CN114075108A - 醛的氘代和制备氘代醛中的应用 - Google Patents
醛的氘代和制备氘代醛中的应用 Download PDFInfo
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- CN114075108A CN114075108A CN202010834414.XA CN202010834414A CN114075108A CN 114075108 A CN114075108 A CN 114075108A CN 202010834414 A CN202010834414 A CN 202010834414A CN 114075108 A CN114075108 A CN 114075108A
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- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 title abstract 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 22
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 13
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000011941 photocatalyst Substances 0.000 claims abstract description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 11
- 229910052786 argon Inorganic materials 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 238000004440 column chromatography Methods 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 8
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 5
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000007789 gas Substances 0.000 claims abstract description 4
- 230000002153 concerted effect Effects 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- 150000001299 aldehydes Chemical class 0.000 claims description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
- -1 etc. Chemical compound 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 238000003786 synthesis reaction Methods 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical class O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 238000007664 blowing Methods 0.000 claims description 3
- 238000009987 spinning Methods 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- DIBSCKQIZZVKMG-UHFFFAOYSA-N 2-phenylbutanal Chemical class CCC(C=O)C1=CC=CC=C1 DIBSCKQIZZVKMG-UHFFFAOYSA-N 0.000 claims description 2
- UIXIZFIUMREAFZ-UHFFFAOYSA-N 2-phenylpentanal Chemical class CCCC(C=O)C1=CC=CC=C1 UIXIZFIUMREAFZ-UHFFFAOYSA-N 0.000 claims description 2
- BPBDVCVMDGMPEW-UHFFFAOYSA-N 2-pyridin-2-ylacetaldehyde Chemical class O=CCC1=CC=CC=N1 BPBDVCVMDGMPEW-UHFFFAOYSA-N 0.000 claims description 2
- YGCZTXZTJXYWCO-UHFFFAOYSA-N 3-phenylpropanal Chemical class O=CCCC1=CC=CC=C1 YGCZTXZTJXYWCO-UHFFFAOYSA-N 0.000 claims description 2
- MQGVOSGGRHAKOE-UHFFFAOYSA-N 3-pyridin-3-ylpropanal Chemical class O=CCCC1=CC=CN=C1 MQGVOSGGRHAKOE-UHFFFAOYSA-N 0.000 claims description 2
- GDJNTTIGXNNPQF-UHFFFAOYSA-N 4-pyridin-4-ylbutanal Chemical class O=CCCCC1=CC=NC=C1 GDJNTTIGXNNPQF-UHFFFAOYSA-N 0.000 claims description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N Carbazole Natural products C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 2
- 150000001555 benzenes Chemical class 0.000 claims description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 2
- 150000001716 carbazoles Chemical class 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 150000002240 furans Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- 150000002475 indoles Chemical class 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229940100595 phenylacetaldehyde Drugs 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003222 pyridines Chemical class 0.000 claims description 2
- 150000003248 quinolines Chemical class 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 230000002195 synergetic effect Effects 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims description 2
- 150000003557 thiazoles Chemical class 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims 1
- 150000003384 small molecules Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 3
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 56
- 238000005160 1H NMR spectroscopy Methods 0.000 description 25
- 239000007788 liquid Substances 0.000 description 13
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 239000007787 solid Substances 0.000 description 12
- 150000001335 aliphatic alkanes Chemical class 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 241001313099 Pieris napi Species 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 150000001924 cycloalkanes Chemical class 0.000 description 2
- 125000004431 deuterium atom Chemical group 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- BGNGWHSBYQYVRX-WFVSFCRTSA-N 2-deuterio-4-(dimethylamino)benzaldehyde Chemical compound [2H]C1=CC(N(C)C)=CC=C1C=O BGNGWHSBYQYVRX-WFVSFCRTSA-N 0.000 description 1
- AVPYQKSLYISFPO-MICDWDOJSA-N 4-chloro-2-deuteriobenzaldehyde Chemical compound ClC=1C=C(C(C=O)=CC=1)[2H] AVPYQKSLYISFPO-MICDWDOJSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-MICDWDOJSA-N BrC=1C=C(C(C=O)=CC=1)[2H] Chemical compound BrC=1C=C(C(C=O)=CC=1)[2H] ZRYZBQLXDKPBDU-MICDWDOJSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- QGJXVBICNCIWEL-MMIHMFRQSA-N [2H]C(C(C=C1)=CC2=C1N(CC)C1=CC=CC=C21)=O Chemical compound [2H]C(C(C=C1)=CC2=C1N(CC)C1=CC=CC=C21)=O QGJXVBICNCIWEL-MMIHMFRQSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- PJKVFARRVXDXAD-BNEYPBHNSA-N deuterio(naphthalen-2-yl)methanone Chemical compound [2H]C(=O)c1ccc2ccccc2c1 PJKVFARRVXDXAD-BNEYPBHNSA-N 0.000 description 1
- HUMNYLRZRPPJDN-RAMDWTOOSA-N deuterio(phenyl)methanone Chemical compound [2H]C(=O)C1=CC=CC=C1 HUMNYLRZRPPJDN-RAMDWTOOSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
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- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/001—Acyclic or carbocyclic compounds
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- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
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- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/004—Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07B59/007—Steroids
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/54—Radicals substituted by oxygen atoms
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- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
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Abstract
本发明属于精细化学品技术领域,具体涉及可见光与有机小分子协同催化的醛的氘代反应制备氘代醛。醛与光催化剂4CzIPN、有机小分子催化剂三异丙基硅基硫醇((i‑Pr)3SiSH)、碳酸钠(NaCO3)、氘代水和有机溶剂混合,向反应瓶中吹氩气,在36W的470nm蓝光照射下反应。旋去溶剂,柱层析得到纯品。
Description
技术领域
本发明属于精细化学品技术领域,具体涉及可见光与有机小分子协同催化的醛的氘代反应在制备氘代醛中的应用。
背景技术
氘代作为标记技术在反应机理的研究,药物的吸收、分布、代谢和排泄(ADME)研究,核磁共振光谱和质谱分析研究中具有重要的作用。近年来,在药物分子中引入氘原子,在保持药物基本药理活性的同时,以增强其代谢和药代动力学特性的研究得到快速的发展。醛在药物和有机合成中无处不在,氘代醛可作为理想的氘代合成砌块,用于构建更为复杂的分子结构。氘代醛目前的合成方法包括LiAlD4还原相应的酯后再氧化,Schwartz试剂(由LiAlD4制备)还原相应的酰胺,Pd/Rh-共催化还原羰基化反应,羧酸的脱氧氘代反应。考虑到有机合成中的原子和步骤经济性,制备氘代醛最理想的方法是氢氘交换反应(HIE)。在这一方面,已经报道了两例Ir-和Ru-催化的HIE反应,但是这些反应的氘代率不高且区域选择性不好,往往会得到芳香环碳氢键氘代的副产物。此外,将氘原子引入到结构复杂的醛中也是有机合成中的挑战(E.P.K.Olsen,T.Singh,P.Harris,P.G.Andersson,R.Madsen,J.Am.Chem.Soc.2015,137,834;J.T.Spletstoser,J.M.White,A.R.Tunoori,G.I.Georg,J.Am.Chem.Soc.2007,129,3408;M.Y.S.Ibrahim,S.E.Denmark,Angew.Chem.Int.Ed.2018,57,10362;M.Zhang,X.-A.Yuan,C.-J.Zhu and J.Xie,Angew.Chem.Int.Ed.2019,58,312.W.J.Kerr,M.Reid,T.Tuttle,Angew.Chem.Int.Ed.2017,56,7808;E.S.Isbrandt,J.K.Vandavasi,W.Zhang,M.P.Jamshidi,S.G.Newman,Synlett 2017,28,2851;H.Geng,X.Chen,J.Gui,Y.Zhang,Z.Shen,P.Qian,J.Chen,S.Zhang,W.Wang,Nature Catal.2019,2,1071;W.Liu,L.-L.Zhao,M.Melaimi,L.Cao,X.Xu,J.Bouffard,G.Bertrand,X.Yan,Chem.2019,5,2484.)。
发明内容
本发明的目的是提供芳香醛和脂肪醛醛基碳氢键直接氘代来合成氘代醛的方法。
本发明的可见光与有机小分子协同催化的醛的氘代反应制备氘代醛的合成路线如下(方程式1)。
方程式1:
其中醛A包括取代的或未取代的苯,取代的或未取代的吡啶,取代的或未取代的喹啉,取代的或未取代的噻唑,取代的或未取代的吲哚,取代的或未取代的咔唑,取代的或未取代的呋喃,取代的或未取代的苯乙醛,取代的或未取代的苯丙醛,取代的或未取代的苯丁醛,取代的或未取代的苯戊醛,取代的或未取代的2-吡啶乙醛,取代的或未取代的3-吡啶丙醛,取代的或未取代的4-吡啶丁醛等。所述取代的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、三氟甲基、三氟甲氧基、酰胺基、C1-C6的烃基、C1-C6的烷氧基、C1-C6的烷巯基、C1-C4的烷基取代的羰氧基和C1-C4的烷氧基取代的羰氧基中的一种或多种。
本发明的方法是:将醛A与光催化剂4CzIPN、有机小分子催化剂三异丙基硅基硫醇((i-Pr)3SiSH)、碳酸钠(NaCO3)、氘代水和有机溶剂混合,向反应瓶中吹氩气,在36W的470nm蓝光照射下进行反应。柱层析得到纯品。
本反应中醛、光催化剂4CzIPN、有机小分子催化剂(i-Pr)3SiSH、碳酸钠和氘代水的摩尔比是1∶0.001-0.2∶0.01-1∶0.01-1∶10-200。
反应温度可在-30-80℃范围内进行,反应不需要对光反应器降温,最佳的反应温度为20-50℃。
本反应的反应时间为12-72小时,最佳反应时间为36-48小时。
在本发明中所使用的有机溶剂可以是醇,如乙醇、甲醇等;烷烃或环烷烃,如环己烷、正己烷、正戊烷、正庚烷、石油醚、汽油等;醚,如乙醚、四氢呋喃等;氯代烷烃,如二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷等;乙酸乙酯,二甲基亚砜,N,N-二甲基甲酰胺,N,N-二甲基乙酰胺,乙腈。最佳的有机溶剂为乙酸乙酯、二氯甲烷。
本反应在不加4CzIPN或不加(i-Pr)3SiSH或不光照的条件下,均不能发生。
本反应可以对复杂的醛类分子和药物进行后期氘代修饰,得到表1中的化合物。其具体包括下述步骤:将复杂的醛类分子或药物与光催化剂4CzIPN、有机小分子催化剂三异丙基硅基硫醇((i-Pr)3SiSH)、碳酸钠(NaCO3)、氘代水和有机溶剂混合,向反应瓶中吹氩气,在36W的470nm蓝光照射下进行反应。柱层析得到纯品。
本反应中醛、光催化剂4CzIPN、有机小分子催化剂(i-Pr)3SiSH、碳酸钠和氘代水的摩尔比是1∶0.001-0.2∶0.01-1∶0.01-1∶10-200。
反应温度可在-30-80℃范围内进行,反应不需要对光反应器降温,最佳的反应温度为20-50℃。
本反应的反应时间为12-72小时,最佳反应时间为36-48小时。
在本发明中所使用的有机溶剂可以是醇,如乙醇、甲醇等;烷烃或环烷烃,如环己烷、正己烷、正戊烷、正庚烷、石油醚、汽油等;醚,如乙醚、四氢呋喃等;氯代烷烃,如二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷等;乙酸乙酯,二甲基亚砜,N,N-二甲基甲酰胺,N,N-二甲基乙酰胺,乙腈。最佳的有机溶剂为乙酸乙酯、二氯甲烷。
本反应在不加4CzIPN或不加(i-Pr)3SiSH或不光照的条件下,均不能发生。
表1可见光与有机小分子协同催化的醛的氘代反应对复杂的醛分子和药物进行修饰
具体实施方式
下述的实施例中,熔点未经校正,收率未经优化。
实施例1:(2S,5R)-2-异丙基-5-甲基环己基3甲酰基苯甲酸酯-甲酰基-d1的合成:
称取0.2mmol(2S,5R)-2-异丙基-5-甲基环己基3甲酰苯甲酸酯,0.01mmol光催化剂4CzIPN,0.08mmol三异丙基硅基硫醇((i-Pr)3SiSH),0.08mmol碳酸钠(NaCO3)于8mL反应瓶中,再加入1mL乙酸乙酯溶液,1mL氘代水,向反应瓶中吹氩气30s,在36W的470nm蓝光照射下反应36小时,旋去溶剂,柱层析(石油醚∶乙酸乙酯=20∶1)得到黄色液体,收率88%,氘代率91%。1H NMR(400MHz,CDCl3)δ10.10(s,0.09H),8.53(s,1H),8.32(d,J=7.6Hz,1H),8.09(d,J=7.6Hz,1H),7.64(t,J=7.6Hz,1H),5.00(td,J=10.8,4.4Hz,1H),2.13(d,J=12.0Hz,1H),1.95(dtd,J=13.6,6.8,2.4Hz,1H),1.80-1.70(m,2H),1.65-1.51(m,2H),1.14(dd,J=23.2,11.6Hz,2H),1.03-0.88(m,7H),0.81(d,J=6.8Hz,3H).13C NMR(100MHz,CDCl3)δ191.3(t,J=28Hz),165.1,136.6(t,J=3.5Hz),135.3,133.0,132.0,131.3,129.3,75.6,47.3,41.0,34.3,31.6,26.6,23.6,22.1,20.9,16.5.HRMS(ESI)calcd forC18H24DO3[M+H]+290.1861,found 290.1862.
实施例2:3-(甲酰基-d)苯基2-(4-异丁基苯基)丙酸酯的合成:
称取0.2mmol 3-甲酰基苯基2-(4-异丁基苯基)丙酸酯,0.01mmol光催化剂4CzIPN,0.08mmol三异丙基硅基硫醇((i-Pr)3SiSH),0.08mmol碳酸钠(NaCO3)于8mL反应瓶中,再加入1mL乙酸乙酯溶液,1mL氘代水,向反应瓶中吹氩气30s,在36W的470nm蓝光照射下反应36小时,旋去溶剂,柱层析(石油醚∶乙酸乙酯=20∶1)得到黄色液体,收率80%,氘代率93%。1H NMR(400MHz,CDCl3)δ9.95(s,0.07H),7.71(d,J=7.6Hz,1H),7.51(dt,J=15.6,4.8Hz,2H),7.35-7.23(m,3H),7.16(t,J=6.4Hz,2H),3.96(q,J=7.2Hz,1H),2.47(d,J=7.2Hz,2H),1.87(tt,J=13.2,6.8Hz,1H),1.61(d,J=7.2Hz,3H),0.91(d,J=6.8Hz,6H).13C NMR(100MHz,CDCl3)δ191.0(t,J=27.5Hz),173.0,151.5,141.1,137.6(t,J=3.5Hz),136.9,130.1,129.7,127.8,127.4,127.3,122.2,45.3,45.1,30.3,22.5,18.6.HRMS(ESI)calcd for C20H22DO3[M+H]+312.1704,found 312.1706.
实施例3:6-(3-((3r,5r,7r)-金刚烷-1-基)-4-甲氧基苯基)-2萘醛-d1的合成:
称取0.2mmol 6-(3-((3r,5r,7r)-金刚烷-1-基)-4-甲氧基苯基)-2萘醛,0.01mmol光催化剂4CzIPN,0.08mmol三异丙基硅基硫醇((i-Pr)3SiSH),0.08mmol碳酸钠(NaCO3)于8mL反应瓶中,再加入1mL乙酸乙酯溶液,1mL氘代水,向反应瓶中吹氩气30s,在36W的470nm蓝光照射下反应36小时,旋去溶剂,柱层析(石油醚∶乙酸乙酯=20∶1)得到白色固体,收率82%,氘代率96%,熔点236-237℃.1H NMR(400MHz,CDCl3)δ10.16(s,0.07H),8.35(s,1H),8.04(dd,J=4.8,3.2Hz,2H),7.97(s,2H),7.88-7.81(m,1H),7.61(d,J=2.4Hz,1H),7.56(dd,J=8.4,2.4Hz,1H),7.01(d,J=8.4Hz,1H),3.91(s,3H),2.18(s,6H),2.11(s,3H),1.81(s,6H).13C NMR(100MHz,CDCl3)δ191.9(t,J=27Hz),159.1,142.3,139.1,136.9,134.3,133.7(t,J=3.1Hz),132.3,131.4,131.3,129.9,129.8,129.2,126.9,126.0,125.8,125.0,123.2,112.2,55.2,40.6,37.2,37.1,29.1.HRMS(ESI)calcdfor C28H28DO2[M+H]+398.2225,found 398.2224.
用同样的方法可以合成下列氘代醛,但并不限定本发明。
2-萘甲醛-d1:白色固体,收率88%,氘代率93%,熔点86-87℃.1H NMR(400MHz,CDCl3)δ10.16(s,0.07H),8.33(s,1H),8.11-7.82(m,4H),7.76-7.46(m,2H).HRMS(ESI)calcd for C11H8DO[M+H]+158.0711,found 158.0712.
4-氟甲醛-d1:无色液体,收率73%,氘代率96%。1H NMR(400MHz,CDCl3)δ9.97(s,0.04H),7.99-7.87(m,2H),7.26-7.15(m,2H).HRMS(ESI)calcd for C7H5DFO[M+H]+126.0460,found 126.0461.
4-氯苯甲醛-d1:白色固体,收率81%,氘代率95%,熔点44-45℃.1H NMR(400MHz,CDCl3)δ9.99(s,0.05H),7.84(d,J=8.4Hz,2H),7.52(d,J=8.4Hz,2H).HRMS(ESI)calcdfor C7H5DClO[M+H]+142.0164,found 142.0164.
4-溴苯甲醛-d1:白色固体,收率62%,氘代率95%,熔点76-77℃.1H NMR(400MHz,CDCl3)δ9.98(s,0.05H),7.76(d,J=8.4Hz,2H),7.69(d,J=8.4Hz,2H).HRMS(ESI)calcdfor C7H5DBrO[M+H]+185.9659,found 185.9660
4-碘苯甲醛-d1:白色固体,收率83%,氘代率90%,熔点98-99℃.1H NMR(400MHz,CDCl3)δ9.98(s,0.1H),7.94(d,J=8.4Hz,2H),7.62(d,J=8.4Hz,2H).HRMS(ESI)calcdfor C7H5DIO[M+H]+233.9521,found 233.9518.
4-叔丁基甲醛-d1:无色液体,收率89%,氘代率99%。1H NMR(400MHz,CDCl3)δ9.98(s,0.01H),7.82(d,J=8.0Hz,2H),7.55(d,J=8.0Hz,2H),1.36(s,9H).HRMS(ESI)calcdfor C11H14DO[M+H]+164.1180,found 164.1181.
3,4-二甲基苯甲醛-d1:无色液体,收率75%,氘代率99%。1H NMR(400MHz,CDCl3)δ9.93(s,0.01H),7.80-7.52(m,2H),7.28(d,J=7.6Hz,1H),2.46-2.19(m,6H).HRMS(ESI)calcd for C9H10DO[M+H]+136.0867,found 136.0867.
3-甲基-4-氟苯甲醛-d1:无色液体,收率79%,氘代率99%。1H NMR(400MHz,CDCl3)δ9.93(s,0.01H),7.80-7.69(m,2H),7.15(t,J=8.8Hz,1H),2.35(d,J=2.0Hz,3H).HRMS(ESI)calcd for C8H7DFO[M+H]+140.0616,found 140.0616.
3,5-二叔丁基苯甲醛-d1:无色液体,收率72%,氘代率99%。1H NMR(400MHz,CDCl3)δ10.01(s,0.01H),7.77-7.69(m,2H),7.26(s,1H),1.37(s,18H).HRMS(ESI)calcdfor C15H22DO[M+H]+220.1806,found 220.1808.
(3-甲酰基苯基)氨基甲酸叔丁酯-d1:白色固体,收率91%,氘代率99%,熔点88-89℃.1H NMR(400MHz,CDCl3)δ9.98(s,0.01H),7.94(s,1H),7.64(d,J=7.6Hz,1H),7.56(d,J=7.6Hz,1H),7.45(t,J=7.6Hz,1H),6.78(s,1H),1.53(s,9H).HRMS(ESI)calcd forC12H15DNO3[M+H]+223.1187,found 223.1186.
4-甲巯基苯甲醛-d1:无色液体,收率76%,氘代率99%。1H NMR(400MHz,CDCl3)δ9.92(s,0.01H),7.77(d,J=8.0Hz,2H),7.32(d,J=8.0Hz,2H),2.53(s,3H).HRMS(ESI)calcd for C8H8DOS[M+H]+154.0431,found 154.0431.
4-二甲胺基苯甲醛-d1:白色固体,收率93%,氘代率98%,熔点67-69℃.1H NMR(400MHz,CDCl3)δ9.73(s,0.02H),7.73(d,J=8.8Hz,2H),6.68(d,J=8.8Hz,2H),3.09-3.02(m,0.18H).HRMS(ESI)calcd for C9H5D7NO[M+H]+157.1353,found 157.1356.
苯并[d][1,3]二恶唑-5-甲醛-d1:无色液体,收率74%,氘代率99%。1H NMR(400MHz,CDCl3)δ9.81(s,0.01H),7.42(d,J=8.0Hz,1H),7.34(s,1H),6.94(d,J=8.0Hz,1H),6.13-6.01(m,1.66H).HRMS(ESI)calcd for C8H6DO3[M+H]+152.0452,found152.0454.
2,3-二氢苯并[b][1,4]二恶英-6-甲醛-d1:白色固体,收率91%,氘代率99%,熔点44-45℃.1H NMR(400MHz,CDCl3)δ9.82(s,0.01H),7.40(dd,J=4.4,2.4Hz,2H),6.98(d,J=8.8Hz,1H),4.36-4.32(m,2H),4.31-4.27(m,2H).HRMS(ESI)calcd for C9H8DO3[M+H]+166.0609,found 166.0610.
3-(4,4,5,5-四甲基-1,3,2-二氧杂硼烷-2-基)苯甲醛-d1:无色液体,收率79%,氘代率98%。1H NMR(400MHz,CDCl3)δ10.05(s,0.02H),8.31(s,1H),8.06(d,J=7.2Hz,1H),8.03-7.95(m,1H),7.53(t,J=7.6Hz,1H),1.37(s,12H).HRMS(ESI)calcd for C13H17DBO3[M+H]+234.1406,found 234.1403.
2,6-二叔丁基-4-羟基苯甲醛-d1:白色固体,收率89%,氘代率90%,熔点136-137℃.1H NMR(400MHz,CDCl3)δ9.86(s,0.1H),7.74(s,2H),5.88(s,1H),1.48(s,18H).HRMS(ESI)calcd for C15H22DO2[M+H]+236.1755,found 236.1756.
2,6-二氯苯甲醛-d1:白色固体,收率49%,氘代率99%,熔点54-55℃.1H NMR(400MHz,CDCl3)δ10.50(s,0.01H),7.40(s,3H).HRMS(ESI)calcd for C7H4DCl2O[M+H]+175.9775,found 175.9776.
1-甲苯基-1H-吲哚-5-甲醛-d1:白色固体,收率71%,氘代率99%,熔点120-121℃.1H NMR(400MHz,CDCl3)δ10.03(s,0.01H),8.11(d,J=8.4Hz,1H),8.07(s,1H),7.86(dd,J=8.4,1.2Hz,1H),7.79(d,J=8.4Hz,2H),7.68(d,J=3.6Hz,1H),7.26(d,J=8.0Hz,2H),6.78(d,J=3.6Hz,1H),2.35(s,3H).HRMS(ESI)calcd for C16H13DNO3S[M+H]+301.0752,found 301.0750.
9-乙基-9H-咔唑-3-甲醛-d1:白色固体,收率87%,氘代率99%,熔点84-85℃.1HNMR(400MHz,CDCl3)δ10.04(s,0.01H),8.53(d,J=3.6Hz,1H),8.15-8.05(m,1H),8.00-7.91(m,1H),7.50(t,J=7.6Hz,1H),7.39(dd,J=9.2,5.6Hz,2H),7.29(t,J=7.6Hz,1H),4.41-4.22(m,2H),1.49-1.35(m,3H).HRMS(ESI)calcd for C15H13DNO[M+H]+225.1133,found 225.1134.
3-(苯并[d][1,3]二氧杂-5-基)-2-甲基丙醛-d1:无色液体,收率74%,氘代率99%。1H NMR(400MHz,CDCl3)δ9.70(d,J=1.6Hz,0.01H),6.73(d,J=8.0Hz,1H),6.66(d,J=1.6Hz,1H),6.61(dd,J=8.0,1.6Hz,1H),5.93(s,1.72H),3.00(dd,J=13.6,5.6Hz,1H),2.67-2.47(m,2H),1.08(d,J=6.8Hz,3H).HRMS(ESI)calcd for C11H12DO3[M+H]+194.0922,found 194.0924.
3-(苯并[d][1,3]二氧杂-5-基)-2,2-二甲基丙醛-d1:无色液体,收率79%,氘代率100%。1H NMR(400MHz,CDCl3)δ6.71(d,J=7.6Hz,1H),6.64(s,1H),6.58(d,J=7.6Hz,1H),5.91(s,1.72H),2.38(s,2H),0.88(s,6H).HRMS(ESI)calcd for C12H14DO3[M+H]+208.1078,found 208.1080.
3-(4-异丙基苯基)-2-甲基丙醛-d1:无色液体,收率85%,氘代率99%。1H NMR(400MHz,CDCl3)δ9.72(d,J=1.6Hz,0.01H),7.16(d,J=8.0Hz,2H),7.09(d,J=8.0Hz,2H),3.04(dt,J=11.2,5.6Hz,1H),2.88(dt,J=13.6,6.8Hz,1H),2.67(dt,J=12.8,6.8Hz,1H),2.61-2.51(m,1H),1.24(d,J=6.8Hz,6H),1.09(d,J=6.8Hz,3H).HRMS(ESI)calcd for C13H18DO[M+H]+192.1493,found 192.1494.
上述实施例中所合成的化合物为以下结构所示的化合物:
Claims (7)
1.可见光与有机小分子协同催化的醛的氘代反应制备氘代醛的方法,其特征是将1当量的醛与0.1-20mmol%的光催化剂4CzIPN、1-100mmol%的有机小分子催化剂三异丙基硅基硫醇((i-Pr)3SiSH)、1-100mmol%的碳酸钠(NaCO3)、10-200当量的氘代水和溶剂混合,向反应瓶中吹氩气,在36W的470nm蓝光照射下反应,旋去溶剂,柱层析得到纯品,
其中醛A包括取代的或未取代的苯,取代的或未取代的吡啶,取代的或未取代的喹啉,取代的或未取代的噻唑,取代的或未取代的吲哚,取代的或未取代的咔唑,取代的或未取代的呋喃,取代的或未取代的苯乙醛,取代的或未取代的苯丙醛,取代的或未取代的苯丁醛,取代的或未取代的苯戊醛,取代的或未取代的2-吡啶乙醛,取代的或未取代的3-吡啶丙醛,取代的或未取代的4-吡啶丁醛等。所述取代的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、三氟甲基、三氟甲氧基、酰胺基、C1-C6的烃基、C1-C6的烷氧基、C1-C6的烷巯基、C1-C4的烷基取代的羰氧基和C1-C4的烷氧基取代的羰氧基中的一种或多种。
3.权利要求1或2所述的合成方法,其特征在于所述的醛、光催化剂4CzIPN、有机小分子催化剂(i-Pr)3SiSH、碳酸钠和氘代水的摩尔比是1∶0.001-0.2∶0.01-1∶0.01-1∶10-200。
4.权利要求1或2所述的合成方法,其特征在于有机溶剂可以是乙醇、甲醇、环己烷、正己烷、正戊烷、正庚烷、石油醚、乙醚、四氢呋喃、二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷等、乙酸乙酯、二甲基亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、乙腈中的一种或多种。
5.按照权利要求1或2所述的合成方法,其特征在于最佳反应溶剂为乙酸乙酯。
6.按照权利要求1或2所述的合成方法,其特征在于所述的反应时间为12-72小时,最佳反应时间为36-48小时。
7.按照权利要求1或2所述的合成方法,其特征在于所述的最佳反应温度为20-50℃。
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---|---|---|---|---|
CN114805002A (zh) * | 2022-06-06 | 2022-07-29 | 遵义医科大学 | 一种还原或氘代还原芳香族烯烃、醛或酮的方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018099271A1 (zh) * | 2016-12-01 | 2018-06-07 | 深圳大学 | 一种制备氘代化学品的方法及氘代化学品 |
CN109293484A (zh) * | 2018-10-22 | 2019-02-01 | 南京大学 | 从羧酸以铱配合物为催化剂蓝光照射下制备氘代醛的方法 |
CN111533676A (zh) * | 2020-05-06 | 2020-08-14 | 浙江大学 | 一种吲哚类化合物的氘代合成方法 |
-
2020
- 2020-08-19 CN CN202010834414.XA patent/CN114075108A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018099271A1 (zh) * | 2016-12-01 | 2018-06-07 | 深圳大学 | 一种制备氘代化学品的方法及氘代化学品 |
CN109293484A (zh) * | 2018-10-22 | 2019-02-01 | 南京大学 | 从羧酸以铱配合物为催化剂蓝光照射下制备氘代醛的方法 |
CN111533676A (zh) * | 2020-05-06 | 2020-08-14 | 浙江大学 | 一种吲哚类化合物的氘代合成方法 |
Non-Patent Citations (3)
Title |
---|
JIANYANG DONG: "Formyl-selective deuteration of aldehydes with D2O via synergistic organic and photoredox catalysis", CHEM. SCI., vol. 11, no. 4, pages 1026, XP055836652, DOI: 10.1039/C9SC05132E * |
JIAN-YANG DONG: "Visible-light-mediated deuteration of aldehydes with D2O via polarity-matched reversible hydrogen atom transfer", TETRAHEDRON, vol. 82, pages 131946 - 131952 * |
YUETENG ZHANG, ET AL.: "Deuteration of Formyl Groups via a Catalytic Radical H/D Exchange Approach", ACS CATAL., vol. 10, no. 3, pages 2226, XP055836660, DOI: 10.1021/acscatal.9b05300 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114805002A (zh) * | 2022-06-06 | 2022-07-29 | 遵义医科大学 | 一种还原或氘代还原芳香族烯烃、醛或酮的方法 |
CN114805002B (zh) * | 2022-06-06 | 2023-08-22 | 遵义医科大学 | 一种还原或氘代还原芳香族烯烃、醛或酮的方法 |
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