CN106905257B - 一种制备2,5-二取代-1,3,4-噁二唑的方法 - Google Patents
一种制备2,5-二取代-1,3,4-噁二唑的方法 Download PDFInfo
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- -1 2, 5-disubstituted-1, 3, 4-oxadiazole Chemical class 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 27
- 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 abstract description 60
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000001301 oxygen Substances 0.000 claims abstract description 31
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 239000012298 atmosphere Substances 0.000 claims abstract description 4
- AKKLAJYCGVIWBS-UHFFFAOYSA-N O=[N].CC1(C)CCCC(C)(C)N1 Chemical compound O=[N].CC1(C)CCCC(C)(C)N1 AKKLAJYCGVIWBS-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000003999 initiator Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 87
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 57
- 150000005072 1,3,4-oxadiazoles Chemical class 0.000 claims description 33
- 230000035484 reaction time Effects 0.000 claims description 30
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 28
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims description 28
- 239000003208 petroleum Substances 0.000 claims description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 238000006555 catalytic reaction Methods 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000002808 molecular sieve Substances 0.000 claims description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 239000006096 absorbing agent Substances 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 238000013459 approach Methods 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
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- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 27
- 238000007243 oxidative cyclization reaction Methods 0.000 abstract description 3
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- 230000002745 absorbent Effects 0.000 abstract 2
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 abstract 1
- 230000003197 catalytic effect Effects 0.000 abstract 1
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 52
- 238000002474 experimental method Methods 0.000 description 35
- 239000000047 product Substances 0.000 description 28
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 26
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 26
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 26
- 239000007800 oxidant agent Substances 0.000 description 26
- 230000001590 oxidative effect Effects 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- 239000000376 reactant Substances 0.000 description 25
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 239000005864 Sulphur Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005806 3,4,5-trimethoxybenzyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1C([H])([H])* 0.000 description 1
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005401 electroluminescence Methods 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000007144 microwave assisted synthesis reaction Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- AFIAKQAEMNXRFL-UHFFFAOYSA-N n-benzylbenzohydrazide Chemical compound C=1C=CC=CC=1C(=O)N(N)CC1=CC=CC=C1 AFIAKQAEMNXRFL-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/107—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with two aryl or substituted aryl radicals attached in positions 2 and 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
本发明提供了一种催化氧化环化制备式(II)所示的1,3,4‑噁二唑的方法,所述方法为:以结构如式(I)所示的甲酰腙化合物为原料,以空气或氧气气氛下,以硝酸铁为催化剂,以2,2,6,6‑四甲基哌啶氮氧化物为引发剂,在吸水剂的作用下,在吸水剂的作用下,在有机溶剂中,于25~60℃下反应3~12h,所得反应液经后处理得到式(II)所示的1,3,4‑噁二唑化合物;本发明反应速度快、条件温和,操作方便,成本低,反应安全,整个过程对环境友好,无污染。
Description
(一)技术领域
本发明涉及一种催化氧化环化制备2,5-二取代-1,3,4-噁二唑的方法。
(二)背景技术
2,5-二取代-1,3,4-噁二唑类化合物及其衍生物因具有独特的光学活性和生物活性而受到了化学界的广泛关注,该类化合物在农药、医药、材料等领域都有广泛的应用。一些2,5-二取代-1,3,4-噁二唑衍生物还具有光敏性质,可用于生产荧光剂、闪烁剂等,尤其可作为感光高分子材料应用于电致发光仪器。将2,5-二取代-1,3,4-噁二唑环引入不同的化合物结构中,通过结构修饰能生成一系列具有广谱生物活性的化合物及电致发光材料。
由噁二唑类化合物形成的配合物和聚合物拥有特殊的稳定性能,有些还具有荧光,且成膜性好,并具有良好的电子传输性能,可以制成极具应用前景的有机电致发光材料、纤维及成膜材料。正是其广泛的应用前景,极大地促进了1,3,4-噁二唑衍生物的合成研究。因此,1,3,4-噁二唑衍生物的合成也成了人们研究的热点。近年来合成1,3,4-噁二唑类化合物的方法有传统方法、微波辅助合成法、固相合成法等。
2000年,Liras等人在-10~25℃下,在二氯甲烷中用三氟乙酸酐处理二元酰肼,合成了不对称二取代1,3,4-噁二唑,其中使用的三氟乙酸酐不仅价格昂贵,而且不够绿色、安全。[Liras S,Allen M P,Segelstein B.Synth.Commun.,2000,30(3):437-443.]
2001年,Tandon等用BF3·Et2O作催化剂,以乙酰氯和水合肼为原料,在二氧六环中回流2h合成了对称的1,3,4-噁二唑,该方法底物毒性较大并对环境污染较强。[Tandon VK,Chhor R B.Synth Commun.,2001,31(11):1727-1732.]
2006年,James等用MeCN/i-Pr2NEt作催化剂,常温下催化环合酰肼得到1,3,4-噁二唑化合物,该法反应时间较长。[James C A,Poirmer B,Martel A,et al.TetrahedronLett.,2006,47:511-514.]
2007年,Souldozi等从取代的苯甲酸第一次一步合成了1,3,4-噁二唑化合物。该方法中的叶立德底物不易得到,会生成大量的三废污染。[Souldozi A,RamazaniA.Tetrahedron Lett.,2007,48:2617-2620.]
2011年,Srimanta等第一次用铜催化氧化环化酰腙一步合成二取代的1,3,4-噁二唑化合物。但是铜属于重金属对生物危害较大。[Srimanta Guin,Tuhin Ghosh,Org.Lett.,2011,13,5976-5979]
2014年Arvind等人首次使用光催化经历氧化环化成功合成1,3,4-噁二唑化合物。该反应的步骤较多,周期较长。[Arvind K.Yadav,Lal Dhar S.Vadav,Tetrahedron Lett.,2014,55,2065-2069]
综上所述,以前合成2,5-二取代1,3,4-噁二唑化合物的方法,存在不少缺点与不足,如:成本较高,不够绿色环保,反应温度较高,反应周期较长等等。因此,发明一个成本较低,绿色环保,反应温度温和,反应时间较短的合成工艺将会有极大意义。
(三)发明内容
本发明旨在解决上述氧化环化体系存在的问题,而提供一种成本低廉、条件温和、高效、对环境友好的催化氧化成环制备相应的噁二唑化合物的方法。
本发明采用的技术方案是:
一种催化氧化环化制备式(II)所示的1,3,4-噁二唑的方法,所述方法按如下步骤进行:
以结构如式(I)所示的甲酰腙化合物为原料,以空气或氧气气氛下,以硝酸铁为催化剂,以2,2,6,6-四甲基哌啶氮氧化物为引发剂,在吸水剂的作用下,在吸水剂的作用下,在有机溶剂中,于25~60℃下反应3~12h,所得反应液经后处理得到式(II)所示的1,3,4-噁二唑化合物;所述TEMPO、硝酸铁与式(I)所示的甲酰腙化合物物质的量之比为0.08~0.15:0.05~0.15:1;
式(I)、(II)中:
所述的R1为氢或氢被甲基、甲氧基、羟基、氯、溴、碘、三氟甲基或硝基取代;
所述的R2为C3~5的脂肪基、2-噻吩基、1-萘基、C6芳基或C6~9取代芳基,所述取代芳基上的H被甲基、甲氧基、三氟甲基、氟、氯、溴取代。
进一步,所述有机溶剂为下列之一:苯、甲苯、二甲苯、二氯甲烷、二氯乙烷、氯仿、乙酸乙酯或四氢呋喃。
进一步,所述有机溶剂的加入量以式(I)所示的甲酰腙化合物的物质的量计为6~10mL/mmol。
进一步,所述的吸水剂为无水硫酸镁、无水硫酸钠或4A分子筛。
再进一步,所述无水硫酸镁或无水硫酸钠与式(I)所示的甲酰腙化合物物质的量之比为1.5~3.0:1.0。
再进一步,所述4A分子筛的质量以式(I)所示的甲酰腙化合物物质的量来计为1~4g/mmol。
进一步,所述的反应温度为40℃,反应时间为6h。
本发明所述反应液的后处理方法为:反应结束后,所述反应液用二氯甲烷萃取,合并有机相,用饱和食盐水洗涤、无水硫酸钠干燥,浓缩,浓缩物用柱层析分离,以石油醚:乙酸乙酯体积比为5~10:1为洗脱剂进行洗脱,收集含目标产物的洗脱液,得到式(II)所示的1,3,4-噁二唑产物。
与现有技术相比,本发明的有益效果主要体现在:
1、反应速度快、条件温和,操作方便,反应速度快,反应效率高。
2、原料价廉易得,且反应在常压下即可顺利进行,成本低,反应安全。
3、以空气或氧气为氧化剂,其反应的副产物为水,不会对环境造成污染反应后只需简单处理即可得到无重金属污染的产物,整个过程对环境不会造成任何污染,是一种绿色的合成方法。
(三)具体实施方式
下面结合具体实施例对本发明进行进一步描述,但本发明的保护范围并不仅限于此:
实施例1:
在100mL的配有磁子搅拌的厚壁耐压管中,向体系中加入N-(苯甲基)苯甲酰肼(即结构式(I)中的R1为H;R2为苯基)0.5mmol(112.0mg),二氯乙烷5.0mL,硝酸铁10mol%(20.2mg),TEMPO 10mol%(7.8mg),无水硫酸镁2.0eq.(120.4mg),通过反复抽放氧气,使得整个体系处于全氧气气氛,35℃下反应6h,反应结束后,加入10mL水与10mL二氯甲烷,分出有机层,水层用二氯甲烷萃取(3×10mL),合并后的有机层用饱和食盐水洗涤,无水硫酸钠干燥,将蒸除溶剂后的残渣经柱层析分析,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得102.1mg收率为92%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ8.15–8.08(m,4H),7.66–7.60(m,6H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ163.99,131.99,129.37,126.65,123.33.
实施例2:
所用的反应物为N-(4-氟苯甲基)苯甲酰腙(即结构式(I)中的R1为H;R2为4-氟苯基)0.5mmol(121.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二氯乙烷5.0mL,催化剂硝酸铁的用量为12mol%(24.2mg),TEMPO的用量为10mol%(7.8mg),无水硫酸镁的用量为1.5eq.(90.3mg),反应温度为40℃,反应时间为8h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得111.8mg收率93%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.16–8.07(m,4H),7.57–7.48(m,3H),7.21(t,J=8.6Hz,2H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ164.49,163.68,163.65,131.69,129.14,129.06,129.00,126.80,123.71,116.42,116.24.
实施例3:
所用的反应物为N-(4-三氟甲基苯甲基)苯甲酰腙(即结构式(I)中的R1为H,;R2为4-三氟甲基苯基)0.5mmol(146.1mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为甲苯5.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为12mol%(9.4mg),4A分子筛0.5g,反应温度为45℃,反应时间为8h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得134.9mg收率93%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.41(s,1H),8.37(d,J=7.9Hz,1H),8.20–8.16(m,2H),7.84(d,J=7.8Hz,1H),7.71(t,J=7.8Hz,1H),7.62–7.55(m,3H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ165.07,163.40,132.06,130.05,129.81,129.18,128.28,128.25,128.22,127.08,124.84,123.78,123.75,123.59.
实施例4:
所用的反应物为N-(2-溴苯甲基)苯甲酰腙(即结构式(I)中的R1为H;R2为2-溴苯基)0.5mmol(151.6mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯5.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为12mol%(9.4mg),4A分子筛2.0g,反应温度为45℃,反应时间为8h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得137.0mg收率91%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.19–8.13(m,2H),8.06(dd,J=7.8,1.7Hz,1H),7.77(dd,J=8.0,1.1Hz,1H),7.59–7.51(m,3H),7.48(td,J=7.6,1.2Hz,1H),7.40(td,J=7.8,1.7Hz,1H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ165.05,163.44,134.54,132.44,131.83,131.59,129.04,127.57,126.98,125.20,123.68,121.42.
实施例5:
所用的反应物为N-(2-氟-6-氯苯甲基)苯甲酰腙(即结构式(I)中的R1为H;R2为2-氟-6-氯苯基)0.5mmol(138.4mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯4.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为12mol%(9.4mg),无水硫酸镁的用量为2.0eq.(120.4mg),反应温度为45℃,反应时间为8h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得126.4mg收率92%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.17–8.12(m,2H),7.60–7.49(m,4H),7.40(dt,J=8.2,0.9Hz,1H),7.24–7.18(m,1H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ165.68,160.40,157.71,135.59,135.57,133.30,133.23,132.01,129.09,127.11,126.18,126.15,123.56,114.89,114.72.
实施例6:
所用的反应物为N-(3,4-二甲基苯甲基)苯甲酰腙(即结构式(I)中的R1为H;R2为3,4-二甲基苯基)0.5mmol(126.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为氯仿4.0mL,催化剂硝酸铁的用量为5mol%(10.1mg),TEMPO的用量为15mol%(11.7mg),4A分子筛1.5g,反应温度为45℃,反应时间为8h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得107.7mg收率86%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.17–8.09(m,2H),7.90(s,1H),7.84(d,J=7.8Hz,1H),7.56–7.49(m,3H),7.26(d,J=7.8Hz,1H),2.33(d,J=12.2Hz,6H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ164.75,164.18,140.92,137.47,131.48,130.21,128.94,127.81,126.78,124.34,124.01,121.34,19.89,19.64.
实施例7:
所用的反应物为N-(3,4,5-三甲氧基苯甲基)苯甲酰腙(即结构式(I)中的R1为H;R2为3,4,5-三甲氧基苯基)0.5mmol(157.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯5.0mL,催化剂硝酸铁的用量为12mol%(24.2mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为2.5eq.(150.5mg),反应温度为45℃,反应时间为9h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得134.3mg收率86%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.13–8.10(m,2H),7.56–7.49(m,3H),7.34(s,2H),3.96(s,6H),3.92(s,3H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ164.40,164.35,153.61,141.15,131.62,128.96,126.82,118.87,104.18,60.91,56.33.
实施例8:
所用的反应物为N-(4-甲氧基苯基甲基)苯甲酰腙(即结构式(I)中的R1为H;R2为4-甲氧基苯基)0.5mmol(127.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯3.0mL,催化剂硝酸铁的用量为15mol%(30.3mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为3.0eq.(180.6mg),反应温度为60℃,反应时间为12h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得107.3mg收率85%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.15–8.11(m,2H),8.11–8.05(m,2H),7.54(qd,J=5.0,1.9Hz,3H),7.09–7.00(m,2H),3.90(s,3H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ164.53,164.12,162.36,131.52,129.02,128.70,126.82,124.07,116.42,114.52,55.46.
实施例9:
所用的反应物为N-(1-萘甲基)苯甲酰腙(即结构式(I)中的R1为H;R2为1-萘基)0.5mmol(137.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯3.0mL,催化剂硝酸铁的用量为15mol%(30.3mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为3.0eq.(180.6mg),反应温度为60℃,反应时间为9h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得96.7mg收率71%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ9.31(d,J=8.6Hz,1H),8.26(dd,J=7.3,0.9Hz,1H),8.23–8.17(m,2H),8.03(d,J=8.2Hz,1H),7.93(d,J=8.1Hz,1H),7.75–7.68(m,1H),7.62–7.53(m,5H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ164.07,133.80,132.51,131.71,129.05,128.62,128.29,128.10,126.97,126.66,126.18,124.80,120.43.
实施例10:
所用的反应物为N-(2-噻吩甲基)苯甲酰腙(即结构式(I)中的R1为H;R2为2-噻吩基)0.5mmol(115.1mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为四氢呋喃3.0mL,催化剂硝酸铁的用量为15mol%(30.3mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为3.0eq.(180.6mg),反应温度为55℃,反应时间为12h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得79.9mg收率70%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.14(dt,J=8.1,2.3Hz,2H),7.86(dd,J=3.7,1.1Hz,1H),7.64–7.50(m,4H),7.22(dd,J=5.0,3.7Hz,1H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ164.06,160.88,131.76,130.15,129.77,129.08,128.19,126.96,125.27,123.73.
实施例11:
所用的反应物为N-(苯乙基)苯甲酰腙(即结构式(I)中的R1为H;R2为苯乙基)0.5mmol(126.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为乙酸乙酯4.0mL,催化剂硝酸铁的用量为15mol%(30.3mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为3.0eq.(180.6mg),反应温度为45℃,反应时间为12h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得113.9mg收率91%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.07–7.99(m,2H),7.56–7.49(m,3H),7.36–7.31(m,2H),7.28–7.24(m,3H),3.26(ddd,J=8.5,6.8,1.8Hz,2H),3.22–3.17(m,2H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ166.08,164.72,139.50,131.51,128.96,128.64,128.27,126.73,126.63,123.95,32.63,27.34;HRMS m/z(M+1)+calcd forC16H15N2O+:251.1184,found:251.1183.
实施例12:
所用的反应物为N-(异戊基)苯甲酰腙(即结构式(I)中的R1为H;R2为异丁基)0.5mmol(102.1mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯3.0mL,催化剂硝酸铁的用量为15mol%(30.3mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为3.0eq.(180.6mg),反应温度为55℃,反应时间为9h,用石油醚:乙酸乙酯(5:1)洗脱得到相应的1,3,4-噁二唑产物,得88.0mg收率87%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.03(d,J=7.9Hz,2H),7.50(q,J=6.6,6.1Hz,3H),2.81(d,J=7.1Hz,2H),2.23(dq,J=13.6,6.8Hz,1H),1.05(d,J=6.7Hz,6H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ166.25,164.64,131.42,128.94,126.70,124.08,34.13,27.16,22.24;HRMS m/z(M+1)+calcd for C12H15N2O+:203.1184,found:203.1176.
实施例13:
所用的反应物为N-(正己基)苯甲酰腙(即结构式(I)中的R1为H;R2为正戊基)0.5mmol(109.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯4.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为12mol%(9.4mg),无水硫酸镁的用量为2.5eq.(150.5mg),反应温度为45℃,反应时间为9h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得82.2mg收率82%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.04(dd,J=7.9,1.7Hz,2H),7.55–7.47(m,3H),2.93(t,J=7.6Hz,2H),1.85(q,J=7.5Hz,2H),1.46–1.36(m,4H),0.93(t,J=7.1Hz,3H).
核磁共振碳谱:13C NMR(126MHz,Chloroform-d)δ166.99,164.62,131.42,128.93,126.70,124.08,31.12,26.24,25.38,22.15,13.81.
实施例14:
所用的反应物为N-(正丁基)苯甲酰腙(即结构式(I)中的R1为H;R2为正丙基)0.5mmol(95.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯5.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为8mol%(6.2mg),无水硫酸镁的用量为1.5eq.(120.4mg),反应温度为35℃,反应时间为6h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得86.7mg收率92%。
核磁共振氢谱:1H NMR(500MHz,Chloroform-d)δ8.04(dd,J=7.8,1.6Hz,2H),7.51(q,J=6.7,6.2Hz,3H),2.91(t,J=7.5Hz,2H),1.90(h,J=7.4Hz,2H),1.07(t,J=7.4Hz,3H).
核磁共振碳谱:13C NMR(125MHz,Chloroform-d)δ166.83,164.68,131.44,128.96,126.73,124.12,27.31,20.12,13.60.
实施例15:
所用的反应物为N-(特戊基)苯甲酰腙(即结构式(I)中的R1为H;R2为叔丁基)0.5mmol(102.1mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯4.0mL,催化剂硝酸铁的用量为5mol%(10.1mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为2.0eq.(120.4mg),反应温度为35℃,反应时间为9h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得92.0mg收率91%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ7.99(dd,J=8.0,1.6Hz,2H),7.63–7.54(m,3H),1.42(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ172.67,163.77,131.71,129.29,126.37,123.58,32.02,27.77.
实施例16:
所用的反应物为N-(特戊基)间甲基苯甲酰腙(即结构式(I)中的R1为甲基,在苯环的间位;R2为叔丁基)0.5mmol(109.2mg),实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯5.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为10mol%(7.8mg),无水硫酸镁的用量为2.0eq.(120.4mg),反应温度为35℃,反应时间为12h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得103.9mg收率96%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ7.84–7.76(m,2H),7.49–7.41(m,2H),2.40(s,3H),1.42(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ172.59,163.84,138.78,132.36,129.18,126.65,123.57,123.50,32.00,27.77,20.76.
实施例17:
所用的反应物为N-(特戊基)间甲基苯甲酰腙(即结构式(I)中的R1为甲基,在苯环的邻位;R2为叔丁基)0.5mmol(109.2mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯4.0mL,催化剂硝酸铁的用量为12mol%(24.2mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为3.0eq.(180.6mg),反应温度为55℃,反应时间为3h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得102.8mg收率95%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ7.89(dd,J=7.8,1.2Hz,1H),7.50–7.35(m,3H),1.41(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ172.16,164.00,137.32,131.61,131.16,128.60,126.33,122.77,31.91,27.75,21.25.
实施例18:
所用的反应物为N-(特戊基)对甲氧基苯甲酰腙(即结构式(I)中的R1为甲氧基,在苯环的对位;R2为叔丁基)0.5mmol(117.1mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯3.0mL,催化剂硝酸铁的用量为15mol%(30.3mg),TEMPO的用量为12mol%(9.4mg),无水硫酸钠的用量为2.0eq.(120.4mg),反应温度为25℃,反应时间为12h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得96.4mg收率83%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ7.92(d,J=8.9Hz,2H),7.12(d,J=8.9Hz,2H),3.84(s,3H),1.41(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ172.12,163.69,161.83,128.19,115.97,114.73,55.44,31.96,27.80.
实施例19:
所用的反应物为N-(特戊基)对甲氧基苯甲酰腙(即结构式(I)中的R1为羟基,在苯环的邻位;R2为叔丁基)0.5mmol(109.1mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯4.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为2.5eq.(150.5mg),反应温度为25℃,反应时间为12h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得96.2mg收率89%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ10.21(s,1H),7.77(dd,J=7.8,1.7Hz,1H),7.48–7.43(m,1H),7.08(dd,J=8.3,0.8Hz,1H),7.01(td,J=7.8,1.1Hz,1H),1.42(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ171.99,163.37,156.24,133.26,128.35,119.72,117.01,109.51,32.01,27.80.
实施例20:
所用的反应物为N-(特戊基)对溴苯甲酰腙(即结构式(I)中的R1为溴,在苯环的对位;R2为叔丁基)0.5mmol(141.7mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二甲苯3.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为10mol%(7.8mg),无水硫酸钠的用量为3.0eq.(180.6mg),反应温度为45℃,反应时间为12h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得132.3mg收率94%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ7.91(d,J=8.5Hz,2H),7.77(d,J=8.5Hz,2H),1.41(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ172.89,163.14,132.39,128.30,125.32,122.76,32.05,27.76.
实施例21:
所用的反应物为N-(特戊基)邻氯苯甲酰腙(即结构式(I)中的R1为氯,在苯环的邻位;R2为叔丁基)0.5mmol(119.4mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为乙酸乙酯4.0mL,催化剂硝酸铁的用量为12mol%(24.2mg),TEMPO的用量为12mol%(9.4mg),无水硫酸钠的用量为1.5eq.(90.3mg),反应温度为45℃,反应时间为9h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得114.8mg收率97%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ7.97(dd,J=7.7,1.7Hz,1H),7.69(dd,J=8.1,1.2Hz,1H),7.63(td,J=7.7,1.7Hz,1H),7.55(td,J=7.6,1.3Hz,1H),1.42(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ173.58,162.51,133.50,132.23,131.68,131.47,128.25,123.32,32.52,28.21.
实施例22:
所用的反应物为N-(特戊基)邻碘苯甲酰腙(即结构式(I)中的R1为碘,在苯环的邻位;R2为叔丁基)0.5mmol(165.1mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二氯甲烷5.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为10mol%(7.8mg),无水硫酸镁的用量为1.5eq.(90.3mg),反应温度为45℃,反应时间为5h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得157.5mg收率96%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ8.10(dd,J=8.0,1.0Hz,1H),7.80(dd,J=7.7,1.6Hz,1H),7.60(td,J=7.6,1.1Hz,1H),7.35(td,J=7.7,1.7Hz,1H),1.43(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ173.55,164.35,141.09,133.36,131.83,129.59,129.00,96.03,32.54,28.32.
实施例23:
所用的反应物为N-(特戊基)对三氟甲基苯甲酰腙(即结构式(I)中的R1为三氟甲基,在苯环的对位;R2为叔丁基)0.5mmol(136.2mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二氯乙烷4.0mL,催化剂硝酸铁的用量为10mol%(20.2mg),TEMPO的用量为12mol%(9.4mg),无水硫酸镁的用量为1.5eq.(90.3mg),反应温度为35℃,反应时间为6h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得127.1mg收率94%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ8.19(d,J=8.1Hz,1H),7.93(d,J=8.3Hz,1H),1.43(s,4H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ173.34,162.81,131.53,131.27,127.30,127.25,126.31,126.28,126.25,126.22,124.79,32.11,27.73.
实施例24:
所用的反应物为N-(特戊基)-3,5-二甲基苯甲酰腙(即结构式(I)中的R1为甲基,在苯环的3,5位;R2为叔丁基)0.5mmol(116.2mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二氯甲烷3.0mL,催化剂硝酸铁的用量为5mol%(10.1mg),TEMPO的用量为8mol%(6.2mg),无水硫酸镁的用量为2.0eq.(120.4mg),反应温度为35℃,反应时间为9h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得108.3mg收率94%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ7.59(s,2H),7.20(s,1H),2.33(s,6H),1.41(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ138.61,133.12,123.94,123.45,32.02,27.79,20.68.
实施例25:
所用的反应物为N-(特戊基)-2-甲基-3-硝基苯甲酰腙(即结构式(I)中的R1为甲基和硝基,分别在苯环的2位与3位;R2为叔丁基)0.5mmol(130.6mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二氯乙烷4.0mL,催化剂硝酸铁的用量为12mol%(24.2mg),TEMPO的用量为12mol%(9.4mg),无水硫酸镁的用量为2.0eq.(120.4mg),反应温度为40℃,反应时间为9h,用石油醚:乙酸乙酯(8:1)洗脱得到相应的1,3,4-噁二唑产物,得115.3mg收率89%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ8.19–8.12(m,1H),8.10–8.02(m,1H),7.64(t,J=8.0Hz,1H),2.60(s,3H),1.43(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ172.90,162.70,151.75,133.02,130.69,127.70,126.23,125.59,32.03,27.75,16.07.
实施例26:
所用的反应物为N-(特戊基)-3,4,5-三甲氧基苯甲酰腙(即结构式(I)中的R1为氯,在苯环的邻位;R2为叔丁基)0.5mmol(146.2mg),实验方法和步骤同实施例1,实验方法和步骤同实施例1,所用氧化剂为氧气,溶剂为二氯乙烷4.0mL,催化剂硝酸铁的用量为15mol%(30.3mg),TEMPO的用量为15mol%(11.7mg),无水硫酸镁的用量为3.0eq.(180.6mg),反应温度为55℃,反应时间为9h,用石油醚:乙酸乙酯(10:1)洗脱得到相应的1,3,4-噁二唑产物,得117.6mg收率81%。
核磁共振氢谱:1H NMR(500MHz,DMSO-d6)δ7.25(s,2H),3.88(s,6H),3.75(s,3H),1.43(s,9H).
核磁共振碳谱:13C NMR(125MHz,DMSO-d6)δ172.68,163.76,153.42,140.44,118.84,103.92,60.21,56.19,32.08,27.82.
本说明书实施例所述的内容仅仅是对发明构思的实现形式的列举,本发明的保护范围不应当被视为仅限于实施例所陈述的具体形式,本发明的保护范围也及于本领域技术人员根据本发明构思所能够想到的等同技术手段。
Claims (8)
1.一种催化氧化环化制备式(II)所示的1,3,4-噁二唑的方法,其特征在于,所述方法按如下步骤进行:
以结构如式(I)所示的甲酰腙化合物为原料,以空气或氧气气氛下,以硝酸铁为催化剂,以2,2,6,6-四甲基哌啶氮氧化物为引发剂,在吸水剂的作用下,在有机溶剂中,于25~60℃下反应3~12h,所得反应液经后处理得到式(II)所示的1,3,4-噁二唑化合物;所述TEMPO、硝酸铁与式(I)所示的甲酰腙化合物物质的量之比为0.08~0.15:0.05~0.15:1;
式(I)、(II)中:
所述的R1为氢或氢被甲基、甲氧基、羟基、氯、溴、碘、三氟甲基或硝基取代;
所述的R2为C3~5的脂肪基、2-噻吩基、1-萘基、C6芳基或C6~9取代芳基,所述取代芳基上的H被甲基、甲氧基、三氟甲基、氟、氯、溴取代。
2.如权利要求1所述的方法,其特征在于:所述有机溶剂为下列之一:苯、甲苯、二甲苯、二氯甲烷、二氯乙烷、氯仿、乙酸乙酯或四氢呋喃。
3.如权利要求1所述的方法,其特征在于:所述有机溶剂的加入量以式(I)所示的甲酰腙化合物的物质的量计为6~10mL/mmol。
4.如权利要求1所述的方法,其特征在于:所述的吸水剂为无水硫酸镁、无水硫酸钠或4A分子筛。
5.如权利要求4所述的方法,其特征在于:所述无水硫酸镁或无水硫酸钠与式(I)所示的甲酰腙化合物物质的量之比为1.5~3.0:1.0。
6.如权利要求4所述的方法,其特征在于:所述4A分子筛的质量以式(I)所示的甲酰腙化合物物质的量来计为1~4g/mmol。
7.如权利要求1所述的方法,其特征在于:所述的反应温度为40℃,反应时间为6h。
8.如权利要求1所述的方法,其特征在于所述反应液的后处理方法为:反应结束后,所述反应液用二氯甲烷萃取,合并有机相,用饱和食盐水洗涤、无水硫酸钠干燥,浓缩,浓缩物用柱层析分离,以石油醚:乙酸乙酯体积比为5~10:1为洗脱剂进行洗脱,收集含目标产物的洗脱液,得到式(II)所示的1,3,4-噁二唑产物。
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