CN1974566A - Chiral ionic compound containing pyrrolidinyl radical and its prepn and application - Google Patents
Chiral ionic compound containing pyrrolidinyl radical and its prepn and application Download PDFInfo
- Publication number
- CN1974566A CN1974566A CN 200610155221 CN200610155221A CN1974566A CN 1974566 A CN1974566 A CN 1974566A CN 200610155221 CN200610155221 CN 200610155221 CN 200610155221 A CN200610155221 A CN 200610155221A CN 1974566 A CN1974566 A CN 1974566A
- Authority
- CN
- China
- Prior art keywords
- ionic compound
- pyrrolidyl
- chiral ionic
- negatively charged
- charged ion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000008040 ionic compounds Chemical class 0.000 title claims abstract description 65
- -1 halide ion Chemical class 0.000 claims abstract description 42
- 238000002360 preparation method Methods 0.000 claims abstract description 42
- 150000002500 ions Chemical class 0.000 claims abstract description 29
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 48
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 22
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 10
- 229960002429 proline Drugs 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 229930182821 L-proline Natural products 0.000 claims description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 238000005649 metathesis reaction Methods 0.000 claims description 3
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- 229940126062 Compound A Drugs 0.000 claims description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000005642 Oleic acid Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- RMLHVYNAGVXKKC-UHFFFAOYSA-N [SH2]=N.C(F)(F)F Chemical compound [SH2]=N.C(F)(F)F RMLHVYNAGVXKKC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 2
- 125000000129 anionic group Chemical group 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229960001860 salicylate Drugs 0.000 claims description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052799 carbon Inorganic materials 0.000 abstract description 2
- 239000012069 chiral reagent Substances 0.000 abstract description 2
- 239000003495 polar organic solvent Substances 0.000 abstract description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 48
- 238000001556 precipitation Methods 0.000 description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 28
- GIEFFCXIJRRYFW-UHFFFAOYSA-N Br[BrH]Br.c1ccncc1 Chemical compound Br[BrH]Br.c1ccncc1 GIEFFCXIJRRYFW-UHFFFAOYSA-N 0.000 description 20
- 230000006837 decompression Effects 0.000 description 20
- 238000006386 neutralization reaction Methods 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000004821 distillation Methods 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 235000019441 ethanol Nutrition 0.000 description 10
- 229910017053 inorganic salt Inorganic materials 0.000 description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 238000006957 Michael reaction Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 3
- 238000006845 Michael addition reaction Methods 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 238000003810 ethyl acetate extraction Methods 0.000 description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- PIAOLBVUVDXHHL-VOTSOKGWSA-N β-nitrostyrene Chemical compound [O-][N+](=O)\C=C\C1=CC=CC=C1 PIAOLBVUVDXHHL-VOTSOKGWSA-N 0.000 description 3
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- GYPOFOQUZZUVQL-UHFFFAOYSA-N 2h-isoquinolin-3-one Chemical compound C1=CC=C2C=NC(O)=CC2=C1 GYPOFOQUZZUVQL-UHFFFAOYSA-N 0.000 description 2
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- JVZRCNQLWOELDU-UHFFFAOYSA-N 4-Phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=NC=C1 JVZRCNQLWOELDU-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 2
- HQABEHZXAJHCLV-UHFFFAOYSA-N isoquinolin-1-ylmethanol Chemical compound C1=CC=C2C(CO)=NC=CC2=C1 HQABEHZXAJHCLV-UHFFFAOYSA-N 0.000 description 2
- ZIXWTPREILQLAC-UHFFFAOYSA-N isoquinolin-8-ol Chemical compound C1=NC=C2C(O)=CC=CC2=C1 ZIXWTPREILQLAC-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 description 2
- 229910000108 silver(I,III) oxide Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 1
- ONSYFGRVJCIZKU-UHFFFAOYSA-N 2-hydroxybenzoic acid;pyridine Chemical compound C1=CC=NC=C1.OC(=O)C1=CC=CC=C1O ONSYFGRVJCIZKU-UHFFFAOYSA-N 0.000 description 1
- MRVSZQKAFLMKIB-UHFFFAOYSA-N 2-phenylacetic acid;pyridine Chemical compound C1=CC=NC=C1.OC(=O)CC1=CC=CC=C1 MRVSZQKAFLMKIB-UHFFFAOYSA-N 0.000 description 1
- BPSNETAIJADFTO-UHFFFAOYSA-N 2-pyridinylacetic acid Chemical compound OC(=O)CC1=CC=CC=N1 BPSNETAIJADFTO-UHFFFAOYSA-N 0.000 description 1
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 1
- ARKMGCQJRTXBID-UHFFFAOYSA-N C1=CC=CC2=NC3=CC=CC=C3C=C12.[Br] Chemical compound C1=CC=CC2=NC3=CC=CC=C3C=C12.[Br] ARKMGCQJRTXBID-UHFFFAOYSA-N 0.000 description 1
- ITGBBYZXQXULJY-UHFFFAOYSA-N CC1=NC=CC=C1.[Br] Chemical compound CC1=NC=CC=C1.[Br] ITGBBYZXQXULJY-UHFFFAOYSA-N 0.000 description 1
- JMBLXOBJSDWWOK-UHFFFAOYSA-N CC=1C=NC=CC1.[Br] Chemical compound CC=1C=NC=CC1.[Br] JMBLXOBJSDWWOK-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- ITIONVBQFUNVJV-UHFFFAOYSA-N Etomidoline Chemical compound C12=CC=CC=C2C(=O)N(CC)C1NC(C=C1)=CC=C1OCCN1CCCCC1 ITIONVBQFUNVJV-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- FKIRXOYSFKQUNW-JTQLQIEISA-N N1[C@@H](CCC1)CN1CC=CC=C1 Chemical compound N1[C@@H](CCC1)CN1CC=CC=C1 FKIRXOYSFKQUNW-JTQLQIEISA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- CBQGZUMEDTWXSG-UHFFFAOYSA-N [Br].C1(=CC=CC=C1)C1=CC=NC=C1 Chemical compound [Br].C1(=CC=CC=C1)C1=CC=NC=C1 CBQGZUMEDTWXSG-UHFFFAOYSA-N 0.000 description 1
- UYSYSHMOEBBNLK-UHFFFAOYSA-N [Br].N=1CC(C=CC1)=O Chemical compound [Br].N=1CC(C=CC1)=O UYSYSHMOEBBNLK-UHFFFAOYSA-N 0.000 description 1
- ACSCMCSWNBKLTP-UHFFFAOYSA-N [Br].OCC1=NC2=CC=CC=C2C=C1 Chemical compound [Br].OCC1=NC2=CC=CC=C2C=C1 ACSCMCSWNBKLTP-UHFFFAOYSA-N 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 238000005575 aldol reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000005902 aminomethylation reaction Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- AZFMSHWYDZIRNV-UHFFFAOYSA-N benzenesulfonic acid;pyridine Chemical compound C1=CC=NC=C1.OS(=O)(=O)C1=CC=CC=C1 AZFMSHWYDZIRNV-UHFFFAOYSA-N 0.000 description 1
- MRBFBZXMHKMEKW-UHFFFAOYSA-N benzoic acid;pyridine Chemical compound C1=CC=NC=C1.OC(=O)C1=CC=CC=C1 MRBFBZXMHKMEKW-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- PGPUNHSUUYYDIT-UHFFFAOYSA-N bromine;1h-quinolin-2-one Chemical compound [Br].C1=CC=C2NC(=O)C=CC2=C1 PGPUNHSUUYYDIT-UHFFFAOYSA-N 0.000 description 1
- QKFMLWHPUKEKMG-UHFFFAOYSA-N bromine;quinoline Chemical compound [Br].N1=CC=CC2=CC=CC=C21 QKFMLWHPUKEKMG-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- CVRPBLIUUZQSQN-UHFFFAOYSA-N dodecane-1-sulfonate pyridin-1-ium Chemical compound c1cc[nH+]cc1.CCCCCCCCCCCCS([O-])(=O)=O CVRPBLIUUZQSQN-UHFFFAOYSA-N 0.000 description 1
- YRIUSKIDOIARQF-UHFFFAOYSA-N dodecyl benzenesulfonate Chemical compound CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 YRIUSKIDOIARQF-UHFFFAOYSA-N 0.000 description 1
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 1
- 229940071161 dodecylbenzenesulfonate Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000003148 prolines Chemical class 0.000 description 1
- NRTYMEPCRDJMPZ-UHFFFAOYSA-N pyridine;2,2,2-trifluoroacetic acid Chemical compound C1=CC=NC=C1.OC(=O)C(F)(F)F NRTYMEPCRDJMPZ-UHFFFAOYSA-N 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- HREHOXSRYOZKNT-UHFFFAOYSA-N quinolin-2-ylmethanol Chemical compound C1=CC=CC2=NC(CO)=CC=C21 HREHOXSRYOZKNT-UHFFFAOYSA-N 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 description 1
- 229940006198 sodium phenylacetate Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- MZSDGDXXBZSFTG-UHFFFAOYSA-M sodium;benzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=CC=C1 MZSDGDXXBZSFTG-UHFFFAOYSA-M 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Catalysts (AREA)
Abstract
The chiral ionic compound containing pyrrolidinyl radical has the general expression of A+B-, A+ is one of ions as shown, and B- is halide ion X- or non- halide ion Y-. The chiral ionic compound has high heat stability, and is non-intersoluble with non-polar organic solvent and easy to recover and reuse. Owing to the contained pyrrolidinyl radical segment and the chiral carbon connected to high rigid nitrogenous heterocycle, the chiral ionic compound may be used as chiral reagent, catalyst, chiral material, etc for organic asymmetric catalysis, material preparation and other fields.
Description
(1) technical field
The present invention relates to a kind of chiral ionic compound that contains pyrrolidyl with and its production and application.
(2) background technology
Recently decades, along with the particularly development of medicine industry of chemical industry, people increase day by day to the demand of high optical purity compound.Chiral organic micromolecule catalyst is because it is environmentally friendly, low price, do not use characteristics such as expensive transition metal and chiral ligand, source be abundant and be subjected to various countries researchist's attention day by day.Since people such as List find that natural L-proline(Pro) and I type aldol condensation enzyme have similar katalysis and successfully be used for direct asymmetric Aldol reaction, be new focus and the forward position that the organic micromolecule catalyst of representative becomes the asymmetric synthesis field just gradually with the L-proline(Pro).
Studies show that in a large number proline(Pro) (1) and derivative thereof simple in structure, that nature content is abundant show extraordinary catalytic performance (J.Am.Chem.Soc.2002,124,6798-6799 as organic catalyst in multiple asymmetric catalysis; Chem.Commun.2002,620-621; Org.Lett.2003,5,1249-1251; J.Am.Chem.Soc.2004,126,9558-9559; Tetrahedron 2005,61,8669-8676).Design, synthesized a series of proline(Pro) amides as people such as T.Zhou, wherein amides catalyzer (2) shows excellent catalytic performance in asymmetric Adol reaction, ee reaches as high as 99%, broken the traditional concept (J.Am.Chem.Soc.2003 of " the proline(Pro) acid amides does not have catalytic activity ", 125,5262-5263); H.Torii, people such as M.Nakadai have synthesized proline(Pro) tetranitroazole derivative (3), and this catalyzer can carry out efficient asymmetric direct Adol reaction in the presence of auxiliary agent water, product ee value can reach 98% (Angew.Chem.Int.Ed.2004,43,1983-1986); J.Franzen research group is parent synthesis of chiral catalyzer (4) with the proline(Pro), find that this catalyzer is to multiple asymmetric reaction, especially Adol, Mannich, aminomethylation reaction are had excellent catalytic performance, product ee value all can reach more than 95%, reaches as high as 98%.This catalyzer be considered to a kind of universal organic micromolecule catalyst (J.Am.Chem.Soc.2005,127,18296-18304); People such as S.MitSumori are raw material with the L-oxyproline, through series reaction synthesis of chiral catalyzer (5), use it for trans asymmetric Mannich reaction, product yield can reach 92%, the ee value reach as high as 99% (J.Am.Chem.Soc.2006,128,1040-1041); Recently, researchers such as Cao Chunli have synthesized bifunctional organic catalyst-tetramethyleneimine thiocarbamide (6), and be applied to asymmetric Michael addition reaction, product yield can reach 98%, the ee value is up to 99%, and dr value 99/1 shows excellent catalytic performance (Org.Lett.2006,8,2901-2904); The chain organic catalyst (7) that waits people's design, the recyclable utilization of synthetic of ancestral, in the Michael addition reaction, show good catalytic performance (yield 95% equally, ee value 90%), and this reaction can be carried out at aqueous phase, this catalyzer is owing to there is the existence of fluorine atom to be convenient to separate, thereby can recycle easily (Org.Lett.2006,8,3077-3079); People such as Zhu Mingkui report and also show supereminent catalytic capability by novel organic catalyst (8) in the asymmetry catalysis building-up reactions (Tetrahedron:Asymmetry 2006,17,491-493); Researchists such as S.Luo design, synthesized tetramethyleneimine-imidazole chiral ionic liquid, it show the catalytic performance of excellence in the Michael addition reaction, the ee value reach as high as 99% (Angew.Chem.Int.Ed.2006,45,3093-3097).
Though the organic micromolecule catalyst research based on the L-proline(Pro) is just at the early-stage, the discovery of these novel chiral amine catalysts has but indicated in this research field is containing bigger opportunity to develop.
(3) summary of the invention
The purpose of this invention is to provide a kind of new chiral ionic compound that contains pyrrolidyl, its preparation method is provided simultaneously, and as the application of catalyzer in asymmetric catalysis.
The technical solution used in the present invention is as follows:
A kind of chiral ionic compound that contains pyrrolidyl, general formula are A
+B
-, described A
+Shown in one of formula (I)～formula (IV), described B
-Be halide-ions X
-Or non-halide-ions Y
-, described Y
-For one of following: Tetrafluoroboric acid negatively charged ion, phosphofluoric acid negatively charged ion, trifluoromethanesulfonic acid negatively charged ion, fluoroform sulfimide negatively charged ion, beta-naphthalenesulfonic-acid negatively charged ion, Phenylsulfonic acid negatively charged ion, dodecyl sodium sulfonate negatively charged ion, to Witco 1298 Soft Acid negatively charged ion, trifluoroacetic acid negatively charged ion, acetate negatively charged ion, phenylformic acid negatively charged ion, anionic salicylate, toluylic acid negatively charged ion, oleic acid negatively charged ion, stearic acid negatively charged ion, described halide-ions X
-Be Cl
-, Br
-Or I
-,
In formula (I)～formula (IV), R
1Be benzyl, phenyl, substituted-phenyl or hydrogen; R
2, R
3, R
4, R
5, R
6, R
7Independent separately is alkane, phenyl, substituted-phenyl, hydroxyl, methylol or the trifluoromethyl of hydrogen, C1～C5.
Described A
+Preferably suc as formula shown in (II), B
-Be halide-ions, further, be bromide anion; Perhaps described A
+Shown in (II), described B
-Be Y
-
Further, the R described in formula (I)～formula (IV)
1, R
2, R
3, R
4, R
5, R
6, R
7Independent separately is hydrogen.
The preparation of the above-mentioned chiral ionic compound that contains pyrrolidyl is according to B
-Different and adopt different preparation methods.Preparation B
-Be halide-ions X
-Chiral ionic compound, adopt quaterisation; Preparation B
-Be non-halide-ions Y
-Chiral ionic compound, adopt replacement(metathesis)reaction.
Be illustrated respectively below:
With A
+Shown in (II), B
-Be Br
-Be example, can be prepared as follows the chiral ionic compound that contains pyrrolidyl accordingly: the L-proline(Pro) deutero-substituted pyrrolidin hydrobromate shown in formula V and isoquinilone derivatives back flow reaction in organic solvent, reaction solution through neutralize the described chiral ionic compound that contains pyrrolidyl, reaction formula is as follows:
The amount of substance that feeds intake ratio is the substituted pyrrolidin hydrobromate: isoquinilone derivatives is 0.5～2.0: 1, described organic solvent is one of following: ethanol, acetonitrile, 1,2-ethylene dichloride, 1,4-dioxane, toluene, N, dinethylformamide, the consumption of organic solvent is that reaction substrate is tetramethyleneimine hydrobromate and isoquinilone derivatives total mass 5～15 times, preferred 10 times.
Work as A
+During for other, can use corresponding raw material to carry out quaterisation, prepare corresponding chiral ionic compound according to last method.
A in the described chiral ionic compound that contains pyrrolidyl
+Shown in (II), B
-Be Y
-The time, can be prepared in accordance with the following methods: with general formula is A
+X
-Compound and M
+Y
-Carry out replacement(metathesis)reaction, promptly get described chiral ionic compound A
+Y
-, described X
-, Y
-For described as defined above, described M
+Be selected from one of following: Li
+, Na
+, K
+, Ag
+, Pb
+, NH
4 +, reaction formula is as follows:
The aforesaid chiral ionic compound that contains pyrrolidyl has good application as catalyzer in asymmetric reaction especially Michael reaction.
The present invention compared with prior art provides a kind of new chiral ionic compound, and its Heat stability is good does not dissolve each other with non-polar organic solvent, is easy to recycle.This compounds is because of containing the pyrrolidyl fragment, and chiral carbon is connecting the nitrogen heterocyclic ring that fine rigidity is arranged, and therefore can be used as chiral reagent, catalyzer, chiral material etc. is applied to fields such as organic asymmetry catalysis, material.
(4) embodiment:
Below with specific embodiment technical scheme of the present invention is described, but protection scope of the present invention is not limited thereto:
Embodiment 1 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridinium tribromide salt
Add [(2S)-(+)-2-bromomethyl] tetramethyleneimine hydrobromate (0.1mol), pyridine (purity 98% in the 100mL there-necked flask, 0.1mol) and acetonitrile (40mL), back flow reaction 12h, neutralization back decompression precipitation, with the each 20ml washing of ether 3 times, obtain the target chiral ionic compound behind the redistillation precipitation, yield 94%.
Embodiment 2～13 described 1-[(2-(S)-pyrrolidyls) methyl] pyridinium tribromide salt all can be according to this method preparation.
Embodiment 2 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridine trifluoroacetate
Take by weighing 1-[(2-(the S)-pyrrolidyl of embodiment 1 preparation) methyl] pyridinium tribromide salt 0.050mol, use the 50mL water dissolution.Taking by weighing 0.025mol silver suboxide (purity 99%) joins in the 250mL there-necked flask, add 100mL trifluoracetic acid (purity 99% again, 0.050mol) aqueous solution, after stirring to clarify, slowly add 1-[(2-(S)-pyrrolidyl) methyl] aqueous solution of pyridinium tribromide salt, generation Silver monobromide precipitation, stirring reaction 1h removes by filter precipitation, and underpressure distillation removes water, obtain the target chiral ionic compound, yield 98%.
Embodiment 3 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridinium tetrafluoroborate salt
Take by weighing 1-[(2-(S)-pyrrolidyl) methyl] pyridinium tribromide salt 0.050mol, use the 50mL water dissolution.Taking by weighing 0.025mol silver suboxide (purity 99%) joins in the 250mL there-necked flask, add 100mL Tetrafluoroboric acid (purity 98% again, 0.050mol) aqueous solution, after stirring to clarify, slowly add 1-[(2-(S)-pyrrolidyl) methyl] aqueous solution of pyridinium tribromide salt, generation Silver monobromide precipitation, stirring reaction 1h removes by filter precipitation, and underpressure distillation removes water, obtain the target chiral ionic compound, yield 97%.
Embodiment 4 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridine hexafluorophosphate
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, Potassium Hexafluorophosphate 0.050mol and acetone 60mL, at room temperature reaction 48h, remove by filter inorganic salt, distillation removes acetone, obtain the target chiral ionic compound, yield 94%.
Embodiment 5 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridylacetic acid(HPAC) salt
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, sodium acetate 0.050mol and acetone 60mL, at room temperature reaction 48h, remove by filter inorganic salt, distillation removes acetone, obtain the target chiral ionic compound, yield 95%.
Embodiment 6 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridine benzoate
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, Sodium Benzoate 0.050mol and acetone 60mL, room temperature reaction 48h removes by filter inorganic salt, and distillation removes acetone, obtain the target chiral ionic compound, yield 94%.
Embodiment 7 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridine phenylacetate
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, sodium phenylacetate 0.050mol and acetone 60mL, at room temperature reaction 48h, remove by filter inorganic salt, distillation removes acetone, obtain the target chiral ionic compound, yield 92%.
Embodiment 8 1-[(2-(S)-pyrrolidyl) methyl] the pyridine salicylate preparation
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, sodium salicylate 0.050mol and methyl alcohol 60mL, at room temperature reaction 48h, remove by filter inorganic salt, distillation removes methyl alcohol, obtain the target chiral ionic compound, yield 93%.
Embodiment 9 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridine benzene sulfonate
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, benzene sulfonic acid sodium salt 0.050mol and methyl alcohol 60mL, at room temperature reaction 48h, remove by filter inorganic salt, distillation removes methyl alcohol, obtain the target chiral ionic compound, yield 95%.
Embodiment 10 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridine beta-naphthalenesulfonic-acid salt
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, 0.050mol sodium and methyl alcohol 60mL, room temperature reaction 48h removes by filter inorganic salt, and distillation removes methyl alcohol, obtain the target chiral ionic compound, yield 93%.
Embodiment 11 1-[(2-(S)-pyrrolidyl) methyl] add 1-[(2-(S)-pyrrolidyl in the preparation 100mL there-necked flask of pyridine dodecane sulfonate) methyl] pyridinium tribromide salt 0.050mol, sodium laurylsulfonate 0.050mol and acetone 60mL, room temperature reaction 48h, remove by filter inorganic salt, distillation removes acetone, obtain the target chiral ionic compound, yield 95%.
Embodiment 12 1-[(2-(S)-pyrrolidyl) methyl] pyridine is to the preparation of dodecylbenzene sulfonate
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, to Sodium dodecylbenzene sulfonate 0.050mol and acetone 60mL, room temperature reaction 48h removes by filter inorganic salt, and distillation removes acetone, obtain the target chiral ionic compound, yield 92%.
Embodiment 13 1-[(2-(S)-pyrrolidyl) methyl] preparation of pyridine oleate
Add 1-[(2-(S)-pyrrolidyl in the 100mL there-necked flask) methyl] pyridinium tribromide salt 0.050mol, sodium oleate 0.050mol and acetone 60mL, room temperature reaction 48h removes by filter inorganic salt, and distillation removes acetone, obtain the target chiral ionic compound, yield 95%.
Embodiment 14 1-[(2-(S)-pyrrolidyl) methyl]-preparation of 2-picoline bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 2-picoline 0.1mol and acetonitrile 60mL, back flow reaction 12h, neutralization back decompression precipitation, with ethyl acetate washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 95%.
Embodiment 15 1-[(2-(S)-pyrrolidyl) methyl]-preparation of 3-pyridone bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 3-pyridone 0.1mol and ethanol 60mL, back flow reaction 24h, neutralization back decompression precipitation, with ether washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 91%.
Embodiment 16 1-[(2-(S)-pyrrolidyl) methyl]-preparation of 3-5-flumethiazine bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 3-5-flumethiazine 0.1mol and acetonitrile 60mL, back flow reaction 12h, neutralization back decompression precipitation, with ether washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 96%.
Embodiment 17 1-[(2-(S)-pyrrolidyl) methyl]-preparation of 4-phenylpyridine bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 4-phenylpyridine 0.1mol and toluene 60mL, back flow reaction 24h, neutralization back decompression precipitation, with ether washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 86%.
Embodiment 18 1-[(2-(S)-pyrrolidyl) methyl]-preparation of 3-picoline bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 3-picoline 0.1mol and acetonitrile 60mL, back flow reaction 12h, neutralization back decompression precipitation, with ether washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 95%.
Embodiment 19 1-[(2-(S)-pyrrolidyl) methyl]-preparation of 4-4-hydroxymethylpiperidine bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 4-4-hydroxymethylpiperidine 0.1mol and N, dinethylformamide 60mL, back flow reaction 20h, neutralization back decompression precipitation, with ethyl acetate washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 96%.
Embodiment 20 1-[(2-(S)-pyrrolidyl) methyl] preparation of quinoline bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, quinoline 0.1mol and acetonitrile 60mL, back flow reaction 24h, neutralization back decompression precipitation, with ether washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 92%.
Embodiment 21 1-[(2-(S)-pyrrolidyl) methyl]-preparation of 2-hydroxyquinoline bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 2-hydroxyquinoline 0.1mol and 1,4-dioxane 60mL, behind the back flow reaction 48h, neutralization back decompression precipitation, with ethyl acetate washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 88%.
Embodiment 22 1-[(2-(S)-pyrrolidyl) methyl]-preparation of 2-hydroxymethyl quinoline bromine salt
Add [(2S)-(+)-2-bromomethyl] tetramethyleneimine hydrobromate (0.1mol), 2-hydroxymethyl quinoline (99% in the 100mL there-necked flask, 0.1mol) and 1,4-dioxane (60mL), back flow reaction 48h, neutralization back decompression precipitation, (3 * 20mL), the redistillation precipitation gets the target chiral ionic compound, yield 93% with the ethyl acetate washing.
Embodiment 23 1-[(2-(S)-pyrrolidyl) methyl]-preparation of oxine bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, oxine 0.1mol and 1,4-dioxane 60mL, back flow reaction 48h, neutralization back decompression precipitation, with ethyl acetate washing 3 times, each 20mL, the redistillation precipitation obtains the target chiral ionic compound, yield 92%.
Embodiment 24 2-[(2-(S)-pyrrolidyl) methyl] preparation of isoquinoline 99.9 bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, isoquinoline 99.9 0.1mol and acetonitrile 60mL, back flow reaction 24h, decompression precipitation in neutralization back is used ethyl alcohol recrystallization, filtration obtains the target chiral ionic compound, yield 98%.
Embodiment 25 2-[(2-(S)-pyrrolidyl) methyl]-preparation of 1-hydroxyl isoquinoline 99.9 bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 1-hydroxyl isoquinoline 99.9 0.1mol and acetonitrile 60mL, back flow reaction 24h, decompression precipitation in neutralization back is used ethyl alcohol recrystallization, filtration obtains the target chiral ionic compound, yield 92%.
Embodiment 26 2-[(2-(S)-pyrrolidyl) methyl]-preparation of 1-methylol isoquinoline 99.9 bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 1-methylol isoquinoline 99.9 0.1mol and acetonitrile 60mL, back flow reaction 24h, decompression precipitation in neutralization back is used ethyl alcohol recrystallization, filtration obtains the target chiral ionic compound, yield 96%.
Embodiment 27 2-[(2-(S)-pyrrolidyl) methyl]-preparation of 3-hydroxyl isoquinoline 99.9 bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 3-hydroxyl isoquinoline 99.9 0.1mol and acetonitrile 60mL, back flow reaction 24h, decompression precipitation in neutralization back is used ethyl alcohol recrystallization, filtration obtains the target chiral ionic compound, yield 92%.
Embodiment 28 2-[(2-(S)-pyrrolidyl) methyl]-preparation of 8-hydroxyl isoquinoline 99.9 bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, 8-hydroxyl isoquinoline 99.9 0.1mol and acetonitrile 60mL, back flow reaction 24h, decompression precipitation in neutralization back is used ethyl alcohol recrystallization, filtration obtains the target chiral ionic compound, yield 95%.
Embodiment 29 1-[(2-(S)-pyrrolidyl) methyl] preparation of acridine bromine salt
Add in the 100mL there-necked flask [(2S)-(+)-and the 2-bromomethyl] tetramethyleneimine hydrobromate 0.1mol, acridine 0.1mol and acetonitrile 60mL, back flow reaction 24h, neutralization back decompression precipitation, with ether washing 3 times, each 20mL, obtain the target chiral ionic compound behind the redistillation precipitation, yield 89%.
Embodiment 30 1-[(2-(S)-pyrrolidyl) diphenyl-methyl] preparation of pyridinium tribromide salt
Add in the 100mL there-necked flask [(2S)-(+)-and 2-bromo diphenyl-methyl] tetramethyleneimine hydrobromate 0.1mol, pyridine 0.1mol and acetonitrile 60mL, back flow reaction 48h, decompression precipitation in neutralization back is used ethyl alcohol recrystallization, filtration obtains the target chiral ionic compound, yield 80%.
Embodiment 31 1-[(2-(S)-pyrrolidyl) dibenzyl methyl] preparation of pyridinium tribromide salt
Add in the 100mL there-necked flask [(2S)-(+)-and 2-bromo dibenzyl methyl] tetramethyleneimine hydrobromate 0.1mol, pyridine 0.1mol and acetonitrile 60mL, back flow reaction 48h, decompression precipitation in neutralization back is used ethyl alcohol recrystallization, filtration obtains the target chiral ionic compound, yield 90%.
Embodiment 32 1-[(2-(S)-pyrrolidyl) preparation of pyridinium tribromide salt two (3,5-two trifluoromethyls) phenmethyl)
Add in the 100mL there-necked flask [(2S)-(+)-2-bromo two (3,5-two trifluoromethyls) phenmethyl] tetramethyleneimine hydrobromate 0.1mol, pyridine 0.1mol and acetonitrile 60mL, back flow reaction 48h, neutralization back decompression precipitation, use ethyl alcohol recrystallization, filtration obtains the target chiral ionic compound, yield 87%.
Embodiment 33 1-[(2-(S)-pyrrolidyl) methyl] application of pyridinium tribromide salt in the Michael reaction
Add 1-[(2-(S)-pyrrolidyl in two mouthfuls of flasks of 20mL) methyl] pyridinium tribromide salt 0.001mol, beta-nitrostyrene 0.005mol, pimelinketone 0.010mol and N-methyl, N '-hexyl tetrafluoroborate 4g, at room temperature reaction 24h, ethyl acetate extraction 3 times, each 20mL, distillation removes solvent, obtain chipal compounds 2-(2S)-(2-nitro-1-(1R) phenyl-ethyl) pimelinketone, yield 98%, dr are 90: 10, ee value 87%.
Embodiment 34 2-[(2-(S)-pyrrolidyl) methyl] application of isoquinoline 99.9 bromine salt in the Michael reaction
Add 2-[(2-(S)-pyrrolidyl in two mouthfuls of flasks of 20mL) methyl] isoquinoline 99.9 bromine salt 0.001mol, beta-nitrostyrene 0.005mol, pimelinketone 0.010mol and N-methyl, N '-hexyl tetrafluoroborate 4g, at room temperature reaction 20h, ethyl acetate extraction 3 times, each 20mL, distillation removes solvent, obtain chipal compounds 2-(2S)-(2-nitro-1-(1R) phenyl-ethyl) pimelinketone, yield 97%, dr are 93: 7, ee value 98%.
Embodiment 35 2-[(2-(S)-pyrrolidyl) methyl] application of isoquinoline 99.9 hexafluorophosphate in the Michael reaction
Add 2-[(2-(S)-pyrrolidyl in two mouthfuls of flasks of 20mL) methyl] isoquinoline 99.9 hexafluorophosphate 0.001mol, beta-nitrostyrene 0.005mol, pimelinketone 0.010mol and N-methyl, N '-hexyl tetrafluoroborate 4g, at room temperature reaction 20h, ethyl acetate extraction 3 times, each 20mL, distillation removes solvent, obtain chipal compounds 2-(2S)-(2-nitro-1-(1R) phenyl-ethyl) pimelinketone, yield 97%, dr are 96: 4, ee value 92.8%.
Claims (10)
1. a chiral ionic compound that contains pyrrolidyl is characterized in that described ionic compound general formula is A
+B
-, described A
+Shown in one of formula (I)～formula (IV), described B
-Be halide-ions X
-Or non-halide-ions Y
-, described Y
-For one of following: Tetrafluoroboric acid negatively charged ion, phosphofluoric acid negatively charged ion, trifluoromethanesulfonic acid negatively charged ion, fluoroform sulfimide negatively charged ion, beta-naphthalenesulfonic-acid negatively charged ion, Phenylsulfonic acid negatively charged ion, dodecyl sodium sulfonate negatively charged ion, to Witco 1298 Soft Acid negatively charged ion, trifluoroacetic acid negatively charged ion, acetate negatively charged ion, phenylformic acid negatively charged ion, anionic salicylate, toluylic acid negatively charged ion, oleic acid negatively charged ion, stearic acid negatively charged ion, described halide-ions X
-Be Cl
-, Br
-Or I
-,
In formula (I)～formula (IV), R
1Be benzyl, phenyl, substituted-phenyl or hydrogen; R
2, R
3, R
4, R
5, R
6, R
7Independent separately is alkane, phenyl, substituted-phenyl, hydroxyl, methylol or the trifluoromethyl of hydrogen, C1～C5.
2. the chiral ionic compound that contains pyrrolidyl as claimed in claim 1 is characterized in that described B
-Be halide-ions, described A
+Shown in formula (II).
3. the chiral ionic compound that contains pyrrolidyl as claimed in claim 2 is characterized in that described B
-Be Br
-
4. the chiral ionic compound that contains pyrrolidyl as claimed in claim 1 is characterized in that described A
+Shown in formula (II), described B
-Be Y
-
5. as the described chiral ionic compound that contains pyrrolidyl of one of claim 1～4, it is characterized in that described R
1, R
2, R
3, R
4, R
5, R
6, R
7Independent separately is hydrogen.
6. one kind prepares the method that contains the chiral ionic compound of pyrrolidyl as claimed in claim 1, A in the described chiral ionic compound that contains pyrrolidyl
+Shown in (II), B
-Be bromide anion, it is characterized in that described method is: the L-proline(Pro) deutero-substituted pyrrolidin hydrobromate shown in formula V and isoquinilone derivatives back flow reaction in organic solvent, reaction solution through neutralize the described chiral ionic compound that contains pyrrolidyl, the amount of substance that feeds intake ratio is the substituted pyrrolidin hydrobromate: isoquinilone derivatives is 0.5～2.0: 1, described organic solvent is one of following: ethanol, acetonitrile, 1, the 2-ethylene dichloride, 1, the 4-dioxane, toluene, N, dinethylformamide
7. preparation as claimed in claim 6 contains the method for the chiral ionic compound of pyrrolidyl, and the consumption that it is characterized in that described organic solvent is tetramethyleneimine hydrobromate and isoquinilone derivatives total mass 5～15 times.
8. one kind prepares the method that contains the chiral ionic compound of pyrrolidyl as claimed in claim 1, A in the described chiral ionic compound that contains pyrrolidyl
+Shown in (II), B
-Be Y
-, it is characterized in that described method is for being A with general formula
+X
-Compound and M
+Y
-Compound carry out replacement(metathesis)reaction, promptly get described chiral ionic compound A
+Y
-, described X
-, Y
-For described as defined above, described M
+Be selected from one of following: Li
+, Na
+, K
+, Ag
+, Pb
+, NH
4 +
As the described chiral ionic compound of pyrrolidyl that contains of one of claim 1～8 as the asymmetric reaction Application of Catalyst.
10. the application that contains the chiral ionic compound of pyrrolidyl as the Michael catalysts as claimed in claim 9.
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| CN101143862B (en) * | 2007-10-26 | 2010-06-23 | 浙江工业大学 | Ionic compound containing chiral amine-thiourea (urea) and its preparation method and application |
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