JP5858884B2 - Imidazole compounds having a thiophene ring - Google Patents
Imidazole compounds having a thiophene ring Download PDFInfo
- Publication number
- JP5858884B2 JP5858884B2 JP2012180348A JP2012180348A JP5858884B2 JP 5858884 B2 JP5858884 B2 JP 5858884B2 JP 2012180348 A JP2012180348 A JP 2012180348A JP 2012180348 A JP2012180348 A JP 2012180348A JP 5858884 B2 JP5858884 B2 JP 5858884B2
- Authority
- JP
- Japan
- Prior art keywords
- imidazole
- methyl
- thienyl
- thienylmethyl
- dichlorophenyl
- 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.)
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- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 title claims description 25
- 150000002460 imidazoles Chemical class 0.000 title description 2
- -1 imidazole compound Chemical class 0.000 claims description 45
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 41
- 239000000126 substance Substances 0.000 claims description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
- 239000000243 solution Substances 0.000 description 36
- 238000000034 method Methods 0.000 description 28
- 238000004809 thin layer chromatography Methods 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 21
- 239000000843 powder Substances 0.000 description 21
- 238000003786 synthesis reaction Methods 0.000 description 21
- 239000013078 crystal Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 15
- 230000003595 spectral effect Effects 0.000 description 15
- WPDWOCRJBPXJFM-UHFFFAOYSA-N 2-bromo-1-phenylpropan-1-one Chemical compound CC(Br)C(=O)C1=CC=CC=C1 WPDWOCRJBPXJFM-UHFFFAOYSA-N 0.000 description 14
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 229910052802 copper Inorganic materials 0.000 description 12
- 239000010949 copper Substances 0.000 description 12
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 10
- 239000003963 antioxidant agent Substances 0.000 description 9
- 230000003078 antioxidant effect Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- HSLBDBXGRIKBMV-UHFFFAOYSA-N 2-thiophen-2-ylethanimidamide;hydrochloride Chemical compound Cl.NC(=N)CC1=CC=CS1 HSLBDBXGRIKBMV-UHFFFAOYSA-N 0.000 description 8
- 229910000679 solder Inorganic materials 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical class ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- URAGJMBGNVOIJC-UHFFFAOYSA-N thiophene-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=CS1 URAGJMBGNVOIJC-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- CLSHQIDDCJTHAJ-UHFFFAOYSA-N 2-thienylacetonitrile Chemical compound N#CCC1=CC=CS1 CLSHQIDDCJTHAJ-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- KQHLBMVGQBPSMT-UHFFFAOYSA-N 2-bromo-1-(2,4-dichlorophenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC=C(Cl)C=C1Cl KQHLBMVGQBPSMT-UHFFFAOYSA-N 0.000 description 4
- YPKHWACIODYBCI-UHFFFAOYSA-N 2-bromo-1-(3,4-dichlorophenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC=C(Cl)C(Cl)=C1 YPKHWACIODYBCI-UHFFFAOYSA-N 0.000 description 4
- GUKJZTNQTFJSGH-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC=C(Cl)C=C1 GUKJZTNQTFJSGH-UHFFFAOYSA-N 0.000 description 4
- CCGONRWWYRBSPE-UHFFFAOYSA-N 5-methyl-4-phenyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=CC=CC=2)=C(C)NC=1CC1=CC=CS1 CCGONRWWYRBSPE-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 4
- FKGDMSJKLIQBQS-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(Cl)C(Cl)=C1 FKGDMSJKLIQBQS-UHFFFAOYSA-N 0.000 description 3
- SAKMPXRILWVZEG-UHFFFAOYSA-N 2-bromo-1-(4-chlorophenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC=C(Cl)C=C1 SAKMPXRILWVZEG-UHFFFAOYSA-N 0.000 description 3
- OQLCVXVVASQZLX-UHFFFAOYSA-N 2-bromo-1-naphthalen-1-ylethanone Chemical compound C1=CC=C2C(C(=O)CBr)=CC=CC2=C1 OQLCVXVVASQZLX-UHFFFAOYSA-N 0.000 description 3
- FGZJTYQVOKKPSJ-UHFFFAOYSA-N 2-bromo-1-naphthalen-1-ylpropan-1-one Chemical compound C1=CC=C2C(C(=O)C(Br)C)=CC=CC2=C1 FGZJTYQVOKKPSJ-UHFFFAOYSA-N 0.000 description 3
- YHXHHGDUANVQHE-UHFFFAOYSA-N 2-bromo-1-naphthalen-2-ylethanone Chemical compound C1=CC=CC2=CC(C(=O)CBr)=CC=C21 YHXHHGDUANVQHE-UHFFFAOYSA-N 0.000 description 3
- UIJVLGGVVHJTOX-UHFFFAOYSA-N 2-bromo-1-naphthalen-2-ylpropan-1-one Chemical compound C1=CC=CC2=CC(C(=O)C(Br)C)=CC=C21 UIJVLGGVVHJTOX-UHFFFAOYSA-N 0.000 description 3
- AZPLRCJPSVXMPS-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=CC(Cl)=CC=2)Cl)=C(C)NC=1CC1=CC=CS1 AZPLRCJPSVXMPS-UHFFFAOYSA-N 0.000 description 3
- WBUMYHMJGIZAOB-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC=C(Cl)C=C1Cl WBUMYHMJGIZAOB-UHFFFAOYSA-N 0.000 description 3
- KRAKQGGXKYXFSG-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=C(Cl)C(Cl)=CC=2)=C(C)NC=1CC1=CC=CS1 KRAKQGGXKYXFSG-UHFFFAOYSA-N 0.000 description 3
- NQTRLYAPBVZGIX-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC=C(Cl)C(Cl)=C1 NQTRLYAPBVZGIX-UHFFFAOYSA-N 0.000 description 3
- GZPXCUISVLEUMB-UHFFFAOYSA-N 5-methyl-4-naphthalen-1-yl-2-thiophen-2-yl-1h-imidazole Chemical compound N=1C(C=2C3=CC=CC=C3C=CC=2)=C(C)NC=1C1=CC=CS1 GZPXCUISVLEUMB-UHFFFAOYSA-N 0.000 description 3
- XRHGBXQLOKKVFX-UHFFFAOYSA-N 5-methyl-4-naphthalen-2-yl-2-thiophen-2-yl-1h-imidazole Chemical compound N=1C(C=2C=C3C=CC=CC3=CC=2)=C(C)NC=1C1=CC=CS1 XRHGBXQLOKKVFX-UHFFFAOYSA-N 0.000 description 3
- LMMVLKWKBWKSDI-UHFFFAOYSA-N 5-methyl-4-phenyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC=CC=C1 LMMVLKWKBWKSDI-UHFFFAOYSA-N 0.000 description 3
- OJIHVZZPDKXFBI-UHFFFAOYSA-N 5-methyl-4-phenyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC=CC=C1 OJIHVZZPDKXFBI-UHFFFAOYSA-N 0.000 description 3
- AFKHOXWOEQIUPN-UHFFFAOYSA-N 5-naphthalen-1-yl-2-thiophen-2-yl-1h-imidazole Chemical compound C1=CSC(C=2NC(=CN=2)C=2C3=CC=CC=C3C=CC=2)=C1 AFKHOXWOEQIUPN-UHFFFAOYSA-N 0.000 description 3
- HIORPXUGSNEOGV-UHFFFAOYSA-N 5-naphthalen-2-yl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C=C(C=2C=C3C=CC=CC3=CC=2)NC=1CC1=CC=CS1 HIORPXUGSNEOGV-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000009736 wetting Methods 0.000 description 3
- ADCYRBXQAJXJTD-UHFFFAOYSA-N 1-(4-chlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(Cl)C=C1 ADCYRBXQAJXJTD-UHFFFAOYSA-N 0.000 description 2
- QQLIGMASAVJVON-UHFFFAOYSA-N 1-naphthalen-1-ylethanone Chemical compound C1=CC=C2C(C(=O)C)=CC=CC2=C1 QQLIGMASAVJVON-UHFFFAOYSA-N 0.000 description 2
- XSAYZAUNJMRRIR-UHFFFAOYSA-N 2-acetylnaphthalene Chemical compound C1=CC=CC2=CC(C(=O)C)=CC=C21 XSAYZAUNJMRRIR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229910000881 Cu alloy Inorganic materials 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003822 epoxy resin Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 239000013081 microcrystal Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229920000647 polyepoxide Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000004381 surface treatment Methods 0.000 description 2
- GSXCEVHRIVLFJV-UHFFFAOYSA-N thiophene-3-carbonitrile Chemical compound N#CC=1C=CSC=1 GSXCEVHRIVLFJV-UHFFFAOYSA-N 0.000 description 2
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RMIJMXPBQBQCHQ-UHFFFAOYSA-N 1-(2,3-dichlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC(Cl)=C1Cl RMIJMXPBQBQCHQ-UHFFFAOYSA-N 0.000 description 1
- FBMTWRZQBRHOPF-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(Cl)C=C1Cl FBMTWRZQBRHOPF-UHFFFAOYSA-N 0.000 description 1
- KRBDEZHXQICPAA-UHFFFAOYSA-N 1-(2,5-dichlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC(Cl)=CC=C1Cl KRBDEZHXQICPAA-UHFFFAOYSA-N 0.000 description 1
- ICSKLVVLACKLMV-UHFFFAOYSA-N 1-(2,6-dichlorophenyl)propan-1-one Chemical compound CCC(=O)C1=C(Cl)C=CC=C1Cl ICSKLVVLACKLMV-UHFFFAOYSA-N 0.000 description 1
- BTSCBJDORATYKJ-UHFFFAOYSA-N 1-(2-chlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC=C1Cl BTSCBJDORATYKJ-UHFFFAOYSA-N 0.000 description 1
- KFXWPKDEAPLDKF-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC(Cl)=CC(Cl)=C1 KFXWPKDEAPLDKF-UHFFFAOYSA-N 0.000 description 1
- PQWGFUFROKIJBO-UHFFFAOYSA-N 1-(3-chlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC(Cl)=C1 PQWGFUFROKIJBO-UHFFFAOYSA-N 0.000 description 1
- XWAIBCLYBCOGPX-UHFFFAOYSA-N 2-bromo-1-(2,3-dichlorophenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC=CC(Cl)=C1Cl XWAIBCLYBCOGPX-UHFFFAOYSA-N 0.000 description 1
- SALZDJISFJXDLZ-UHFFFAOYSA-N 2-bromo-1-(2,6-dichlorophenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=C(Cl)C=CC=C1Cl SALZDJISFJXDLZ-UHFFFAOYSA-N 0.000 description 1
- QXBPNBFQCNGDTQ-UHFFFAOYSA-N 2-bromo-1-(2-chlorophenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC=CC=C1Cl QXBPNBFQCNGDTQ-UHFFFAOYSA-N 0.000 description 1
- GNIPVINPPLXVNW-UHFFFAOYSA-N 2-bromo-1-(3,5-dichlorophenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC(Cl)=CC(Cl)=C1 GNIPVINPPLXVNW-UHFFFAOYSA-N 0.000 description 1
- OFNMQTRHMBQQEA-UHFFFAOYSA-N 2-bromo-1-(3-chlorophenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC=CC(Cl)=C1 OFNMQTRHMBQQEA-UHFFFAOYSA-N 0.000 description 1
- JDTDCUUREQULBB-UHFFFAOYSA-N 2-chloro-1-(2,5-dichlorophenyl)propan-1-one Chemical compound CC(Cl)C(=O)C1=CC(Cl)=CC=C1Cl JDTDCUUREQULBB-UHFFFAOYSA-N 0.000 description 1
- YQBPDHQJIIDKEO-UHFFFAOYSA-N 2-chloro-1-(4-chlorophenyl)propan-1-one Chemical compound CC(Cl)C(=O)C1=CC=C(Cl)C=C1 YQBPDHQJIIDKEO-UHFFFAOYSA-N 0.000 description 1
- VYOLNYSIZIEAOP-UHFFFAOYSA-N 2-chloro-1-naphthalen-1-ylethanone Chemical compound C1=CC=C2C(C(=O)CCl)=CC=CC2=C1 VYOLNYSIZIEAOP-UHFFFAOYSA-N 0.000 description 1
- XRCRRENQSPVZIB-UHFFFAOYSA-N 2-chloro-1-naphthalen-1-ylpropan-1-one Chemical compound C1=CC=C2C(C(=O)C(Cl)C)=CC=CC2=C1 XRCRRENQSPVZIB-UHFFFAOYSA-N 0.000 description 1
- NYJAUILLKSDBMH-UHFFFAOYSA-N 2-chloro-1-naphthalen-2-ylethanone Chemical compound C1=CC=CC2=CC(C(=O)CCl)=CC=C21 NYJAUILLKSDBMH-UHFFFAOYSA-N 0.000 description 1
- AJLOJLVEADHPJX-UHFFFAOYSA-N 2-chloro-1-naphthalen-2-ylpropan-1-one Chemical compound C1=CC=CC2=CC(C(=O)C(Cl)C)=CC=C21 AJLOJLVEADHPJX-UHFFFAOYSA-N 0.000 description 1
- AXCPQHPNAZONTH-UHFFFAOYSA-N 2-chloro-1-phenylpropan-1-one Chemical compound CC(Cl)C(=O)C1=CC=CC=C1 AXCPQHPNAZONTH-UHFFFAOYSA-N 0.000 description 1
- USSYWBMZTAVASW-UHFFFAOYSA-N 2-iodo-1-naphthalen-2-ylethanone Chemical compound C1=CC=CC2=CC(C(=O)CI)=CC=C21 USSYWBMZTAVASW-UHFFFAOYSA-N 0.000 description 1
- FTEBUJXUGHBSIX-UHFFFAOYSA-N 2-iodo-1-naphthalen-2-ylpropan-1-one Chemical compound C1=CC=CC2=CC(C(=O)C(I)C)=CC=C21 FTEBUJXUGHBSIX-UHFFFAOYSA-N 0.000 description 1
- VNLDDWAMUIGYCA-UHFFFAOYSA-N 2-iodo-1-phenylpropan-1-one Chemical compound CC(I)C(=O)C1=CC=CC=C1 VNLDDWAMUIGYCA-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- FGEMXCIELABZBO-UHFFFAOYSA-N 2-thiophen-2-ylethanimidamide Chemical compound NC(=N)CC1=CC=CS1 FGEMXCIELABZBO-UHFFFAOYSA-N 0.000 description 1
- GWZCLMWEJWPFFA-UHFFFAOYSA-N 2-thiophen-3-ylacetonitrile Chemical compound N#CCC=1C=CSC=1 GWZCLMWEJWPFFA-UHFFFAOYSA-N 0.000 description 1
- MKZCIVBMCPIMNP-UHFFFAOYSA-N 2-thiophen-3-ylethanimidamide Chemical compound NC(=N)CC=1C=CSC=1 MKZCIVBMCPIMNP-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OAJIXOMIGXMKIQ-UHFFFAOYSA-N 4-(2,3-dichlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=C(Cl)C=CC=2)Cl)=C(C)NC=1CC1=CC=CS1 OAJIXOMIGXMKIQ-UHFFFAOYSA-N 0.000 description 1
- CMMKLECAWSLBKA-UHFFFAOYSA-N 4-(2,3-dichlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=C(Cl)C=CC=2)Cl)=C(C)NC=1CC=1C=CSC=1 CMMKLECAWSLBKA-UHFFFAOYSA-N 0.000 description 1
- OTPKXLNNFKSUSU-UHFFFAOYSA-N 4-(2,3-dichlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC=CC(Cl)=C1Cl OTPKXLNNFKSUSU-UHFFFAOYSA-N 0.000 description 1
- RUCBTCHTQMNUJV-UHFFFAOYSA-N 4-(2,3-dichlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC=CC(Cl)=C1Cl RUCBTCHTQMNUJV-UHFFFAOYSA-N 0.000 description 1
- BDVGOTXDMQJXPL-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=CC(Cl)=CC=2)Cl)=C(C)NC=1CC=1C=CSC=1 BDVGOTXDMQJXPL-UHFFFAOYSA-N 0.000 description 1
- MNLJHXLXNVEPKZ-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC=C(Cl)C=C1Cl MNLJHXLXNVEPKZ-UHFFFAOYSA-N 0.000 description 1
- BKAFXHIWXPHQQV-UHFFFAOYSA-N 4-(2,5-dichlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=CC=C(Cl)C=2)Cl)=C(C)NC=1CC1=CC=CS1 BKAFXHIWXPHQQV-UHFFFAOYSA-N 0.000 description 1
- FUYRZFMTSWJXQK-UHFFFAOYSA-N 4-(2,5-dichlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=CC=C(Cl)C=2)Cl)=C(C)NC=1CC=1C=CSC=1 FUYRZFMTSWJXQK-UHFFFAOYSA-N 0.000 description 1
- DLJTYPWFHOECHV-UHFFFAOYSA-N 4-(2,5-dichlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC(Cl)=CC=C1Cl DLJTYPWFHOECHV-UHFFFAOYSA-N 0.000 description 1
- PJNSMOOZGIEKOV-UHFFFAOYSA-N 4-(2,5-dichlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC(Cl)=CC=C1Cl PJNSMOOZGIEKOV-UHFFFAOYSA-N 0.000 description 1
- KFFGFGPZKSISPI-UHFFFAOYSA-N 4-(2,6-dichlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=CC=CC=2Cl)Cl)=C(C)NC=1CC1=CC=CS1 KFFGFGPZKSISPI-UHFFFAOYSA-N 0.000 description 1
- YPNBNKXNEZCTML-UHFFFAOYSA-N 4-(2,6-dichlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=CC=CC=2Cl)Cl)=C(C)NC=1CC=1C=CSC=1 YPNBNKXNEZCTML-UHFFFAOYSA-N 0.000 description 1
- SSICRODIDJJVKD-UHFFFAOYSA-N 4-(2,6-dichlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=C(Cl)C=CC=C1Cl SSICRODIDJJVKD-UHFFFAOYSA-N 0.000 description 1
- NQLBJGFAVRFCSE-UHFFFAOYSA-N 4-(2,6-dichlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=C(Cl)C=CC=C1Cl NQLBJGFAVRFCSE-UHFFFAOYSA-N 0.000 description 1
- XSKOEWYVZCIAME-UHFFFAOYSA-N 4-(2-chlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=CC=CC=2)Cl)=C(C)NC=1CC1=CC=CS1 XSKOEWYVZCIAME-UHFFFAOYSA-N 0.000 description 1
- KHHLFHNHYAZMEX-UHFFFAOYSA-N 4-(2-chlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C(=CC=CC=2)Cl)=C(C)NC=1CC=1C=CSC=1 KHHLFHNHYAZMEX-UHFFFAOYSA-N 0.000 description 1
- MIZGLHZDGGVWGK-UHFFFAOYSA-N 4-(2-chlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC=CC=C1Cl MIZGLHZDGGVWGK-UHFFFAOYSA-N 0.000 description 1
- FRYQAPXRYKXDOD-UHFFFAOYSA-N 4-(2-chlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC=CC=C1Cl FRYQAPXRYKXDOD-UHFFFAOYSA-N 0.000 description 1
- VXLUYLSFFDEFMU-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=C(Cl)C(Cl)=CC=2)=C(C)NC=1CC=1C=CSC=1 VXLUYLSFFDEFMU-UHFFFAOYSA-N 0.000 description 1
- VBEXUNWVTSEUJX-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC=C(Cl)C(Cl)=C1 VBEXUNWVTSEUJX-UHFFFAOYSA-N 0.000 description 1
- BXSPISNXKDPWFX-UHFFFAOYSA-N 4-(3,5-dichlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=C(Cl)C=C(Cl)C=2)=C(C)NC=1CC1=CC=CS1 BXSPISNXKDPWFX-UHFFFAOYSA-N 0.000 description 1
- SYTZLYNPCJHXAW-UHFFFAOYSA-N 4-(3,5-dichlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=C(Cl)C=C(Cl)C=2)=C(C)NC=1CC=1C=CSC=1 SYTZLYNPCJHXAW-UHFFFAOYSA-N 0.000 description 1
- QGTGCENJQALSRJ-UHFFFAOYSA-N 4-(3,5-dichlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC(Cl)=CC(Cl)=C1 QGTGCENJQALSRJ-UHFFFAOYSA-N 0.000 description 1
- VTRAJOHPQUCRPQ-UHFFFAOYSA-N 4-(3,5-dichlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC(Cl)=CC(Cl)=C1 VTRAJOHPQUCRPQ-UHFFFAOYSA-N 0.000 description 1
- SVFFRLWAFWISOP-UHFFFAOYSA-N 4-(3-chlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=C(Cl)C=CC=2)=C(C)NC=1CC1=CC=CS1 SVFFRLWAFWISOP-UHFFFAOYSA-N 0.000 description 1
- APFLNNIPRNCROG-UHFFFAOYSA-N 4-(3-chlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=C(Cl)C=CC=2)=C(C)NC=1CC=1C=CSC=1 APFLNNIPRNCROG-UHFFFAOYSA-N 0.000 description 1
- LAGLEODBHOLGIK-UHFFFAOYSA-N 4-(3-chlorophenyl)-5-methyl-2-thiophen-2-yl-1h-imidazole Chemical compound CC=1NC(C=2SC=CC=2)=NC=1C1=CC=CC(Cl)=C1 LAGLEODBHOLGIK-UHFFFAOYSA-N 0.000 description 1
- YOKGRBVMFMFKGC-UHFFFAOYSA-N 4-(3-chlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC=CC(Cl)=C1 YOKGRBVMFMFKGC-UHFFFAOYSA-N 0.000 description 1
- NJMCITXDPWIKPE-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-methyl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=CC(Cl)=CC=2)=C(C)NC=1CC1=CC=CS1 NJMCITXDPWIKPE-UHFFFAOYSA-N 0.000 description 1
- CBVCNOORMHRIHF-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-methyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=CC(Cl)=CC=2)=C(C)NC=1CC=1C=CSC=1 CBVCNOORMHRIHF-UHFFFAOYSA-N 0.000 description 1
- PSSHNGWGOMRTMU-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-methyl-2-thiophen-3-yl-1h-imidazole Chemical compound CC=1NC(C2=CSC=C2)=NC=1C1=CC=C(Cl)C=C1 PSSHNGWGOMRTMU-UHFFFAOYSA-N 0.000 description 1
- RKCOMOAQGKVOTL-UHFFFAOYSA-N 5-(4-chlorophenyl)-2-thiophen-2-yl-1h-imidazole Chemical compound C1=CC(Cl)=CC=C1C1=CNC(C=2SC=CC=2)=N1 RKCOMOAQGKVOTL-UHFFFAOYSA-N 0.000 description 1
- WDNVPSXCUZHQFQ-UHFFFAOYSA-N 5-methyl-4-naphthalen-1-yl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C3=CC=CC=C3C=CC=2)=C(C)NC=1CC1=CC=CS1 WDNVPSXCUZHQFQ-UHFFFAOYSA-N 0.000 description 1
- HRRMODFOIICBED-UHFFFAOYSA-N 5-methyl-4-naphthalen-1-yl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C3=CC=CC=C3C=CC=2)=C(C)NC=1CC=1C=CSC=1 HRRMODFOIICBED-UHFFFAOYSA-N 0.000 description 1
- OKSNUIJPYJZGDI-UHFFFAOYSA-N 5-methyl-4-naphthalen-1-yl-2-thiophen-3-yl-1h-imidazole Chemical compound N=1C(C=2C3=CC=CC=C3C=CC=2)=C(C)NC=1C=1C=CSC=1 OKSNUIJPYJZGDI-UHFFFAOYSA-N 0.000 description 1
- ANZCMUFPRHSLDT-UHFFFAOYSA-N 5-methyl-4-naphthalen-2-yl-2-(thiophen-2-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=C3C=CC=CC3=CC=2)=C(C)NC=1CC1=CC=CS1 ANZCMUFPRHSLDT-UHFFFAOYSA-N 0.000 description 1
- GLDLMSZVGFVPCE-UHFFFAOYSA-N 5-methyl-4-naphthalen-2-yl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=C3C=CC=CC3=CC=2)=C(C)NC=1CC=1C=CSC=1 GLDLMSZVGFVPCE-UHFFFAOYSA-N 0.000 description 1
- KTSWHACEVPKNHT-UHFFFAOYSA-N 5-methyl-4-naphthalen-2-yl-2-thiophen-3-yl-1h-imidazole Chemical compound N=1C(C=2C=C3C=CC=CC3=CC=2)=C(C)NC=1C=1C=CSC=1 KTSWHACEVPKNHT-UHFFFAOYSA-N 0.000 description 1
- HNHUUNAISXXRQU-UHFFFAOYSA-N 5-methyl-4-phenyl-2-(thiophen-3-ylmethyl)-1h-imidazole Chemical compound N=1C(C=2C=CC=CC=2)=C(C)NC=1CC=1C=CSC=1 HNHUUNAISXXRQU-UHFFFAOYSA-N 0.000 description 1
- JODHXIYFKXJNEN-UHFFFAOYSA-N 5-phenyl-2-thiophen-2-yl-1h-imidazole Chemical compound C1=CSC(C=2NC=C(N=2)C=2C=CC=CC=2)=C1 JODHXIYFKXJNEN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- IEJHDRTZXXKBMP-UHFFFAOYSA-N IC(C(=O)C1=CC=CC2=CC=CC=C12)C Chemical compound IC(C(=O)C1=CC=CC2=CC=CC=C12)C IEJHDRTZXXKBMP-UHFFFAOYSA-N 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 240000006413 Prunus persica var. persica Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- LQBJWKCYZGMFEV-UHFFFAOYSA-N lead tin Chemical compound [Sn].[Pb] LQBJWKCYZGMFEV-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- QSELGEUCFNFITD-UHFFFAOYSA-N thiophene-2-carboximidamide Chemical compound NC(=N)C1=CC=CS1 QSELGEUCFNFITD-UHFFFAOYSA-N 0.000 description 1
- JKCKRNYECSTMLV-UHFFFAOYSA-N thiophene-3-carboximidamide Chemical compound NC(=N)C=1C=CSC=1 JKCKRNYECSTMLV-UHFFFAOYSA-N 0.000 description 1
- CAUZIIYPBLBRFI-UHFFFAOYSA-N thiophene-3-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C=1C=CSC=1 CAUZIIYPBLBRFI-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
Description
本発明は、チオフェン環を有する新規なイミダゾール化合物に関するものである。 The present invention relates to a novel imidazole compound having a thiophene ring.
本発明に類似のイミダゾール化合物として、例えば、特許文献１には、化学式(IV)で示される２−（２−チエニル）−４−（４−クロロフェニル）イミダゾールが開示され、特許文献２には、化学式(V)で示される２−（２−チエニル）−４−フェニルイミダゾールが開示されている。しかしながら、これらの文献には本発明のイミダゾール化合物の開示はない。 As an imidazole compound similar to the present invention, for example, Patent Document 1 discloses 2- (2-thienyl) -4- (4-chlorophenyl) imidazole represented by the chemical formula (IV). 2- (2-thienyl) -4-phenylimidazole represented by the chemical formula (V) is disclosed. However, these documents do not disclose the imidazole compound of the present invention.
本発明は、チオフェン環を有する新規なイミダゾール化合物を提供することを目的とする。 An object of the present invention is to provide a novel imidazole compound having a thiophene ring.
本発明者等は、前記の課題を解決するために鋭意検討を重ねた結果、化学式(I)、化学式(II)又は化学式(III)で示されるチオフェン環を有するイミダゾール化合物を合成し得ることを認め、本発明を完成するに至ったものである。
当該イミダゾール化合物は、２−チエニル基又は３−チエニル基が、イミダゾール環の２位に直接又はメチレン基を介して結合している。
As a result of intensive studies in order to solve the above-mentioned problems, the present inventors have been able to synthesize imidazole compounds having a thiophene ring represented by chemical formula (I), chemical formula (II) or chemical formula (III). Acknowledgment has led to the completion of the present invention.
In the imidazole compound, a 2-thienyl group or a 3-thienyl group is bonded to the 2-position of the imidazole ring directly or via a methylene group.
本発明のチオフェン環を有するイミダゾール化合物は、金属、特に銅（銅合金を含む）の表面の酸化防止剤や、エポキシ樹脂の硬化剤又は硬化促進剤として、また医農薬分野の中間原料としても有用なものである。 The imidazole compound having a thiophene ring of the present invention is useful as an antioxidant on the surface of metals, particularly copper (including copper alloys), as a curing agent or curing accelerator for epoxy resins, and as an intermediate material in the field of medicine and agrochemicals. It is a thing.
以下、本発明について詳細に説明する。
本発明のチオフェン環を有するイミダゾール化合物（以下、チオフェン環含有イミダゾール化合物と云う）は、
５−メチル−４−フェニル−２−（２−チエニル）イミダゾール、
４−（２−クロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
４−（３−クロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
４−（４−クロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
４−（２，３−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
４−（２，４−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
４−（２，５−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
４−（２，６−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
４−（３，４−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
４−（３，５−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾール、
５−メチル−４−（１−ナフチル）−２−（２−チエニル）イミダゾール、
５−メチル−４−（２−ナフチル）−２−（２−チエニル）イミダゾール、
５−メチル−４−フェニル−２−（３−チエニル）イミダゾール、
４−（２−クロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
４−（３−クロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
４−（４−クロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
４−（２，３−ジクロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
４−（２，４−ジクロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
４−（２，５−ジクロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
４−（２，６−ジクロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
４−（３，４−ジクロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
４−（３，５−ジクロロフェニル）−５−メチル−２−（３−チエニル）イミダゾール、
５−メチル−４−（１−ナフチル）−２−（３−チエニル）イミダゾール、
５−メチル−４−（２−ナフチル）−２−（３−チエニル）イミダゾール、
（以上、化学式（Ｉ）において、ｎが０であるチオフェン環含有イミダゾール化合物）、
５−メチル−４−フェニル−２−（２−チエニルメチル）イミダゾール、
４−（２−クロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
４−（３−クロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
４−（４−クロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
４−（２，３−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
４−（２，４−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
４−（２，５−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
４−（２，６−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
４−（３，４−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
４−（３，５−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾール、
５−メチル−４−（１−ナフチル）−２−（２−チエニルメチル）イミダゾール、
５−メチル−４−（２−ナフチル）−２−（２−チエニルメチル）イミダゾール、
５−メチル−４−フェニル−２−（３−チエニルメチル）イミダゾール、
４−（２−クロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
４−（３−クロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
４−（４−クロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
４−（２，３−ジクロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
４−（２，４−ジクロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
４−（２，５−ジクロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
４−（２，６−ジクロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
４−（３，４−ジクロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
４−（３，５−ジクロロフェニル）−５−メチル−２−（３−チエニルメチル）イミダゾール、
５−メチル−４−（１−ナフチル）−２−（３−チエニルメチル）イミダゾール、
５−メチル−４−（２−ナフチル）−２−（３−チエニルメチル）イミダゾール、
（以上、化学式（Ｉ）において、ｎが１であるチオフェン環含有イミダゾール化合物）、
４−（１−ナフチル）−２−（２−チエニル）イミダゾール及び
４−（２−ナフチル）−２−（２−チエニルメチル）イミダゾールである。
Hereinafter, the present invention will be described in detail.
The imidazole compound having a thiophene ring of the present invention (hereinafter referred to as a thiophene ring-containing imidazole compound)
5-methyl-4-phenyl-2- (2-thienyl) imidazole,
4- (2-chlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
4- (3-chlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
4- (4-chlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
4- (2,3-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
4- (2,4-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
4- (2,5-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
4- (2,6-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
4- (3,4-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
4- (3,5-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole,
5-methyl-4- (1-naphthyl) -2- (2-thienyl) imidazole,
5-methyl-4- (2-naphthyl) -2- (2-thienyl) imidazole,
5-methyl-4-phenyl-2- (3-thienyl) imidazole,
4- (2-chlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
4- (3-chlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
4- (4-chlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
4- (2,3-dichlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
4- (2,4-dichlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
4- (2,5-dichlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
4- (2,6-dichlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
4- (3,4-dichlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
4- (3,5-dichlorophenyl) -5-methyl-2- (3-thienyl) imidazole,
5-methyl-4- (1-naphthyl) -2- (3-thienyl) imidazole,
5-methyl-4- (2-naphthyl) -2- (3-thienyl) imidazole,
(Thus, a thiophene ring-containing imidazole compound in which n is 0 in the chemical formula (I)),
5-methyl-4-phenyl-2- (2-thienylmethyl) imidazole,
4- (2-chlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
4- (3-chlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
4- (4-chlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
4- (2,3-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
4- (2,4-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
4- (2,5-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
4- (2,6-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
4- (3,4-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
4- (3,5-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole,
5-methyl-4- (1-naphthyl) -2- (2-thienylmethyl) imidazole,
5-methyl-4- (2-naphthyl) -2- (2-thienylmethyl) imidazole,
5-methyl-4-phenyl-2- (3-thienylmethyl) imidazole,
4- (2-chlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
4- (3-chlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
4- (4-chlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
4- (2,3-dichlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
4- (2,4-dichlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
4- (2,5-dichlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
4- (2,6-dichlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
4- (3,4-dichlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
4- (3,5-dichlorophenyl) -5-methyl-2- (3-thienylmethyl) imidazole,
5-methyl-4- (1-naphthyl) -2- (3-thienylmethyl) imidazole,
5-methyl-4- (2-naphthyl) -2- (3-thienylmethyl) imidazole,
(Thus, a thiophene ring-containing imidazole compound in which n is 1 in chemical formula (I)),
4- (1-naphthyl) -2- (2-thienyl) imidazole and 4- (2-naphthyl) -2- (2-thienylmethyl) imidazole.
本発明のチオフェン環含有イミダゾール化合物は、公知の方法に準拠して合成することが出来る。例えば、反応式(A)に示されるように、２位ハロゲン化アルキルアリールケトン化合物と、チオフェン環を有するアミジン化合物（以下、チオフェン環含有アミジン化合物と云う）とを脱ハロゲン化水素剤の存在下、有機溶媒中で加熱反応をさせることにより合成することができる。 The thiophene ring-containing imidazole compound of the present invention can be synthesized according to a known method. For example, as shown in the reaction formula (A), a 2-position halogenated alkyl aryl ketone compound and an amidine compound having a thiophene ring (hereinafter referred to as a thiophene ring-containing amidine compound) are present in the presence of a dehydrohalogenating agent. It can be synthesized by heating reaction in an organic solvent.
前述の反応において、チオフェン環含有アミジン化合物の使用量は、２位ハロゲン化アルキルアリールケトン化合物に対して、０．８〜１．５倍モルが好ましく、より好ましくは０．９〜１．１倍モルの割合とすればよい。脱ハロゲン化水素剤の使用量は、２位ハロゲン化アルキルアリールケトン化合物に対して、１〜１０倍当量の割合が好ましい。 In the above-mentioned reaction, the amount of the thiophene ring-containing amidine compound used is preferably 0.8 to 1.5 times, more preferably 0.9 to 1.1 times the mol of the 2-position halogenated alkylaryl ketone compound. A mole ratio may be used. The amount of the dehydrohalogenating agent used is preferably a ratio of 1 to 10 times equivalent to the 2-position halogenated alkyl aryl ketone compound.
前記の２位ハロゲン化アルキルアリールケトン化合物としては、２−クロロプロピオフェノン、２−ブロモプロピオフェノン、２−ヨードプロピオフェノン、２−ブロモ−２′−クロロプロピオフェノン、２−ブロモ−３′−クロロプロピオフェノン、２，４′−ジクロロプロピオフェノン、２−ブロモ−４′−クロロプロピオフェノン、２−ブロモ−２′，３′−ジクロロプロピオフェノン、２−ブロモ−２′，４′−ジクロロプロピオフェノン、２，２′，５′−トリクロロプロピオフェノン、２−ブロモ−２′，６′−ジクロロプロピオフェノン、２−ブロモ−３′，４′−ジクロロプロピオフェノン、２−ブロモ−３′，５′−ジクロロプロピオフェノン、２−クロロ−１′−アセトナフトン、２−ブロモ−１′−アセトナフトン、２−ヨード−１′−アセトナフトン、２−クロロ−１′−プロピオナフトン、２−ブロモ−１′−プロピオナフトン、２−ヨード−１′−プロピオナフトン、２−クロロ−２′−アセトナフトン、２−ブロモ−２′−アセトナフトン、２−ヨード−２′−アセトナフトン、２−クロロ−２′−プロピオナフトン、２−ブロモ−２′−プロピオナフトン及び２−ヨード−２′−プロピオナフトン等が挙げられる。 Examples of the 2-position halogenated alkyl aryl ketone compound include 2-chloropropiophenone, 2-bromopropiophenone, 2-iodopropiophenone, 2-bromo-2'-chloropropiophenone, 2-bromo- 3'-chloropropiophenone, 2,4'-dichloropropiophenone, 2-bromo-4'-chloropropiophenone, 2-bromo-2 ', 3'-dichloropropiophenone, 2-bromo-2 ', 4'-dichloropropiophenone, 2,2', 5'-trichloropropiophenone, 2-bromo-2 ', 6'-dichloropropiophenone, 2-bromo-3', 4'-dichloropro Piophenone, 2-bromo-3 ', 5'-dichloropropiophenone, 2-chloro-1'-acetonaphthone, 2-bromo-1'-acetonaphthone, -Iodo-1'-acetonaphthone, 2-chloro-1'-propionnaphthone, 2-bromo-1'-propionnaphthone, 2-iodo-1'-propionnaphthone, 2-chloro-2'-acetonaphthone, 2-bromo-2 ' -Acetonaphthone, 2-iodo-2'-acetonaphthone, 2-chloro-2'-propionnaphthone, 2-bromo-2'-propionnaphthone and 2-iodo-2'-propionnaphthone.
これらの２位ハロゲン化アルキルアリールケトン化合物は、アルキルアリールケトン化合物の２位をハロゲン化することにより得られる。２位のハロゲン化としては、塩素化又はヨウ素化も可能であるが、アルキルアリールケトン化合物１モルに対し、１モルの臭素を反応させる臭素化反応が最も簡便である。 These 2-position halogenated alkyl aryl ketone compounds are obtained by halogenating the 2-position of the alkyl aryl ketone compound. The halogenation at the 2-position can be chlorinated or iodinated, but the bromination reaction in which 1 mol of bromine is reacted with 1 mol of the alkyl aryl ketone compound is the simplest.
前記のアルキルアリールケトン化合物としては、プロピオフェノン、２′−クロロプロピオフェノン、３′−クロロプロピオフェノン、４′−クロロプロピオフェノン、２′，３′−ジクロロプロピオフェノン、２′，４′−ジクロロプロピオフェノン、２′，５′−ジクロロプロピオフェノン、２′，６′−ジクロロプロピオフェノン、３′，４′−ジクロロプロピオフェノン、３′，５′−ジクロロプロピオフェノン、１−アセトナフトン、２−アセトナフトン、１−プロピオナフトン及び２−プロピオナフトン等が挙げられる。これらは公知の化合物であり、試薬として市販されているものを使用することができる。 Examples of the alkyl aryl ketone compound include propiophenone, 2'-chloropropiophenone, 3'-chloropropiophenone, 4'-chloropropiophenone, 2 ', 3'-dichloropropiophenone, 2' 4,4'-dichloropropiophenone, 2 ', 5'-dichloropropiophenone, 2', 6'-dichloropropiophenone, 3 ', 4'-dichloropropiophenone, 3', 5'-dichloropro Piophenone, 1-acetonaphthone, 2-acetonaphthone, 1-propionnaphthone, 2-propionnaphthone, etc. These are known compounds, and those commercially available as reagents can be used.
前記のチオフェン環含有アミジン化合物は、公知の方法に準拠して合成することが出来る。すなわち、反応式(B)に示されるように、前駆体のチオフェン環を有するニトリル化合物を塩化水素ガス及びエタノール等の低級アルコールと反応させ、イミデート・塩酸塩に変換し、更にアンモニアと反応させることによって、チオフェン環含有アミジン化合物を合成することができる。 The thiophene ring-containing amidine compound can be synthesized according to a known method. That is, as shown in the reaction formula (B), a nitrile compound having a precursor thiophene ring is reacted with a lower alcohol such as hydrogen chloride gas and ethanol, converted into an imidate / hydrochloride, and further reacted with ammonia. Thus, a thiophene ring-containing amidine compound can be synthesized.
前記のチオフェン環含有アミジン化合物としては、
２−チオフェンカルボキシミドアミド、
３−チオフェンカルボキシミドアミド、
２−チオフェンアセトイミドアミド、
３−チオフェンアセトイミドアミド
及びこれらの塩酸塩等の無機酸塩や酢酸塩等の有機酸塩が挙げられる。
As the thiophene ring-containing amidine compound,
2-thiophenecarboximidamide,
3-thiophenecarboximidamide,
2-thiophenacetimidoamide,
Examples thereof include inorganic acid salts such as 3-thiophenacetimidoamide and hydrochlorides thereof, and organic acid salts such as acetates.
前記のチオフェン環を有するニトリル化合物としては、２−シアノチオフェン、３−シアノチオフェン、２−チオフェンアセトニトリル及び３−チオフェンアセトニトリルが挙げられる。これらは公知の化合物であり、試薬として市販されているものを使用することができる。 Examples of the nitrile compound having a thiophene ring include 2-cyanothiophene, 3-cyanothiophene, 2-thiopheneacetonitrile, and 3-thiopheneacetonitrile. These are known compounds, and those commercially available as reagents can be used.
前記の脱ハロゲン化水素剤は公知のものを制限なく使用できる。このような脱ハロゲン化水素剤としては、例えば、水酸化ナトリウム、水酸化カリウム、水酸化カルシウム、炭酸ナトリウム、炭酸カリウム、重炭酸ナトリウム、重炭酸カリウムのような無機アルカリ類、トリエチルアミン、１，８−ジアザビシクロ［５，４，０］−７−ウンデセン（ＤＢＵ）のような有機塩基類、ナトリウムメトキシド、カリウムｔｅｒｔ−ブトキシドのような金属アルコキシド類等が挙げられる。 Any known dehydrohalogenating agent can be used without limitation. Examples of such a dehydrohalogenating agent include inorganic alkalis such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, 1,8 -Organic bases such as diazabicyclo [5,4,0] -7-undecene (DBU), metal alkoxides such as sodium methoxide and potassium tert-butoxide, and the like.
前記の有機溶媒は、２位ハロゲン化アルキルアリールケトン化合物とチオフェン環含有アミジン化合物を溶解することができ、かつ反応に関与しないものであれば公知のものを制限なく使用できる。このような溶媒として、例えば、イソプロピルアルコール、ｔｅｒｔ−ブタノールなどのアルコール類、ヘキサン、トルエンなどの炭化水素類、クロロホルム、クロロベンゼンなどのハロゲン化炭化水素類、酢酸エチルなどのエステル類、アセトニトリルなどのニトリル類、テトラヒドロフラン、ジオキサン、エチレングリコールジメチルエーテルなどのエーテル類、Ｎ，Ｎ−ジメチルホルムアミド（ＤＭＦ）、Ｎ，Ｎ−ジメチルアセトアミド（ＤＭＡＣ）などのアミド類、ジメチルスルホキシド（ＤＭＳＯ）等が挙げられ、これらの溶媒を組み合わせて使用してもよい。 Any known organic solvent can be used without limitation as long as it can dissolve the 2-position halogenated alkylaryl ketone compound and the thiophene ring-containing amidine compound and does not participate in the reaction. Examples of such solvents include alcohols such as isopropyl alcohol and tert-butanol, hydrocarbons such as hexane and toluene, halogenated hydrocarbons such as chloroform and chlorobenzene, esters such as ethyl acetate, and nitriles such as acetonitrile. , Ethers such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, amides such as N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), dimethyl sulfoxide (DMSO), and the like. A combination of solvents may be used.
反応温度は、室温〜還流温度が好ましく、反応時間は、１〜１０時間が好ましい。反応は、通常大気圧下で行えばよい。 The reaction temperature is preferably room temperature to reflux temperature, and the reaction time is preferably 1 to 10 hours. The reaction may be usually performed under atmospheric pressure.
以上の反応条件下で生成したチオフェン環含有イミダゾール化合物は、通常の後処理によって単離することができる。
例えば、反応終了後の反応混合物を水層と有機溶媒層に分配し、有機溶媒層を水で洗浄することにより結晶として析出する粗製のチオフェン環含有イミダゾール化合物を得ることができ、それを再結晶操作等により精製することができる。
The thiophene ring-containing imidazole compound produced under the above reaction conditions can be isolated by ordinary post-treatment.
For example, the reaction mixture after completion of the reaction is divided into an aqueous layer and an organic solvent layer, and the organic solvent layer is washed with water to obtain a crude thiophene ring-containing imidazole compound, which is recrystallized. It can be purified by operation or the like.
以下、本発明を実施例に示した合成試験によって具体的に説明するが、本発明はこれらに限定されるものではない。なお、２−チオフェンカルボキシミドアミド塩酸塩及び２−ブロモプロピオフェノンの合成例を、参考例１及び２に示す。 Hereinafter, the present invention will be specifically described with reference to synthesis tests shown in Examples, but the present invention is not limited thereto. Reference examples 1 and 2 show synthesis examples of 2-thiophenecarboximidamide hydrochloride and 2-bromopropiophenone.
〔参考例１〕
＜２−チオフェンカルボキシミドアミド塩酸塩の合成＞
２−シアノチオフェン１１０．８ｇ（１．０１５ｍｏｌ）、脱水エタノール４９．４ｇ（１．０７２ｍｏｌ）及び脱水ジクロロメタン５５ｇからなる溶液に、冷却下５〜１０℃にて、塩化水素ガス５４．８ｇ（１．２２ｍｏｌ）を吹き込み５時間撹拌後、冷蔵庫に４℃／３日間放置して固体を析出させた。該反応懸濁液を減圧乾固して、赤桃色結晶性固体の２−チオフェンイミド酸エチル塩酸塩１９４．９ｇ（１．０１７ｍｏｌ、収率１００％）を得た。
該固体を粉砕し、氷冷下に振とうしながら、アンモニア３２．０ｇ（１．８８ｍｏｌ）及び脱水エタノール１７７ｇからなる溶液を少量ずつ加えた後、４時間撹拌し、室温に戻して更に一晩撹拌した。この懸濁液を減圧濃縮し１８４ｇのアメ状濃縮物を得た。該濃縮物にヘキサン／ジクロロメタン溶液（２：１体積比）３８０ｍｌを加え撹拌して結晶を析出させた。該結晶をろ取し、ヘキサン／ジクロロメタン溶液で洗浄後、減圧下に乾燥して、桃白色粉末状の２−チオフェンカルボキシミドアミド塩酸塩１４７．０ｇ（０．９０４ｍｏｌ、収率８９．１％）を得た。
[Reference Example 1]
<Synthesis of 2-thiophenecarboximidamide hydrochloride>
To a solution consisting of 110.8 g (1.015 mol) of 2-cyanothiophene, 49.4 g (1.072 mol) of dehydrated ethanol and 55 g of dehydrated dichloromethane, 54.8 g (1. 22 mol) was blown and stirred for 5 hours, and then left in a refrigerator at 4 ° C./3 days to precipitate a solid. The reaction suspension was dried under reduced pressure to obtain 194.9 g (1.017 mol, yield: 100%) of 2-thiophenimidic acid ethyl hydrochloride as a red pink crystalline solid.
The solid was pulverized, and a solution consisting of 32.0 g (1.88 mol) of ammonia and 177 g of dehydrated ethanol was added little by little while shaking under ice cooling, followed by stirring for 4 hours, returning to room temperature and further overnight. Stir. This suspension was concentrated under reduced pressure to obtain 184 g of a candy-like concentrate. To the concentrate, 380 ml of a hexane / dichloromethane solution (2: 1 volume ratio) was added and stirred to precipitate crystals. The crystals were collected by filtration, washed with a hexane / dichloromethane solution, and then dried under reduced pressure to give 147.0 g (0.904 mol, yield 89.1%) of 2-thiophenecarboximidamide hydrochloride in the form of a peach white powder. Got.
〔参考例２〕
＜２−ブロモプロピオフェノン／トルエン溶液の調製＞
プロピオフェノン４１．４ｇ（０．３０９ｍｏｌ）及びメタノール６８ｇからなる溶液に、５５〜６０℃にて、臭素４９．２ｇ（０．３０８ｍｏｌ）を１５分かけて滴下した。次いで、反応液を冷却後、濃縮物が７２ｇになるまで減圧濃縮した。濃縮物をトルエン１２９ｇ及び食塩水２６０ｇに分配し、トルエン層を食塩水で洗浄した後、硫酸ナトリウムで乾燥して、淡黄色透明の２−ブロモプロピオフェノン（０．３０９ｍｏｌ）／トルエン溶液を得た。
[Reference Example 2]
<Preparation of 2-bromopropiophenone / toluene solution>
To a solution composed of 41.4 g (0.309 mol) of propiophenone and 68 g of methanol, 49.2 g (0.308 mol) of bromine was added dropwise at 55-60 ° C. over 15 minutes. Next, the reaction solution was cooled and then concentrated under reduced pressure until the concentrate became 72 g. The concentrate was distributed between 129 g of toluene and 260 g of brine, and the toluene layer was washed with brine and dried over sodium sulfate to obtain a pale yellow transparent 2-bromopropiophenone (0.309 mol) / toluene solution. It was.
〔実施例１〕
＜５−メチル−４−フェニル−２−（２−チエニル）イミダゾールの合成＞
２−チオフェンカルボキシミドアミド塩酸塩５０．２ｇ（０．３０９ｍｏｌ）をＮ，Ｎ−ジメチルアセトアミド１６５ｇに５０℃にて加温溶解させ、炭酸カリウム１１１ｇ（０．８０３ｍｏｌ）を加えて５０℃／５分間撹拌後、参考例２において調製した２−ブロモプロピオフェノン／トルエン溶液を５０〜５５℃にて５０分かけて滴下した。滴下終了後、７０℃／２時間３０分間撹拌した。
次いで、反応懸濁液を冷却後、水８００ｍｌと撹拌し、分液した有機層を水８００ｍｌで洗浄し結晶を析出させた。結晶をろ取しトルエン、次いで熱水で分散洗浄し、減圧下に乾燥して黄褐色粉末５７．６ｇを得た。該粉末をアセトニトリルより再結晶して、乳白色粉末４８．５ｇを得た。
[Example 1]
<Synthesis of 5-methyl-4-phenyl-2- (2-thienyl) imidazole>
2-thiophenecarboximidamide hydrochloride 50.2 g (0.309 mol) was dissolved in 165 g of N, N-dimethylacetamide at 50 ° C. with heating, and 111 g (0.803 mol) of potassium carbonate was added thereto for 50 ° C./5 minutes. After stirring, the 2-bromopropiophenone / toluene solution prepared in Reference Example 2 was added dropwise at 50 to 55 ° C. over 50 minutes. After completion of dropping, the mixture was stirred at 70 ° C./2 hours 30 minutes.
Next, the reaction suspension was cooled and stirred with 800 ml of water, and the separated organic layer was washed with 800 ml of water to precipitate crystals. The crystals were collected by filtration, dispersed and washed with toluene and then with hot water, and dried under reduced pressure to obtain 57.6 g of a tan powder. The powder was recrystallized from acetonitrile to obtain 48.5 g of milky white powder.
得られた粉末の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp214−216℃
・TLC(シリカゲル，アセトン)：Rf=0.67
・1H NMR(DMSO-d6)：δ=2.07(s,3H),6.92−7.68(m,8H).
・MS(EI)：m/z(%)=240(M+,100),198(2),171(2),163(2),130(11),120(3),110(6),103(8),95(4),77(5).
これらのスペクトルデータから、得られた粉末は、化学式(VI)で示される５−メチル−４−フェニル−２−（２−チエニル）イミダゾールであるものと同定した。収率６５．３％
The melting point of the obtained powder, Rf value of thin layer chromatography, 1 H NMR and mass spectrum data were as follows.
・ Mp214-216 ℃
・ TLC (silica gel, acetone): Rf = 0.67
1 H NMR (DMSO-d 6 ): δ = 2.07 (s, 3H), 6.92-7.68 (m, 8H).
MS (EI): m / z (%) = 240 (M + , 100), 198 (2), 171 (2), 163 (2), 130 (11), 120 (3), 110 (6) 103 (8), 95 (4), 77 (5).
From these spectrum data, the obtained powder was identified to be 5-methyl-4-phenyl-2- (2-thienyl) imidazole represented by the chemical formula (VI). Yield 65.3%
〔実施例２〕
＜４−（４−クロロフェニル）−５−メチル−２−（２−チエニル）イミダゾールの合成＞
まず、参考例２のプロピオフェノンを４′−クロロプロピオフェノンに代えて、参考例２の方法に準拠して２−ブロモ−４′−クロロプロピオフェノン／トルエン溶液を調製した。
次いで、実施例１の２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−４′−クロロプロピオフェノン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、乳白色粉末を得た。
[Example 2]
<Synthesis of 4- (4-chlorophenyl) -5-methyl-2- (2-thienyl) imidazole>
First, a 2-bromo-4′-chloropropiophenone / toluene solution was prepared according to the method of Reference Example 2 by replacing the propiophenone of Reference Example 2 with 4′-chloropropiophenone.
Subsequently, the 2-bromopropiophenone / toluene solution of Example 1 was replaced with a 2-bromo-4′-chloropropiophenone / toluene solution, and a synthetic test was performed in accordance with the method of Example 1 to obtain a milky white powder. Got.
得られた粉末の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp214−216℃
・TLC(シリカゲル，アセトン)：Rf=0.67
・1H NMR(DMSO-d6)：δ=2.48(s,3H),7.12−7.69(m,7H).
・MS(EI)：m/z(%)=274(M+,100),238(6),198(3),164(4),137(8),129(4),110(7),95(5).
これらのスペクトルデータから、得られた粉末は、化学式(VII)で示される４−（４−クロロフェニル）−５−メチル−２−（２−チエニル）イミダゾールであるものと同定した。収率５１．９％
The melting point of the obtained powder, Rf value of thin layer chromatography, 1 H NMR and mass spectrum data were as follows.
・ Mp214-216 ℃
・ TLC (silica gel, acetone): Rf = 0.67
1 H NMR (DMSO-d 6 ): δ = 2.48 (s, 3H), 7.12-7.69 (m, 7H).
MS (EI): m / z (%) = 274 (M + , 100), 238 (6), 198 (3), 164 (4), 137 (8), 129 (4), 110 (7) 95 (5).
From these spectral data, the obtained powder was identified as 4- (4-chlorophenyl) -5-methyl-2- (2-thienyl) imidazole represented by the chemical formula (VII). Yield 51.9%
〔実施例３〕
＜４−（２，４−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾールの合成＞
まず、参考例２のプロピオフェノンを２′，４′−ジクロロプロピオフェノンに代えて、参考例２の方法に準拠して２−ブロモ−２′，４′−ジクロロプロピオフェノン／トルエン溶液を調製した。
次いで、実施例１の２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−２′，４′−ジクロロプロピオフェノン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、乳白色粉末を得た。
Example 3
<Synthesis of 4- (2,4-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole>
First, the 2-bromo-2 ', 4'-dichloropropiophenone / toluene solution was used in accordance with the method of Reference Example 2 by replacing the propiophenone of Reference Example 2 with 2', 4'-dichloropropiophenone. Was prepared.
Next, a synthesis test was performed in accordance with the method of Example 1 by replacing the 2-bromopropiophenone / toluene solution of Example 1 with a 2-bromo-2 ′, 4′-dichloropropiophenone / toluene solution. A milky white powder was obtained.
得られた粉末の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp266−268℃
・TLC(シリカゲル，アセトン)：Rf=0.67
・1H NMR(DMSO-d6)：δ=2.18(s,3H),7.11−7.68(m,6H).
・MS(EI)：m/z(%)=310(M+2,68),308(M+,100),273(5),232(3),205(3),172(4),164(6),136(10),110(9),95(7).
これらのスペクトルデータから、得られた粉末は、化学式(VIII)で示される４−（２，４−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾールであるものと同定した。収率３６．１％
The melting point of the obtained powder, Rf value of thin layer chromatography, 1 H NMR and mass spectrum data were as follows.
・ Mp266-268 ℃
・ TLC (silica gel, acetone): Rf = 0.67
1 H NMR (DMSO-d 6 ): δ = 2.18 (s, 3H), 7.11-7.68 (m, 6H).
MS (EI): m / z (%) = 310 (M + 2,68), 308 (M + , 100), 273 (5), 232 (3), 205 (3), 172 (4), 164 (6), 136 (10), 110 (9), 95 (7).
From these spectral data, the obtained powder was identified as 4- (2,4-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole represented by the chemical formula (VIII). Yield 36.1%
〔実施例４〕
＜４−（３，４−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾールの合成＞
まず、参考例２のプロピオフェノンを３′，４′−ジクロロプロピオフェノンに代えて、参考例２の方法に準拠して２−ブロモ−３′，４′−ジクロロプロピオフェノン／トルエン溶液を調製した。
次いで、実施例１の２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−３′，４′−ジクロロプロピオフェノン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、クリーム色微結晶を得た。
Example 4
<Synthesis of 4- (3,4-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole>
First, the 2-bromo-3 ', 4'-dichloropropiophenone / toluene solution was replaced with 3', 4'-dichloropropiophenone in Reference Example 2 in accordance with the method of Reference Example 2 instead of 3 ', 4'-dichloropropiophenone. Was prepared.
Subsequently, a synthesis test was performed in accordance with the method of Example 1 by replacing the 2-bromopropiophenone / toluene solution of Example 1 with a 2-bromo-3 ′, 4′-dichloropropiophenone / toluene solution. A cream-colored microcrystal was obtained.
得られた結晶の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp201−203℃
・TLC(シリカゲル，アセトン)：Rf=0.67
・1H NMR(DMSO-d6)：δ=2.46(s,3H),7.13−7.86(m,6H).
・MS(EI)：m/z(%)=310(M+2, 68),308(M+,100),272(5),237(4),198(3),172(3),163(5),136(9),110(9),95(6).
これらのスペクトルデータから、得られた結晶は、化学式(IX)で示される４−（３，４−ジクロロフェニル）−５−メチル−２−（２−チエニル）イミダゾールであるものと同定した。収率５４．５％
The melting point of the obtained crystal, Rf value of thin layer chromatography, 1 H NMR and mass spectral data were as follows.
・ Mp201-203 ℃
・ TLC (silica gel, acetone): Rf = 0.67
1 H NMR (DMSO-d 6 ): δ = 2.46 (s, 3H), 7.13-7.86 (m, 6H).
MS (EI): m / z (%) = 310 (M + 2, 68), 308 (M + , 100), 272 (5), 237 (4), 198 (3), 172 (3), 163 (5), 136 (9), 110 (9), 95 (6).
From these spectral data, the obtained crystal was identified as 4- (3,4-dichlorophenyl) -5-methyl-2- (2-thienyl) imidazole represented by the chemical formula (IX). Yield 54.5%
〔実施例５〕
＜５−メチル−４−（１−ナフチル）−２−（２−チエニル）イミダゾールの合成＞
まず、参考例２のプロピオフェノンを１−プロピオナフトンに代えて、参考例２の方法に準拠して２−ブロモ−１′−プロピオナフトン／トルエン溶液を調製した。
次いで、実施例１の２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−１′−プロピオナフトン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、緑白色結晶を得た。
Example 5
<Synthesis of 5-methyl-4- (1-naphthyl) -2- (2-thienyl) imidazole>
First, a 2-bromo-1′-propionnaphthone / toluene solution was prepared in accordance with the method of Reference Example 2 by replacing the propiophenone of Reference Example 2 with 1-propionophone.
Subsequently, the 2-bromopropiophenone / toluene solution of Example 1 was replaced with a 2-bromo-1′-propionnaphthone / toluene solution, and a synthetic test was performed according to the method of Example 1 to obtain greenish white crystals. It was.
得られた結晶の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp287−290℃
・TLC(シリカゲル，メタノール)：Rf=0.55
・1H NMR(DMSO-d6)：δ=2.25(s,3H),7.12−8.24(m,10H).
・MS(EI)：m/z(%)=290(M+,100),248(2),221(6),180(15),166(3),153(11),139(5),127(5),110(4),95(2).
これらのスペクトルデータから、得られた結晶は、化学式(X)で示される５−メチル−４−（１−ナフチル）−２−（２−チエニル）イミダゾールであるものと同定した。収率４９．９％
The melting point of the obtained crystal, Rf value of thin layer chromatography, 1 H NMR and mass spectral data were as follows.
・ Mp287-290 ℃
・ TLC (silica gel, methanol): Rf = 0.55
1 H NMR (DMSO-d 6 ): δ = 2.25 (s, 3H), 7.12-8.24 (m, 10H).
MS (EI): m / z (%) = 290 (M + , 100), 248 (2), 221 (6), 180 (15), 166 (3), 153 (11), 139 (5) , 127 (5), 110 (4), 95 (2).
From these spectrum data, the obtained crystal was identified as 5-methyl-4- (1-naphthyl) -2- (2-thienyl) imidazole represented by the chemical formula (X). Yield 49.9%
〔実施例６〕
＜５−メチル−４−（２−ナフチル）−２−（２−チエニル）イミダゾールの合成＞
まず、参考例２のプロピオフェノンを２−プロピオナフトンに代えて、参考例２の方法に準拠して２−ブロモ−２′−プロピオナフトン／トルエン溶液を調製した。
次いで、実施例１の２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−２′−プロピオナフトン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、乳白色粉末を得た。
Example 6
<Synthesis of 5-methyl-4- (2-naphthyl) -2- (2-thienyl) imidazole>
First, a 2-bromo-2′-propionnaphthone / toluene solution was prepared according to the method of Reference Example 2 by replacing the propiophenone of Reference Example 2 with 2-propionophone.
Subsequently, the 2-bromopropiophenone / toluene solution of Example 1 was replaced with a 2-bromo-2'-propionnaphthone / toluene solution, and a synthetic test was performed according to the method of Example 1 to obtain a milky white powder. .
得られた粉末の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp209−210℃
・TLC(シリカゲル，アセトン)：Rf=0.70
・1H NMR(DMSO-d6)：δ=2.51(s,3H),7.14−8.16(m,10H).
・MS(EI)：m/z(%)=290(M+,100),248(2),221(3),180(10),153(10),139(6),127(4),110(4),95(3).
これらのスペクトルデータから、得られた粉末は、化学式(XI)で示される５−メチル−４−（２−ナフチル）−２−（２−チエニル）イミダゾールであるものと同定した。収率４０．５％
The melting point of the obtained powder, Rf value of thin layer chromatography, 1 H NMR and mass spectrum data were as follows.
・ Mp209-210 ℃
・ TLC (silica gel, acetone): Rf = 0.70
-1 H NMR (DMSO-d 6 ): δ = 2.51 (s, 3H), 7.14-8.16 (m, 10H).
MS (EI): m / z (%) = 290 (M + , 100), 248 (2), 221 (3), 180 (10), 153 (10), 139 (6), 127 (4) 110 (4), 95 (3).
From these spectral data, the obtained powder was identified as 5-methyl-4- (2-naphthyl) -2- (2-thienyl) imidazole represented by the chemical formula (XI). Yield 40.5%
〔実施例７〕
＜５−メチル−４−フェニル−２−（３−チエニル）イミダゾールの合成＞
まず、参考例１の２−シアノチオフェンを３−シアノチオフェンに代えて、参考例１の方法に準拠して３−チオフェンカルボキシミドアミド塩酸塩を調製した。
次いで、実施例１の２−チオフェンカルボキシミドアミド塩酸塩を３−チオフェンカルボキシミドアミド塩酸塩に代えて、実施例１の方法に準拠して合成試験を行い、乳白色粉末を得た。
Example 7
<Synthesis of 5-methyl-4-phenyl-2- (3-thienyl) imidazole>
First, 3-thiophenecarboximidamide hydrochloride was prepared in accordance with the method of Reference Example 1 by replacing 2-cyanothiophene of Reference Example 1 with 3-cyanothiophene.
Subsequently, a synthetic test was performed in accordance with the method of Example 1 by replacing 2-thiophenecarboxamideamide hydrochloride of Example 1 with 3-thiophenecarboxamideamide hydrochloride to obtain a milky white powder.
得られた粉末の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp220−224℃
・TLC(シリカゲル，アセトン)：Rf=0.68
・1H NMR(DMSO-d6)：δ=2.46(s,3H),7.21−7.86(m,8H).
・MS(EI)：m/z(%)=240(M+,100),171(2),130(13),120(3),110(7),103(9),89(4),77(5).
これらのスペクトルデータから、得られた粉末は、化学式(XII)で示される５−メチル−４−フェニル−２−（３−チエニル）イミダゾールであるものと同定した。収率６９．２％
The melting point of the obtained powder, Rf value of thin layer chromatography, 1 H NMR and mass spectrum data were as follows.
・ Mp220-224 ℃
・ TLC (silica gel, acetone): Rf = 0.68
1 H NMR (DMSO-d 6 ): δ = 2.46 (s, 3H), 7.21-7.86 (m, 8H).
MS (EI): m / z (%) = 240 (M + , 100), 171 (2), 130 (13), 120 (3), 110 (7), 103 (9), 89 (4) 77 (5).
From these spectral data, the obtained powder was identified as 5-methyl-4-phenyl-2- (3-thienyl) imidazole represented by the chemical formula (XII). Yield 69.2%
〔実施例８〕
＜５−メチル−４−フェニル−２−（２−チエニルメチル）イミダゾールの合成＞
まず、参考例１の２−シアノチオフェンを２−チオフェンアセトニトリルに代えて、参考例１の方法に準拠して２−チオフェンアセトイミドアミド塩酸塩を調製した。
次いで、実施例１の２−チオフェンカルボキシミドアミド塩酸塩を２−チオフェンアセトイミドアミド塩酸塩に代えて、実施例１の方法に準拠して合成試験を行い、ベージュ色微結晶を得た。
Example 8
<Synthesis of 5-methyl-4-phenyl-2- (2-thienylmethyl) imidazole>
First, 2-thiophenacetimidoamide hydrochloride was prepared according to the method of Reference Example 1 by replacing 2-cyanothiophene of Reference Example 1 with 2-thiophene acetonitrile.
Subsequently, a synthesis test was performed according to the method of Example 1 by replacing 2-thiophenecarboximide amide hydrochloride of Example 1 with 2-thiophenacetimidoamide hydrochloride to obtain beige microcrystals.
得られた結晶の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp144−146℃
・TLC(シリカゲル，アセトン)：Rf=0.64
・1H NMR(DMSO-d6)：δ=2.34(s,3H),4.16(s,2H),6.94−7.61(m,8H).
・MS(EI)：m/z(%)=254(M+,100),239(6),221(6),209(14),169(4),157(9),129(8),109(7),97(9),77(6).
これらのスペクトルデータから、得られた結晶は、化学式(XIII)で示される５−メチル−４−フェニル−２−（２−チエニルメチル）イミダゾールであるものと同定した。収率３５．４％
The melting point of the obtained crystal, Rf value of thin layer chromatography, 1 H NMR and mass spectral data were as follows.
・ Mp144-146 ℃
・ TLC (silica gel, acetone): Rf = 0.64
1 H NMR (DMSO-d 6 ): δ = 2.34 (s, 3H), 4.16 (s, 2H), 6.94-7.61 (m, 8H).
MS (EI): m / z (%) = 254 (M + , 100), 239 (6), 221 (6), 209 (14), 169 (4), 157 (9), 129 (8) 109 (7), 97 (9), 77 (6).
From these spectral data, the obtained crystal was identified as 5-methyl-4-phenyl-2- (2-thienylmethyl) imidazole represented by the chemical formula (XIII). Yield 35.4%
〔実施例９〕
＜４−（２，４−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾールの合成＞
まず、参考例１の２−シアノチオフェンを２−チオフェンアセトニトリルに代えて、参考例１の方法に準拠して２−チオフェンアセトイミドアミド塩酸塩を調製し、参考例２のプロピオフェノンを２′，４′−ジクロロプロピオフェノンに代えて、参考例２の方法に準拠して２−ブロモ−２′，４′−ジクロロプロピオフェノン／トルエン溶液を調製した。
次いで、実施例１の２−チオフェンカルボキシミドアミド塩酸塩を２−チオフェンアセトイミドアミド塩酸塩に代えて、２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−２′，４′−ジクロロプロピオフェノン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、ベージュ色結晶を得た。
Example 9
<Synthesis of 4- (2,4-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole>
First, 2-thiothiophene of Reference Example 1 was replaced with 2-thiophene acetonitrile to prepare 2-thiophenacetimidoamide hydrochloride according to the method of Reference Example 1, and propiophenone of Reference Example 2 was 2 ′. Instead of 4,4′-dichloropropiophenone, a 2-bromo-2 ′, 4′-dichloropropiophenone / toluene solution was prepared according to the method of Reference Example 2.
Subsequently, the 2-thiophenecarboximidamide hydrochloride of Example 1 was replaced with 2-thiophenacetimidoamide hydrochloride, and the 2-bromopropiophenone / toluene solution was replaced with 2-bromo-2 ′, 4′-dichloropropio. Instead of the phenone / toluene solution, a synthesis test was performed according to the method of Example 1 to obtain beige crystals.
得られた結晶の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp156−158℃
・TLC(シリカゲル，アセトン)：Rf=0.60
・1H NMR(DMSO-d6)：δ=2.10(s,3H),4.15(s,2H),6.95−7.62(m,6H).
・MS(EI)：m/z(%)=324(M+2,70),322(M+,100),307(6),287(14),277(17),225(6),190(4),165(4),150(7),136(6),125(4),109(11),97(17).
これらのスペクトルデータから、得られた結晶は、化学式(XIV)で示される４−（２，４−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾールであるものと同定した。収率４２．８％
The melting point of the obtained crystal, Rf value of thin layer chromatography, 1 H NMR and mass spectral data were as follows.
・ Mp156-158 ℃
・ TLC (silica gel, acetone): Rf = 0.60
1 H NMR (DMSO-d 6 ): δ = 2.10 (s, 3H), 4.15 (s, 2H), 6.95-7.62 (m, 6H).
MS (EI): m / z (%) = 324 (M + 2, 70), 322 (M + , 100), 307 (6), 287 (14), 277 (17), 225 (6), 190 (4), 165 (4), 150 (7), 136 (6), 125 (4), 109 (11), 97 (17).
From these spectral data, the obtained crystal was identified as 4- (2,4-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole represented by the chemical formula (XIV). Yield 42.8%
〔実施例１０〕
＜４−（３，４−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾールの合成＞
まず、参考例１の２−シアノチオフェンを２−チオフェンアセトニトリルに代えて、参考例１の方法に準拠して２−チオフェンアセトイミドアミド塩酸塩を調製し、参考例２のプロピオフェノンを３′，４′−ジクロロプロピオフェノンに代えて、参考例２の方法に準拠して２−ブロモ−３′，４′−ジクロロプロピオフェノン／トルエン溶液を調製した。
次いで、実施例１の２−チオフェンカルボキシミドアミド塩酸塩を２−チオフェンアセトイミドアミド塩酸塩に代えて、２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−３′，４′−ジクロロプロピオフェノン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、ベージュ色結晶を得た。
Example 10
<Synthesis of 4- (3,4-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole>
First, 2-thiothiophene of Reference Example 1 was replaced with 2-thiophene acetonitrile to prepare 2-thiophenacetimidoamide hydrochloride according to the method of Reference Example 1, and propiophenone of Reference Example 2 was converted to 3 ′. Instead of 4,4′-dichloropropiophenone, a 2-bromo-3 ′, 4′-dichloropropiophenone / toluene solution was prepared according to the method of Reference Example 2.
Subsequently, 2-thiophenecarboximidamide hydrochloride of Example 1 was replaced with 2-thiophenacetimidoamide hydrochloride, and 2-bromopropiophenone / toluene solution was replaced with 2-bromo-3 ′, 4′-dichloropropio. Instead of the phenone / toluene solution, a synthesis test was performed according to the method of Example 1 to obtain beige crystals.
得られた結晶の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp157−158℃
・TLC(シリカゲル，アセトン)：Rf=0.69
・1H NMR(DMSO-d6)：δ=2.36(s,3H),4.16(s,2H),6.95−7.81(m,6H).
・MS(EI)：m/z(%)=324(M+2,68),322(M+,100),307(5),289(7),277(13),225(5),197(8),173(2),165(4),150(5),136(3),125(4),109(9),97(17),84(4).
これらのスペクトルデータから、得られた結晶は、化学式(XV)で示される４−（３，４−ジクロロフェニル）−５−メチル−２−（２−チエニルメチル）イミダゾールであるものと同定した。収率２２．０％
The melting point of the obtained crystal, Rf value of thin layer chromatography, 1 H NMR and mass spectral data were as follows.
・ Mp157-158 ℃
・ TLC (silica gel, acetone): Rf = 0.69
1 H NMR (DMSO-d 6 ): δ = 2.36 (s, 3H), 4.16 (s, 2H), 6.95-7.81 (m, 6H).
MS (EI): m / z (%) = 324 (M + 2,68), 322 (M + , 100), 307 (5), 289 (7), 277 (13), 225 (5), 197 (8), 173 (2), 165 (4), 150 (5), 136 (3), 125 (4), 109 (9), 97 (17), 84 (4).
From these spectral data, the obtained crystal was identified as 4- (3,4-dichlorophenyl) -5-methyl-2- (2-thienylmethyl) imidazole represented by the chemical formula (XV). Yield 22.0%
〔実施例１１〕
＜４−（１−ナフチル）−２−（２−チエニル）イミダゾールの合成＞
まず、参考例２のプロピオフェノンを１−アセトナフトンに代えて、参考例２の方法に準拠して２−ブロモ−１′−アセトナフトン／トルエン溶液を調製した。
次いで、実施例１の２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−１′−アセトナフトン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、暗黄白色結晶を得た。
Example 11
<Synthesis of 4- (1-naphthyl) -2- (2-thienyl) imidazole>
First, a 2-bromo-1′-acetonaphthone / toluene solution was prepared according to the method of Reference Example 2 by replacing propiophenone of Reference Example 2 with 1-acetonaphthone.
Next, the 2-bromopropiophenone / toluene solution of Example 1 was replaced with a 2-bromo-1′-acetonaphthone / toluene solution, and a synthetic test was performed according to the method of Example 1 to obtain dark yellowish white crystals. Obtained.
得られた結晶の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp202−205℃
・TLC(シリカゲル，アセトン)：Rf=0.70
・1H NMR(DMSO-d6)：δ=7.16−8.79(m).
・MS(EI)：m/z(%)=276(M+,100),248(3),221(4),167(43),139(18),127(3),110(5),96(3).
これらのスペクトルデータから、得られた結晶は、化学式(XVI)で示される４−（１−ナフチル）−２−（２−チエニル）イミダゾールであるものと同定した。収率１９．５％
The melting point of the obtained crystal, Rf value of thin layer chromatography, 1 H NMR and mass spectral data were as follows.
・ Mp202-205 ℃
・ TLC (silica gel, acetone): Rf = 0.70
1 H NMR (DMSO-d 6 ): δ = 7.16-8.79 (m).
MS (EI): m / z (%) = 276 (M + , 100), 248 (3), 221 (4), 167 (43), 139 (18), 127 (3), 110 (5) , 96 (3).
From these spectrum data, the obtained crystal was identified as 4- (1-naphthyl) -2- (2-thienyl) imidazole represented by the chemical formula (XVI). Yield 19.5%
〔実施例１２〕
＜４−（２−ナフチル）−２−（２−チエニルメチル）イミダゾールの合成＞
まず、参考例１の２−シアノチオフェンを２−チオフェンアセトニトリルに代えて、参考例１の方法に準拠して２−チオフェンアセトイミドアミド塩酸塩を調製し、参考例２のプロピオフェノンを２−アセトナフトンに代えて、参考例２の方法に準拠して２−ブロモ−２′−アセトナフトン／トルエン溶液を調製した。
次いで、実施例１の２−チオフェンカルボキシミドアミド塩酸塩を２−チオフェンアセトイミドアミド塩酸塩に代えて、２−ブロモプロピオフェノン／トルエン溶液を２−ブロモ−２′−アセトナフトン／トルエン溶液に代えて、実施例１の方法に準拠して合成試験を行い、オレンジ色粉末を得た。
Example 12
<Synthesis of 4- (2-naphthyl) -2- (2-thienylmethyl) imidazole>
First, 2-thiothiophene of Reference Example 1 was replaced with 2-thiophene acetonitrile, and 2-thiophenacetimidoamide hydrochloride was prepared according to the method of Reference Example 1, and propiophenone of Reference Example 2 was changed to 2- Instead of acetonaphthone, a 2-bromo-2′-acetonaphthone / toluene solution was prepared according to the method of Reference Example 2.
Subsequently, 2-thiophenecarboximide amide hydrochloride of Example 1 was replaced with 2-thiophenacetimidoamide hydrochloride, and 2-bromopropiophenone / toluene solution was replaced with 2-bromo-2'-acetonaphthone / toluene solution. Then, a synthesis test was performed according to the method of Example 1 to obtain an orange powder.
得られた粉末の融点、薄層クロマトグラフィーのＲｆ値、１Ｈ ＮＭＲ及びマススペクトルデータは、以下のとおりであった。
・mp148−150℃
・TLC(シリカゲル，アセトン)：Rf=0.59
・1H NMR(DMSO-d6)：δ=4.28(s,2H),6.96−8.29(m,11H).
・MS(EI)：m/z(%)=290(M+,100),257(3),245(10),206(9),179(8),167(6),153(4),139(11),127(5),109(3),97(8).
これらのスペクトルデータから、得られた粉末は、化学式(XVII)で示される４−（２−ナフチル）−２−（２−チエニルメチル）イミダゾールであるものと同定した。収率２１．９％
The melting point of the obtained powder, Rf value of thin layer chromatography, 1 H NMR and mass spectrum data were as follows.
・ Mp148-150 ℃
・ TLC (silica gel, acetone): Rf = 0.59
1 H NMR (DMSO-d 6 ): δ = 4.28 (s, 2H), 6.96-8.29 (m, 11H).
MS (EI): m / z (%) = 290 (M + , 100), 257 (3), 245 (10), 206 (9), 179 (8), 167 (6), 153 (4) , 139 (11), 127 (5), 109 (3), 97 (8).
From these spectral data, the obtained powder was identified as 4- (2-naphthyl) -2- (2-thienylmethyl) imidazole represented by the chemical formula (XVII). Yield 21.9%
〔実施例１３〕
まず、実施例１〜１２において合成したチオフェン環含有イミダゾール化合物と、これらとは別に２−フェニルイミダゾール（２ＰＺ、四国化成工業製）を有効成分とする銅の酸化防止剤を各々調製した。次いで、該防止剤に銅を接触させることにより銅の表面に化成皮膜を形成させた。そして、銅に対する溶融半田の濡れ時間を測定して、イミダゾール化合物が作用する銅表面への酸化防止性能を評価した。この場合、溶融半田の濡れ時間が短い程、イミダゾール化合物の酸化防止性能が優れているものと判定される。
評価試験の詳細は、次のとおりである。
（１）酸化防止剤の調製
イミダゾール化合物、酸、金属塩及びハロゲン化合物を、表１記載の組成となるようにイオン交換水に溶解させた後、アンモニア水でｐＨを調整して酸化防止剤を調製した。
（２）表面処理方法
材質が金属銅の試験片（５ｍｍ×５０ｍｍ×０．３ｍｍの銅版）を脱脂し、次いでソフトエッチングを行い、所定温度の酸化防止剤に所定時間浸漬して、銅の表面に化成皮膜を形成させた後、水洗して乾燥した。
（３）濡れ時間の測定
表面処理を行った試験片を、ポストフラックス（ＪＳ−６４ＭＳＳ、弘輝製）に浸漬して、半田濡れ性試験器（ＳＡＴ−２０００、レスカ製）を使用して半田濡れ時間（秒）を測定した。使用した半田は錫−鉛系共晶半田（Ｈ６３Ａ−Ｂ２０、千住金属工業製）であり、測定条件は半田温度２４０℃、浸漬深さ２ｍｍ、浸漬スピード１６ｍｍ／秒とした。
なお、半田濡れ時間を測定した試験片は、（Ａ）表面処理直後のものと、（Ｂ）温度４０℃、湿度９０％ＲＨの恒温恒湿器に入れて９６時間放置したものと、（Ｃ）さらに２００℃で１０分間加熱したものである。
得られた試験結果は、表１に示したとおりであった。
Example 13
First, a copper antioxidant containing 2-thiolimidazole (2PZ, manufactured by Shikoku Kasei Kogyo Co., Ltd.) as an active ingredient was prepared separately from the thiophene ring-containing imidazole compound synthesized in Examples 1 to 12 and these. Next, a chemical conversion film was formed on the surface of copper by bringing the inhibitor into contact with copper. And the wetting time of the molten solder with respect to copper was measured, and the antioxidant performance to the copper surface on which an imidazole compound acts was evaluated. In this case, it is determined that the shorter the wet time of the molten solder, the better the antioxidant performance of the imidazole compound.
The details of the evaluation test are as follows.
(1) Preparation of antioxidant After dissolving an imidazole compound, an acid, a metal salt, and a halogen compound in ion-exchanged water so as to have the composition shown in Table 1, the pH is adjusted with ammonia water to thereby add an antioxidant. Prepared.
(2) Surface treatment method A test piece (copper plate of 5 mm × 50 mm × 0.3 mm) made of metallic copper is degreased, then soft-etched, and immersed in an antioxidant at a predetermined temperature for a predetermined time to obtain a copper surface. After the chemical conversion film was formed on, it was washed with water and dried.
(3) Measurement of wetting time The surface-treated test piece is immersed in post flux (JS-64MSS, manufactured by Hiroki) and solder wetted using a solder wettability tester (SAT-2000, manufactured by Resuka). Time (seconds) was measured. The solder used was tin-lead eutectic solder (H63A-B20, manufactured by Senju Metal Industry), and the measurement conditions were a solder temperature of 240 ° C., an immersion depth of 2 mm, and an immersion speed of 16 mm / second.
In addition, the test piece which measured the solder wetting time includes (A) a sample immediately after the surface treatment, (B) a sample left in a constant temperature and humidity chamber at a temperature of 40 ° C. and a humidity of 90% RH for 96 hours, and (C ) Further heated at 200 ° C. for 10 minutes.
The test results obtained were as shown in Table 1.
表１に示した試験結果によれば、本願発明のチオフェン環含有イミダゾール化合物を有効成分として含有する酸化防止剤は、銅の表面に耐湿性及び耐熱性に優れた化成皮膜を形成させることができるので、銅表面の酸化防止に有用である。 According to the test results shown in Table 1, the antioxidant containing the thiophene ring-containing imidazole compound of the present invention as an active ingredient can form a chemical conversion film excellent in moisture resistance and heat resistance on the surface of copper. Therefore, it is useful for preventing oxidation of the copper surface.
本発明によれば、金属、特に銅（銅合金を含む）の表面の酸化防止剤や、エポキシ樹脂の硬化剤又は硬化促進剤として、また医農薬分野の中間原料としても有用なチオフェン環含有イミダゾール化合物を提供することができる。 According to the present invention, a thiophene ring-containing imidazole useful as an antioxidant on the surface of metals, particularly copper (including copper alloys), as a curing agent or curing accelerator for epoxy resins, and as an intermediate material in the field of medicine and agrochemicals. A compound can be provided.
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