CN110372595A - A kind of Actinochemical synthesis of imidazoles alkyl compound - Google Patents
A kind of Actinochemical synthesis of imidazoles alkyl compound Download PDFInfo
- Publication number
- CN110372595A CN110372595A CN201810326762.9A CN201810326762A CN110372595A CN 110372595 A CN110372595 A CN 110372595A CN 201810326762 A CN201810326762 A CN 201810326762A CN 110372595 A CN110372595 A CN 110372595A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- alcohol
- imines
- heteroaryl
- reaction
- 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
- -1 imidazoles alkyl compound Chemical class 0.000 title claims abstract description 63
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 12
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 53
- 150000002466 imines Chemical class 0.000 claims abstract description 30
- 239000003054 catalyst Substances 0.000 claims abstract description 17
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 235000019441 ethanol Nutrition 0.000 claims description 21
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 11
- 150000002430 hydrocarbons Chemical class 0.000 claims description 10
- 239000004408 titanium dioxide Substances 0.000 claims description 10
- 239000011261 inert gas Substances 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 6
- 239000013078 crystal Substances 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 239000007789 gas Substances 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 150000002191 fatty alcohols Chemical class 0.000 claims description 2
- 150000008282 halocarbons Chemical class 0.000 claims description 2
- 229910052734 helium Inorganic materials 0.000 claims description 2
- 239000001307 helium Substances 0.000 claims description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- URUWNYQVXHOQAM-UHFFFAOYSA-N n-benzylpropan-2-imine Chemical compound CC(C)=NCC1=CC=CC=C1 URUWNYQVXHOQAM-UHFFFAOYSA-N 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims 9
- HNMOJSWAFOVRNN-UHFFFAOYSA-N 2-(4-methoxyphenyl)-4,5-diphenyl-1,3-di(propan-2-yl)-2H-imidazole Chemical compound CC(C)N1C(N(C(=C1C2=CC=CC=C2)C3=CC=CC=C3)C(C)C)C4=CC=C(C=C4)OC HNMOJSWAFOVRNN-UHFFFAOYSA-N 0.000 claims 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 6
- 230000035484 reaction time Effects 0.000 abstract description 3
- 230000009471 action Effects 0.000 abstract description 2
- 230000006698 induction Effects 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 22
- 229910052799 carbon Inorganic materials 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 125000002619 bicyclic group Chemical group 0.000 description 9
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 5
- 229910052724 xenon Inorganic materials 0.000 description 5
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- MIYKHJXFICMPOJ-UHFFFAOYSA-N n-benzyl-1-phenylmethanimine Chemical compound C=1C=CC=CC=1CN=CC1=CC=CC=C1 MIYKHJXFICMPOJ-UHFFFAOYSA-N 0.000 description 4
- 238000007789 sealing Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000003107 substituted aryl group Chemical group 0.000 description 4
- 229910052723 transition metal Inorganic materials 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000001678 irradiating effect Effects 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 238000007146 photocatalysis Methods 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000005416 organic matter Substances 0.000 description 2
- 230000001699 photocatalysis Effects 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- ZYMCBJWUWHHVRX-UHFFFAOYSA-N (4-nitrophenyl)-phenylmethanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 ZYMCBJWUWHHVRX-UHFFFAOYSA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- BVOMRRWJQOJMPA-UHFFFAOYSA-N 1,2,3-trithiane Chemical compound C1CSSSC1 BVOMRRWJQOJMPA-UHFFFAOYSA-N 0.000 description 1
- IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical compound C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical class C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 1
- XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- AVHCHJKMIGPLIZ-UHFFFAOYSA-N 4h-1,3,4-thiadiazine Chemical compound N1C=CSC=N1 AVHCHJKMIGPLIZ-UHFFFAOYSA-N 0.000 description 1
- GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 description 1
- 229910017488 Cu K Inorganic materials 0.000 description 1
- 229910017541 Cu-K Inorganic materials 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
- WZHKCFDUDKJGBA-UHFFFAOYSA-N N1CCNCC1.S1C=CC=C1 Chemical compound N1CCNCC1.S1C=CC=C1 WZHKCFDUDKJGBA-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 150000007960 acetonitrile Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000012675 alcoholic extract Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- XXRGLCKZBCIEKO-DLMDZQPMSA-N azocine Chemical compound C/1=C/C=C\N=C/C=C\1 XXRGLCKZBCIEKO-DLMDZQPMSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical compound O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N trans-decahydronaphthalene Natural products C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention belongs to photochemistry organic synthesis field, in particular to a kind of Actinochemical synthesis of imidazoles alkyl compound, comprising: in the presence of light and photochemical catalyst, pure and mild imines is reacted to obtain imidazoles alkyl compound.The present invention is using the pure and mild imines being dissolved in inert organic solvents under the induction of ultraviolet light or visible light, under the action of photochemical catalyst, by controlling the reaction time, the reaction for synthesizing imidazoles alkyl compound by the pure and mild imines of green low toxicity is realized, imidazoles alkyl compound can be obtained.Moreover, the product yield high of the method for the present invention, selectivity are good.The separation yield of product reaches as high as 95% or more, selectively reaches as high as 99% or more.Also, preparation process of the invention is simple, and product can be obtained by single step reaction, economic and environment-friendly and easy to operate, practicability with higher.
Description
Technical field
The invention belongs to photochemistry technical field of organic synthesis, in particular to the photochemistry of a kind of imidazoles alkyl compound is closed
At method.
Background technique
Industrially, imidazoles alkyl compound is widely used in the important chemistry on pharmacy, insecticide and herbicide
Intermediate and product.And imidazolidine structural unit is in the ligand prothetic group and organic micromolecule catalyst of transition-metal catalyst
On have important application.Its traditional preparation methods is being condensed to yield by 1,2- diamines and formaldehyde, a large amount of uses of formaldehyde
It will cause serious environmental pollution.The complex of nearest transition metal Lewis acid catalyst such as Ag, Cu may be implemented by electron deficient
Azomethine ylide and 1, the 3- Dipolar Cycloaddition of imines construct imidazoles alkyl compound, it is with higher non-right to react
The even certain enantioselectivity of stereoselectivity is reflected, but the transition metal and organic ligand that must use in reaction are deposited
Environment is unfriendly and preparation is complicated, price costly the shortcomings that.
In recent years, the light-catalysed research of out-phase achieves considerable progress.It is urged as a kind of out-phase light being widely studied
Agent, TiO2It is cheap to ph stability with environmental-friendly, good light stability, the advantages that rich reserves.In ultraviolet light
Under irradiation, TiO2Separation of charge can occur for photochemical catalyst, generate hole and electronics pair, cause respective table in conduction band and valence band
Face oxidation and reduction reaction, while the second level free-radical oxidation species such as hydroxyl radical free radical generated, ultra-oxygen anion free radical, mistake
Oxygen hydroperoxyl radical etc. can be CO without almost all of organic matter is selectively aoxidized2And H2O, therefore as a kind of advanced oxidation skill
Art is widely used in eliminating in water and in terms of indoor pollutant.But due to titanium dioxide photoproduction hole and second level free radical
Strong oxidizing property makes the TiO in general water phase2Conductor photocatalysis system can directly cause organic matter permineralization.Even exist
Under inert atmosphere in organic solvent, because of redox potential (the 2.9V vs standard hydrogen electricity that titanium dioxide photoproduction hole is high
Pole), it can trigger the non-selectivity scission of link of nearly all organic compound, and then cause and take out hydrogen, take out halogen, free radical addition etc. is non-
Selective process.Therefore TiO2Photocatalysis is seldom applied to the organic synthesis with high synthesis value.
Imidazoles alkyl structure is constructed by acid catalyzed 1,3- Dipolar Cycloaddition.Existing research is thought, either sharp
With transition metal Lewis acid composition catalyst or small organic moleculeAcid catalyst all cannot be low using green
Malicious, cheap and easily-available alcohol and imines realizes the synthesis imidazolidine compound of 1,3- Dipolar Cycloaddition high yield.This is mainly
Because alcohol can neither cannot function as again the generation of dipole body as dipolarophile body in the reaction system of Lewis acid and alcohol and imines
1,3- Dipolar Cycloaddition between imines and imines can only occur for 1,3- Dipolar Cycloaddition.
Summary of the invention
To improve the above problem, the present invention provides a kind of Actinochemical synthesis of imidazoles alkyl compound, including following
Step:
In the presence of light and photochemical catalyst, pure and mild imines is reacted, and obtains imidazoles alkyl compound.
According to an embodiment of the invention, the photochemical catalyst can be titanium dioxide, the titanium dioxide is selected from mixed crystal
One of type P25 titanium dioxide, anatase titanium dioxide, rutile titanium dioxide etc., two or more；
The light can be one of ultraviolet light, visible light or sunlight, two or more；
The light source of the light can be xenon lamp；The power of the xenon lamp can be 200-400 watts, such as 300 watts；
The alcohol is the organic molecule in molecular structure with alcoholic extract hydroxyl group, it is preferably unsubstituted or by it is one or more (such as 1,
2,3,4,5) inertia group such as alkyl, naphthenic base, Heterocyclylalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryl
Alkyl, heteroaryl alkyl, cycloalkyl-alkyl, hetercycloalkylalkyl, alkyl oxy, cycloalkyl oxy, Heterocyclylalkyl oxygroup, aryl
Or mixtures thereof oxygroup, the fatty alcohol of heteroaryl oxygroup substitution, aromatic alcohol, such as can be methanol, ethyl alcohol, 2- methyl-1-the third
Alcohol, 1- hexanol, benzyl alcohol, 4- methoxy benzyl alcohol, 2- pyridinemethanol or in which the mixture of two or more；As methanol,
Ethyl alcohol, 2- methyl-1-propyl alcohol, benzyl alcohol, 4- methoxy benzyl alcohol；
The imines is the organic molecule in molecular structure with imines carbon-to-nitrogen double bon, preferably by it is one or more (such as 1,
2,3,4,5) inertia group such as alkyl, naphthenic base, Heterocyclylalkyl, aryl, substituted aryl, heteroaryl, aryl alkyl, heteroaryl
Alkyl, cycloalkyl-alkyl, hetercycloalkylalkyl, alkyl oxy, cycloalkyl oxy, Heterocyclylalkyl oxygroup, aryloxy, heteroaryl
Or mixtures thereof the aromatic imine of oxygroup substitution, fatty imines, such as can be N- benzylidenei benzylamine, N- benzylidenei benzene
Amine, N- benzylidenei propylamine, N-2- propylidene benzylamine or in which the mixture of two or more；
Obtained product imidazoles alkyl compound can be to be unsubstituted, by one or more (such as 1,2,3,4,5) bases
Group such as alkyl, naphthenic base, Heterocyclylalkyl, aryl, heteroaryl, aryl alkyl, heteroaryl alkyl, cycloalkyl-alkyl, Heterocyclylalkyl
The imidazolidine that alkyl, alkyl oxy, cycloalkyl oxy, Heterocyclylalkyl oxygroup, aryloxy, heteroaryl oxygroup replace, such as can
To be 1,3- dibenzyl -4,5- diphenyl-imidazole alkane, 1,3- dibenzyl -2- methyl -4,5- diphenyl-imidazole alkane, 1,3- dibenzyl
Base -2,4,5- triphenylimidazolyl alkane, 1,3- diisopropyl -2- (4- methoxyphenyl) -4,5- diphenyl-imidazole alkane, 1,3- dibenzyl
Base -2- (4- methoxyphenyl) -4,5- diphenyl-imidazole alkane or in which the mixture of two or more；
According to an embodiment of the invention, the imidazoles alkyl compound is preferably selected from following group by one or more
Such as alkyl, naphthenic base, Heterocyclylalkyl, substituted aryl, heteroaryl, alkyl oxy, cycloalkyl oxy, Heterocyclylalkyl oxygroup, aryl
Oxygroup, heteroaryl oxygroup replace；
According to an embodiment of the invention, the reaction can be optionally added into or be added without solvent；
The solvent can be inert organic solvents, can be selected from it is inert at reaction conditions, especially not with raw material
Any organic solvent chemically reacted with product, including for example selected from following a kind of, two or more of mixtures: ester
Class solvent, such as ethyl acetate or butyl acetate；Hydrocarbon solvent, such as benzene,toluene,xylene, hexane and ring
Hexane；Halogenated hydrocarbon solvent, such as methylene chloride, chloroform, 1,2- dichloroethanes and chlorobenzene；Or other solvents, such as
N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-Methyl pyrrolidone (NMP), acetonitrile or pyridine；
According to an embodiment of the invention, the solvent is preferably acetonitrile, n,N-Dimethylformamide (DMF), dimethyl
Sulfoxide (DMSO)；
According to an embodiment of the invention, the molar ratio of the photochemical catalyst and imines and alcohol can be 1:(1-200):
(1-100), preferably 1:(1-10): (1-10), such as 1:2:4,1:1:2,1:2.5:5；
The concentration of the photochemical catalyst in the reaction system can be 0.1-20g/L, such as 0.5g/L, 1g/L, 2g/L,
10g/L；
According to an embodiment of the invention, the concentration of the alcohol in the reaction system is 0.01-10mol/L, such as 1mol/
L,2mol/L；
According to an embodiment of the invention, the concentration of the imines in the reaction system is 0.01-10mol/L, such as
0.5mol/L；
According to an embodiment of the invention, the reaction can carry out in transparency reactor, for example, it is closed transparent anti-
Answer device；
According to an embodiment of the invention, the reaction preferably carries out in an inert atmosphere；The inert atmosphere can be
The atmosphere such as nitrogen, helium, argon gas；
The pressure of the inert atmosphere can be 0.01MPa；
The reaction time of the reaction can be -24 hours 10 minutes, such as 15,20,24 hours；
Reaction temperature can be 10-50 DEG C, such as 25 DEG C.
According to an embodiment of the invention, also generating water while the reaction obtains imidazoles alkyl compound.
According to an embodiment of the invention, the preparation method may comprise steps of: being first dissolved in pure and mild imines
In inert organic solvents or alcohol itself solvent, rear and photochemical catalyst is added in transparent vessel and constitutes reaction system, to transparent appearance
It is passed through inert gas in device, is reacted, has been reacted with the reaction system in light source irradiation transparent vessel while stirring
Product imidazoles alkyl compound is obtained after.
Term is explained and definition
Term " alkyl " is interpreted as the preferred linear chain or branched chain saturation monovalent hydrocarbon for indicating to have 1~40 carbon atom,
Such as C1-6Alkyl."C1-6Alkyl " is interpreted as the preferred linear chain or branched chain saturation for indicating to have 1,2,3,4,5 or 6 carbon atom
Monovalent hydrocarbon, such as methyl, ethyl, propyl, butyl, amyl, hexyl, isopropyl, isobutyl group, sec-butyl, tert-butyl, isoamyl
Base, 2- methyl butyl, 1- methyl butyl, 1- ethyl propyl, 1,2- dimethyl propyl, neopentyl, 1,1- dimethyl propyl, 4- first
Base amyl, 3- methyl amyl, 2- methyl amyl, 1- methyl amyl, 2- ethyl-butyl, 1- ethyl-butyl, 3,3- dimethylbutyl,
2,2- dimethylbutyl, 1,1- dimethylbutyl, 2,3- dimethylbutyl, 1,3- dimethylbutyl or 1,2- dimethylbutyl or
Their isomers.Particularly, the group has 1,2,3 or 4 carbon atom (" C1-4Alkyl "), such as methyl, ethyl, third
Base, butyl, isopropyl, isobutyl group, sec-butyl, tert-butyl, more particularly, the group have 1,2 or 3 carbon atom (" C1-3
Alkyl "), such as methyl, ethyl, n-propyl or isopropyl.
Term " naphthenic base " be understood to mean that saturation monovalent monocyclic or bicyclic hydrocarbon ring, have such as 3~20 carbon
Atom, preferably " C3-10Naphthenic base ".Term " C3-10Naphthenic base " be understood to mean that saturation monovalent monocyclic or bicyclic hydrocarbon ring,
With 3,4,5,6,7,8,9 or 10 carbon atoms.The C3-10Naphthenic base can be monocycle alkyl, such as cyclopropyl, cyclobutyl, ring
Amyl, cyclohexyl, suberyl, cyclooctyl, cyclononyl or cyclodecyl or for example decahydronaphthalene naphthalene nucleus of bicyclic alkyl.
Term " Heterocyclylalkyl " means the monovalent monocyclic being saturated or bicyclic hydrocarbon ring, preferably comprises 1-5 and is independently selected from N, O
With the hetero atom of S, preferably " 3-10 membered heterocycloalkyl ".Term " 3-10 membered heterocycloalkyl " means the monovalent monocyclic or bicyclic of saturation
Hydrocarbon ring, it includes 1-5, preferably 1-3 are selected from the hetero atom of N, O and S.The Heterocyclylalkyl can be by the carbon atom
Either one or two of or nitrogen-atoms (if present) connect with the rest part of molecule.Particularly, the Heterocyclylalkyl can wrap
It includes but is not limited to: 4 member rings, such as azetidinyl, oxetanyl；5 member rings, such as tetrahydrofuran base, dioxole
Base, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, pyrrolinyl；Or 6 member rings, such as THP trtrahydropyranyl, piperidyl, morpholinyl, two
Thiophene alkyl, thiomorpholine base, piperazinyl or trithiane base；Or 7 member rings, such as Diazesuberane basic ring.Optionally, the heterocycle alkane
Base can be benzo-fused.The heterocycle can be it is bicyclic, such as, but not limited to 5,5 member rings, such as hexahydro cyclopentano [c]
Pyrroles -2 (1H)-basic ring or 5,6 membered bicyclics, such as hexahydropyrrolo simultaneously [1,2-a] pyrazine -2 (1H)-basic ring.The nitrogen atom
Ring can be that part is unsaturated, i.e., it may include one or more double bonds, such as, but not limited to 2,5- dihydro -1H- pyrroles
Base, 4H- [1,3,4] thiadiazine base, 4,5- dihydro-oxazole base or 4H- [Isosorbide-5-Nitrae] thiazine basic ring, alternatively, it can be it is benzo-fused
, such as, but not limited to dihydro-isoquinoline basic ring.
Term " aryl " indicate the monovalence armaticity with 6~20 carbon atoms or partial aromatic monocycle, it is bicyclic or
Tricyclic hydrocarbon ring.Term " substituted aryl " indicates the aryl being substituted by one or more substituents.The substituent group be selected from-F ,-
Cl、-Br、-I、-OH、-CN、-NO2、-NH2,=O, C1-40Alkyl, C1-40Alkyl oxy, C2-40Alkenyl, C2-40Alkynyl, C3-20Ring
Alkyl, C3-20Cycloalkyl oxy, C3-20Cycloalkylsulfanyl." aryl " preferably " C6-14Aryl ".Term " C6-14Aryl " is interpreted as
It is preferred that indicating the monocycle with the monovalence armaticity of 6,7,8,9,10,11,12,13 or 14 carbon atoms or partial aromatic, double
Ring or tricyclic hydrocarbon ring (" C6-14Aryl "), especially with the ring (" C of 6 carbon atoms6Aryl "), such as phenyl.For example, " replacing
Aryl " includes but is not limited to: 4- chlorphenyl, 2- chlorphenyl, 4- fluorophenyl, 4- bromophenyl, 4- iodophenyl, 3- chlorphenyl, 4- tri-
Trifluoromethylphenyl, 4- aminomethyl phenyl, 2- aminomethyl phenyl, 3- aminomethyl phenyl, 2,5- di-tert-butyl-phenyls, 4- cyano-phenyl, 4- first
Phenyl, 4- dimethylaminophenyl, 4- formylphenyl, 4- acetyl phenyl, 4- nitrobenzophenone, 4- ethenylphenyl；It is described
Aryl can be selected from xenyl, or the ring (" C with 9 carbon atoms9Aryl "), such as indanyl or indenyl, either
Ring (" C with 10 carbon atoms10Aryl "), such as tetrahydro naphthyl, ihydro naphthyl or naphthalene, or there are 13 carbon originals
The ring (" C of son13Aryl "), such as fluorenyl, or the ring (" C with 14 carbon atoms14Aryl "), such as anthryl.
Term " heteroaryl " is understood to include such monovalent monocyclic, bicyclic or tricyclic aromatic ring system, has preferably 5
~20 annular atoms and the hetero atoms that 1-5 is independently selected from N, O and S are preferably comprised, such as " 5-14 unit's heteroaryl ".Term " takes
For heteroaryl " indicate the heteroaryl being substituted by one or more substituents.The substituent group be selected from-F ,-Cl ,-Br ,-I ,-OH ,-
CN、-NO2、-NH2,=O, C1-40Alkyl, C1-40Alkyl oxy, C2-40Alkenyl, C2-40Alkynyl, C3-20Naphthenic base, C3-20Cycloalkyloxy group
Base, C3-20Cycloalkylsulfanyl.Term " 5-14 unit's heteroaryl " is understood to include such monovalent monocyclic, bicyclic or tricyclic aromatic
Ring system has 5,6,7,8,9,10,11,12,13 or 14 carbon atoms of annular atom, especially 5 or 6 or 9 or 10, and it is wrapped
Containing 1-5, preferably 1-3 is respectively independently selected from the hetero atom of N, O and S, also, at each occurrence can be in addition benzo-fused
's.Particularly, heteroaryl is selected from thienyl, furyl, pyrrole radicals, oxazolyl, thiazolyl, imidazole radicals, pyrazolyl, isoxazole
Base, isothiazolyl, oxadiazoles base, triazolyl, thiadiazolyl group, thiophene -4H- pyrazolyl etc. and their benzo derivative, such as
Benzofuranyl, benzothienyl, benzoxazolyl, benzo isoxazolyl, benzimidazolyl, benzotriazole base, indazolyl, Yin
Diindyl base, isoindolyl etc.；Or pyridyl group, pyridazinyl, pyrimidine radicals, pyrazinyl, triazine radical etc. and their benzo derivative,
Such as quinolyl, quinazolyl, isoquinolyl etc.；Or azocine base, indolizine base, purine radicals etc. and their benzo derive
Object；Or cinnoline base, phthalazinyl, quinazolyl, quinoxalinyl, naphthyridines base, pteridyl, carbazyl, acridinyl, phenazinyl, pheno thiophene
Piperazine base, phenoxazine base etc..
Beneficial effect
The pure and mild imines serial electronic transfer coupling hydrogen migration of photocatalysis to selectively, dehydration contracting are utilized the invention discloses a kind of
The method of conjunction -1,3- Dipolar Cycloaddition synthesis imidazoles alkyl compound.The present invention is utilized and is dissolved in inert organic solvents
Pure and mild imines under the induction of ultraviolet light or visible light, under the action of photochemical catalyst, by control the reaction time, realize
The reaction that imidazoles alkyl compound is synthesized by the pure and mild imines of green low toxicity, can be obtained imidazoles alkyl compound.Moreover, of the invention
Product yield high, the selectivity of method are good.The separation yield of product reaches as high as 95% or more, selectively reach as high as 99% with
On.Also, preparation process of the invention is simple, and product can be obtained by single step reaction, economic and environment-friendly and easy to operate, tool
There is higher practicability.
Imidazoles alkyl compound of the invention can be used as the drug that relieves the pain, antibacterials and synthetic intermediate for other changes
Close the synthesis of object.
Detailed description of the invention
Fig. 1 is 1 product of embodiment1H-NMR nuclear magnetic spectrum.
Fig. 2 is 1 product of embodiment13C-NMR nuclear magnetic spectrum.
Fig. 3 is the HR-ESI-MS map of 1 product of embodiment.
Fig. 4 is 2 product of embodiment1H-NMR nuclear magnetic spectrum.
Fig. 5 is 2 product of embodiment13C-NMR nuclear magnetic spectrum.
Fig. 6 is the monocrystalline map of 2 product of embodiment.
Fig. 7 is the HR-ESI-MS map of 2 product of embodiment.
Fig. 8 is 3 product of embodiment1H-NMR nuclear magnetic spectrum.
Fig. 9 is 3 product of embodiment13C-NMR nuclear magnetic spectrum.
Figure 10 is the HR-ESI-MS map of 3 product of embodiment.
Figure 11 is 4 product of embodiment1H-NMR nuclear magnetic spectrum.
Figure 12 is 4 product of embodiment13C-NMR nuclear magnetic spectrum.
Figure 13 is the HR-ESI-MS map of 4 product of embodiment.
Specific embodiment
Technical solution of the present invention is described in detail below by way of illustrative specific embodiment.But it should not be by these
Embodiment is construed to limiting the scope of the invention.All technologies realized based on above content of the present invention are encompassed by this
Invention is intended in the range of protection.
Unless otherwise indicated, documented raw material and reagent are commercial product.
Instrument and equipment:1H-NMR and13C-NMR spectrogram uses 600 Liquid NMR instrument of Bruker Avance III
It is acquired, Fig. 1,4,8,9,11,12 solvent for use are deuterated acetonitrile, and Fig. 2,5 solvent for use are deuterated chloroform.
X-ray single crystal diffraction data structure spectrogram 6 comes from Rigaku Raxis Rapid IP X-ray single crystal diffractometer,
Radiation source is Cu-K α line
High resolution mass spectrum spectrogram 3,7,10,13 picks up from SolariX mass spectrograph, and using electrospray ionisation source, ionization mode is
Positive ion mode.
Embodiment 1
By mixed crystal type P25 titanium dioxide and N- benzylidenei benzylamine (PhCH=NCH2Ph the molar ratio of 1:1) is pressed
(0.5mmol:0.5mmol) is added in the temperature control transparent reaction bottle for fill methanol simultaneously 25 DEG C of temperature control, so that mixed crystal type P25 dioxy
Changing the concentration of titanium in the reaction system is 10g/L, and the concentration of imines in the reaction system is 0.5mol/L, and closed sealing is passed through
Inert gas, and make the inert gas pressure 0.01MPa in temperature control transparent reaction bottle, controlled at 25 DEG C of stirring half an hour
So that imines absorption is reached balance, then irradiate temperature control transparent reaction bottle with 300 watts of xenon lamp and is kept for 25 DEG C of temperature, irradiation 24
Stop reaction after hour, pillar layer separation reaction product, reaction product is mainly 1,3- dibenzyl -4,5- hexichol shown in following formula
Base imidazolidine, separation yield are 95%, and selectivity is 98%, the compound1H-NMR and13C-NMR nuclear magnetic data is shown in respectively
Fig. 1 and 2, HR-ESI-MS map are shown in Fig. 3.
Embodiment 2
By anatase titanium dioxide and N- benzylidenei benzylamine (PhCH=NCH2Ph), ethyl alcohol presses 1:2:4
The molar ratio of (0.25mmol:0.5mmol:1mmol) is added in the temperature control transparent reaction bottle for fill acetonitrile simultaneously 25 DEG C of temperature control,
So that the concentration of anatase titanium dioxide in the reaction system is 1g/L, the concentration of ethyl alcohol in the reaction system is 2mol/L,
Closed sealing is passed through inert gas, and makes the inert gas pressure 0.01MPa in temperature control transparent reaction bottle, controlled at 25 DEG C
And stirring half an hour makes Ethanol Adsorption reach balance, then irradiates temperature control transparent reaction bottle with 300 watts of xenon lamp and keeps temperature
25 DEG C, stop reaction after irradiating 24 hours, pillar layer separation product, reaction product is mainly 1,3- dibenzyl shown in following formula
Base -2- methyl -4,5- diphenyl-imidazole alkane, yield 90%, selectivity are 95%, the compound1H-NMR and13C-NMR
Nuclear magnetic data is shown in that Figure 4 and 5, monocrystalline map are shown in Fig. 6 (monoclinic system, space group P121/c1, unit cell volume respectively), HR-ESI-MS map is shown in Fig. 7.
Embodiment 3
By rutile titanium dioxide and N- benzylidenei benzylamine (PhCH=NCH2Ph), benzyl alcohol presses 1:1:2
The molar ratio of (0.5mmol:0.5mmol:1mmol) is added in the temperature control transparent reaction bottle for filling DMF, so that rutile-type
The concentration of titanium dioxide in the reaction system is 2g/L, and the concentration of imines in the reaction system is 0.5mol/L, and benzyl alcohol is anti-
Answering the concentration in system is 1mol/L, and closed sealing is passed through inert gas, and makes the inert gas pressure in temperature control transparent reaction bottle
Power is 0.01MPa, controlled at 25 DEG C and stirs half an hour and adsorbs benzyl alcohol and imines to reach balance, then use sunlight
Irradiation temperature control transparent reaction bottle is simultaneously kept for 25 DEG C of temperature, stops reaction, pillar layer separation product after irradiating 20 hours, reaction produces
If owner's 1,3- dibenzyl -2,4 shown in following formula, 5- triphenylimidazolyl alkane, yield 94%, selectivity is 99%, should
Compound1H-NMR and13C-NMR nuclear magnetic data is shown in that Fig. 8 and 9, HR-ESI-MS map are shown in Figure 10 respectively.
Embodiment 4
By anatase titania and rutile titanium dioxide and N- benzylidenei benzylamine (PhCH=NCH2Ph), 4- methoxy
Base benzyl alcohol is added to the control for filling DMSO by the molar ratio of 1:1:5:10 (0.1mmol:0.1mmol:0.5mmol:1mmol)
In warm transparent reaction bottle, so that the concentration of anatase titania and rutile titanium dioxide in the reaction system is 0.5g/L,
The concentration of imines and 4- methoxy benzyl alcohol in the reaction system is respectively 0.5mol/L, 1mol/L, and closed sealing is passed through inertia
Gas, and make the inert gas pressure 0.01MPa in temperature control transparent reaction bottle, make Asia controlled at 25 DEG C of stirring half an hour
Amine and the absorption of 4- methoxy benzyl alcohol reach balance, then irradiate temperature control transparent reaction bottle with 300 watts of xenon lamp and keep temperature
25 DEG C, stop reaction after irradiating 15 hours, reaction product is mainly 1,3- dibenzyl -2- (4- methoxyphenyl) -4,5- bis-
Phenylimidazolidiness, separation yield are 92%, and selectivity is 99%, the compound1H-NMR and13C-NMR nuclear magnetic data difference
See that Figure 11 and 12, HR-ESI-MS map are shown in Figure 13.
More than, embodiments of the present invention are illustrated.But the present invention is not limited to above embodiment.It is all
Within the spirit and principles in the present invention, any modification, equivalent substitution, improvement and etc. done should be included in guarantor of the invention
Within the scope of shield.
Claims (10)
1. a kind of Actinochemical synthesis of imidazoles alkyl compound, which comprises the following steps:
In the presence of light and photochemical catalyst, pure and mild imines is reacted, and obtains imidazoles alkyl compound.
2. synthetic method according to claim 1, which is characterized in that the photochemical catalyst can be titanium dioxide, described
Titanium dioxide is selected from one of mixed crystal type P25 titanium dioxide, anatase titanium dioxide, rutile titanium dioxide etc., two
Kind is a variety of.
3. synthetic method according to claim 1 or 2, which is characterized in that the light can be ultraviolet light, visible light or
One of sunlight, two or more.
4. synthetic method according to claim 1-3, which is characterized in that the alcohol is that have alcohol in molecular structure
The organic molecule of hydroxyl, it is preferably unsubstituted or by one or more inertia groups such as alkyl, naphthenic base, Heterocyclylalkyl, aryl, take
For aryl, heteroaryl, substituted heteroaryl, aryl alkyl, heteroaryl alkyl, cycloalkyl-alkyl, hetercycloalkylalkyl, alkyl oxygen
Or mixtures thereof base, cycloalkyl oxy, Heterocyclylalkyl oxygroup, aryloxy, the fatty alcohol of heteroaryl oxygroup substitution, aromatic alcohol,
Such as can be methanol, ethyl alcohol, 2- methyl-1-propyl alcohol, 1- hexanol, benzyl alcohol, 4- methoxy benzyl alcohol, 2- pyridinemethanol or its
In two or more mixture；Such as methanol, ethyl alcohol, 2- methyl-1-propyl alcohol, benzyl alcohol, 4- methoxy benzyl alcohol.
5. synthetic method according to claim 1-4, which is characterized in that the imines is that have in molecular structure
The organic molecule of imines carbon-to-nitrogen double bon, preferably by one or more inertia groups such as alkyl, naphthenic base, Heterocyclylalkyl, aryl, take
For aryl, heteroaryl, substituted heteroaryl, aryl alkyl, heteroaryl alkyl, cycloalkyl-alkyl, hetercycloalkylalkyl, alkyl oxygen
Aromatic imine, fatty imines or its mixing that base, cycloalkyl oxy, Heterocyclylalkyl oxygroup, aryloxy, heteroaryl oxygroup replace
Object, for example, can be N- benzylidenei benzylamine, N- benzylidenei aniline, N- benzylidenei propylamine, N-2- propylidene benzylamine or its
In two or more mixture.
6. synthetic method according to claim 1-5, which is characterized in that the imidazoles alkyl compound can be
It is unsubstituted, by one or more selected from following group for example alkyl, naphthenic base, Heterocyclylalkyl, aryl, heteroaryl, aryl alkyl,
Heteroaryl alkyl, cycloalkyl-alkyl, hetercycloalkylalkyl, alkyl oxy, cycloalkyl oxy, Heterocyclylalkyl oxygroup, aryloxy,
The imidazolidine that heteroaryl oxygroup replaces, such as can be 1,3- dibenzyl -4,5- diphenyl-imidazole alkane, 1,3- dibenzyl -2- first
Base -4,5- diphenyl-imidazole alkane, 1,3- dibenzyl -2,4,5- triphenylimidazolyl alkane, 3- benzyl -1- isopropyl -4,4- dimethyl -
5- phenylimidazolidiness, 1,3- diisopropyl -2- (4- methoxyphenyl) -4,5- diphenyl-imidazole, 1,3- dibenzyl -2- (4- first
Phenyl) -4,5- diphenyl-imidazole alkane or in which the mixture of two or more.
7. synthetic method according to claim 1-6, which is characterized in that the reaction can be optionally added into or
It is added without solvent；
The solvent can be inert organic solvents, can be selected from it is inert at reaction conditions, especially not with raw material and production
Any organic solvent that product chemically react, including for example selected from following a kind of, two or more of mixtures: esters are molten
Agent, such as ethyl acetate or butyl acetate；Hydrocarbon solvent, such as benzene,toluene,xylene, hexane and hexamethylene；
Halogenated hydrocarbon solvent, such as methylene chloride, chloroform, 1,2- dichloroethanes and chlorobenzene；Or other solvents, such as N, N- bis-
Methylformamide (DMF), dimethyl sulfoxide (DMSO), N-Methyl pyrrolidone (NMP), acetonitrile or pyridine.
8. synthetic method according to claim 1-7, which is characterized in that the photochemical catalyst and imines and alcohol
Molar ratio can be 1:(1-200): (1-100), preferably 1:(1-10): (1-10), such as 1:2:4,1:1:2,1:2.5:5；
The concentration of the photochemical catalyst in the reaction system can be 0.1-20g/L, such as 0.5g/L, 1g/L, 2g/L, 10g/L；
The concentration of the alcohol in the reaction system is 0.01-10mol/L, such as 1mol/L, 2mol/L；
The concentration of the imines in the reaction system is 0.01-10mol/L, such as 0.5mol/L.
9. synthetic method according to claim 1-8, which is characterized in that the reaction is preferably in an inert atmosphere
It carries out；The inert atmosphere can be the atmosphere such as nitrogen, helium, argon gas；
Preferably, the temperature of the reaction can be 10-50 DEG C, such as 25 DEG C.
10. -9 described in any item synthetic methods according to claim 1, which is characterized in that the preparation method may include with
Pure and mild imines: being first dissolved in inert organic solvents or alcohol itself solvent by lower step, and rear and photochemical catalyst is added to transparent appearance
Reaction system is constituted in device, inert gas is passed through into transparent vessel, while stirring in light source irradiation transparent vessel
Reaction system reacted, obtain product imidazoles alkyl compound after the reaction was completed.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810326762.9A CN110372595B (en) | 2018-04-12 | 2018-04-12 | Photochemical synthesis method of imidazolidine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810326762.9A CN110372595B (en) | 2018-04-12 | 2018-04-12 | Photochemical synthesis method of imidazolidine compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110372595A true CN110372595A (en) | 2019-10-25 |
| CN110372595B CN110372595B (en) | 2020-12-22 |
Family
ID=68243240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810326762.9A Expired - Fee Related CN110372595B (en) | 2018-04-12 | 2018-04-12 | Photochemical synthesis method of imidazolidine compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110372595B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111533717A (en) * | 2020-06-01 | 2020-08-14 | 谷利军 | Method for synthesizing 3-arylmethylbenzo [ b ] furan compound under blue light excitation |
-
2018
- 2018-04-12 CN CN201810326762.9A patent/CN110372595B/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111533717A (en) * | 2020-06-01 | 2020-08-14 | 谷利军 | Method for synthesizing 3-arylmethylbenzo [ b ] furan compound under blue light excitation |
| CN111533717B (en) * | 2020-06-01 | 2023-02-07 | 谷利军 | Method for synthesizing 3-arylmethylbenzo [ b ] furan compound under blue light excitation |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110372595B (en) | 2020-12-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lash | Metal complexes of carbaporphyrinoid systems | |
| Baryshnikov et al. | Electronic structure, aromaticity and spectra of hetero [8] circulenes | |
| Uskokovic et al. | Asymmetric synthesis of allo-heteroyohimbine alkaloids | |
| Shen et al. | Self-assembled supramolecular cages containing dinuclear ruthenium (II) polypyridyl complexes | |
| CN109180411A (en) | A kind of photocatalysis fixed point deuterate new method of unsaturated carbon carbon bond | |
| Lautrette et al. | Tuning the Guest‐Binding Ability of a Helically Folded Capsule by In Situ Modification of the Aromatic Oligoamide Backbone | |
| Kim et al. | Assembly and X-ray crystal structures of heterometallic multiporphyrins with complementary coordination between ruthenium (II) and tin (IV) porphyrins | |
| Dance et al. | A new three-dimensionally nonmolecular cadmium-sulfur lattice in crystalline bis (DMF) tetradeca (2-methylbenzenethiolato) heptacadmium | |
| Wenkert et al. | Preparation and H (3) isomerization of C (15)-substituted deplancheine derivatives. Synthesis of geissoschizol and geissoschizine | |
| CN110372595A (en) | A kind of Actinochemical synthesis of imidazoles alkyl compound | |
| Kochem et al. | Characterization of a Dinuclear Copper (II) Complex and Its Fleeting Mixed‐Valent Copper (II)/Copper (III) Counterpart | |
| KOBAYASHI et al. | Transformation of tazettine to pretazettine | |
| Khoury et al. | Metal ion-induced self assembly of open-chain tetrapyrrole derivatives: Double stranded dinuclear complexes from 10-oxo-5, 15-biladienes | |
| CN105541527B (en) | A kind of photochemical oxidation method of fabricated by dehydrogenating alcohol aldehyde ketone | |
| Vicente et al. | Porphyrins with fused exocyclic rings | |
| CN111423331A (en) | Photochemical catalytic synthesis method of aryl alkyl ether | |
| Iwasa et al. | 13-hydroxylation of tetrahydroberberine in cell suspension cultures of some Corydalis species | |
| CN109232421A (en) | Single acid imide peri-condensed fullerene derivative and the preparation method and application thereof | |
| JP5925381B2 (en) | Compound [4- (2-amino-10-methyl-4-oxo-6,7,8,9-tetrahydro-4a, 7-epiminopyrimido [4,5-b] [1,4] diazepine-5 (4H) -Yl) benzoyl] -glutamate and its production | |
| Benayad et al. | Biomimetic assembly of leucoridine A | |
| Wang et al. | Three bilindione isomers: synthesis, characterization and reactivity of biliverdin analogs | |
| CN106632330B (en) | A kind of pyrido [2 ', 1 ':2,3] piperidines [1,6-a] indoles salt and its synthetic method | |
| CN110713436B (en) | Method for carrying out 1, 4-conjugated reduction by photochemical catalysis of alpha, beta-ketene compound | |
| Mangeney et al. | Rearrangement of catharanthine.(V). 21-Cyanocatharanthine | |
| KR100747613B1 (en) | Triazatrinaphthyrins and the use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20201222 |