CN117986245A - Detection reagent for metal alkoxide, preparation and application thereof - Google Patents
Detection reagent for metal alkoxide, preparation and application thereof Download PDFInfo
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- CN117986245A CN117986245A CN202410128076.6A CN202410128076A CN117986245A CN 117986245 A CN117986245 A CN 117986245A CN 202410128076 A CN202410128076 A CN 202410128076A CN 117986245 A CN117986245 A CN 117986245A
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- 229910052751 metal Inorganic materials 0.000 title claims abstract description 60
- 238000001514 detection method Methods 0.000 title claims abstract description 58
- 239000002184 metal Substances 0.000 title claims abstract description 58
- 150000004703 alkoxides Chemical class 0.000 title claims abstract description 43
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 claims abstract description 20
- -1 2-oxazolidinone compound Chemical class 0.000 claims description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- 150000001875 compounds Chemical class 0.000 claims description 32
- 238000004809 thin layer chromatography Methods 0.000 claims description 26
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical group CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 16
- 229910052749 magnesium Inorganic materials 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 12
- 238000004458 analytical method Methods 0.000 claims description 10
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 7
- 229910052700 potassium Inorganic materials 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 6
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052796 boron Inorganic materials 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 229910052752 metalloid Inorganic materials 0.000 claims description 2
- 229960003512 nicotinic acid Drugs 0.000 claims description 2
- 235000001968 nicotinic acid Nutrition 0.000 claims description 2
- 239000011664 nicotinic acid Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims 3
- 150000001408 amides Chemical class 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- XAAKCCMYRKZRAK-UHFFFAOYSA-N isoquinoline-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NC=CC2=C1 XAAKCCMYRKZRAK-UHFFFAOYSA-N 0.000 claims 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims 1
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 claims 1
- ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 claims 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 16
- 230000015572 biosynthetic process Effects 0.000 abstract description 12
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 238000001308 synthesis method Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000011777 magnesium Substances 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 7
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- CRGZYKWWYNQGEC-UHFFFAOYSA-N magnesium;methanolate Chemical compound [Mg+2].[O-]C.[O-]C CRGZYKWWYNQGEC-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- JGQDBVXRYDEWGM-UHFFFAOYSA-N quinoxaline-6-carboxylic acid Chemical compound N1=CC=NC2=CC(C(=O)O)=CC=C21 JGQDBVXRYDEWGM-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000006894 reductive elimination reaction Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 125000005305 thiadiazolinyl group Chemical group 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000004846 x-ray emission Methods 0.000 description 2
- CGXLVFZJJOXEDF-UHFFFAOYSA-N 1,8-naphthyridine-3-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CN=C21 CGXLVFZJJOXEDF-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VAJFEOKPKHIPEN-UHFFFAOYSA-N 4-methyl-1,3-oxazolidin-2-one Chemical compound CC1COC(=O)N1 VAJFEOKPKHIPEN-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004606 5,6,7,8-tetrahydroisoquinolinyl group Chemical group C1(=NC=CC=2CCCCC12)* 0.000 description 1
- ZSIFASRPEVGACI-UHFFFAOYSA-N 5-ethyl-1,3-oxazolidin-2-one Chemical compound CCC1CNC(=O)O1 ZSIFASRPEVGACI-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006477 desulfuration reaction Methods 0.000 description 1
- 230000023556 desulfurization Effects 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ADAHADRJWVCICR-UHFFFAOYSA-N isoquinoline-6-carboxylic acid Chemical compound C1=NC=CC2=CC(C(=O)O)=CC=C21 ADAHADRJWVCICR-UHFFFAOYSA-N 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- ABSWXCXMXIZDSN-UHFFFAOYSA-L magnesium;hexadecanoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCC([O-])=O ABSWXCXMXIZDSN-UHFFFAOYSA-L 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 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 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 238000003921 particle size analysis Methods 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006476 reductive cyclization reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/90—Plate chromatography, e.g. thin layer or paper chromatography
-
- 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
- C07D413/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/90—Plate chromatography, e.g. thin layer or paper chromatography
- G01N30/94—Development
Landscapes
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Abstract
The invention provides a detection reagent of metal alkoxide, which has a structure of a formula III,Wherein R 1-R5 is defined as the specification. The invention also provides a synthesis method of the detection reagent and application of the detection reagent in the synthesis production of metal alkoxides and TLC and HPLC-MS detection in mutual conversion.
Description
Technical Field
The invention belongs to the field of analytical chemistry, and particularly relates to a detection reagent of metal alkoxide, preparation thereof and application thereof as a detection reagent in synthesis production and interconversion of metal alkoxide.
Technical Field
Metal alkoxides are also known as metal alkoxides or metal acid esters. The general formula is M (OR) n, wherein M represents metal, R represents alkyl, cycloalkyl, aryl, aralkyl, acyl and the like, and n is a natural number greater than OR equal to 1. The structure of the catalyst at least comprises one M-O-C bond (M=metal) including single metal alkoxide, double metal alkoxide and multi-metal salt. In principle, the chemical nature of metal alkoxides is relatively simple, but the number of reaction species resulting from these properties is quite striking. The physicochemical properties of metal alkoxides are determined by a number of different parameters, the most important of which are the electronegativity of the metal, the steric structure of the ligand and the acidity of the corresponding alcohol. Since the synthesis of silicon and boron alkoxides by Ebelman et al in 1846, nearly all metal and metalloid alkoxides of the periodic table have been studied so far. More than two thirds of the elements of the periodic table can be made into alkoxides. The reactivity of the catalyst can lead the catalyst to have wide application in the aspects of inorganic synthesis, organic synthesis, directional catalytic polymerization, sol-Gel preparation of functional materials, and the like.
The metal alkoxide compound is a water-sensitive metal alkoxide, is a reducing agent which has wide application, high efficiency, economy and convenience, and can be used for various organic synthesis reactions, such as reductive cyclization, reductive elimination, reductive cleavage, conjugated double bond reduction, desulfurization, reduction of various functional groups and the like. In addition, many researchers have used metal alkoxides as catalysts in the synthesis of organic compounds, especially in the synthesis of ketoxime compounds (dressing agents). Among the most commonly used methods for synthesizing metal alkoxide compounds are: direct synthesis, alkyl magnesium, alcoholysis/lipolysis, and the like.
In the production, detection and identification and product application processes, structural characterization is mainly performed by means of XRD (X-ray diffraction), TEM (transmission electron microscope), UV (ultraviolet spectrum), FTIR (infrared spectrum), DTA (differential thermal gravimetric analysis), LDPSA laser particle size analysis and the like. Or the hydrolysate is subjected to analysis such as XRF (X-ray fluorescence spectroscopy), XPS (X-ray photoelectron spectroscopy), XRD (X-ray diffraction), SEM (scanning electron microscope), and GC (gas chromatograph). The reaction can also be monitored by observing some typical experimental phenomena occurring during production and experiments, such as boiling reflux, color change, bubble generation and disappearance, etc.
These methods all face the problems of complicated sample configuration and the need to use special expensive instruments, and many scientific research and production units do not have these conditions. And the detection period is long, the qualitative and quantitative processes are not visual enough, and a plurality of inconveniences exist in organic synthesis and even industrial production.
Therefore, in the field of metal alkoxide production and scientific research, there is an urgent need for a simple and rapid method for central detection and identification calibration in metal alkoxide production and application.
Disclosure of Invention
Aiming at the defects of the central control detection and identification calibration method in the production and application of metal alkoxide in the prior art, the invention provides a detection reagent of metal alkoxide and an analysis method using the detection reagent. The method is simple and convenient to operate, greatly reduces the cost and time of analysis and detection, monitors the metal alkoxide reaction qualitatively and quantitatively, and has good application prospect.
The invention adopts the following technical scheme: the invention provides a detection reagent of metal alkoxide, which has the following structure:
Wherein R 1 is optionally substituted nitrogen-containing heteroaryl, preferably pyridine, pyrimidine, pyrazine, quinoline and isoquinoline heteroaryl;
R 2、R3、R4、R5 is each independently H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, preferably hydrogen, methyl, ethyl, ethoxy.
The invention also provides a preparation method of the detection reagent (the compound shown in the formula III), which comprises the following steps:
The compounds of the formula I and the formula II react under the catalysis of DMAP to prepare the compound of the formula III,
Wherein, the structure of the compound of the formula I, the formula II and the formula III is as follows:
R 1 is optionally substituted nitrogen-containing heteroaryl, preferably pyridine, pyrimidine, pyrazine, quinoline and isoquinoline heteroaryl;
R 2、R3、R4、R5 is each independently H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, preferably hydrogen, methyl, ethyl, ethoxy.
The invention also provides a method for the detection and analysis of metal alkoxides comprising using a combination of a compound of formula III according to the invention and a metal alkoxide.
The invention discloses a detection reagent of metal alkoxide (compound in formula III), which can be rapidly and quantitatively converted into corresponding ester at room temperature, thereby being conveniently applied to TLC, HPLC-MS and other methods for monitoring and detecting the production process.
The invention has the beneficial effects that:
1. The substituted acyl oxazolidone (formula III) compound disclosed by the invention is used for a detection reagent for metal alkoxide for the first time, the content change of the metal alkoxide in the reaction can be monitored, the reaction is monitored in real time, and compared with the traditional detection by an instrument, the time and the material consumption are saved; the reaction can be monitored conveniently in a simple laboratory without purchasing expensive professional analysis instruments, so that the operation is more convenient.
2. The detection reagent (the compound of the formula III) of the metal alkoxide is simple and convenient to synthesize, can be more convenient for laboratory application, and has wider application prospect in organic synthesis.
Drawings
FIG. 15 TLC thin layer chromatography of reaction of ethoxy-3-nicotinoyl oxazolidin-2-one with metal alkoxide
Wherein Y represents detection reagent 5-ethoxy-3-nicotinoyl oxazolidin-2-ketone, A, B, C represents sample tube A, sample tube B and sample tube C respectively, namely detection results of products after reaction of detection reagent 5-ethoxy-3-nicotinoyl oxazolidin-2-ketone with octanol sodium in sample tube A, tert-amyl alcohol potassium in sample tube B and 2-methoxyethanol magnesium in sample tube C respectively in TLC thin layer chromatography.
FIG. 25 TLC thin layer chromatography of ethoxy-3-nicotinoyl oxazolidin-2-one in magnesium alkoxide exchange reaction
Wherein Y represents 5-ethoxy-3-nicotinoyl oxazolidin-2-one, D represents a thin layer chromatography detection result of a product after the reaction of 5-ethoxy-3-nicotinoyl oxazolidin-2-one and raw material magnesium methoxide, and E represents a thin layer chromatography detection result of a reaction product of 5-ethoxy-3-nicotinoyl oxazolidin-2-one and product magnesium hexadecanoate.
FIG. 35 TLC detection results of ethoxy-3-nicotinoyl oxazolidin-2-one at various times of magnesium alkoxide exchange reaction
Wherein Y represents 5-ethoxy-3-nicotinoyl oxazolidin-2-one, D represents the product of the reaction of 5-ethoxy-3-nicotinoyl oxazolidin-2-one and magnesium methoxide, and the rest represents TLC thin layer chromatography detection results of the reaction monitoring condition analysis of 5-ethoxy-3-nicotinoyl oxazolidin-2-one and magnesium methoxide at different times.
FIG. 4 Mass spectrum of 3- (quinoline-6-carbonyl) oxazolidine-2-one as detection reagent
FIG. 5 mass spectrum of the reaction product of 3- (quinoline-6-carbonyl) oxazolidin-2-one and magnesium methoxide as detection reagent
FIG. 6 mass spectrum of the reaction product of 3- (quinoline-6-carbonyl) oxazolidin-2-one and magnesium cetyl alkoxide as detection reagent
Detailed Description
Specific embodiments of the present invention will be described in further detail below with reference to examples and drawings. For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations thereof such as "comprises" or "comprising", etc. will be understood to include the stated elements and steps without excluding the presence of other material elements or steps.
In addition, numerous specific details are set forth in the following description in order to provide a better illustration of the invention.
It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In some embodiments, materials, methods, means, etc. well known to those skilled in the art are not described in detail in order to highlight the gist of the present invention.
Hereinafter, embodiments of the present invention are described in detail. However, these embodiments are exemplary, the invention is not limited thereto, and the invention is defined by the scope of the claims.
"Optionally substituted" in the present invention means that any hydrogen atom in the group of the parent nucleus may be substituted with a substituent. The substituent may be 1, or 1 or more substituents, which may be the same or different.
The "substituent" is not particularly limited as long as it is a group capable of achieving the technical effects of the present invention.
As the group of the "substituent", halogen, alkyl, hydroxyl, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, and the like can be mentioned, but are not limited thereto. The above substituent may be further substituted with a substituent.
The subscripts n and m in C n-Cm of the invention in each case denote the number of carbon atoms in the group. For example, C 1-C6 represents a group containing 1 to 6 carbon atoms. The alkyl groups present in the definition of substituents may be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, sec-butyl, isobutyl or tert-butyl. Alkoxy groups are derived from the alkyl groups mentioned. Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy. Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-trifluoroethoxy 1, 2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-difluoroethoxy and 2, 2-trichloroethoxy.
Halogen in the present invention is typically fluorine, chlorine, bromine or iodine. Accordingly, this also applies to halogens, such as haloalkyl, which are bonded to other structures. The haloalkyl group preferably has a chain length of 1 to 6 carbon atoms, more preferably a chain length of 1 to 4 carbon atoms. Examples of the alkyl groups of the haloalkyl group, such as fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2-trifluoroethyl, 2-fluoroethyl 2-chloroethyl, pentafluoroethyl, 1-difluoro-2, 2-trichloroethyl, 2, 3-tetrafluoroethyl and 2, 2-trichloroethyl.
"Aryl" in the present invention refers to a monovalent monocyclic or bicyclic aromatic hydrocarbon group of 6 to 10 ring atoms, such as, but not limited to, phenyl or naphthyl.
"Heteroaryl" in the present invention encompasses: a 5 to 10 membered aromatic monocyclic ring, an aromatic fused ring, wherein the aromatic monocyclic ring contains one or more (e.g., 1 to 4, or in certain embodiments 1 to 3) heteroatoms selected from N, O and S and the remaining atoms are carbon; an aromatic fused ring comprising one or more (e.g., 1 to 4, or in certain embodiments 1 to 3) heteroatoms selected from N, O and S and the remaining ring atoms being carbon, and wherein at least one heteroatom is present in the aromatic ring. For example, heteroaryl includes a 5-to 10-membered heterocycloalkyl aromatic ring fused with a 5-to 10-membered cycloalkyl or heterocycloalkyl ring. For such fusions where only one ring contains one or more heteroatoms, the point of attachment may be on either ring. When the total number of S and O atoms in the heteroaryl group exceeds 1, these heteroatoms are not adjacent to each other. In certain embodiments, the total number of S and O atoms in the heteroaryl group is no more than 2. In certain embodiments, the total number of S and O atoms in the aromatic heterocycle is no more than 1. Examples of heteroaryl groups include, but are not limited to (numbered from the attachment position at position 1) 2-pyridyl, 3-pyridyl, 4-pyridyl, 2, 3-pyridazinyl, 3, 4-pyridazinyl, 2, 4-pyrimidinyl, 3, 5-pyrimidinyl, 2, 3-pyrazolinyl, 2, 4-imidazolinyl, isoxazolinyl, oxazolinyl, thiazolinyl, thiadiazolinyl (thiadiazolinyl), tetrazolyl, thienyl, benzothiophenyl (benzothiophenyl), furyl (furyl), benzofuryl, benzimidazolinyl, indolinyl, pyrazinyl, triazolyl, quinolinyl, pyrazolyl, and 5,6,7, 8-tetrahydroisoquinolinyl.
In the present invention, "nitrogen-containing heteroaryl" means that the heteroaryl group contains at least one nitrogen atom, preferably, but not limited to, pyridine, pyrimidine, pyrazine, quinoline and isoquinoline.
In the present invention, the "metal alkoxide compound" is a water-sensitive metal alkoxide, and the metal includes, but is not limited to, na, K, mg, ca, zn, be, B, al, ga, sn, ti or other metal elements.
"Alkenyl" in the context of the present invention means a radical having one or more carbon-carbon double bonds and having 2 to 12, 2 to 10 or 2 to 6 carbon atoms. Exemplary alkenyl groups include, but are not limited to, vinyl or allyl.
"Alkynyl" in the context of the present invention means a group having one or more carbon-carbon triple bonds and having 2 to 12 or 2 to 6 carbon atoms.
The invention firstly discloses a detection reagent of metal alkoxide, which has a structure shown in a formula III,
Wherein R 1 is optionally substituted nitrogen-containing heteroaryl;
R 2、R3、R4、R5 is independently H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl.
In a preferred technical scheme, R 1 is preferably one of pyridine, pyrimidine, pyrazine, quinoline and isoquinoline. R 2、R3、R4、R5 is preferably hydrogen, methyl, ethyl, ethoxy.
The invention also provides a preparation method of the detection reagent (the compound shown in the formula III), which comprises the following steps:
The compounds of the formula I and the formula II react under the catalysis of a catalyst to prepare the compound of the formula III,
Wherein, the structure of the compound of the formula I, the formula II and the formula III is as follows:
R 1 is optionally substituted nitrogen-containing heteroaryl;
R 2、R3、R4、R5 is independently H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl.
In a preferred technical scheme, R 1 is preferably one of pyridine, pyrimidine, pyrazine, quinoline and isoquinoline. R 2、R3、R4、R5 is preferably hydrogen, methyl, ethyl, ethoxy.
Preferably, the condensing agent in the preparation method is dicyclohexylcarbodiimide, and the catalyst is 4-dimethylaminopyridine; the reaction is carried out in an organic solvent, preferably methylene chloride; the reaction temperature is room temperature; the reaction time is 16h-20h; preferably, the molar ratio of the compound of formula I, the compound of formula II, the condensing agent and the catalyst is 1:1.05-1.2:1.05-1.2:0.10-0.12.
The invention also provides the use of a compound of formula III in a detection assay for a metal alkoxide, comprising the step of contacting the compound of formula III with the metal alkoxide. The metal of the metal alkoxide can be Na, K, mg, ca, zn, be, B, al, ga, sn, ti and other metal elements, preferably one of Na, K and Mg.
Preferably, the use of the compounds of formula III according to the invention in the detection analysis of metal alkoxides is for Thin Layer Chromatography (TLC) or liquid chromatography-mass spectrometry (HPLC-MS).
Preferably, when the compound of formula iii is applied as TLC in a detection assay of metal alkoxides, it comprises the steps of: 1) Preparing a solution of a compound of formula III and a solvent for later use; 2) Dropwise adding a reaction solution of a metal salt and alcohol to the step 1); 3) And (3) carrying out thin layer chromatography detection on the liquid obtained in the step (2). The solvent in the step 1) is preferably ethyl acetate; the step 2) is preferably stirred or shaken. The developing agent in the step 3) is preferably n-hexane: ethyl acetate=1:1.
Preferably, when the compound of formula III is applied to the detection analysis of metal alkoxides as HPLC-MS, it comprises the following steps: 1) Preparing a compound of formula III into a solution for later use; 2) Dropwise adding a reaction solution of a metal salt and alcohol to the step 1); 3) And (3) performing HPLC-MS detection on the liquid obtained in the step (2).
The experimental methods used in the following examples are all conventional methods unless otherwise specified; the reagents, materials, etc. used in the examples described below are commercially available unless otherwise specified.
Example 1: synthesis of 5-ethoxy-3-nicotinoyl oxazolidin-2-one
To a 50mL dry three-necked flask with stirring apparatus, 20mL of dry dichloromethane was added. Then, 1.00g of nicotinic acid, 1.17g of 5-ethoxy-1, 3-oxazolidin-2-one, 1.84g of dicyclohexylcarbodiimide and 0.10g of 4-dimethylaminopyridine were added in this order. The reaction mixture was stirred at room temperature for 16 hours, filtered through a buchner funnel with silica gel and the filter cake was rinsed with 10mL of dichloromethane. The filtrate was concentrated and column chromatographed on 200 mesh silica gel to give 1.66g of 5-ethoxy-3-nicotinoyl oxazolidin-2-one as a white solid in 86.51%.
HPLC-MS(ESI):[M+1]+＝237.09。
Example 2: synthesis of 3- (quinoline-6-carbonyl) oxazolidin-2-one
To a 50mL dry three-necked flask with stirring apparatus, 20mL of dry dichloromethane was added. Then, 1.00g of 6-isoquinolinecarboxylic acid, 0.55g of 2-oxazolidinone, 1.31g of dicyclohexylcarbodiimide and 0.07g of 4-dimethylaminopyridine were added in this order. The reaction mixture was stirred at room temperature for 16 hours, filtered through a buchner funnel with silica gel and the filter cake was rinsed with 10mL of dichloromethane. The filtrate was concentrated and column chromatographed on 200 mesh silica gel to give 1.23g of 3- (quinoline-6-carbonyl) oxazolidin-2-one as a white solid in 87.93% yield. HPLC-MS (ESI) [ m+1] + = 243.08.
Example 3: synthesis of 3- (quinoxaline-6-carbonyl) oxazolidin-2-one
To a 50mL dry three-necked flask with stirring apparatus, 20mL of dry dichloromethane was added. Then, 1.00g of 6-quinoxalinecarboxylic acid, 0.55g of 2-oxazolidinone, 1.30g of dicyclohexylcarbodiimide and 0.08g of 4-dimethylaminopyridine were added in this order. The reaction mixture was stirred at room temperature for 16 hours, filtered through a buchner funnel with silica gel and the filter cake was rinsed with 10mL of dichloromethane. The filtrate was concentrated and column chromatographed on 200 mesh silica gel to give 1.11g of 3- (quinoxaline-6-carbonyl) oxazolidin-2-one as a white solid in a yield of 79.48%.
HPLC-MS(ESI):[M+1]+＝244.07。
Example 4: synthesis of 4-methyl-3- (quinoxaline-6-carbonyl) oxazolidin-2-one
To a 50mL dry three-necked flask with stirring apparatus, 20mL of dry dichloromethane was added. Then, 1.00g of 6-quinoxalinecarboxylic acid, 0.64g of 4-methyl oxazolidin-2-one, 1.30g of dicyclohexylcarbodiimide and 0.08g of 4-dimethylaminopyridine were added in this order. The reaction mixture was stirred at room temperature for 18 hours, filtered through a buchner funnel with silica gel and the filter cake was rinsed with 10mL of dichloromethane. The filtrate was concentrated and column chromatographed on 200 mesh silica gel to give 1.24g of 4-methyl-3- (quinoxaline-6-carbonyl) oxazolidin-2-one as a white solid in a yield of 83.95%. HPLC-MS (ESI) [ m+1] + = 258.09.
Example 5: synthesis of 5-ethyl-3- (1, 8-naphthyridine-3-carbonyl) oxazolidin-2-one
To a 50mL dry three-necked flask with stirring apparatus, 20mL of dry dichloromethane was added. 1.00g of 1, 8-naphthyridine-3-carboxylic acid, 0.79g of 5-ethyl oxazolidin-2-one, 1.42g of dicyclohexylcarbodiimide and 0.08g of 4-dimethylaminopyridine were then added in sequence. The reaction mixture was stirred at room temperature for 20 hours, filtered through a buchner funnel with silica gel and the filter cake was rinsed with 10mL of dichloromethane. The filtrate was concentrated and column chromatographed on 200 mesh silica gel to give 0.97g of 5-ethyl-3- (1, 8-naphthyridine-3-carbonyl) oxazolidin-2-one as a white solid in 62.27% yield. HPLC-MS (ESI) [ m+1] + = 272.10.
Example 6: detection reagent 5-ethoxy-3-nicotinoyl oxazolidin-2-ketone and metal alkoxide reaction detection
100Mg of 5-ethoxy-3-nicotinoyl oxazolidin-2-one was dissolved in ethyl acetate to prepare a 2 milligrams per milliliter solution. First, about 1.0mL of the ethyl acetate solution of 3-quinolinyloxazolidine-2-one was taken and placed in three 5mL sample tubes, labeled as sample tube A, sample tube B and sample tube C, respectively. 2-3 drops of octanol sodium, potassium tert-amyl alcohol and 2-methoxyethanol magnesium are respectively added into A, B, C of the sample tubes, and stirred or oscillated for about 5-10 seconds.
5-Ethoxy-3-nicotinoyl oxazolidin-2-one was monitored with sample tube A, sample tube B and sample tube C by TLC and LCMS. TLC developing reagent was n-hexane: the ethyl acetate=1:1, and the detection result is shown in the attached figure 1, so that the detection method has a good separation effect on a TLC thin layer, and can be well applied to detection and monitoring of the reaction in which the metal alkoxide participates. HPLC-MS data shows that sample tube A is HPLC-MS (ESI) [ M+1] + = 272.10. The B sample tube was HPLC-MS (ESI) [ M+1] + = 222.15. The C sample tube is HPLC-MS (ESI) [ M+1] + =182.08, and the HPLC-MS can rapidly and accurately detect and monitor the reaction.
Example 7: detection reagent 3- (quinoline-6-carbonyl) oxazolidine-2-ketone for detection and analysis in exchange reaction of magnesium methoxide and magnesium cetyl alkoxide
After 4g of magnesium strips are soaked in dilute hydrochloric acid, the magnesium strips are quickly washed by absolute methanol and are wiped dry, the magnesium strips are added into 20mL of absolute methanol, 30mg of iodine is weighed and also put into a reaction flask, the mixture is heated to 90 ℃ and refluxed for 2 hours, absolute hexadecanol is added, and the temperature is raised to 120 ℃ for reaction for 8 hours.
0.5ML of the prepared ethyl acetate solution of 2 mg/mL of 3- (quinoline-6-carbonyl) oxazolidin-2-one was added to the reaction mixture of methanol and magnesium for 2 hours, and the mixture was labeled as a sample tube D. The reaction solution after 8 hours of heating is marked as a sample tube E, and is stirred or oscillated for about 5-10 seconds. 3- (quinoline-6-carbonyl) oxazolidin-2-one was monitored by TLC with sample tube D and sample tube E, with n-hexane as developing reagent: ethyl acetate=1:1, the detection result is shown in fig. 2, and the reaction progress can be rapidly analyzed by using the detection reagent of the invention, wherein TLC can well show the reaction condition. And the solutions in the sample tube D and the sample tube E are respectively sent to HPLC-MS for detection. The results of the reaction were also accurately and rapidly analyzed by hplc-MS, giving [ m+1] + = 188.07 and [ m+1] + =398.31, respectively.
Example 8: application of detection reagent 5-ethoxy-3-nicotinoyl oxazolidin-2-ketone in magnesium methoxide and 2-methoxyethanol magnesium exchange reaction
After 4g of magnesium strips are soaked in dilute hydrochloric acid, the magnesium strips are quickly washed by absolute methanol and are wiped dry, the magnesium strips are added into 20mL of absolute methanol, 30mg of iodine is weighed and also put into a reaction flask, the mixture is heated to 90 ℃ and refluxed for 2 hours, then absolute 2-methoxyethanol is added, and the temperature is raised to 120 ℃ for reaction.
Taking 0.5mL of prepared ethyl acetate solution of 2 mg/mL of 5-ethoxy-3-nicotinoyl oxazolidin-2-one, adding reaction liquid of methanol and magnesium for 2h and reaction liquid of 0.5h,1h,2h,4h,8h and 12h after heating, stirring or oscillating for about 5-10 seconds. The 5-ethoxy-3-nicotinoyl oxazolidin-2-one was monitored by TLC with each sample tube, with n-hexane as developing solvent: ethyl acetate=1:1, and the detection result is shown in figure 3 of the specification. And each sample was separately subjected to HPLC-MS to obtain results of magnesium alkoxide exchange reaction at different reaction times, and it was found that [ M+1] + = 138.05 was gradually decreased and that the molecular ion peak of [ M+1] + = 182.08 was gradually increased.
Claims (10)
1. A detection reagent for metal alkoxide is characterized by having a structure of formula III,
Wherein R 1 is optionally substituted nitrogen-containing heteroaryl, preferably one of pyridine, pyrimidine, pyrazine, quinoline and isoquinoline; r 2、R3、R4、R5 is each independently H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, preferably hydrogen, methyl, ethyl, ethoxy.
2. The detection reagent according to claim 1, wherein the preparation of the compound of formula III comprises the steps of: the compounds of the formula I and the formula II are subjected to amide condensation reaction to prepare the compound of the formula III, and the synthetic route is as follows:
R 1 is optionally substituted nitrogen-containing heteroaryl;
R 2、R3、R4、R5 is independently H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl.
3. The detection reagent according to claim 2, wherein the compound of formula i and formula ii is prepared by amide condensation reaction to obtain the compound of formula iii, and the carboxylic acid may be pyridine carboxylic acid, pyrimidine carboxylic acid, pyrazine carboxylic acid, quinoline carboxylic acid and isoquinoline carboxylic acid, preferably nicotinic acid; the amine is a substituted 2-oxazolidinone compound.
4. The reagent according to claim 2, wherein the condensing agent used in the acid amine condensation reaction of the compounds of the formula I and the formula II is dicyclohexylcarbodiimide and the catalyst is 4-dimethylaminopyridine; the reaction is carried out in an organic solvent, preferably methylene chloride; the reaction temperature is room temperature; the reaction time is 16h-20h; preferably, the molar ratio of the compound of formula I, the compound of formula II, the condensing agent and the catalyst is 1:1.05-1.2:1.05-1.2:0.10-0.12.
5. A method for detecting and analyzing metal alkoxide is characterized by comprising the following steps: contacting the compound of formula III with a metal alkoxide.
6. The method according to claim 5, wherein the metal of the metal alkoxide is one of Na, K, mg, ca, zn, be, B, al, ga, sn and Ti, preferably one of Na, K and Mg.
7. Use of a compound of formula iii in the detection and analysis of metal alkoxides and metalloid alkoxides, characterized in that the use is Thin Layer Chromatography (TLC) or liquid chromatography-mass spectrometry (HPLC-MS).
8. The application according to claim 7, wherein the application is TLC, and the application process comprises the steps of: 1) Preparing a solution of a compound of formula III and a solvent for later use; 2) Dropwise adding a reaction solution of a metal salt and alcohol to the step 1); 3) And (3) carrying out thin-layer chromatography detection on the liquid obtained in the step (2) under the action of a developing agent.
9. The use according to claim 8, wherein in step 1) the solvent ethyl acetate; the step 2) also comprises the process of stirring or oscillating; the developing agent in the step 3) is preferably n-hexane: ethyl acetate=1:1.
10. The use according to claim 7, wherein the use is HPLC-MS, and the application process comprises the steps of: 1) Preparing a compound of formula III into a solution for later use; 2) Dropwise adding a reaction solution of a metal salt and alcohol to the step 1); 3) And (3) performing HPLC-MS detection on the liquid obtained in the step (2).
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