and saturated saline solution are used for post-treatment, and the corresponding beta-carbonyl sulfoxide 4' is separated through column chromatography, and the yield is 56%. Characterization of data: white solid (m.p.89-90℃);1H NMR(400MHz,Chloroform-d) δ7.76(d,J＝8.0Hz,2H),7.63(d,J＝8.0Hz,2H),7.46(d, J＝8.0Hz,2H),7.25(d,J＝8.0Hz,2H),4.42(dd,J＝14.4Hz,102.8Hz,2H);13C{1H}NMR(100MHz,Chloroform-d)δ190.9, 145.7,142.1,137.9,133.6,129.8,129.1,126.0,66.1,22.0; IR(KBr):νmax 2948,1671,1385,1179,1047(S＝O),808,498; HRMS(ESI,m/z)calcd.for C15H13ClNaO2S+[M+Na]+ 315.0217,found, 315.0215.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 4' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 4 by column chromatography, wherein the yield is 74%.
Characterization of data: white solid (m.p.80-82℃);1H NMR(400MHz,CDCl3) δ7.85(d,J＝8.0Hz,2H),7.23-7.21(m,6H),2.5(s,3H), 2.37(s,3H);13C NMR(101MHz,CDCl3)δ160.6,152.8,139.3, 134.1,132.4,129.6,129.4,129.4,126.0,124.8,124.4,21.5, 14.3.IR(KBr):νmax3025,1588,1477,1255,1161,1089,810, 477;HRMS(ESI,m/z)calcd.for C17H14ClNNaOS+[M+Na]+ 338.0377, found 338.0376.
EXAMPLE 4 Synthesis of Compound 5
Step 1) to a 100ml round bottom flask was added 4-bromostyrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, the temperature is maintained at 10-20 ℃ after the dropwise addition, the reaction is stirred until the reaction is complete, ethyl acetate and saturated saline solution are used for post-treatment, and the corresponding beta-carbonyl sulfoxide 5' is separated through column chromatography, so that the yield is 66%. Characterization of data: white solid (m.p.118-119℃);1H NMR(400MHz,Chloroform-d)δ7.74(d,J＝8.0Hz,2H),7.61(d,J＝8.0Hz,4H),7.49(d, J＝8.0Hz,2H),4.38(dd,J＝14.4Hz,74.4Hz,2H);13C{1H} NMR(100MHz,Chloroform-d)δ190.5,141.6,138.2,134.9,132.4,130.5,130.1,129.9,125.9,65.7;IR(KBr):νmax 2945, 1671,1582,1389,1043(S＝O),817,515;HRMS(ESI,m/z)calcd.for C14H10BrClNaO2S+[M+Na]+ 378.9166,found,378.9168.
Step 2): to the dried reaction tube was added 5' (0.3 mmol) of β -carbonyl sulfoxide, acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 5 by column chromatography to obtain the yield of 73%.
Characterization of data: white solid (m.p.96-97℃);1H NMR(400MHz,CDCl3) δ7.85(d,J＝8.0Hz,2H),7.55(d,J＝8.0Hz,2H),7.26-7.20(m,4H),2.53(s,3H);13C NMR(101MHz,CDCl3)δ161.1,151.3, 133.3,132.8,132.1,129.7,129.5,127.4,126.4,126.0,123.3, 14.3.IR(KBr):νmax 3131,2922,1892,1584,1478,1256,1165, 1089,1012,810,478;HRMS(ESI,m/z)calcd.for C16H11BrClNNaOS+[M+Na]+ 401.9325,found,401.9326.
EXAMPLE 5 Synthesis of Compound 7
Step 1) to a 100ml round bottom flask was added 1-bromo-2-butanone (1.0 mmol), 4-chlorophenylthiol (1.0 mmol), potassium carbonate (1 eqv) and 10ml ethanol and stirred at room temperature for about 2h until reaction was complete. The ethanol in the reaction solution was distilled under reduced pressure, followed by post-treatment with ethyl acetate and saturated brine, and the ethyl acetate phase was taken and distilled again under reduced pressure to remove ethyl acetate. CH 2Cl2 (10 ml) was added, m-CPBA (1 eqv) was slowly added with stirring in an ice water bath, and after half an hour of reaction, the mixture was post-treated with dichloro and saturated brine, and the corresponding beta-carbonyl sulfoxide 7' was isolated by column chromatography in 71% yield. Characterization of data: white solid (m.p.90-92℃);1H NMR(400 MHz,CDCl3)δ7.59(d,J＝8.0Hz,2H),7.51(d,J＝8.0Hz, 2H),3.82(dd,J＝13.6,33.2Hz,2H),2.60-2.43(m,2H)1.02 (t,J＝8.0Hz,3H);13C NMR(101MHz,CDCl3)δ202.1,141.6, 138.0,129.9,125.7,67.9,38.6,7.3.IR(KBr):νmax 3055,2943, 1704,1353,1032,819,743,494;HRMS(ESI,m/z)calcd.for C10H11ClNaO2S+[M+Na]+ 253.0060,found 253.0062.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 7' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 7 by column chromatography, wherein the yield is 45%.
Characterization of data: colorless transparent oily liquid ;1H NMR(400MHz,CDCl3)δ7.21 (d,J＝8.0Hz,2H),7.13(d,J＝8.0Hz,2H),2.75(q,J＝8.0 Hz,2H),2.44(s,3H),1.21(t,J＝8.0Hz,3H);13C NMR(101 MHz,CDCl3)δ162.7,159.7,135.6,131.6,129.1,128.4,122.3, 33.0,29.4,14.1.IR(KBr):νmax 3105,1687,1516,1341,1093, 807,696,478;HRMS(ESI,m/z)calcd.for C12H12ClNNaOS+[M+Na]+276.0220,found,276.0221.
EXAMPLE 6 Synthesis of Compound 8
Step 1) to a 100ml round bottom flask was added 1-bromoppinacolone (1.0 mmol), 4-chlorophenylthiol (1.0 mmol), potassium carbonate (1 eqv) and 10ml ethanol and stirred at room temperature for about 2h until reaction was complete. The ethanol in the reaction solution was distilled under reduced pressure, followed by post-treatment with ethyl acetate and saturated brine, and the ethyl acetate phase was taken and distilled again under reduced pressure to remove ethyl acetate. CH 2Cl2 (10 ml) was added, m-CPBA (1 eqv) was slowly added with stirring in an ice water bath, and after half an hour of reaction, the mixture was post-treated with dichloro and saturated brine, and the corresponding beta-carbonyl sulfoxide 8' was isolated by column chromatography in 77% yield. Characterization of data: white solid (m.p.48℃);1H NMR(400MHz,CDCl3) δ7.65(d,J＝8.0Hz,2H),7.50(d,J＝8.0Hz,2H),4.01(dd, J＝14.2,139.2Hz,2H),1.06(s,9H);13C NMR(101MHz,CDCl3) δ207.5,142.6,137,9,129.7,126.0,65.5,44.8,25.7;IR (KBr):νmax 2931,1640,1477,1362,1042,819,743,494;HRMS(ESI,m/z)calcd.for C12H15ClNaO2S+[M+Na]+ 281.0373,found, 281.0374.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 8' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 8 by column chromatography, wherein the yield is 83%.
Characterization of data: white solid (m.p.103℃);1H NMR(400MHz,CDCl3)δ 7.19(d,J＝8.0Hz,2H),7.09(d,J＝8.0Hz,2H),2.41(s, 3H),1.36(s,9H);13C NMR(101MHz,CDCl3)δ161.7,158.7,134.6, 130.6,128.1,127.4,121.3,32.0,28.4,13.1.IR(KBr):νmax2973,1597,1469,1298,1089,1003,810,481;HRMS(ESI,m/z) calcd.for C14H16ClNNaOS+[M+Na]+304.0533,found,324.0222.
EXAMPLE 7 Synthesis of Compound 9
Step 1) to a 100ml round bottom flask was added 2-vinylthiophene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and stirred at room temperature for 5min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, the temperature is maintained at 10-20 ℃ after the dropwise addition, the reaction is stirred until the reaction is complete, ethyl acetate and saturated saline solution are used for post-treatment, and the corresponding beta-carbonyl sulfoxide 9' is separated through column chromatography, and the yield is 55%. Characterization of data: white solid (m.p.105-106℃);1H NMR(400MHz,Chloroform-d)δ 7.73(d,J＝5.2Hz,1H),7.67(d,J＝4.0Hz,1H),7.61(d, J＝8.0Hz,2H),7.47(d,J＝8.0Hz,2H),7.13(t,J＝4.4Hz, 1H),4.32(dd,J＝13.6Hz,87.6Hz,2H);13C{1H}NMR(100MHz, Chloroform-d)δ183.3,143.7,141.8,138.2,136.3,134.7, 129.8,128.8,125.9,66.4;IR(KBr):νmax 2928,1642,1414,1291, 1047(S＝O),785,739,587,497,443;HRMS(ESI,m/z)calcd.for C12H9ClNaO2S2 +[M+Na]+ 306.9625,found,306.9627.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 9' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 9 by column chromatography, wherein the yield is 92%.
Characterization of data: white solid (m.p.85℃);1H NMR(400MHz,CDCl3)δ 7.56-7.55(m,1H),7.37-7.36(m,1H),7.26-7.20(m,4H), 7.09-7.07(m,1H),2.52(s,3H);13C NMR(101MHz,CDCl3)δ160.5, 149.5,133.6,132.7,129.7,129.4,128.7,127.7,127.3,126.3,124.1,14.3.HRMS(ESI,m/z)calcd.for C16H12ClNNaOS+[M+Na]+ 324.7772,found,324.7774.
EXAMPLE 8 Synthesis of Compound 10
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, the temperature is maintained at 10-20 ℃ after the dropwise addition, the reaction is stirred until the reaction is complete, the mixture is subjected to aftertreatment by ethyl acetate and saturated saline, and the corresponding beta-carbonyl sulfoxide 10' is separated by column chromatography, and the yield is 91%. Characterization of data: white solid (m.p.78℃);1H NMR(400MHz,Chloroform-d)δ7.86(d, J＝8.0Hz,2H),7.64-7.58(m,3H),7.47-7.43(m,4H),4.44(dd, J＝14.4Hz,97.2Hz,2H);13C{1H}NMR(100MHz,Chloroform-d) δ191.4,141.9,138.0,136.0,134.5,130.0,129.1,128.9, 126.0,66.1;IR(KBr):νmax 3049,2904,1675,1450,1301,1204, 1034(S＝O),821,744,547;HRMS(ESI,m/z)calcd.for C14H11ClNaO2S+[M+Na]+ 301.0060,found,301.0061.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 10' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating by column chromatography to obtain the target product 10 with the yield of 99%.
Characterization of data: white solid (m.p.85℃);1H NMR(400MHz,CDCl3)δ 7.97(d,J＝8.0Hz,2H),7.42(t,J＝8.0Hz,2H),7.36(t, J＝8.0Hz,1H),7.23-7.22(m,4H),2.54(s,3H);13C NMR(101 MHz,CDCl3)δ160.9,152.4,133.9,132.6,129.6,129.4,129.1, 128.9,127.5,126.0,125.3,14.3.IR(KBr):νmax 3058,1588,1477,1255,1089,815,682,477;HRMS(ESI,m/z)calcd.for C16H12ClNNaOS+[M+Na]+ 324.0220,found,324.0222.
EXAMPLE 9 Synthesis of Compound 12
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-methyl thiophenol (1.5 mmol) is slowly added dropwise, the temperature is maintained at 10-20 ℃ after the dropwise addition, the reaction is stirred until the reaction is complete, ethyl acetate and saturated saline solution are used for aftertreatment, and the corresponding beta-carbonyl sulfoxide 12' is separated through column chromatography, so that the yield is 75%. Characterization of data: white solid (m.p.43℃);1H NMR(400MHz,Chloroform-d)δ 7.88(d,J＝8.0Hz,2H),7.61-7.54(m,3H),7.45(t,J＝8.0 Hz,2H),7.30(d,J＝8.0Hz,2H),4.42(dd,J＝14.0Hz,116Hz,2H),2.39(s,3H);13C{1H}NMR(100MHz,Chloroform-d)δ 191.6,142.4,140.1,136.2,134.3,130.2,129.0,124.5,66.3, 21.7;IR(KBr):νmax 3061,1679,1450,1276,1051(S＝O),808, 688,502;HRMS(ESI,m/z)calcd.for C15H14NaO2S+[M+Na]+ 281.0607, found,281.0606.
Step 2): to the dried reaction tube was added beta-carbonyl sulfoxide 12' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 12 by column chromatography to obtain the yield of 41%.
Characterization of data: pale yellow oily liquid ;1H NMR(400MHz,CDCl3)δ8.01(d, J＝8.0Hz,2H),7.42(t,J＝8.0Hz,2H),7.34(t,J＝8.0Hz, 1H),7.23(d,J＝8.0Hz,2H),7.07(d,J＝8.0Hz,2H),2.52 (s,4H),2.29(s,3H);13C NMR(101MHz,CDCl3)δ160.6,151.8, 136.6,131.5,130.0,128.8,128.8,127.8,126.4,125.9,21.1, 14.3.IR(KBr):νmax 2922,2361,1580,1490,1255,1170,1084,763,691,486;HRMS(ESI,m/z)calcd.for C17H15NNaOS+[M+Na]+ 304.0767,found,304.0768.
EXAMPLE 10 Synthesis of Compound 14
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-bromothiophenol (1.5 mmol) is slowly added dropwise, the temperature is maintained at 10-20 ℃ after the dropwise addition, the reaction is stirred until the reaction is complete, ethyl acetate and saturated saline solution are used for aftertreatment, and the corresponding beta-carbonyl sulfoxide 14' is separated by column chromatography, so that the yield is 74%. Characterization of data: white solid (m.p.81-82℃);1H NMR(400MHz,Chloroform-d)δ7.86 (d,J＝8.0Hz,2H),7.64-7.55(m,5H),7.46(t,J＝7.6Hz, 2H),4.44(dd,J＝14.4Hz,98.0Hz,2H);13C{1H}NMR(100MHz, Chloroform-d)δ191.4,142.6,136.0,134.5,132.7,129.1, 128.9,126.3,126.1,66.1;IR(KBr):νmax 3049,2904,1675,1276, 1030(S＝O),821,724,523;HRMS(ESI,m/z)calcd.for C14H11BrNaO2S+[M+Na]+ 344.9555,found,344.9553.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 14' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 14 by column chromatography, wherein the yield is 85%.
Characterization of data: white solid (m.p.75℃);1H NMR(400MHz,CDCl3)δ 7.97(d,J＝8.0Hz,2H),7.42(t,J＝8.0Hz,2H),7.36(m, 3H),7.16(d,J＝8.0Hz,2H),2.54(s,3H);13C NMR(101MHz, CDCl3)δ160.9,152.5,134.5,132.3,129.7,129.1,128.9, 127.4,126.0,125.0,14.3.IR(KBr):νmax 3055,2926,2361,1879,1584,1473,1084,807,665,469;HRMS(ESI,m/z)calcd. for C16H12BrNNaOS+[M+Na]+ 367.9715,found,367.9716.
EXAMPLE 11 Synthesis of Compound 16
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Step 1) to a 100ml round bottom flask was added alpha-chloroacetophenone (1.0 mmol), benzyl mercaptan (1.0 mmol), potassium carbonate (1 eqv) and 10ml ethanol and stirred at room temperature for about 2h to completion. The ethanol in the reaction solution was distilled under reduced pressure, followed by post-treatment with ethyl acetate and saturated brine, and the ethyl acetate phase was taken and distilled again under reduced pressure to remove ethyl acetate. CH 2Cl2 (10 ml) was added, m-CPBA (1 eqv) was slowly added with stirring in an ice water bath, and after half an hour of reaction, the mixture was post-treated with dichloro and saturated brine, and the corresponding beta-carbonyl sulfoxide 16' was isolated by column chromatography in 69% yield. Characterization of data: white solid (m.p.52℃);1H NMR(400 MHz,CDCl3)δ7.91(d,J＝8.0Hz,2H),7.63(t,J＝8.0Hz, 1H),7.49(t,J＝8.0Hz,2H),7.36-7.34(m,5H),4.32-4.23(m, 2H),4.15-4.11(m,2H);13C NMR(101MHz,CDCl3)δ192.8,136.1, 134.5,130.6,129.3,129.1,128.8,128.8,57.8,57.8;IR(KBr): νmax 3131,2875,1679,1400,1302,1200,1042,751,686,478; HRMS(ESI,m/z)calcd.for C15H14NaO2S+[M+Na]+ 281.0607,found, 281.0608.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 16' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 16 by column chromatography, wherein the yield is 52%.
Characterization of data: pale yellow oily liquid ;1H NMR(400MHz,CDCl3)δ7.75 (d,J＝8.0Hz,2H),7.34(t,J＝8.0Hz,2H),7.27-7.15(m, 6H),4.20(s,2H),2.51(s,3H);13C NMR(101MHz,CDCl3)δ160.2, 149.1,137.5,129.0,128.6,128.5,128.1,128.0,127.3,125.5, 38.,14.2.IR(KBr):νmax 3028,1580,1443,1264,1067,982,691,464;HRMS(ESI,m/z)calcd.for C17H15NNaOS+[M+Na]+ 304.0767, found,304.0767.
EXAMPLE 11 Synthesis of Compound 17
Step 1) to a 100ml round bottom flask was added alpha-chloroacetophenone (1.0 mmol), n-hexanethiol (1.0 mmol), potassium carbonate (1 eqv mmol) and 10ml ethanol and stirred at room temperature for about 2h to completion. The ethanol in the reaction solution was distilled under reduced pressure, followed by post-treatment with ethyl acetate and saturated brine, and the ethyl acetate phase was taken and distilled again under reduced pressure to remove ethyl acetate. CH2Cl2 (10 ml) was added, m-CPBA (1 eqv) was slowly added with stirring in an ice water bath, after half an hour of reaction, the mixture was post-treated with dichloro and saturated brine, and the corresponding beta-carbonyl sulfoxide 17' was isolated by column chromatography in 61% yield. Characterization of data: white solid (m.p.51-52℃);1H NMR(400MHz,CDCl3)δ7.99(d,J＝8.0Hz,2H),7.64(t,J＝8.0Hz, 1H),7.52(t,J＝8.0Hz,2H),4.86(dd,J＝14.0,61.2Hz,2H), 2.96-2.80(m,2H),1.86-1.79(m,2H),1.53-1.40(m,2H),1.36-1.25(m,2H),0.90-0.87(m,3H);13C NMR(101MHz,CDCl3) δ192.3,136.2,134.6,129.1,129.0,60.4,53.3,31.5,28.5, 22.6,22.5,14.1;IR(KBr):νmax 2926,1671,1447,1282,1200, 1024,729,571;HRMS(ESI,m/z)calcd.for C14H20NaO2S+[M+Na]+ 275.1076,found,275.1077.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide 17' (0.3 mmol), acetonitrile (3 ml) as a reaction substrate and a solvent, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 17 by column chromatography, wherein the yield is 60%.
Characterization of data: colorless transparent oily liquid ;1H NMR(400MHz,CDCl3)δ7.91 (d,J＝8.0Hz,2H),7.41(t,J＝8.0Hz,2H),7.31-7.28(m, 1H),2.99(t,J＝8.0Hz,2H),2.50(s,3H),1.66-1.58(m,2H),1.42-1.36(m,2H),1.28-1.20(m,4H),0.86-0.83(m,3H);13C NMR (101MHz,CDCl3)δ160.1,148.3,128.9,128.7,128.4,128.0, 125.4,34.1,31.4,29.8,28.4,22.6,14.1.IR(KBr):νmax 2926, 1580,1444,1268,1179,1068,982,763,691;HRMS(ESI,m/z)calcd.for C16H21NNaOS+[M+Na]+ 298.1236,found,298.1236.
EXAMPLE 12 Synthesis of Compound 18
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, after the addition, the temperature is maintained at 10-20 ℃ and the reaction is stirred until the reaction is complete, the mixture is treated with ethyl acetate and saturated saline water, and the corresponding beta-carbonyl sulfoxide is obtained through column chromatography separation.
Step 2): to the dried reaction tube were added β -carbonyl sulfoxide (0.3 mmol), butyronitrile (1.8 mmol) and CH 2Cl2 (3 ml) as solvents, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 18 by column chromatography, wherein the yield is 93%.
Characterization of data: white solid (m.p.45-48℃);1H NMR(400MHz,CDCl3) δ7.98(d,J＝8.0Hz,2H),7.42(t,J＝8.0Hz,2H),7.35(t, J＝8.0Hz,1H),7.23-7.19(m,4H),2.82(t,J＝8.0Hz,2H),2.91-1.82(m,2H),1.04(t,J＝8.0Hz,3H);13C NMR(101MHz, CDCl3)δ164.3,152.4,134.0,132.3,129.3,129.2,129.1, 128.8,127.6,126.0,124.8,30.3,20.6,13.8.IR(KBr):νmax3058,2931,1580,1473,1089,815,682,490;HRMS(ESI,m/z) calcd.for C18H16ClNNaOS+[M+Na]+ 352.0533,found,352.0534.
EXAMPLE 13 Synthesis of Compound 20
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, after the addition, the temperature is maintained at 10-20 ℃ and the reaction is stirred until the reaction is complete, the mixture is treated with ethyl acetate and saturated saline water, and the corresponding beta-carbonyl sulfoxide is obtained through column chromatography separation.
Step 2): to the dried reaction tube were added β -carbonyl sulfoxide (0.3 mmol), cyclopentanitrile (1.8 mmol) and CH 2Cl2 (3 ml) as solvents, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 20 by column chromatography, wherein the yield is 90%.
Characterization of data: white solid (m.p.59-61℃);1H NMR(400MHz,CDCl3) δ7.97(d,J＝8.0Hz,2H),7.42(t,J＝8.0Hz,2H),7.35(t, J＝8.0Hz,1H),7.23-7.18(m,4H),3.33-3.26(m,1H),2.16-2.08(m,2H),2.03-1.94(m,2H),1.87-1.78(m,2H),1.74-1.65(m, 2H);13C NMR(101MHz,CDCl3)δ167.6,152.3,134.2,132.2, 129.4,129.3,129.1,129.0,128.8,127.6,124.5,38.7,31.6, 25.7.IR(KBr):νmax 2926,1571,1469,1178,1084,1003,815,686,490;HRMS(ESI,m/z)calcd.for C20H18ClNNaOS+[M+Na]+ 378.0690,found,378.0690.
EXAMPLE 14 Synthesis of Compound 23
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, after the addition, the temperature is maintained at 10-20 ℃ and the reaction is stirred until the reaction is complete, the mixture is treated with ethyl acetate and saturated saline water, and the corresponding beta-carbonyl sulfoxide is obtained through column chromatography separation.
Step 2): to the dried reaction tube were added β -carbonyl sulfoxide (0.3 mmol), 4-bromobutyronitrile (1.8 mmol) and CH 2Cl2 (3 ml) as solvents, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 23 by column chromatography, wherein the yield is 79%.
Characterization of data: colorless transparent oily liquid ;1H NMR(400MHz,CDCl3)δ7.97 (d,J＝8.0Hz,2H),7.43(t,J＝8.0Hz,2H),,7.27(t,J＝ 8.0Hz,1H),7.26-7.19(m,4H),3.54(t,J＝8.0Hz,2H),3.04 (t,J＝8.0Hz,2H),2.43-2.37(m,2H);13C NMR(101MHz,CDCl3) δ162.7,152.6,133.8,132.5,129.5,129.4,129.3,128.9,127.3,126.1,125.1,32.5,29.5,26.9.IR(KBr):νmax 3058,2922, 1892,1679,1580,1473,1217,1089,810,686,477;HRMS(ESI,m/z)calcd.for C18H15BrClNNaOS+[M+Na]+ 429.9638,found, 429.9638.
EXAMPLE 15 Synthesis of Compound 25
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, after the addition, the temperature is maintained at 10-20 ℃ and the reaction is stirred until the reaction is complete, the mixture is treated with ethyl acetate and saturated saline water, and the corresponding beta-carbonyl sulfoxide is obtained through column chromatography separation.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide (0.3 mmol), adiponitrile (1.8 mmol) and CH 2Cl2 (3 ml) as solvents, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 25 by column chromatography to obtain the yield of 75%.
Characterization of data: colorless transparent oily liquid ;1H NMR(400MHz,CDCl3)δ7.96 (d,J＝8.0Hz,2H),7.45-7.35(m,3H),7.24-7.19(m,4H),2.90 (t,J＝8.0Hz,2H),2.41(t,J＝8.0Hz,2H),2.05-1.97(m, 2H),1.83-1.76(m,2H);13C NMR(101MHz,CDCl3)δ163.0,152.6, 133.7,132.5,129.4,129.4,129.3,128.9,127.3,126.1,125.1, 119.4,27.5,25.8,24.9,17.1.IR(KBr):νmax 2931,2247,1571,1473,1173,1089,1012,691,486;HRMS(ESI,m/z)calcd.for C20H17ClN2NaOS+[M+Na]+ 391.0642,found,391.0644.
EXAMPLE 16 Synthesis of Compound 29
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, after the addition, the temperature is maintained at 10-20 ℃ and the reaction is stirred until the reaction is complete, the mixture is treated with ethyl acetate and saturated saline water, and the corresponding beta-carbonyl sulfoxide is obtained through column chromatography separation.
Step 2): to the dried reaction tube were added β -carbonyl sulfoxide (0.3 mmol), benzyl cyanide (1.8 mmol) and CH 2Cl2 (3 ml) as solvents, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 29 by column chromatography, wherein the yield is 90%.
Characterization of data: white solid (m.p.101℃);1H NMR(400MHz,CDCl3)δ 7.94(d,J＝8.0Hz,2H),7.42-7.28(m,8H),7.24-7.20(m,4H), 4.19(s,2H);13C NMR(101MHz,CDCl3)δ162.3,152.9,135.1, 133.8,132.5,129.4,129.4,129.3,129.0,129.0,128.9,127.4, 126.1,125.2,34.9.IR(KBr):νmax 3058,1896,1563,1473,1084,998,810,686,575,481;HRMS(ESI,m/z)calcd.for C22H16ClNNaOS+[M+Na]+ 400.0533,found,400.0533.
EXAMPLE 17 Synthesis of Compound 30
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, after the addition, the temperature is maintained at 10-20 ℃ and the reaction is stirred until the reaction is complete, the mixture is treated with ethyl acetate and saturated saline water, and the corresponding beta-carbonyl sulfoxide is obtained through column chromatography separation.
Step 2): to the dried reaction tube were added β -carbonyl sulfoxide (0.3 mmol), benzonitrile (1.8 mmol) and CH 2Cl2 (3 ml) as solvents, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product by column chromatography to obtain the target product 30 with the yield of 91%.
Characterization of data: white solid (m.p.144-145℃);1H NMR(400MHz,CDCl3) δ8.14-8.07(m,4H),7.50-7.45(m,5H),7.40(t,J＝8.0Hz,1H),7.28-7.22(m,4H);13C NMR(101MHz,CDCl3)δ160.7,152.6, 133.9,132.5,131.1,129.4,129.4,129.3,129.0,129.0,127.4, 126.8,126.8,14.3.IR(KBr):νmax 3058,2361,1554,1477, 1089,810,682,486;HRMS(ESI,m/z)calcd.for C21H14ClNNaOS+[M+Na]+ 386.0377,found 386.0377.
EXAMPLE 18 Synthesis of Compound 39
Step 1) to a 100ml round bottom flask was added styrene (1.0 mmol), fluoro reagent SelectFluor (2.0 mmol) and 10ml methanol, and after stirring at room temperature for 5 min. Then 10ml of methanol solution containing 4-chlorophenylthiol (1.5 mmol) is slowly added dropwise, after the addition, the temperature is maintained at 10-20 ℃ and the reaction is stirred until the reaction is complete, the mixture is treated with ethyl acetate and saturated saline water, and the corresponding beta-carbonyl sulfoxide is obtained through column chromatography separation.
Step 2): to the dried reaction tube was added β -carbonyl sulfoxide (0.3 mmol), adiponitrile (0.15 mmol) and CH 2Cl2 (3 ml) as solvents, and stirred for 5min. Then adding trifluoromethanesulfonic anhydride (1.1 eqv), maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, carrying out post-treatment by using ethyl acetate and saturated saline, and separating the target product 39 by column chromatography, wherein the yield is 50%.
Characterization of data: yellow solid (m.p.80-81℃);1H NMR(400MHz,CDCl3) δ7.95(d,J＝8.0Hz,4H),7.43-7.34(m,6H),7.22-7.18(m,8H),2.96-2.85(m,4H),2.02-1.94(m,4H);13C NMR(101MHz,CDCl3) δ163.7,152.6,133.9,132.4,129.4,129.3,129.2,128.9,127.4,126.1,125.0,28.0,26.4.IR(KBr):νmax 3144,2926, 1679,1473,1170,1089,1007,815,682;HRMS(ESI,m/z)calcd.for C16H11Cl2NNaOS+[M+Na]+ 357.9831,found,357.9832.
Example 19 conversion reaction 1:
To a reaction vessel containing 5ml of methylene dichloride, sulfur-containing 2,4, 5-trisubstituted oxazole compound 1 (0.5 mmol), m-chloroperoxybenzoic acid (0.75 mmol) were added, the temperature was maintained at 0-30 ℃ and the reaction was stirred until the reaction was complete, and the target product 1a was obtained in 78% yield. The compound can be used for the subsequent desulfonation-functional group conversion reaction under the catalysis of palladium, and the modification of the group at the site of the number 4 oxazole is realized.
Characterization of data: white solid (m.p.133-135℃);1H NMR(400MHz,CDCl3) δ7.93-7.91(m,4H),7.49-7.46(m,5H),2.48(s,3H);13C NMR (101MHz,CDCl3)δ160.7,153.1,140.5,139.0,134.9,130.9, 129.7,129.6,129.0,128.7,125.8,14.0.IR(KBr):νmax 3097,1589,1477,1332,1153,832,760,631,469;HRMS(ESI,m/z)calcd. for C16H12ClNNaO3S+[M+Na]+356.0119,found 356.0119.
Example 20 conversion reaction 2:
Sulfur-containing 2,4, 5-trisubstituted oxazoles 1 (0.5 mmol), ni (dppp) Cl 2 (0.05 mmol) and then 5ml anhydrous tetrahydrofuran were added under nitrogen atmosphere, then methyl magnesium chloride format reagent (3.0M solution in THF, 1.5 mmol) was slowly added dropwise to the reaction system, and the dropwise addition time was controlled to be about 5 min. Maintaining the temperature at 0-30 ℃ and stirring for reaction for 10min, heating and refluxing for 10h until the reaction is complete, and performing post-treatment to obtain the target product 1b with the yield of 56%. The functional group conversion of the oxazole 4 site can be realized by using format reagents with different structures, and a new way is provided for the synthesis of oxazole derivatives.
Characterization of data: colorless transparent oily liquid ;1H NMR(400MHz,CDCl3)δ7.57 (d,J＝8.0Hz,2H),7.42(t,J＝8.0Hz,2H),7.31-7.26(m, 1H),2.48(s,3H),2.38(s,3H);13C NMR(101MHz,CDCl3)δ159.5, 145.3,131.8,129.5,127.4,125.2,14.1,13.4.IR(KBr):νmax 2926,1580,1443,1272,1012,768,696;HRMS(ESI,m/z)calcd.for C11H11NNaO+[M+Na]+ 196.0733,found 196.0733.
While the foregoing is directed to the preferred embodiments of the present invention, it will be appreciated by those skilled in the art that various modifications and adaptations can be made without departing from the principles of the present invention, and such modifications and adaptations are intended to be comprehended within the scope of the present invention.
Claims (5)
1. The sulfur-containing 2,4, 5-trisubstituted oxazole compound is characterized by having a structure as shown in formula I:
2. The method for producing a sulfur-containing 2,4, 5-trisubstituted oxazole compound according to claim 1, wherein the following reaction formula is shown:
adding styrene, a fluorine reagent Selectfluor and 10ml of methanol into a 100ml round bottom flask, stirring for 5min at room temperature, slowly dripping 10ml of a methanol solution containing 4-chlorophenylthiol, maintaining the temperature at 10-20 ℃ after dripping, stirring for reaction until the reaction is complete, performing post-treatment by using ethyl acetate and saturated saline, and separating by column chromatography to obtain corresponding beta-carbonyl sulfoxide 10';
Step 2): adding beta-carbonyl sulfoxide 10' and acetonitrile as reaction substrates and solvents into a dried reaction tube, stirring for 5min, then adding trifluoromethane sulfonic anhydride, maintaining the temperature at 0-30 ℃ and stirring for reaction until the reaction is complete, performing post-treatment with ethyl acetate and saturated saline solution, and separating by column chromatography to obtain a target product 10, namely the sulfur-containing 2,4, 5-trisubstituted oxazole compound shown in the formula I.
3. The use of the sulfur-containing 2,4, 5-trisubstituted oxazole compounds as defined in claim 1 as intermediates in organic synthesis functional group conversion reactions.
4. A process for preparing 2,4, 5-trisubstituted oxazoles from sulfur-containing 2,4, 5-trisubstituted oxazoles as claimed in claim 1, characterized in that sulfur-containing 2,4, 5-trisubstituted oxazoles of formula I, ni (dppp) Cl 2 are mixed uniformly in a reaction vessel under nitrogen atmosphere, then anhydrous tetrahydrofuran is added, then format reagent is slowly added dropwise into the reaction system, and the dropwise addition time is controlled to be about 5 min; maintaining the temperature at 0-30 ℃ and stirring for reaction for 10min, heating and refluxing for 10h until the reaction is complete, and performing post-treatment to obtain a target product 1b, wherein the 1b has a structure shown as the following
5. A process for producing a 2,4, 5-trisubstituted oxazole compound comprising an amount of 2,4, 5-trisubstituted oxazole compound according to claim 4 as an intermediate, wherein: the format reagent is methyl magnesium chloride.
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| CN104402839A (en) * | 2014-10-20 | 2015-03-11 | 同济大学 | (E)-2,4,5-trisubstituted-(1-propenyl)oxazole ring compound and preparation method thereof |
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