AU2021107259A4 - Oxazolone derivative and synthesis method thereof - Google Patents
Oxazolone derivative and synthesis method thereof Download PDFInfo
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- AU2021107259A4 AU2021107259A4 AU2021107259A AU2021107259A AU2021107259A4 AU 2021107259 A4 AU2021107259 A4 AU 2021107259A4 AU 2021107259 A AU2021107259 A AU 2021107259A AU 2021107259 A AU2021107259 A AU 2021107259A AU 2021107259 A4 AU2021107259 A4 AU 2021107259A4
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- SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical class O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 title claims abstract description 32
- 238000001308 synthesis method Methods 0.000 title claims abstract description 14
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical group CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000007800 oxidant agent Substances 0.000 claims abstract description 10
- 230000003647 oxidation Effects 0.000 claims abstract description 10
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 10
- 230000001590 oxidative effect Effects 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 6
- 230000008707 rearrangement Effects 0.000 claims abstract description 5
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 5
- 238000010504 bond cleavage reaction Methods 0.000 claims abstract description 4
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 2
- 239000003570 air Substances 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 2
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 2
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 claims description 2
- 239000012414 tert-butyl nitrite Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 229910000510 noble metal Inorganic materials 0.000 abstract 1
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 238000004896 high resolution mass spectrometry Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960003907 linezolid Drugs 0.000 description 2
- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102100020870 La-related protein 6 Human genes 0.000 description 1
- 108050008265 La-related protein 6 Proteins 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 150000003384 small molecules Chemical class 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The present disclosure provides an oxazolone derivative and a synthesis method
thereof. 4-alkylthio-4-amino-3-butene-2-one is used as a raw material, and is
subjected to oxidation, double bond cleavage and rearrangement and cyclization
under catalysis of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (4-OH-TEMPO)
and oxidation of an oxidant, to one-step construct an oxazolone derivative having a
structure shown in a following general formula I; the oxazolone derivative is widely
used in medicine and other fields. The method does not require catalysis of noble
metals, and has easily-available raw materials, simple and convenient operation, high
efficiency, wide substrate adaptability and diverse functional groups.
Description
[0001] The present disclosure relates to an oxazolone derivative and a synthesis method thereof. 4-alkylthio-4-amino-3-butene-2-one II is subjected to oxidation, double bond cleavage and rearrangement and cyclization under catalysis of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (4-OH-TEMPO) and oxidation of an oxidant, to synthesize an oxazolone derivative. The present disclosure belongs to the field of new medicine research and development.
[0002] Over the years, bacteria have shown increasing drug resistance as antibiotics have become popular around the world and continue to be abused, and new-generation antibiotics have been used to replace traditional antibiotics. It is a global issue to actively find a novel medicine that can deal with bacteria having multi-antibiotic resistance. Oxazolone is a novel fully-synthetic antibacterial agent with great development prospects. In 2000, linezolid was approved by the FDA to be marketed in the United States, and became the first oxazolone medicine approved for clinical use (reference to Tsiodras, Sotirios, et al. The Lancet, 2001, 358, 207.). As a basic skeleton of novel antibiotics, oxazolone compounds have potential values in biological sciences and medicinal chemistry. Therefore, the synthesis of such compounds is of great significance. The development of simple and easily-available reaction substrates to one-step construct the oxazolone compounds provides a greener, conciser and more efficient new way to synthesize the oxazolone compounds with potential biological and pharmaceutical activities.
AcHN N F NF
[0003] 0 Linezolid
[0004] The present disclosure is intended to provide an oxazolone derivative, and a preparation method of such compound.
[0005] In order to achieve the above objective, a technical solution of the present disclosure is as follows:
[0006] An oxazolone derivative has a structure shown in a following general formula I:
R1 ON,:_O Nf~ R3 S R2
[0007]
[0008] where,
[0009] R 1 is aryl, and the aryl has one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl and methoxy, with a number of the substituents of 1;
[0010] R2 is selected from the group consisting of hydrogen, alkyl with 1-2 carbon atoms, benzyl and aryl, and substituent of the aryl is one or more selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl and methoxy, with a number of the substituents of 1; and
[0011] R3 is selected from the group consisting of methyl, ethyl and benzyl.
[0012] According to the present disclosure, preferably
[0013] R 1 maybe aryl, and the aryl may have one or more substituents selected from the group consisting of the fluorine, the chlorine, the bromine, the iodine, the methyl and the methoxy, with a number of the substituents of 1;
[0014] R2 may be selected from the group consisting of the alkyl with 1-2 carbon atoms and the benzyl; and
[0015] R3 may be selected from the group consisting of the methyl, the ethyl and the benzyl.
[0016] According to the present disclosure, more preferably the oxazolone derivative may be one of the following: OMe
Ph O O O O XN -Z \N, MeS Bn MeS Bn
[0017] 1a lb
[0018] A synthesis method of the oxazolone derivative includes the following steps:
[0019] using 4-alkylthio-4-amino-3-butene-2-one IIas a raw material; subjecting the 4-alkylthio-4-amino-3-butene-2-one II to oxidation, double bond cleavage and rearrangement and cyclization in a solvent under catalysis of 4-OH-TEMPO and oxidation of an oxidant; and separating and characterizing a reaction product according to a conventional separation and purification method to obtain an oxazolone derivative I; where
[0020] a synthetic path is as follows: 4-OH-TMPO 0 0 NHR2 Oxidant
Solvent
[0021] - 2 1
[0022] R, R 2 and R3 are the same as those described in the general formula I.
[0023] In the present disclosure, a synthesis method of the raw material 4-alkylthio-4-amino-3-butene-2-one I is referred to Org. Lett. 2017, 19, 3660-3663.
[0024] According to the present disclosure, preferably the solvent may be one or a mixture of more selected from the group consisting of N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), hexamethylphosphoramide (HMPA), toluene, 1,4-dioxane, acetic anhydride (Ac20), ethanol and water; and the 4-alkylthio-4-amino-3-butene-2-one may have a molar concentration in the solvent of 0.01-1.0 mol/L;
[0025] According to the present disclosure, preferably the raw material 4-alkylthio-4-amino-3-butene-2-one and the 4-OH-TEMPO may have a molar ratio of 1:0.01 to 1:0.2, more preferably 1:0.1.
[0026] According to the present disclosure, preferably the oxidant may be one or two selected from the group consisting of ferric nitrate, hydrogen peroxide, potassium persulfate, sodium persulfate, tert-butyl nitrite and p-benzoquinone; and the raw material 4-alkylthio-4-amino-3-butene-2-one and the oxidant may have a molar ratio of 1:1 to 1:2, more preferably 1:1.5.
[0027] According to the present disclosure, preferably the reaction may be conducted under one or more of air, oxygen, nitrogen and argon for 10-120 min, more preferably 30 min.
[0028] According to the present disclosure, preferably the reaction may be conducted at 0-150°C, more preferably 25°C.
[0029] According to the present disclosure, preferably the separation and purification method may be conducted using silica gel column chromatography with an eluent prepared by petroleum ether at 60-90°C and ethyl acetate in a ratio of 5:1
(v/v).
[0030] The beneficial effects of the present disclosure are as follows:
[0031] In the present disclosure, the 4-alkylthio-4-amino-3-butene-2-one is catalyzed by the 4-OH-TEMPO to undergo oxidation/rearrangement/cyclization to synthesize the oxazolone derivative, where the 4-OH-TEMPO as a organic small molecule catalyst provides a free radical environment for the reaction to catalyze the progress of the reaction, thereby avoiding using metal catalysts and providing a new idea for the synthesis of oxazolone medicines. The method of the present disclosure has easily-available raw materials, simple and convenient operation, one-step construction of oxazolone, high yield reaching not less than 80% and diverse functional groups of product.
[0032] In the present disclosure, a synthesis method of 4-alkylthio-4-amino-3-butene-2-one using 1,1-dialkylthio-1-en-3-one is described in Org. Lett. 2017, 19, 3660-3663, and the 4-alkylthio-4-amino-3-butene-2-one is subjected to reaction by catalysis of 4-OH-TEMPO and oxidation of ferric nitrate to generate an oxazolone derivative.
[0033] The present disclosure is further explained in detail below with reference to specific examples, but is not limited thereto.
[0034] Example 1 NHBn 10 mol% 4-OH-TMPO Ph 1.5 eq. Fe(N0 3 ) 3 Ph SMe PhMe, 25°C MeS Bn
[0035] 2a 1a
[0036] A preparation method of a compound la included: 4-alkylthio-4-amino-3-butene-2-one (85 mg, 0.3 mmol), 4-OH-TEMPO (5.2 mg, 0.15 mmol) and ferric nitrate (108.8 mg, 0.45 mmol) were added to a 25 mL reaction tube; toluene (1 mL) was added under Ar protection, and reaction was conducted at 25°C for 30 min. A resulting reaction product was separated by silica gel column chromatography with an eluent prepared by petroleum ether at 60-90°C and ethyl acetate in a ratio of 5:1 (v/v), to obtain a white solid la (71.4 mg, with a yield rate of
%); a target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry (HRMS).
[0037] Characterization data of the compound la is as follows:
[0038] 3-benzyl-4-thiomethyl-1-phenyloxazolone la, white solid. 'HNMR(400 MHz, CDCl3 ) 6 7.88 (d, J=7.8 Hz, 2H, aromatic CH), 7.48-7.07 (m, 8H, aromatic CH), 4.84 (s, 2H, CH2 ), 1.87 (s, 3H , SCH 3). 13C{ 1H} NMR (100 MHz, CDC 3 ) 6 154.3, 142.3, 136.5, 128.9, 128.8, 128.7, 127.9, 127.8, 127.3, 125.3, 116.4, 45.2 (CH 2), 19.0 (SCH 3). HRMS theoretical value of C 17 H1 5N0 2 S [M+H]*: 298.0902; measured value: 298.0901.
[0039] Example 2
[0040] Reaction steps and operations were the same as those described in Example 1, and the difference from Example 1 was that: a reaction substrate was 2b (94 mg, 0.3 mmol). After reaction, a target product lb (77 mg, with a yield of 78%) was obtained after post-treatment. OMe 10 mol% 4-OH-TMPO O 0 OMe 0 NHBn 1.5 eq. Fe(N0 3 )3 O SMe PhMe, 25°C MeS Bn
[0041] U_ 2b lb
[0042] Characterization data of the compound lb is as follows:
[0043] (4-methoxyphenyl)-4-thiomethyl-1-phenyloxazolone 1b, white solid. 'H NMR (400 MHz, CDCl 3 ) 6 7.84 (dd, J=5.2, 3.3 Hz, 2H, aromatic CH), 7.79-7.70 (m, 2H, aromatic CH), 7.58-7.51 (m, 2H, aromatic CH), 7.26-7.19 (m, 2H, aromatic CH), 7.10-6.97 (m, 1H, aromatic CH), 4.91 (s, 2H, CH 2), 3.90 (s, 3H, OCH 3), 2.66 (s, 3H, SCH 3). 13 C{ 1H}NMR (100 MHz, CDC 3) 6 156.2, 146.9, 143.8, 142.9, 136.2, 133.9, 133.6, 128.8, 128.2, 127.9, 127.1, 117.4, 115.6, 55.8 (OCH 3), 44.9 (CH 2 ), 18.6 (SCH 3). HRMS theoretical value of Ci8 H1 7N0 3 S [M+H]*: 328.1007; measured value: 328.1009.
Claims (10)
- CLAIMS: 1. An oxazolone derivative, having a structure shown in a following general formula I:R1 O Or1wherein, R' is aryl, and the aryl has one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl and methoxy, with a number of the substituents of 1; R2 is selected from the group consisting of hydrogen, alkyl with 1-2 carbon atoms, benzyl and aryl, and the aryl has one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl and methoxy, with a number of the substituents of 1; and R3 is selected from the group consisting of methyl, ethyl and benzyl.
- 2. The oxazolone derivative according to claim 1, wherein the R1 is the aryl, and the aryl has one or more substituents selected from the group consisting of the fluorine, the chlorine, the bromine, the iodine, the methyl and the methoxy, with a number of the substituents of 1; R2 is selected from the group consisting of the alkyl with 1-2 carbon atoms and the benzyl; and R3 is selected from the group consisting of the methyl, the ethyl and the benzyl.
- 3. The oxazolone derivative according to claim 1 or 2 being one of the following: OMePh O OOOMeS Bn MeS Bn 1a 1b
- 4. A synthesis method of the oxazolone derivative according to claim 1 or 2, comprising the following steps: using 4-alkylthio-4-amino-3-butene-2-one IIas a raw material; subjecting the4-alkylthio-4-amino-3-butene-2-one IIto oxidation, double bond cleavage and rearrangement and cyclization in a solvent under catalysis of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (4-OH-TEMPO) and oxidation of an oxidant; and separating and characterizing a resulting reaction product according to a conventional separation and purification method to obtain an oxazolone derivative I; wherein a synthetic path is as follows: 4-OH-TMPO 0 0 NHR Oxidant R 0o Solvent, temperature 2 1R', R2 and R 3 are the same as those described in the general formula I.
- 5. The synthesis method of the oxazolone derivative according to claim 4, wherein the solvent is one or a mixture of more selected from the group consisting of N,N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, hexamethylphosphoramide, toluene, 1,4-dioxane, acetic anhydride, ethanol and water; and the 4-alkylthio-4-amino-3-butene-2-one has a molar concentration in the solvent of 0.01-1.0 mol/L.
- 6. The synthesis method of the oxazolone derivative according to claim 4, wherein the raw material 4-alkylthio-4-amino-3-butene-2-one and the 4-OH-TEMPO have a molar ratio of 1:0.01 to 1:0.2, preferably 1:0.1.
- 7. The synthesis method of the oxazolone derivative according to claim 4, wherein the oxidant is one or two selected from the group consisting of ferric nitrate, hydrogen peroxide, potassium persulfate, sodium persulfate, tert-butyl nitrite and p-benzoquinone; and the raw material 4-alkylthio-4-amino-3-butene-2-one and the oxidant have a molar ratio of 1:1 to 1:2, preferably 1:1.5.
- 8. The synthesis method of the oxazolone derivative according to claim 4, wherein the reaction is conducted under one or more of air, oxygen, nitrogen and argon for -120 min, preferably 30 min.
- 9. The synthesis method of the oxazolone derivative according to claim 4, wherein the reaction is conducted at 0-150°C, preferably 25°C.
- 10. The synthesis method of the oxazolone derivative according to claim 4, wherein the separation and purification method is conducted using silica gel column chromatography with an eluent prepared by petroleum ether at 60-90°C and ethyl acetate in a ratio of 5:1 (v/v).
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| AU2021107259A AU2021107259A4 (en) | 2021-08-25 | 2021-08-25 | Oxazolone derivative and synthesis method thereof |
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| AU2021107259A AU2021107259A4 (en) | 2021-08-25 | 2021-08-25 | Oxazolone derivative and synthesis method thereof |
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2021
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