CN108383697A - 一种以卤甲基化合物为原料制备氘代醛的方法 - Google Patents
一种以卤甲基化合物为原料制备氘代醛的方法 Download PDFInfo
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- CN108383697A CN108383697A CN201810146057.0A CN201810146057A CN108383697A CN 108383697 A CN108383697 A CN 108383697A CN 201810146057 A CN201810146057 A CN 201810146057A CN 108383697 A CN108383697 A CN 108383697A
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- phenyl
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- 238000000034 method Methods 0.000 title claims abstract description 21
- 239000002994 raw material Substances 0.000 title claims abstract description 12
- 125000004970 halomethyl group Chemical group 0.000 title claims abstract description 10
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 title claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 58
- 238000002360 preparation method Methods 0.000 claims abstract description 47
- -1 aldehyde compounds Chemical class 0.000 claims abstract description 37
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 3
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims abstract description 3
- 150000003222 pyridines Chemical class 0.000 claims abstract 2
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical group 0.000 claims description 8
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical group C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-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
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 150000002916 oxazoles Chemical class 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 3
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 3
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 150000002460 imidazoles Chemical class 0.000 claims description 2
- 150000002475 indoles Chemical class 0.000 claims description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
- 125000005504 styryl group Chemical group 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 4
- 229910001385 heavy metal Inorganic materials 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 116
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
- 125000001246 bromo group Chemical class Br* 0.000 description 29
- 239000007787 solid Substances 0.000 description 21
- 150000001299 aldehydes Chemical class 0.000 description 14
- 150000001721 carbon Chemical group 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 9
- 150000002170 ethers Chemical class 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- UOXJNGFFPMOZDM-UHFFFAOYSA-N 2-[di(propan-2-yl)amino]ethylsulfanyl-methylphosphinic acid Chemical compound CC(C)N(C(C)C)CCSP(C)(O)=O UOXJNGFFPMOZDM-UHFFFAOYSA-N 0.000 description 3
- SFHYNDMGZXWXBU-LIMNOBDPSA-N 6-amino-2-[[(e)-(3-formylphenyl)methylideneamino]carbamoylamino]-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1NC(=O)N\N=C\C1=CC=CC(C=O)=C1 SFHYNDMGZXWXBU-LIMNOBDPSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical class COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- KOFLVDBWRHFSAB-UHFFFAOYSA-N 1,2,4,5-tetrahydro-1-(phenylmethyl)-5,9b(1',2')-benzeno-9bh-benz(g)indol-3(3ah)-one Chemical compound C1C(C=2C3=CC=CC=2)C2=CC=CC=C2C23C1C(=O)CN2CC1=CC=CC=C1 KOFLVDBWRHFSAB-UHFFFAOYSA-N 0.000 description 1
- GPHCPUFIWQJZOI-UHFFFAOYSA-N 1-(2-bromoethyl)naphthalene Chemical class C1=CC=C2C(CCBr)=CC=CC2=C1 GPHCPUFIWQJZOI-UHFFFAOYSA-N 0.000 description 1
- GQFITODJWOIYPF-UHFFFAOYSA-N 1-(bromomethyl)-2-iodobenzene Chemical class BrCC1=CC=CC=C1I GQFITODJWOIYPF-UHFFFAOYSA-N 0.000 description 1
- HXBMIQJOSHZCFX-UHFFFAOYSA-N 1-(bromomethyl)-2-nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1CBr HXBMIQJOSHZCFX-UHFFFAOYSA-N 0.000 description 1
- JDNPUJCKXLOHOW-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethoxy)benzene Chemical class FC(F)(F)OC1=CC=C(CBr)C=C1 JDNPUJCKXLOHOW-UHFFFAOYSA-N 0.000 description 1
- KQNBRMUBPRGXSL-UHFFFAOYSA-N 1-(bromomethyl)-4-chlorobenzene Chemical class ClC1=CC=C(CBr)C=C1 KQNBRMUBPRGXSL-UHFFFAOYSA-N 0.000 description 1
- VTPQLJUADNBKRM-UHFFFAOYSA-N 1-(bromomethyl)-4-ethenylbenzene Chemical class BrCC1=CC=C(C=C)C=C1 VTPQLJUADNBKRM-UHFFFAOYSA-N 0.000 description 1
- WZRKSPFYXUXINF-UHFFFAOYSA-N 1-(bromomethyl)-4-methylbenzene Chemical class CC1=CC=C(CBr)C=C1 WZRKSPFYXUXINF-UHFFFAOYSA-N 0.000 description 1
- HZQLUIZFUXNFHK-UHFFFAOYSA-N 1-(bromomethyl)-4-phenylbenzene Chemical class C1=CC(CBr)=CC=C1C1=CC=CC=C1 HZQLUIZFUXNFHK-UHFFFAOYSA-N 0.000 description 1
- QZNQSIHCDAGZIA-UHFFFAOYSA-N 1-(bromomethyl)-4-tert-butylbenzene Chemical class CC(C)(C)C1=CC=C(CBr)C=C1 QZNQSIHCDAGZIA-UHFFFAOYSA-N 0.000 description 1
- LZSYGJNFCREHMD-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)benzene Chemical class BrCC1=CC=CC=C1Br LZSYGJNFCREHMD-UHFFFAOYSA-N 0.000 description 1
- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical class BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N 1-naphthalen-1-ylnaphthalene Chemical compound C1=CC=C2C(C=3C4=CC=CC=C4C=CC=3)=CC=CC2=C1 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
- OHZAHWOAMVVGEL-UHFFFAOYSA-N 2,2'-bithiophene Chemical compound C1=CSC(C=2SC=CC=2)=C1 OHZAHWOAMVVGEL-UHFFFAOYSA-N 0.000 description 1
- QGXNHCXKWFNKCG-UHFFFAOYSA-N 2-(bromomethyl)benzonitrile Chemical class BrCC1=CC=CC=C1C#N QGXNHCXKWFNKCG-UHFFFAOYSA-N 0.000 description 1
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 description 1
- HTFNVAVTYILUCF-UHFFFAOYSA-N 2-[2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methyl-11-methylsulfonylpyrimido[4,5-b][1,4]benzodiazepin-6-one Chemical compound CCOc1cc(ccc1Nc1ncc2N(C)C(=O)c3ccccc3N(c2n1)S(C)(=O)=O)C(=O)N1CCC(CC1)N1CCN(C)CC1 HTFNVAVTYILUCF-UHFFFAOYSA-N 0.000 description 1
- GSFNQBFZFXUTBN-UHFFFAOYSA-N 2-chlorothiophene Chemical compound ClC1=CC=CS1 GSFNQBFZFXUTBN-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WKGHUAZJNBXABN-UHFFFAOYSA-N 3-bromo-2-chloro-6-methyl-5-nitropyridine Chemical compound CC1=NC(Cl)=C(Br)C=C1[N+]([O-])=O WKGHUAZJNBXABN-UHFFFAOYSA-N 0.000 description 1
- CQQSQBRPAJSTFB-UHFFFAOYSA-N 4-(bromomethyl)benzoic acid Chemical class OC(=O)C1=CC=C(CBr)C=C1 CQQSQBRPAJSTFB-UHFFFAOYSA-N 0.000 description 1
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical class BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical class CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 1
- AULWPXHFRBLPAE-UHFFFAOYSA-N 6-chloropyridine Chemical compound ClC1=C=CC=C[N]1 AULWPXHFRBLPAE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 229940074654 diuril Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000007037 hydroformylation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 208000006278 hypochromic anemia Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 150000004002 naphthaldehydes Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- NLRKCXQQSUWLCH-UHFFFAOYSA-N nitrosobenzene Chemical compound O=NC1=CC=CC=C1 NLRKCXQQSUWLCH-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
-
- C—CHEMISTRY; METALLURGY
- 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
-
- C—CHEMISTRY; METALLURGY
- 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
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
本发明提供了一种以卤甲基化合物为原料制备氘代醛的方法。所述方法包括如下步骤:在吡啶类化合物存在的溶剂和D2O混合液中,加入卤甲基化合物,在0℃~100℃下进行反应;然后加入亚硝基苯类化合物继续反应,最后反应液经酸化得到目标产物。本发明的方法所采用的原料均廉价易得,无需昂贵试剂或者重金属原料,而且反应条件简单,无需高温等苛刻条件,即本发明所述制备方法成本低廉、操作简单、氘代率高,可达97%,目标产物易纯化且收率高,最高可达95%。而且本发明所述方法的底物使适用性广,可制备多种氘代醛化合物。
Description
技术领域
本发明属于化合物的制备领域,更具体地,涉及一种以卤甲基化合物作为原料制备氘代醛的方法。
背景技术
醛类化合物在许多化学转化中具有不可替代的作用。氘化醛及其衍生物具有多种实际应用,如代谢途径探针和反应机理研究。尽管醛的合成已经得到了广泛研究,但是1-氘代醛的有效合成仍然非常具有挑战性,因此,人们一直致力于拓展氘化醛合成的方法。
传统的氘代醛的制备方法主要包括相应酯的氘化还原,然后氧化,使用D2气体进行酰氯的Rosenmund还原,二硫醇保护的醛的H/D交换,还原二氢-1,3-恶嗪和亚苄基二吡啶鎓二溴化物的水解。但是,这些方法大多需要繁琐的多步骤操作,昂贵的氘代试剂,或是苛刻的反应条件。此外,最近已经开发出新的氘代醛合成方法,如Cp2ZrDCl与叔酰胺反应,氧代羧酸的脱羧,钌催化的直接H/D交换等虽然取得了比较好的进步,但是合成中仍然存在许多挑战性的难题有待解决,特别是当前方法中使用的高温反应条件,底物范围有限,试剂可用性少以及氘代率低等,限制了这些方法的实际应用。
因此,提供一种成本低廉、操作简单、无重金属、易纯化、高收率和高氘代率的氘代醛制备方法具有十分广阔的应用前景。
发明内容
本发明的目的在于提供一种以卤甲基化合物作为原料制备氘代醛的方法。本发明所述制备方法以廉价易得的芳基甲基卤化物为起始物,采用方便经济的合成策略通过“一锅法”高效制备氘代醛。所述方法不仅反应条件简单、无重金属、无昂贵试剂、目标产物产物易纯化,而且制备成本低廉、氘代率高,目标产物的收率高。
本发明的上述目的是通过以下方案予以实现的:
一种以卤甲基化合物为原料制备氘代醛的方法,所述方法包括如下步骤:在吡啶类化合物存在的溶剂和D2O混合液中,加入卤甲基化合物,在0℃~100℃下进行反应;然后加入亚硝基苯类化合物继续反应,最后反应液经酸化得到目标产物。
优选地,所述制备方法包括如下步骤:在式Ⅱ所示化合物存在的溶剂、无机弱碱盐和D2O 混合液中,加入式Ⅲ所示化合物,在0℃~100℃下反应;然后再加入式Ⅳ所示化合物继续反应,最后经酸化得到式Ⅰ所示目标产物;
其中,R为苯基、取代苯基、芳香杂环、取代芳香杂环、苯乙烯基或取代苯乙烯基中的一种;
X为卤素;
R1和R2分别为氢、卤素、硝基、氰基、1至4个碳原子的烷基或取代甲基、1至4个碳原子的烷氧基或取代烷氧基或1至4个碳原子的烷基氨基。
优选地,所述芳香杂环选自:萘、联萘、联苯、呋喃、苯并呋喃、吡咯、吲哚、噻吩、苯并噻吩、吡啶、噻唑、喹啉、异喹啉、咪唑、苯并咪唑、噁唑、苯并噁唑、嘧啶、苯并嘧啶、吖啶或嘌呤。
优选地,所述芳香杂环选自:萘、联萘、联苯、苯并噻吩、吡啶、喹啉、噻唑或噁唑。
优选地,取代苯基、取代芳香杂环和取代苯乙烯基中的取代基分别选自:卤素、氨基、硝基、羟基、氰基、1至8个碳原子的烷基或取代烷基、1至8个碳原子的环烷基或取代环烷基、1至8个碳原子的烷氧基或取代烷氧基、1至8个碳原子的烯烃或取代烯烃、1至8个碳原子的烷基取代的氨基、1至8个碳原子的羧基、1至8个碳原子的烷氧基羰基、2至8个碳原子的酰基、2至8个碳原子的酰胺基、苯基、取代苯基或杂环中的一种或多种。
优选地,取代苯基、取代芳香杂环和取代苯乙烯基中的取代基分别选自:卤素、氨基、硝基、羟基、氰基、羧基、苯基、取代苯基、1至4个碳原子的烷基或取代烷基、1至3个碳原子的环烷基或取代环烷基、1至4个碳原子的烷氧基或取代烷氧基、1至4个碳原子的烯烃或取代烯烃、苯基或取代苯基中的一种或多种。
优选地,取代苯基、取代芳香杂环和取代苯乙烯基中的取代基分别选自:氟、氯、溴、碘、硝基、氰基、羧基、甲基、三氟甲基、叔丁基、甲氧基、三氟甲氧基、乙烯基、苯基、氰基取代苯基、氟取代苯基或甲基取代苯基中的一种或多种。
优选地,R1为氢、甲基或乙基。
优选地,所述反应的温度为20℃~80℃。
优选地,式Ⅲ化合物、式Ⅱ化合物、无机弱碱盐、D2O、式Ⅳ化合物和酸的摩尔比为1:0.1~20:1~20:1~1000:1~20:1~1000。
更优选地,式Ⅲ化合物、式Ⅱ化合物、无机弱碱盐、D2O、式Ⅳ化合物和酸的摩尔比为1:1~10:2~10:20~200:1~5:5~20。
更优选地,式Ⅲ化合物、式Ⅱ化合物、无机弱碱盐、D2O和式Ⅳ化合物和酸的摩尔比为 1:4:4:111:2:72。
优选地,加入式Ⅲ化合物后的反应时间为5~15h;加入式Ⅳ化合物后的反应是时间为 2~6h。
更优选地,加入式Ⅲ化合物后的反应时间为10h;加入式Ⅳ化合物后的反应是时间为4h。
优选地,所述反应的温度为20℃~80℃;更优选地,所述反应的温度为室温(20℃~40℃)。
优选地,所述无机弱碱盐为磷酸盐、碳酸盐、焦磷酸盐或醋酸盐。更优选地,所述无机弱碱盐为磷酸盐。
优选地,酸化所用的酸为盐酸、硫酸、硝酸或氢溴酸的水溶液。
优选地,所述酸化过程在冰浴条件下进行。
优选地,所述反应是在二甲基亚砜、1,4-二氧六环,N,N-二甲基甲酰胺、N,N-二乙基甲酰胺、四氢呋喃或乙腈溶液中进行。
与现有技术相比,本发明的优点和有益效果为:
本发明所述氘代醛的制备方法所采用的原料均廉价易得,无需昂贵试剂或者重金属原料,而且反应条件简单,无需高温等苛刻条件,即本发明所述制备方法成本低廉、操作简单、氘代率高,可达97%,目标产物易纯化且收率高,最高可达95%。而且本发明所述方法的底物使适用性广,可制备多种氘代醛化合物。
说明书附图
图1为化合物A1的氢谱图。
图2为化合物A1的碳谱图。
图3为化合物A2的氢谱图。
图4为化合物A2的碳谱图。
图5为化合物A3的氢谱图。
图6为化合物A3的碳谱图。
图7为化合物A4的氢谱图。
图8为化合物A4的碳谱图。
图9为化合物A5的氢谱图。
图10为化合物A5的碳谱图。
具体实施方式
现结合实施例,对本发明作详细描述,但本发明的实施不仅限于此。本发明所用试剂和原料均市售可得或可按文献方法制备。
实施例1:2-氘代萘甲醛(A1)的制备
先将DMSO(3mL)与D2O(1mL)混合搅拌5分钟,然后依次加入2-萘甲基溴(0.5mmol),4-甲基吡啶(2mmol),磷酸钾(2mmol)。在室温下搅拌反应10小时,然后在室温条件下加入4-二甲氨基亚硝基苯(1mmol)。混合反应液在室温下继续反应4小时,然后在冰浴条件下缓慢滴加3M的盐酸溶液12mL,然后继续搅拌1小时,随后停止反应采用如下方法进行后处理:用乙酸乙酯(10mL)对反应液进行萃取,萃取3次并合并有机层,用水以及饱和食盐水洗有机层两次。然后加入无水硫酸钠进行干燥,最后通过硅胶柱进行柱层析(DCM:MeOH=100:1)即可得到产物A1(收率88%,氘代率97%)。
白色固体:1H NMR(300MHz,CDCl3):δ10.15(s,0.04H),8.33(s,1H),7.88-8.01(m,4H), 7.56-7.67(m,2H).13C NMR(75MHz,CDCl3):δ192.0(t,JC-D=26.2Hz),136.5,134.6,134.0, 132.6,129.5,129.1,128.1,127.1,122.8.
实施例2:A2的制备
除以2-硝基苄溴替代实施例1中2-萘甲基溴,反应温度为50℃外,其它条件和步骤与实施例1相同,得到化合物A2(收率56%,氘代率97%)。
淡黄色固体。1H NMR(300MHz,CDCl3):δ10.41(s,0.03H),8.10-8.13(m,1H),7.94-7.97 (m,1H),7.30-7.83(m,2H).13C NMR(75MHz,CDCl3):δ187.8(t,JC-D=29.2Hz),149.6,134.1, 133.7,131.3,129.7,124.5.
实施例3:A3的制备
除以4-氰基苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A3(收率84%,氘代率97%)。
白色固体。1H NMR(600MHz,CDCl3):δ10.09(s,0.03H),7.98(d,2H,J=8.4Hz),7.83(d, 2H,J=8.4Hz).13C NMR(150MHz,CDCl3):δ189.8(t,JC-D=27.0Hz),138.2,132.4,129.4, 117.2,117.1.
实施例4:A4的制备
除以4-氯代苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A4(收率82%,氘代率95%)。
白色固体。1H NMR(600MHz,CDCl3):δ9.98(s,0.05H),7.82(d,2H,J=8.4Hz),7.50(d, 2H,J=8.4Hz).13C NMR(150MHz,CDCl3):δ190.0(t,JC-D=27.0Hz),140.5,134.2,130.4, 129.0.
实施例5:A5的制备
除以2-溴代苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A5(收率81%,氘代率95%)。
淡黄色油状物。1H NMR(300MHz,CDCl3):δ10.36(s,0.05H),7.90-7.93(m,1H),7.63-7.66 (m,1H),7.40-7.47(m,2H).13C NMR(75MHz,CDCl3):δ191.5(t,JC-D=27.0Hz),135.4,133.9, 133.5,129.9,127.9,127.1.
实施例6:A6的制备
除以4-羧基苄溴替代实施例1中2-萘甲基溴,反应温度为80℃外,其它条件和步骤与实施例1相同,得到化合物A6(收率72%,氘代率95%)。
黄色固体。1H NMR(300MHz,DMSO-d6):δ10.07(s,0.05H),8.11(d,2H,J=8.1Hz),7.92 (d,2H,J=8.4Hz).13C NMR(75MHz,DMSO-d6):δ193.3(t,JC-D=27.0Hz),169.2,141.1,138.0, 130.2,129.6.
实施例7:A7的制备
除以4-苯基苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A7(收率79%,氘代率95%)。
白色固体。1H NMR(300MHz,CDCl3):δ10.06(s,0.05H),7.94(d,2H,J=8.4Hz),7.74(d, 2H,J=8.4Hz),7.62-7.66(m,2H),7.39-7.52(m,3H).13C NMR(75MHz,CDCl3):δ191.6(t,JC-D=26.2Hz),147.2,139.7,135.1,130.3,129.1,128.5,127.7,127.4.
实施例8:A8的制备
除以4-2'-氰基苯基苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A8(收率77%,氘代率94%)。
淡黄色固体。1H NMR(600MHz,CDCl3):δ10.08(s,0.06H),8.00(dt,2H,J1=8.4Hz,J2= 2.4Hz),7.79(dd,1H,J1=7.8Hz,J2=0.6Hz),7.72(dt,2H,J1=8.4Hz,J2=2.4Hz),7.69(td,1H, J1=7.8Hz,J2=1.8Hz),7.53(d,1H,J=7.8Hz),7.51(td,1H,J1=7.8Hz,J2=1.2Hz).13C NMR (150MHz,CDCl3):δ190.9(t,JC-D=27.0Hz),143.5,143.4,135.6,133.4,132.6,129.5,129.1, 128.0,117.7,110.8.
实施例9:A9的制备
除以4-三氟甲氧基苄溴替代实施例1中2-萘甲基溴,所用无机弱碱盐为碳酸钾外,其它条件和步骤与实施例1相同,得到化合物A9(收率65%,氘代率95%)。
无色油状物。1H NMR(600MHz,CDCl3):δ10.10(s,0.05H),8.01(d,2H,J=8.4Hz),7.81(d, 2H,J=8.4Hz).13C NMR(150MHz,CDCl3):δ190.2(t,JC-D=27.0Hz),138.1,135.0(q,JC-F= 31.5Hz),129.4,125.6,122.0(q,JC-F=271.5Hz).
实施例10:A10的制备
除以4-叔丁基苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A10(收率71%,氘代率92%)。
无色油状物。1H NMR(300MHz,CDCl3):δ9.98(s,0.08H),7.81(d,2H,J=8.4Hz),7.54(d, 2H,J=8.4Hz),1.35(s,9H).13C NMR(75MHz,CDCl3):δ191.8(t,JC-D=27.0Hz),158.5,134.0, 129.7,126.0,35.4,31.1.
实施例11:A11的制备
除以4-氟-2-甲基代苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A11(收率62%,氘代率96%)。
无色油状物。1H NMR(600MHz,CDCl3):δ10.25(s,0.04H),7.49(dd,1H,J1=7.8Hz,J2= 2.4Hz),7.23(dd,1H,J1=7.8Hz,J2=5.4Hz),7.18(td,1H,J1=7.8Hz,J2=3.0Hz),2.63(s,3H). 13C NMR(150MHz,CDCl3):δ190.2(t,JC-D=27.0Hz),160.0(d,JC-F=244.5Hz),135.8(d,JC-F= 3.0),134.7,132.8(d,JC-F=6.0),120.2(d,JC-F=21.0),116.3(d,JC-F=22.5),17.91.
实施例12:A12的制备
除以4-氟-2-氯代苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A12(收率65%,氘代率96%)。
白色固体。1H NMR(600MHz,CDCl3):δ10.40(s,0.04H),7.97(dd,1H,J1=9.0Hz,J2= 6.0Hz),7.19(dd,1H,J1=8.4Hz,J2=2.4Hz),7.18(td,1H,J1=9.0Hz,J2=2.4Hz).13CNMR (150MHz,CDCl3):δ187.3(t,JC-D=28.5Hz),164.5(d,JC-F=259.5Hz),138.9(d,JC-F=12.0), 131.1(d,JC-F=10.5),128.8,117.4(d,JC-F=25.5),114.6(d,JC-F=22.5).
实施例13:A13的制备
除以5-氯苯并噻吩乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A13(收率95%,氘代率93%)。
淡黄色固体。1H NMR(300MHz,CDCl3):δ10.07(s,0.07H),8.64(d,1H,J=1.5Hz),8.33(s, 0.15H),7.74(d,1H,J=8.7Hz),7.38(dd,1H,J1=8.7Hz,J2=1.8Hz).13C NMR(75MHz, CDCl3):δ184.7(t,JC-D=26.2Hz),144.5,144.2(t,JC-D=27.8Hz),138.4,136.2,135.5,132.7, 126.7,124.5,123.3.
实施例14:A14的制备
除以6-甲基吡啶乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A14(收率91%,氘代率93%)。
淡黄色固体。1H NMR(300MHz,CDCl3):δ8.68(s,0.07H),7.71(s,1H),7.31(d,1H,J= 9.0Hz),6.72(d,1H,J=9.0Hz).13C NMR(75MHz,CDCl3):δ150.0(t,JC-D=27.0Hz),143.6, 139.2,122.9,121.7,112.5,40.5.
实施例15:A15的制备
除以2-环丙基-4-(4-氟苯基)喹啉乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A15(收率93%,氘代率94%)。
白色固体。1H NMR(600MHz,CDCl3):δ10.07(s,0.06H),7.97(d,1H,J=8.4Hz),7.74(t, 1H,J=8.4Hz),7.45(d,1H,J=8.4Hz),7.40(t,1H,J=8.4Hz),7.34-7.36(m,2H),7.26(t,2H,J =8.4Hz),3.22-3.25(m,1H),1.38-1.41(m,2H),1.09-1.12(m,2H).13C NMR(150MHz,CDCl3): δ192.8(t,JC-D=27.0Hz),161.7(d,JC-F=247.5),161.2,152.4,148.5,131.5(d,JC-F=7.5),131.4, 129.5,128.7,126.0,125.7,125.5,124.8,115.2(d,JC-F=22.5),14.0,10.9.
实施例16:A16的制备
除以[1,1'-联二萘]-2,2'-乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1 相同,得到化合物A16(收率70%,氘代率95%)。
白色固体。1H NMR(300MHz,CDCl3):δ9.62(s,0.09H),8.20(d,2H,J=8.4Hz),8.12(d, 2H,J=8.7Hz),8.01(d,2H,J=8.1Hz),7.64(t,2H,J=7.8Hz),7.38(t,2H,J=7.8Hz),7.22(d, 2H,J=8.7Hz).13C NMR(75MHz,CDCl3):δ190.8(t,JC-D=27.0Hz),139.7,135.9,133.5,133.2, 129.8,129.5,128.6,127.9,127.3,122.3.
实施例17:A17的制备
除以1-萘乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A17(收率83%,氘代率94%)。
白色固体。1H NMR(300MHz,CDCl3):δ10.40(s,0.06H),9.25(d,1H,J=8.7Hz),8.08(d, 1H,J=8.4Hz),7.98(dd,1H,J1=7.2Hz,J2=1.2Hz),7.91(d,1H,J=8.1Hz),7.57-7.72(m,3H). 13C NMR(75MHz,CDCl3):δ193.3(t,JC-D=26.2Hz),136.7,135.3,133.7,131.3,130.6,129.1, 128.5,127.0,124.9,124.9.
实施例18:A18的制备
除以2-氰基苄溴替代实施例1中2-萘甲基溴,反应温度为50℃,所用无机弱碱盐为磷酸钠外,其它条件和步骤与实施例1相同,得到化合物A18(收率59%,氘代率96%)。
白色固体。1H NMR(300MHz,CDCl3):δ10.35(s,0.04H),8.04(d,1H,J=7.2Hz),7.73-7.86(m,3H).13C NMR(75MHz,CDCl3):δ188.3(t,JC-D=27.8Hz),136.7,134.3,134.1,133.3,129.6,116.0,113.9.
实施例19:A19的制备
除以4-溴代苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A19(收率82%,氘代率96%)。
白色固体。1H NMR(600MHz,CDCl3):δ9.94(s,0.04H),7.71(d,2H,J=8.4Hz),7.64(d, 2H,J=8.4Hz).13C NMR(150MHz,CDCl3):δ190.2(t,JC-D=27.0Hz),134.5,131.9,130.4, 129.2.
实施例20:A20的制备
除以2-碘代苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A20(收率82%,氘代率96%)。
白色固体。1H NMR(300MHz,CDCl3):δ10.05(s,0.03H),7.92(dd,1H,J1=8.1Hz,J2=0.9 Hz),7.85(dd,1H,J1=7.8Hz,J2=1.8Hz),7.44(td,1H,J1=7.8Hz,J2=0.9Hz),7.26(td,1H,J1=7.8Hz,J2=1.8Hz).13C NMR(75MHz,CDCl3):δ195.4(t,JC-D=27.8Hz),140.6,135.5,135.1, 130.3,128.7,100.7.
实施例21:A21的制备
除以2,4-二氯苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A21(收率70%,氘代率97%)。
白色固体。1H NMR(600MHz,CDCl3):δ10.35(s,0.03H),7.87(d,1H,J=8.4Hz),7.48(d, 1H,J=1.8Hz),7.37(dd,1H,J1=8.4Hz,J2=1.8Hz).13C NMR(150MHz,CDCl3):δ187.7(t, JC-D=28.5Hz),140.6,138.0,130.4,130.0,129.8,127.5.
实施例22:A22的制备
除以4-乙烯基苄溴替代实施例1中2-萘甲基溴,反应温度为80℃外,其它条件和步骤与实施例1相同,得到化合物A22(收率52%,氘代率90%)。
淡黄色固体。1H NMR(600MHz,CDCl3):δ9.99(s,0.10H),7.84(d,2H,J=8.4Hz),7.55(d, 2H,J1=7.8Hz,J2=2.1Hz),6.77(dd,1H,J1=18.0Hz,J2=10.8Hz),5.90(d,1H,J=17.4Hz), 5.44(d,1H,J=11.4Hz).13C NMR(150MHz,CDCl3):δ190.9(t,JC-D=25.5Hz),143.0,135.4, 135.1,129.6,126.2,117.0.
实施例23:A23的制备
除以4-甲基苄溴替代实施例1中2-萘甲基溴,反应温度为100℃外,其它条件和步骤与实施例1相同,得到化合物A23(收率54%,氘代率94%)。
无色油状液体。1H NMR(600MHz,CDCl3):δ9.97(s,0.06H),7.77(d,2H,J=8.4Hz),7.33 (d,2H,J=8.4Hz),2.44(s.3H).13C NMR(150MHz,CDCl3):δ191.2(t,JC-D=27.0Hz),145.0, 133.7,129.3,129.2,21.4.
实施例24:A24的制备
除以3-甲氧基苄溴替代实施例1中2-萘甲基溴,反应温度为10℃外,其它条件和步骤与实施例1相同,得到化合物A24(收率58%,氘代率91%)。
淡黄色油状物。1H NMR(600MHz,CDCl3):δ9.98(s,0.09H),7.43-7.47(m,2H),7.39-7.40 (m,1H),7.17-7.19(m,1H),3.86(s,3H).13C NMR(150MHz,CDCl3):δ191.3(t,JC-D=27.0Hz), 159.7,137.3,129.5,123.0,121.0,111.6,55.0.
实施例25:A25的制备
除以2-氯噻唑-5-乙基溴替代实施例1中2-萘甲基溴,所用无机弱碱盐为磷酸钠外,其它条件和步骤与实施例1相同,得到化合物A25(收率60%,氘代率95%)。
淡黄色油状物。1H NMR(600MHz,CDCl3):δ9.95(s,0.05H),8.18(s,1H).13C NMR(150 MHz,CDCl3):δ180.5(t,JC-D=28.5Hz),159.8,149.0,140.7.
实施例26:A26的制备
除以6-三氟甲基吡啶3-乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例 1相同,得到化合物A26(收率63%,氘代率97%)。
淡黄色固体。1H NMR(300MHz,CDCl3):δ10.22(s,0.03H),9.19(s,1H),8.36(d,1H,J= 8.1Hz),7.87(d,1H,J=8.1Hz).13C NMR(150MHz,CDCl3):δ189.1(t,JC-D=27.8Hz),152.1(q, JC-F=34.5),151.7,137.7,133.0,121.0,119.1(q,JC-F=273.0).
实施例27:A27的制备
除以6-氯吡啶3-乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A27(收率71%,氘代率97%)。
淡黄色固体。1H NMR(300MHz,CDCl3):δ10.10(s,0.03H),8.86(d,1H,J=2.1Hz),8.14 (dd,1H,J1=8.4Hz,J2=2.1Hz),7.50(dd,1H,J1=8.1Hz,J2=0.6Hz).13C NMR(150MHz, CDCl3):δ188.9(t,JC-D=27.0Hz),157.0,152.4,138.0,130.3,125.2.
实施例28:A28的制备
除以5-甲基-2-5’-甲基苯基恶唑-4-乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A28(收率86%,氘代率97%)。
白色固体。1H NMR(600MHz,CDCl3):δ10.00(s,0.03H),7.91(d,2H,J=7.8Hz),7.25(d, 2H,J=8.4Hz),2.68(s,3H),2.39(s,3H).13C NMR(150MHz,CDCl3):δ184.7(t,JC-D=27.0Hz), 160.2,155.7,140.9,135.3,129.1,126.0,123.2,21.0,11.2.
实施例29:A29的制备
除以苯乙烯基乙基溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A29(收率80%,氘代率97%)。
无色油状物。1H NMR(600MHz,CDCl3):δ9.70(d,0.03H,J=7.8Hz),7.56-7.57(m,2H), 7.46(d,1H,J=15.6Hz),7.41-7.45(m,3H),6.70(d,1H,J=16.2Hz).13C NMR(150MHz,CDCl3):δ193.3(t,JC-D=25.5Hz),152.6,134.0,131.2,129.1,128.5(t,JC-D=3Hz),128.4.
实施例30:A30的制备
除以3-甲氧基苄溴替代实施例1中2-萘甲基溴外,其它条件和步骤与实施例1相同,得到化合物A30(收率61%,氘代率95%)。
淡黄色油状物。1H NMR(600MHz,CDCl3):δ9.97(s,0.05H),7.42-7.46(m,2H),7.38-7.39 (m,1H),7.16-7.18(m,1H),3.86(s,3H).13C NMR(150MHz,CDCl3):δ191.3(t,JC-D=27.0Hz), 159.7,137.3,129.5,123.0,121.0,111.6,55.0.
上述实施例所制备的化合物A1~A30的化学名称、结构式、1H-NMR和MS数据详见表1。
表1化合物A1~A30的化学名称、结构式、1H-NMR和MS数据
从上述实施例可知,本发明所述方法可适用的底物范围广,可制备多种氘代醛化合物,且氘代率高,均高于90%,最高可达97%,同时目标产物的产率高,最高可达95%。
以上已对本发明创造的较佳实施例进行了具体说明,但本发明创造并不限于所述实施例,熟悉本领域的技术人员在不违背本发明创造精神的前提下还可做出种种的等同的变型或替换,这些等同的变型或替换均包含在本申请权利要求所限定的范围内。
Claims (10)
1.一种以卤甲基化合物为原料制备氘代醛的方法,其特征在于,在吡啶类化合物存在的溶剂、无机弱碱盐和D2O混合液中,加入卤甲基化合物,在0℃~100℃下进行反应;然后加入亚硝基苯类化合物继续反应,最后反应液经酸化得到目标产物。
2.根据权利要求1所述制备方法,其特征在于,所述方法包括如下步骤:在式Ⅱ所示化合物存在的溶剂、无机弱碱盐和D2O混合液中,加入式Ⅲ所示化合物,在0℃~100℃下反应;然后再加入式Ⅳ所示化合物继续反应,最后经酸化得到式Ⅰ所示目标产物;
;
其中,R为苯基、取代苯基、芳香杂环、取代芳香杂环、苯乙烯基或取代苯乙烯基中的一种;X为卤素;
R1和R2分别为氢、卤素、硝基、氰基、1至4个碳原子的烷基或取代甲基、1至4个碳原子的烷氧基或取代烷氧基或1至4个碳原子的烷基氨基。
3.根据权利要求2所述制备方法,其特征在于,所述芳香杂环选自:萘、联萘、联苯、呋喃、苯并呋喃、吡咯、吲哚、噻吩、苯并噻吩、吡啶、噻唑、喹啉、异喹啉、咪唑、苯并咪唑、噁唑、苯并噁唑、嘧啶、苯并嘧啶、吖啶或嘌呤。
4.根据权利要求2所述制备方法,其特征在于,取代苯基、取代芳香杂环和取代苯乙烯基中的取代基分别选自:卤素、氨基、硝基、羟基、氰基、1至8个碳原子的烷基或取代烷基、1至8个碳原子的环烷基或取代环烷基、1至8个碳原子的烷氧基或取代烷氧基、1至8个碳原子的烯烃或取代烯烃、1至8个碳原子烷基取代的氨基、1至8个碳原子的羧基、1至8个碳原子的烷氧基羰基、2至8个碳原子的酰基、2至8个碳原子的酰胺基、苯基、取代苯基或杂环中的一种或多种。
5.根据权利要求4所述制备方法,其特征在于,取代苯基、取代芳香杂环和取代苯乙烯基中的取代基分别选自:卤素、氨基、硝基、羟基、氰基、羧基、苯基、取代苯基、1至4个碳原子的烷基或取代烷基、1至3个碳原子的环烷基或取代环烷基、1至4个碳原子的烷氧基或取代烷氧基、1至4个碳原子的烯烃或取代烯烃、苯基或取代苯基中的一种或多种。
6.根据权利要求2所述制备方法,其特征在于,所述反应的温度为20℃~80℃。
7.根据权利要求2所述制备方法,其特征在于,式Ⅲ化合物、式Ⅱ化合物、无机弱碱盐、D2O、式Ⅳ化合物和酸的摩尔比为1:0.1~20:1~20:1~1000:1~20:1~1000。
8.根据权利要求2所述制备方法,其特征在于,所述无机弱碱盐为磷酸盐、碳酸盐、焦磷酸盐或醋酸盐。
9.根据权利要求2所述制备方法,其特征在于,酸化所用的酸为盐酸、硫酸、硝酸或氢溴酸的水溶液。
10.根据权利要求2所述制备方法,其特征在于,所述反应是在二甲基亚砜、1,4-二氧六环,N,N-二甲基甲酰胺、N,N-二乙基甲酰胺、四氢呋喃或乙腈溶液中进行。
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