CN115448841B - 一种利用氨水合成伯胺的方法 - Google Patents
一种利用氨水合成伯胺的方法 Download PDFInfo
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- CN115448841B CN115448841B CN202211291477.0A CN202211291477A CN115448841B CN 115448841 B CN115448841 B CN 115448841B CN 202211291477 A CN202211291477 A CN 202211291477A CN 115448841 B CN115448841 B CN 115448841B
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- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 235000011114 ammonium hydroxide Nutrition 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 18
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 17
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 title claims 11
- 229910052709 silver Inorganic materials 0.000 claims abstract 4
- 239000004332 silver Substances 0.000 claims abstract 4
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 239000003054 catalyst Substances 0.000 claims description 20
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 150000001989 diazonium salts Chemical class 0.000 claims description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 4
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims 3
- -1 phenylsulfonyl hydrazone Chemical class 0.000 abstract description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 20
- 150000003141 primary amines Chemical class 0.000 abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 10
- 150000008049 diazo compounds Chemical class 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 235000008206 alpha-amino acids Nutrition 0.000 abstract description 4
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001412 amines Chemical class 0.000 abstract description 3
- 239000002243 precursor Substances 0.000 abstract description 3
- 229910052723 transition metal Inorganic materials 0.000 abstract description 3
- 150000003624 transition metals Chemical class 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 238000006713 insertion reaction Methods 0.000 abstract 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 5
- 150000007857 hydrazones Chemical class 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000002791 soaking Methods 0.000 description 3
- KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 2
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- PHVXTQIROLEEDB-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-n-pyrrolidin-3-ylbenzamide Chemical compound CC1=CC=CC=C1C1CN(CC=2C=CC(=CC=2)C(=O)N(CCC=2C(=CC=CC=2)Cl)C2CNCC2)CCC1 PHVXTQIROLEEDB-UHFFFAOYSA-N 0.000 description 2
- 150000003139 primary aliphatic amines Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- ASQOQJYHIYYTEJ-GBESFXJTSA-N (1r,7s,9as)-7-decyl-2,3,4,6,7,8,9,9a-octahydro-1h-quinolizin-1-ol Chemical compound O[C@@H]1CCCN2C[C@@H](CCCCCCCCCC)CC[C@H]21 ASQOQJYHIYYTEJ-GBESFXJTSA-N 0.000 description 1
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- QBXVXKRWOVBUDB-GRKNLSHJSA-N ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C Chemical compound ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C QBXVXKRWOVBUDB-GRKNLSHJSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 229940125907 SJ995973 Drugs 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010493 gram-scale synthesis Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- XZMHJYWMCRQSSI-UHFFFAOYSA-N n-[5-[2-(3-acetylanilino)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]benzamide Chemical compound CC(=O)C1=CC=CC(NC=2SC=C(N=2)C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C)=C1 XZMHJYWMCRQSSI-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000000135 prohibitive effect Effects 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 150000003335 secondary amines Chemical group 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 150000003512 tertiary amines Chemical group 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种利用氨水合成伯胺的方法，涉及有机合成技术领域。本发明是以廉价的氨水为氮源，以重氮化合物或苯磺酰腙为卡宾前体，在过渡金属银催化下发生卡宾N‑H插入反应合成芳基甲胺、脂肪胺、α‑氨基酸酯等伯胺类化学品。本发明具有成本低、操作简单、产物易纯化、产率高等特点，具有良好的工业前景。
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种利用氨水合成伯胺的方法。
背景技术
脂肪伯胺广泛存在于商品化药物、农药和材料分子中。同时脂肪伯胺也是仲胺、叔胺等官能团的重要合成前体，因此高效合成脂肪伯胺一直是行业研究的热点。目前合成伯胺的方法主要有以下两种：
(1)羰基化合物的还原胺化；
(2)腈的氢化反应
这两种方法均存在原料昂贵，使得合成伯胺的成本居高不下。氨水为大宗工业品具有成本低且来源广泛的特点，利用氨水合成伯胺具有较高的经济价值。但是目前利用氨为原料合成脂肪伯胺存在诸多挑战，例如一些研究人员发现通过铜配合物和手性氢键供体的协同作用，不对称碳宾可以插入NH的N-H键，但这种化学反应的范围仅限于烷基重氮酯。由于氨水合成伯胺的反应体系中存在水的O-H插入竞争反应，且氨与大多数过渡金属配合物通过氮的孤对电子结合(Werner配位)生成稳定的Lewis酸碱复合物，毒化过渡金属催化剂，同时产物(伯胺)的反应活性比初始氨反应活性高，伯胺优先发生连续的卡宾插入(副)反应，从而降低总体化学选择性。因此如何设计新的合成路线，使得氨水能够高效合成伯胺是目前的研究热点。
发明内容
针对现有技术的不足，本发明提供了一种利用氨水合成伯胺的方法，该方法是采用以下技术手段实现的：
本发明是以氨水和重氮化合物为反应原料，在溶剂以及催化剂TpxAg作用下进行反应，通过控制反应温度、反应时间以及物料比，从而一步法合成出伯胺类化合物。本发明的伯胺类化合物便于纯化，且产率高。
本发明的合成路线如下：
其中，式I为重氮化合物，所述重氮化合物中R1为芳基、杂芳基或烷基；
R2为芳基、杂芳基、酯基或烷基；
其中反应温度为25-100℃；反应时间为6-24h。
本发明是在避光、无氧条件下进行的反应。
在一些实施例中，本发明所述重氮化合物结构式如下:
在一些实施例中，本发明控制重氮化合物、氨水以及催化剂的摩尔比为10:50～100:0.1-0.3。
本发明所述溶剂为有机溶剂，优选为二氯甲烷、1,2-二氯乙烷、1,4-二氧六环、甲苯、苯、乙腈、四氢呋喃、N,N-二甲基甲酰胺和二甲基亚砜中的一种或几种。
在本发明中对溶剂用量不作特殊限定，在一些实施例中本发明所述重氮化合物与氨水、催化剂、溶剂的用量比为10mmol:50-100mmol:15mmol-30mmol:0.1-0.3mmol:30-100mL。
本发明还提供了一种利用氨水合成伯胺的方法，该方法是以氨水和N-邻三氟甲基苯磺酰腙化合物为反应原料，在催化剂、碱的作用下进行一步反应后合成得到伯胺产物。
本发明的合成路线如下：
其中，式IV为芳基磺酰腙化合物，且R1为芳基、杂芳基、烯基、炔基、烷基或氢；R2为芳基、杂芳基、酯基或烷基；
反应条件为无氧、避光；
反应温度为60-120℃；
反应时间为12-48h。
在一些实施例中本发明芳基磺酰腙化合物的结构如下：
优选的，在一些是实施例中，本发明所N-邻三氟甲基苯磺酰腙化合物与氨水、碱、催化剂、有机溶剂的用量比为10mmol:50-100mmol:15mmol-30mmol:0.1-0.3mmol:30-100mL。
优选的，在一些实施例中，本发明所述碱为氢化钠、叔丁醇钠、叔丁醇锂、氢氧化钾、氢氧化钠、碳酸钾、碳酸铯和磷酸钾中的一种或几种。
本发明所述TpBr3Ag催化剂的结构式如下：
与现有技术相比，本发明具有以下有益效果：
本发明是以大宗工业品氨水为氮源，以N-邻三氟甲基苯磺酰腙或重氮化合物作为卡宾前体，在催化剂TpBr3Ag作用下进行反应，从而合成二芳基甲基胺和α-氨基酸酯等脂肪族伯胺，该方法具有反应条件温和，操作简便，底物范围宽泛，官能团耐受性好，可克级合成等优点。
附图说明
图1为本发明的合成路线图；
图2为本发明实施例1制备的伯胺化合物1H核磁共振谱图；
图3为本发明实施例1制备的伯胺化合物13C核磁共振谱图；
图4为本发明实施例2制备的伯胺化合物1H核磁共振谱图；
图5为本发明实施例2制备的伯胺化合物13C核磁共振谱图；
图6为本发明实施例3制备的伯胺化合物1H核磁共振谱图；
图7为本发明实施例3制备的伯胺化合物13C核磁共振谱图；
图8为本发明实施例4制备的伯胺化合物1H核磁共振谱图；
图9为本发明实施例4制备的伯胺化合物13C核磁共振谱图；
图10为本发明实施例5制备的伯胺化合物1H核磁共振谱图；
图11为本发明实施例5制备的伯胺化合物13C核磁共振谱图；
图12为本发明实施例6制备的伯胺化合物1H核磁共振谱图；
图13为本发明实施例6制备的伯胺化合物13C核磁共振谱图；
图14为本发明实施例7制备的伯胺化合物1H核磁共振谱图；
图15为本发明实施例7制备的伯胺化合物13C核磁共振谱图。
具体实施方式
为使本发明的目的、特征和优点能够更加明显易懂，下面结合附图对本发明的具体实施方式做详细的说明。附图中给出了本发明的若干实施例。但是，本发明可以以许多不同的形式来实现，并不限于本文所描述的实施例。相反地，提供这些实施例的目的是使对本发明的公开内容更加透彻全面。
实施例1
向10mL的Schlenk管中加入TpBr3Ag催化剂(33.0mg,0.03mmol,10mol％)和碳酸铯(146.6mg,0.45mmol,1.5equiv)，置换氮气。然后用注射器分别将氨水(308μL,28％-30％wt％,0.6mmol,8.0equiv)、超干1,2-二氯乙烷(2mL)以及腙化合物1a(0.3mmol,121.3mg)注入反应管中。将反应体系避光处理，放入80℃油浴中反应24小时。待反应体系冷却后，将反应体系用硅藻土过滤，减压蒸馏除去溶剂，残余物加入HCl的Et2O溶液，并在室温下搅拌1小时以沉淀出白色固体，将其过滤，用冷乙醚洗涤并真空干燥，最终得到胺的盐酸盐产物1c(46.7mg,85％)。具体合成路线如下：
对实施例1制备的化合物1c进行核磁表征，所得数据分别为：
1H NMR(600MHz,DMSO)δ9.30(d,J＝38.4Hz,3H),7.58-7.56(m,4H),7.41-7.38(m,4H),7.35-7.31(m,2H),5.61(s,1H).13C NMR(151MHz,DMSO)δ139.0,129.1,128.6,127.9,57.6.
实施例2
向10mL的Schlenk管中加入TpBr3Ag催化剂(33.0mg,0.03mmol,10mol％)和碳酸铯(146.6mg,0.45mmol,1.5equiv)，置换氮气。然后用注射器分别将氨水(308μL,28％-30％wt％,0.6mmol,8.0equiv)、超干1,2-二氯乙烷(2mL)以及腙化合物2a(0.3mmol,161.6mg)注入反应管中。将反应体系避光处理，放入80℃油浴中反应24小时。待反应体系冷却后，将反应体系用硅藻土过滤，减压蒸馏除去溶剂，残余物加入HCl的Et2O溶液，并在室温下搅拌1小时以沉淀出白色固体，将其过滤，用冷乙醚洗涤并真空干燥，最终得到胺的盐酸盐产物2c(98.7mg,93％)。具体合成路线如下：
对实施例2制备的化合物2c进行核磁表征，所得数据分别为：
1H NMR(500MHz,DMSO)δ9.34(s,3H),7.93(s,1H),7.87(d,J＝8.0Hz,1H),7.85-7.82(m,1H),7.59-7.51(m,3H),7.50-7.44(m,2H),7.38-7.30(m,2H),7.20(t,J＝8.0Hz,1H),5.73(s,1H),1.434(s,3H),1.427(s,3H).13C NMR(126MHz,DMSO)δ163.0(d,J＝244.0Hz),154.8,154.4,142.2(d,J＝7.0Hz),139.7,138.7,137.9,131.9(d,J＝8.2Hz),128.7,128.1,127.3,124.5(d,J＝2.6Hz),123.8,123.0,121.4,116.0(d,J＝21.4Hz),115.2(d,J＝22.7Hz),57.9,47.5,27.79,27.76.19F NMR(470MHz,DMSO)δ(-112.21)-(-112.33)(m)。
实施例3
向10mL的Schlenk管中加入TpBr3Ag催化剂(33.0mg,0.03mmol,10mol％)，置换氮气。然后用注射器分别将氨水(308μL,28％-30％wt％,0.6mmol,8.0equiv)、超干1,2-二氯乙烷(2mL)以及重氮化合物3a(0.3mmol,57.7mg)注入反应管中。将反应体系避光处理，放入60℃油浴中反应12小时。待反应体系冷却后，将反应体系用硅藻土过滤，减压蒸馏除去溶剂，残余物加入HCl的Et2O溶液，并在室温下搅拌1小时以沉淀出白色固体，将其过滤，用冷乙醚洗涤并真空干燥，得到N-H插入产物的盐酸盐。最终得到胺的盐酸盐产物3c(44.4mg,68％)。具体合成路线如下：
对实施例3制备的化合物3c进行核磁表征，所得数据分别为：
1H NMR(500MHz,DMSO)δ9.35(s,3H),8.09(d,J＝5.0Hz,2H),7.92(d,J＝5.5Hz,2H),7.55-7.36(m,4H),5.37(s,1H).13C NMR(151MHz,DMSO)δ141.3,141.1,130.5,128.7,126.9,121.4,54.4。
实施例4
向10mL的Schlenk管中加入TpBr3Ag催化剂(33.0mg,0.03mmol,10mol％)和碳酸铯(146.6mg,0.45mmol,1.5equiv)，置换氮气。然后用注射器分别将氨水(308μL,28％-30％wt％,0.6mmol,8.0equiv)、超干1,2-二氯乙烷(2mL)以及腙化合物4a(0.3mmol,118.3mg)注入反应管中。将反应体系避光处理，放入80℃油浴中反应24小时。待反应体系冷却后，将反应体系用硅藻土过滤，减压蒸馏除去溶剂，残余物加入HCl的Et2O溶液，并在室温下搅拌1小时以沉淀出白色固体，将其过滤，用冷乙醚洗涤并真空干燥，最终得到胺的盐酸盐产物4c(48.4mg,77％)。具体合成路线如下：
对实施例4制备的化合物4c进行核磁表征，所得数据分别为：
1H NMR(500MHz,DMSO)δ9.20(s,3H),7.64(s,1H),7.61-7.54(m,3H),7.42(t,J＝6.5Hz,2H),7.38-7.33(m,1H),7.26(d,J＝3.5Hz,1H),5.67(s,1H).13C NMR(151MHz,DMSO)δ140.2,138.9,129.6,129.2,128.3,128.2,127.8,124.6,54.2.
实施例5
向10mL的Schlenk管中加入TpBr3Ag催化剂(33.0mg,0.03mmol,10mol％)和碳酸铯(146.6mg,0.45mmol,1.5equiv)，置换氮气。然后用注射器分别将氨水(308μL,28％-30％wt％,0.6mmol,8.0equiv)、超干1,2-二氯乙烷(2mL)以及腙化合物5a(0.3mmol,124.2mg)注入反应管中。将反应体系避光处理，放入80℃油浴中反应24小时。待反应体系冷却后，将反应体系进行减压蒸馏，炒样，先将硅胶用溶液(石油醚：三乙胺＝100:1)浸泡，待溶液挥发干后装柱，用过柱机(石油醚:乙酸乙酯＝5:1)过柱纯化。得到淡黄色粘稠液体为α-氨基酸酯化合物5b(46.9mg,81％)。具体合成路线如下：
对实施例5制备的化合物5b进行核磁表征，所得数据分别为：
1H NMR(500MHz,CDCl3)δ7.26(d,J＝8.0Hz,2H),7.16(d,J＝8.0Hz,2H),4.55(s,1H),4.24-4.07(m,2H),2.34(s,3H),1.93(s,2H),1.21(t,J＝7.5Hz,3H).13C NMR(126MHz,CDCl3)δ174.1,137.6,137.5129.4,126.6,61.2,58.5,21.1,14.0。
实施例6
向10mL的Schlenk管中加入TpBr3Ag催化剂(33.0mg,0.03mmol,10mol％)和碳酸铯(146.6mg,0.45mmol,1.5equiv)，置换氮气。然后用注射器分别将氨水(308μL,28％-30％wt％,0.6mmol,8.0equiv)、超干1,2-二氯乙烷(2mL)以及腙化合物6a(0.3mmol,123.7mg)注入反应管中。将反应体系避光处理，放入80℃油浴中反应24小时。待反应体系冷却后，将反应体系进行减压蒸馏，炒样，先将硅胶用溶液(石油醚：三乙胺＝100:1)浸泡，待溶液挥发干后装柱，用过柱机(石油醚:乙酸乙酯＝5:1)过柱纯化。得到淡黄色粘稠液体为α-氨基酸酯化合物6b(49.3mg,86％)。具体合成路线如下：
对实施例6制备的化合物6b进行核磁表征，所得数据分别为：
1H NMR(500MHz,CDCl3)δ7.41-7.33(m,4H),7.33-7.28(m,1H),5.88-5.79(m,1H),5.22-5.15(m,2H),4.64(s,1H),4.63-4.56(m,2H),1.90(s,2H).13C NMR(126MHz,CDCl3)δ173.6,140.2,131.7,128.8,128.0,126.8,118.3,65.7,58.8.
实施例7
向10mL的Schlenk管中加入TpBr3Ag催化剂(33.0mg,0.03mmol,10mol％)，置换氮气。然后用注射器分别将氨水(308μL,28％-30％wt％,0.6mmol,8.0equiv)、超干1,2-二氯乙烷(2mL)以及重氮化合物7a(0.3mmol,158.6mg)注入反应管中。将反应体系避光处理，放入60℃油浴中反应24小时。待反应体系冷却后，将反应体系进行减压蒸馏，炒样，先将硅胶用溶液(石油醚：三乙胺＝100:1)浸泡，待溶液挥发干后装柱，用过柱机(石油醚:乙酸乙酯＝5:1)过柱纯化。得到淡黄色粘稠液体为α-氨基酸酯化合物7b(90.1mg,58％)。具体合成路线如下：
对实施例7制备的化合物7b进行核磁表征，所得数据分别为：
1H NMR(500MHz,CDCl3)δ7.36(d,J＝7.0Hz,2H),7.30(t,J＝7.0Hz,2H),7.26-7.23(m,1H),5.98(ABq,J＝11.0Hz,2H),5.06-4.95(m,2H),4.79(d,J＝2.0Hz,1H),4.59(s,1H),2.76-2.69(m,1H),2.47-2.33(m,2H),2.23-2.17(m,3H),2.02-1.92(m,3H),1.91-1.83(m,1H),1.81-1.72(m,1H),1.69-1.59(m,2H),1.55-1.44(m,4H),1.37-1.24(m,7H),1.18-1.08(m,3H),1.05-0.97(m,1H),0.92(d,J＝6.5Hz,3H),0.88-0.85(m,6H),0.52(s,3H).13C NMR(151MHz,CDCl3)δ173.3,144.5,142.3,140.1,133.7,128.6,127.8,126.7,122.7,117.5,112.7,72.7,58.7,56.6,56.4,45.9,41.6,40.5,39.5,36.1,32.0,31.8,29.1,28.0,27.7,23.8,23.6,22.8,22.5,22.2,18.8,11.9。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
Claims (8)
1.一种利用氨水合成伯胺的方法，其特征在于，所述伯胺的合成路线如下：
其中，式I为重氮化合物，所述重氮化合物为下列化合物中的一种；
所述银催化剂为TpBr3Ag催化剂，结构式如下：
反应条件为无氧、避光。
2.根据权利要求1所述利用氨水合成伯胺的方法，其特征在于，所述溶剂为二氯甲烷、1,2-二氯乙烷、氯仿、甲苯、苯中的一种或几种。
3.根据权利要求1所述利用氨水合成伯胺的方法，其特征在于，所述重氮化合物与氨水、银催化剂的摩尔比为1:4.0～10.0:0.1-0.2。
4.根据权利要求1所述利用氨水合成伯胺的方法，其特征在于，反应温度为50-70℃。
5.一种氨水合成伯胺的方法，其特征在于，所述伯胺的合成路线如下：
其中，式IV为芳基磺酰腙化合物，所述芳基磺酰腙化合物为下列化合物中的一种：
所述银催化剂为TpBr3Ag催化剂，结构式如下：
反应条件为无氧、避光。
6.根据权利要求5所述氨水合成伯胺的方法，其特征在于，所述碱为氢化钠、叔丁醇钠、叔丁醇锂、氢氧化钾、氢氧化钠、碳酸钾、碳酸铯和磷酸钾中的一种或几种。
7.根据权利要求5所述氨水合成伯胺的方法，其特征在于，所述溶剂为二氯甲烷、1,2-二氯乙烷、氯仿、甲苯、苯有机溶剂中的一种或几种。
8.根据权利要求5所述氨水合成伯胺的方法，其特征在于，反应温度为60-100℃。
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| US5091582A (en) * | 1987-04-25 | 1992-02-25 | Bayer Aktiengesellschaft | Process for the preparation of aromatic polyamines |
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2022
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| US5283363A (en) * | 1991-01-26 | 1994-02-01 | Bayer Aktiengesellschaft | Process for the preparation of (hetero)arylalk(en/in)ylamines and (hetero)arylalkinylamines |
| CN108484452A (zh) * | 2018-03-22 | 2018-09-04 | 东北师范大学 | 一种氟烷基磺酰腙的制备方法 |
| CN111848407A (zh) * | 2020-08-10 | 2020-10-30 | 中科合成油技术有限公司 | 一种由合成气制备有机胺的方法 |
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| Iron(III) Corroles and Porphyrins as Superior Catalysts for the Reactions of Diazoacetates with Nitrogen- or Sulfur-Containing Nucleophilic Substrates: Synthetic Uses and Mechanistic Insights;Iris Aviv et al.;《Chem. Eur. J.》;第14卷;第3995-4005页 * |
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