JP5782331B2 - Method for producing imidoyl chloride compound and method for producing various compounds using the same - Google Patents
Method for producing imidoyl chloride compound and method for producing various compounds using the same Download PDFInfo
- Publication number
- JP5782331B2 JP5782331B2 JP2011174074A JP2011174074A JP5782331B2 JP 5782331 B2 JP5782331 B2 JP 5782331B2 JP 2011174074 A JP2011174074 A JP 2011174074A JP 2011174074 A JP2011174074 A JP 2011174074A JP 5782331 B2 JP5782331 B2 JP 5782331B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- chloride
- imidoyl
- general formula
- imidoyl chloride
- 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.)
- Active
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- 150000001805 chlorine compounds Chemical class 0.000 title claims description 83
- 150000001875 compounds Chemical class 0.000 title claims description 33
- 238000004519 manufacturing process Methods 0.000 title claims description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 68
- 239000013078 crystal Substances 0.000 claims description 60
- -1 amide compound Chemical class 0.000 claims description 52
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 claims description 44
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 35
- 239000002904 solvent Substances 0.000 claims description 32
- RXNOYRCWKRFNIM-UHFFFAOYSA-N 2-carbonochloridoylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(Cl)=O RXNOYRCWKRFNIM-UHFFFAOYSA-N 0.000 claims description 29
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 238000005660 chlorination reaction Methods 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- FEWLNYSYJNLUOO-UHFFFAOYSA-N 1-Piperidinecarboxaldehyde Chemical compound O=CN1CCCCC1 FEWLNYSYJNLUOO-UHFFFAOYSA-N 0.000 claims description 8
- 238000002955 isolation Methods 0.000 claims description 8
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 claims description 7
- 150000001491 aromatic compounds Chemical class 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 150000002894 organic compounds Chemical class 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 81
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 34
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 29
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 23
- FYXKZNLBZKRYSS-UHFFFAOYSA-N benzene-1,2-dicarbonyl chloride Chemical class ClC(=O)C1=CC=CC=C1C(Cl)=O FYXKZNLBZKRYSS-UHFFFAOYSA-N 0.000 description 20
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- 239000000047 product Substances 0.000 description 18
- 238000001914 filtration Methods 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 235000019445 benzyl alcohol Nutrition 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 239000011521 glass Substances 0.000 description 11
- 239000012320 chlorinating reagent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- SJWFXCIHNDVPSH-UHFFFAOYSA-N octan-2-ol Chemical compound CCCCCCC(C)O SJWFXCIHNDVPSH-UHFFFAOYSA-N 0.000 description 9
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000012456 homogeneous solution Substances 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 229940073608 benzyl chloride Drugs 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IBSQPLPBRSHTTG-UHFFFAOYSA-N 1-chloro-2-methylbenzene Chemical compound CC1=CC=CC=C1Cl IBSQPLPBRSHTTG-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- QNVRIHYSUZMSGM-UHFFFAOYSA-N hexan-2-ol Chemical compound CCCCC(C)O QNVRIHYSUZMSGM-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- RXOHFPCZGPKIRD-UHFFFAOYSA-N naphthalene-2,6-dicarboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(C(=O)O)=CC=C21 RXOHFPCZGPKIRD-UHFFFAOYSA-N 0.000 description 6
- CQRBMEAOKCDBEA-UHFFFAOYSA-N octan-2-yl formate Chemical compound CCCCCCC(C)OC=O CQRBMEAOKCDBEA-UHFFFAOYSA-N 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000004817 gas chromatography Methods 0.000 description 5
- NZZGQZMNFCTNAM-UHFFFAOYSA-N naphthalene-2,6-dicarbonyl chloride Chemical compound C1=C(C(Cl)=O)C=CC2=CC(C(=O)Cl)=CC=C21 NZZGQZMNFCTNAM-UHFFFAOYSA-N 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- WVDRSXGPQWNUBN-UHFFFAOYSA-N 4-(4-carboxyphenoxy)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=C(C(O)=O)C=C1 WVDRSXGPQWNUBN-UHFFFAOYSA-N 0.000 description 4
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 4
- ZKXGEOSWQSVEBT-UHFFFAOYSA-N 4-[2-(4-carbonochloridoylphenyl)ethenyl]benzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1C=CC1=CC=C(C(Cl)=O)C=C1 ZKXGEOSWQSVEBT-UHFFFAOYSA-N 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N Benzylformate Chemical compound O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- QDFYVTOORDKWQY-UHFFFAOYSA-M 1-(chloromethylidene)piperidin-1-ium;chloride Chemical compound [Cl-].ClC=[N+]1CCCCC1 QDFYVTOORDKWQY-UHFFFAOYSA-M 0.000 description 3
- MFIOEEWGBMJNGG-UHFFFAOYSA-N 1-(dichloromethyl)-4-fluorobenzene Chemical compound FC1=CC=C(C(Cl)Cl)C=C1 MFIOEEWGBMJNGG-UHFFFAOYSA-N 0.000 description 3
- CNDHHGUSRIZDSL-UHFFFAOYSA-N 1-chlorooctane Chemical compound CCCCCCCCCl CNDHHGUSRIZDSL-UHFFFAOYSA-N 0.000 description 3
- QNVRIHYSUZMSGM-LURJTMIESA-N 2-Hexanol Natural products CCCC[C@H](C)O QNVRIHYSUZMSGM-LURJTMIESA-N 0.000 description 3
- OSUWBBMPVXVSOA-UHFFFAOYSA-N 4-(4-carbonochloridoylphenoxy)benzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1OC1=CC=C(C(Cl)=O)C=C1 OSUWBBMPVXVSOA-UHFFFAOYSA-N 0.000 description 3
- QDBOAKPEXMMQFO-UHFFFAOYSA-N 4-(4-carbonochloridoylphenyl)benzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1C1=CC=C(C(Cl)=O)C=C1 QDBOAKPEXMMQFO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000006170 formylation reaction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- QQZOPKMRPOGIEB-UHFFFAOYSA-N n-butyl methyl ketone Natural products CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 3
- AVBRYQRTMPHARE-UHFFFAOYSA-N octyl formate Chemical compound CCCCCCCCOC=O AVBRYQRTMPHARE-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011085 pressure filtration Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- YZBBUYKPTHDZHF-KNVGNIICSA-N (3R)-7,2'-dihydroxy-4'-methoxyisoflavanol Chemical compound OC1=CC(OC)=CC=C1[C@H]1C(O)C2=CC=C(O)C=C2OC1 YZBBUYKPTHDZHF-KNVGNIICSA-N 0.000 description 2
- DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 2
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 2
- PTDNHYVEBIHJBK-UHFFFAOYSA-M 2-chloro-1,3-dimethylimidazol-1-ium;chloride Chemical compound [Cl-].CN1C=C[N+](C)=C1Cl PTDNHYVEBIHJBK-UHFFFAOYSA-M 0.000 description 2
- GLCIPJOIEVLTPR-UHFFFAOYSA-N 2-chlorohexane Chemical compound CCCCC(C)Cl GLCIPJOIEVLTPR-UHFFFAOYSA-N 0.000 description 2
- HKDCIIMOALDWHF-UHFFFAOYSA-N 2-chlorooctane Chemical compound CCCCCCC(C)Cl HKDCIIMOALDWHF-UHFFFAOYSA-N 0.000 description 2
- NEQFBGHQPUXOFH-UHFFFAOYSA-N 4-(4-carboxyphenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(C(O)=O)C=C1 NEQFBGHQPUXOFH-UHFFFAOYSA-N 0.000 description 2
- NPDACUSDTOMAMK-UHFFFAOYSA-N 4-Chlorotoluene Chemical compound CC1=CC=C(Cl)C=C1 NPDACUSDTOMAMK-UHFFFAOYSA-N 0.000 description 2
- SBBQDUFLZGOASY-OWOJBTEDSA-N 4-[(e)-2-(4-carboxyphenyl)ethenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1\C=C\C1=CC=C(C(O)=O)C=C1 SBBQDUFLZGOASY-OWOJBTEDSA-N 0.000 description 2
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- NTBCZVBVNOMMQG-UHFFFAOYSA-M chloromethylidene(diethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)=CCl NTBCZVBVNOMMQG-UHFFFAOYSA-M 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000022244 formylation Effects 0.000 description 2
- 108010023700 galanin-(1-13)-bradykinin-(2-9)-amide Proteins 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 2
- 238000004065 wastewater treatment Methods 0.000 description 2
- RLRHXLXCAWJBGX-UHFFFAOYSA-N 2-chloro-1,3-dimethyl-1,2-dihydroimidazol-1-ium;chloride Chemical compound [Cl-].CN1C=C[NH+](C)C1Cl RLRHXLXCAWJBGX-UHFFFAOYSA-N 0.000 description 1
- IWOQTFYRWHFGMU-UHFFFAOYSA-N 3-[2-(4-carboxyphenyl)ethenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C=CC1=CC=CC(C(O)=O)=C1 IWOQTFYRWHFGMU-UHFFFAOYSA-N 0.000 description 1
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 0 CC(C(C)(C)CC(C)(C)*)OC(C)N(C)C Chemical compound CC(C(C)(C)CC(C)(C)*)OC(C)N(C)C 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 101100010166 Mus musculus Dok3 gene Proteins 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- UWMLSXCBFHQUTH-UHFFFAOYSA-M [chloro(dimethylamino)methylidene]-dimethylazanium;chloride Chemical compound [Cl-].CN(C)C(Cl)=[N+](C)C UWMLSXCBFHQUTH-UHFFFAOYSA-M 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003965 capillary gas chromatography Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- LYZCWDIVOAXKQP-UHFFFAOYSA-N diazinan-3-one Chemical group O=C1CCCNN1 LYZCWDIVOAXKQP-UHFFFAOYSA-N 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- AQEFOGUXEVXUCT-UHFFFAOYSA-N hexan-2-yl formate Chemical compound CCCCC(C)OC=O AQEFOGUXEVXUCT-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- IMNDHOCGZLYMRO-UHFFFAOYSA-N n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1 IMNDHOCGZLYMRO-UHFFFAOYSA-N 0.000 description 1
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 1
- 238000005648 named reaction Methods 0.000 description 1
- REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- QULYNCCPRWKEMF-UHFFFAOYSA-N parachlorobenzotrifluoride Chemical compound FC(F)(F)C1=CC=C(Cl)C=C1 QULYNCCPRWKEMF-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- NDGRWYRVNANFNB-UHFFFAOYSA-N pyrazolidin-3-one Chemical group O=C1CCNN1 NDGRWYRVNANFNB-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明はイミドイルクロリド化合物の新規製造方法に関し、さらにそれを用いた各種化合物の製造方法に関する。 The present invention relates to a novel process for producing imidoyl chloride compounds, and further relates to a process for producing various compounds using the same.
イミドイルクロリド化合物は、有用な有機化合物を温和な条件下で合成する反応ツールとして知られている。その適用例は広く多岐にわたり、芳香族へのホルミル基の導入、カルボン酸から酸クロリドへの変換、アルコール類からハロゲン化炭化水素への変換、カルボン酸とアルコール類からのエステルの合成などが挙げられる。その代表的化合物としては、Ｎ，Ｎ−ジメチルクロロメチレンイミニウムクロリドがあり、これはビルスマイヤー（Ｖｉｌｓｍｅｉｅｒ）試薬と呼ばれている。非特許文献１は、この化合物を、Ｎ，Ｎ−ジメチルホルムアミド（ＤＭＦ）に、塩化チオニル、オキシ塩化リン、ホスゲン、蓚酸ジクロリド等の塩素化剤を作用させて合成する方法を開示する。近年、１，３−ジメチル−２−イミダゾリジノン（ＤＭＩ）から、同様の塩素化剤を用いて２−クロロ−１，３−ジメチルイミダゾリュームクロリドが合成された（非特許文献２参照）。これも幅広い反応に利用することができ、有用な反応ツールとなる。
しかしながら、従来イミドイルクロリド化合物を合成するために提案されている上記塩素化剤は、特殊な排ガス、排水処理設備が必要であったり、安全面で取り扱いが困難であったりする。また、工業的な生産に用いるには高価であり経済性に劣り、実際的な製造材料として広く利用されるには至っていない。
Imidoyl chloride compounds are known as reaction tools for synthesizing useful organic compounds under mild conditions. There are a wide variety of applications, including the introduction of formyl groups into aromatics, conversion of carboxylic acids to acid chlorides, conversion of alcohols to halogenated hydrocarbons, and synthesis of esters from carboxylic acids and alcohols. It is done. A typical compound is N, N-dimethylchloromethyleneiminium chloride, which is called a Vilsmeier reagent. Non-Patent Document 1 discloses a method of synthesizing this compound by reacting N, N-dimethylformamide (DMF) with a chlorinating agent such as thionyl chloride, phosphorus oxychloride, phosgene, or oxalic acid dichloride. Recently, 2-chloro-1,3-dimethylimidazolium chloride was synthesized from 1,3-dimethyl-2-imidazolidinone (DMI) using a similar chlorinating agent (see Non-Patent Document 2). This can also be used for a wide range of reactions and is a useful reaction tool.
However, the chlorinating agent proposed for synthesizing the imidoyl chloride compound conventionally requires special exhaust gas and waste water treatment equipment, or is difficult to handle in terms of safety. Moreover, it is expensive to use for industrial production, is inferior in economic efficiency, and has not been widely used as a practical manufacturing material.
最近、アルコール化合物をそのクロル化物に変換する反応において、ピバロイルクロリドとＮ，Ｎ−ジメチルホルムアミドとを反応させ、反応系内にビルスマイヤー・ハック型錯体を生成させることが提案された（非特許文献３参照）。これにより、各種のアルコール化合物をそのクロル化物に変換できるとされている。 Recently, it has been proposed to react pivaloyl chloride with N, N-dimethylformamide in a reaction to convert an alcohol compound into its chlorinated product to form a Vilsmeier-Hack complex in the reaction system (non- (See Patent Document 3). Thereby, it is said that various alcohol compounds can be converted into their chlorinated products.
上記非特許文献１及び２に開示された塩素化剤であるオキシ塩化リンを使うと燐の排水処理が問題となる。塩化チオニルを使うと二酸化硫黄の排ガス処理設備が必要となる。ホスゲンを使用するには安全上の対策が必須であり、蓚酸ジクロイドは非常に高価であり汎用原料として使用するには難がある。これに対し非特許文献３に開示された方法によれば、アルコール化合物のクロル化反応において上記の塩素化剤を用いる必要はなくなる。しかし、本発明者の確認によると、この反応を通じてビルスマイヤー試薬を単離することはできなかった（後記比較例ｃ５１参照）。また、ピバロイルエステルを副生するとされるなど、そこで示された目的化合物の収率は、必ずしも高いものではなかった（同比較例ｃ５１参照）。さらに、現実的な問題点として、ピバロイルクロリドの臭気はきつく、結局、工業生産において設備上の対策が必要となってしまう。
本発明は、上記従来技術に鑑み、取扱い性に劣る塩素化剤を必要とせず、イミドイルクロリド化合物を合成する新規な製造方法、並びにこれを用い、各種化合物を高収率かつ高純度で得る製造方法の提供を目的とする。
When phosphorus oxychloride, which is a chlorinating agent disclosed in Non-Patent Documents 1 and 2 above, is used, phosphorus wastewater treatment becomes a problem. If thionyl chloride is used, an exhaust gas treatment facility for sulfur dioxide is required. In order to use phosgene, safety measures are essential, and dichroic oxalate is very expensive and difficult to use as a general-purpose raw material. On the other hand, according to the method disclosed in Non-Patent Document 3, it is not necessary to use the chlorinating agent in the chlorination reaction of the alcohol compound. However, according to the confirmation of the present inventors, the Vilsmeier reagent could not be isolated through this reaction (see Comparative Example c51 described later). In addition, the yield of the target compound shown therein was not necessarily high, such as by-producting pivaloyl ester (see Comparative Example c51). Furthermore, as a practical problem, the odor of pivaloyl chloride is severe, and eventually, measures for facilities are required in industrial production.
In view of the above prior art, the present invention does not require a chlorinating agent that is inferior in handleability, and a novel production method for synthesizing an imidoyl chloride compound, and using this, various compounds are obtained in high yield and high purity. The purpose is to provide a manufacturing method.
本発明者らは、アミド化合物にフタル酸クロリド類を塩素化剤として作用させると、相当するイミドイルクロリド化合物を合成できることを見出した。そして、本発明の方法で調製したイミドイルクロリド化合物を、従来本化合物により進行することが知られている多くの化学反応に適用し、安全かつ簡便に、しかも安価かつ高収率・高純度でその反応を達成できることを確認した。さらに、目的とする各化合物の合成反応に上記イミドイルクロリド化合物を適用するに当たり、その反応系をそのまま利用することも、イミドイルクロリド化合物を単離して用いることもでき、目的化合物の単離性等を考慮して好適な合成反応条件を選定しうることを見出した。
本発明は上記知見に基づき完成されたものであり、上記の課題は以下の手段により解決された。
The present inventors have found that when phthalic acid chlorides are allowed to act on amide compounds as chlorinating agents, the corresponding imidoyl chloride compounds can be synthesized. The imidoyl chloride compound prepared by the method of the present invention is applied to many chemical reactions that are conventionally known to proceed with the present compound, and is safe and simple, yet inexpensive, with high yield and high purity. It was confirmed that the reaction could be achieved. Furthermore, when applying the imidoyl chloride compound to the synthesis reaction of each target compound, the reaction system can be used as it is, or the imidoyl chloride compound can be isolated and used. It has been found that suitable synthesis reaction conditions can be selected in consideration of the above.
The present invention has been completed based on the above findings, and the above problems have been solved by the following means.
（１）下記一般式（１）で表されるアミド化合物と下記一般式（２）で表されるフタル酸クロリド化合物を反応させ、下記一般式（３）で表されるイミドイルクロリド化合物を生成させるイミドイルクロリド化合物の製造方法。 (1) The amide compound represented by the following general formula (1) is reacted with the phthalic acid chloride compound represented by the following general formula (2) to produce an imidoyl chloride compound represented by the following general formula (3). A method for producing an imidoyl chloride compound.
（２）一般式（１）で表される化合物が、Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチル尿素、または１，３−ジメチル−２−イミダゾリジノンであり、一般式（２）で表される化合物がフタル酸クロリドである（１）に記載のイミドイルクロリド化合物の製造方法。
（３）前記生成した一般式（３）で表されるイミドイルクロリド化合物をエーテル系溶媒で処理し、無水フタル酸化合物を取り除き、イミドイルクロリド化合物を結晶として取り出す（１）又は（２）に記載のイミドイルクロリド化合物の製造方法。
（４）前記エーテル系溶媒が、１，４−ジオキサン、テトラヒドロフラン、及び１，２−ジメトキシエタンから選ばれる（３）記載のイミドイルクロリド化合物の製造方法。
（５）前記生成した一般式（３）で表されるイミドイルクロリド化合物をトルエン化合物と一般式（１）で表されるアミド化合物の混合溶媒で処理し、無水フタル酸化合物を取り除き、イミドイルクロリド化合物を結晶として取り出す（１）又は（２）に記載のイミドイルクロリド化合物の製造方法。
（６）前記（１）〜（５）のいずれか１項に記載の製造方法で得たイミドイルクロリド化合物を単離し、または単離せずに、あるいは前記イミドイルクロリド化合物の生成の際に、酸素原子を含む有機化合物と接触させ、脱酸素クロル化の反応をさせる脱酸素クロル化生成物の製造方法であって、
前記酸素原子を含む有機化合物が、カルボン酸化合物、アルコール化合物、又はアルデヒド化合物である製造方法。
（７）前記請求項１〜５のいずれか１項に記載の製造方法で得たイミドイルクロリド化合物を単離し、または単離せずに、あるいは前記イミドイルクロリド化合物の生成の際に、電子豊富な芳香族化合物と反応させ、加水分解し芳香核にホルミル基を導入するホルミル基保有芳香族化合物の製造方法。
(2) The compound represented by the general formula (1) is N, N-dimethylformamide, N, N, N ′, N′-tetramethylurea, or 1,3-dimethyl-2-imidazolidinone. The method for producing an imidoyl chloride compound according to (1), wherein the compound represented by the general formula (2) is phthalic acid chloride.
(3) The generated imidoyl chloride compound represented by the general formula (3) is treated with an ether solvent, the phthalic anhydride compound is removed, and the imidoyl chloride compound is taken out as crystals (1) or (2) The manufacturing method of the imidoyl chloride compound of description.
(4) The method for producing an imidoyl chloride compound according to (3), wherein the ether solvent is selected from 1,4-dioxane, tetrahydrofuran, and 1,2-dimethoxyethane.
(5) The imidoyl chloride compound represented by the general formula (3) is treated with a mixed solvent of a toluene compound and an amide compound represented by the general formula (1) to remove the phthalic anhydride compound, and imidoyl The manufacturing method of the imidoyl chloride compound as described in (1) or (2) which takes out a chloride compound as a crystal | crystallization.
(6) The imidoyl chloride compound obtained by the production method according to any one of (1) to (5) is isolated or not isolated, or when the imidoyl chloride compound is produced. A method for producing a deoxygenated chlorinated product, which is brought into contact with an organic compound containing an oxygen atom to cause a deoxygenated chlorination reaction ,
The manufacturing method whose organic compound containing the said oxygen atom is a carboxylic acid compound, an alcohol compound, or an aldehyde compound.
( 7 ) The abundance of electrons when the imidoyl chloride compound obtained by the production method according to any one of claims 1 to 5 is isolated or not isolated, or when the imidoyl chloride compound is produced. A method for producing an aromatic compound having a formyl group, which comprises reacting with an aromatic compound, hydrolyzing it, and introducing a formyl group into an aromatic nucleus.
本発明の製造方法によれば、取扱い性に劣る塩素化剤を必要とせずに、環境負荷の少ない方法でイミドイルクロリド化合物を合成することができる。また、その反応系内で、あるいはこれを単離して用い、各種化合物を高収率かつ高純度で製造することができる。 According to the production method of the present invention, an imidoyl chloride compound can be synthesized by a method having a low environmental load without requiring a chlorinating agent having poor handleability. In addition, various compounds can be produced in high yield and high purity by using them in the reaction system or by isolating them.
［イミドイルクロリド化合物の製造］
本発明の製造方法においては、アミド化合物をフタル酸クロリド化合物と反応させイミドイルクロリド化合物に変換する。必要によりその反応場を所定の塩素化ないしホルミル化反応に適用したり、イミドイルクロリド化合物を単離して上記反応に供することができる。その結果、本発明によれば、従来用いられてきたホスゲン、オキシ塩化リン、塩化チオニル、蓚酸ジクロリドなどの塩素化剤に代えて、安全で安価なフタル酸クロリド化合物を用いることができ、これまで難しかったイミドイルクロリド化合物の合成ないしこれを利用した反応生成物の工業的規模での生産に好適に対応することができる。このような顕著な効果を達成した理由は一部推定を含むが下記のように説明することができる。
[Production of imidoyl chloride compound]
In the production method of the present invention, an amide compound is reacted with a phthalic acid chloride compound to convert it to an imidoyl chloride compound. If necessary, the reaction field can be applied to a predetermined chlorination or formylation reaction, or an imidoyl chloride compound can be isolated and subjected to the above reaction. As a result, according to the present invention, a safe and inexpensive phthalic acid chloride compound can be used instead of the chlorinating agents such as phosgene, phosphorus oxychloride, thionyl chloride, and oxalic acid dichloride which have been conventionally used. It is possible to suitably cope with the synthesis of imidoyl chloride compounds, which have been difficult, or the production of reaction products using the compounds on an industrial scale. The reason for achieving such a remarkable effect partially includes estimation, but can be explained as follows.
例えば、ホスゲンなどに比べ取り扱いやすい塩素化剤として、上記特許文献３のようにピバロイルクロリドを用いることが挙げられる。これにより、所定のイミドイルクロリド化合物を系内に生成させることはできるが、対イオンとしてピバロイルアニオンが残り、イミドイルクロリド化合物を単離することは極めて難しい（下記スキーム１参照）。上記イミドイルクロリド化合物（カチオン）が生成した反応場を利用し、そこに反応基質を導入して塩素化やホルミル化を行うことも考えられるが、イミドイルクロリド化合物の生成反応自体が平衡状態にあるため（下式）、収率の向上には自ずと限界がある（後記比較例ｃ５１参照）。 For example, as a chlorinating agent that is easier to handle than phosgene or the like, pivaloyl chloride is used as in Patent Document 3 above. Thereby, although a predetermined imidoyl chloride compound can be produced in the system, the pivaloyl anion remains as a counter ion, and it is extremely difficult to isolate the imidoyl chloride compound (see Scheme 1 below). Although it is conceivable to use the reaction field generated by the imidoyl chloride compound (cation) and introduce a reaction substrate into it to perform chlorination or formylation, the imidoyl chloride compound formation reaction itself is in an equilibrium state. Therefore, the yield is naturally limited (see Comparative Example c51 below).
一方、オルト位に酸クロリド（クロロカルボニル基）を２個持つフタル酸クロリドを利用する本発明では、ＤＭＦとの反応で平衡が圧倒的に右辺（反応生成物側）に片寄り、系内の反応生成物がイミドイルクロリド化合物（Ｖｉｌｓｍｅｉｅｒ試薬）と無水フタル酸になる方向となる。結果として、カルボキシアニオンが多量に残留して阻害することがなく、必要により、イミドイルクロリド化合物の結晶を析出させ単離することができる。無水フタル酸を溶かす溶媒としてエーテル系溶媒等を用い、高純度のイミドイルクロリド化合物を取得することも可能である。さらに、無水フタル酸になると、系内での逆反応が起こりにくく、その反応場を利用して塩素化ないしホルミル化を進行させる際にも高い収率を実現することができる。 On the other hand, in the present invention using a phthalic acid chloride having two acid chlorides (chlorocarbonyl groups) in the ortho position, the equilibrium is overwhelmingly shifted to the right side (reaction product side) due to the reaction with DMF. The reaction product becomes an imidoyl chloride compound (Vilsmeier reagent) and phthalic anhydride. As a result, a large amount of carboxy anion remains and does not inhibit, and if necessary, crystals of imidoyl chloride compound can be precipitated and isolated. It is also possible to obtain a high-purity imidoyl chloride compound using an ether solvent or the like as a solvent for dissolving phthalic anhydride. Furthermore, when phthalic anhydride is obtained, a reverse reaction hardly occurs in the system, and a high yield can be achieved when chlorination or formylation is advanced using the reaction field.
以下、本発明について、その好ましい実施態様に基づき詳細に説明する。なお、本明細書において＊＊＊化合物というときには、＊＊＊で定義付けられる化合物の総称を意味し、その塩あるいはイオン等を含む意味である。 Hereinafter, the present invention will be described in detail based on preferred embodiments thereof. In the present specification, the term “*** compound” means a generic name of compounds defined by ***, and includes a salt or ion thereof.
・フタル酸クロリド化合物
本発明で用いられるフタル酸クロリド化合物はその置換基が反応に影響しないものならば特に制限はないが、無水フタル酸から既存の方法で調製できる無置換のフタル酸クロリドを用いることが安価で好ましい。具体的には、上記一般式（２）で表される化合物を用いる。一般式（２）中、Ｘは、水素原子、ハロゲン原子、又は炭素数１〜４のアルキル基を表し、塩素原子、臭素原子、メチル基、エチル基であることが好ましく、水素原子、塩素原子、メチル基であることがより好ましい。ｎは１〜４の整数を表す。
-Phthalic acid chloride compound The phthalic acid chloride compound used in the present invention is not particularly limited as long as the substituent does not affect the reaction, but an unsubstituted phthalic acid chloride prepared by an existing method from phthalic anhydride is used. It is cheap and preferable. Specifically, the compound represented by the general formula (2) is used. In the general formula (2), X represents a hydrogen atom, a halogen atom, or an alkyl group having a carbon number of 1-4, a chlorine atom, a bromine atom, a methyl group, an ethyl group, more preferably a hydrogen atom, a chlorine More preferred are an atom and a methyl group. n represents an integer of 1 to 4.
・アミド化合物
アミド化合物にも構造的な制限はないが、ホスゲン等を用いる数多くの例が知られており、それらのいずれにも適応できる。本実施態様においては、上記一般式（１）で表される化合物を用いる。一般式（１）中、Ｒ１及びＲ２は、それぞれ独立に、水素原子、アルキル基、アリール基、又はアラルキル基を表す。このときのアルキル基としては、メチル基、エチル基、イソプロピル基であることが好ましく、メチル基であることがより好ましい。アリール基としては、フェニル基、置換フェニル基であることが好ましく、フェニル基、４−クロロフェニル基、４−メチルフェニル基であることがより好ましい。アラルキル基としては、ベンジル基、置換ベンジル基であることが好ましく、ベンジル基であることがより好ましい。
Ｒ３は、水素原子、アルキル基、アリール基又は置換アミノ基を表す。このときアルキル基としては、メチル基、エチル基、第３ブチル基であることが好ましく、メチル基であることがより好ましい。アリール基としてはフェニル基が好ましい。置換アミノ基としては、ジメチルアミノ基、モノメチルアミノ基、フェニルメチルアミノ基であることが好ましく、ジメチルアミノ基であることがより好ましい。
Ｒ１またはＲ２とＲ３とは環状構造を形成していてもよい。環状構造としては、ピペリジン環、ピロリジン環、アザシクロペンタノン環、ジアザシクロペンタノン環、ジアザシクロヘキサノン環などの構造が挙げられる。
-Amide compound Although there is no structural limitation also in an amide compound, many examples using phosgene etc. are known, and it can apply to all of them. In this embodiment, the compound represented by the general formula (1) is used. In General Formula (1), R 1 and R 2 each independently represent a hydrogen atom, an alkyl group, an aryl group, or an aralkyl group. In this case, the alkyl group is preferably a methyl group, an ethyl group, or an isopropyl group, and more preferably a methyl group. The aryl group is preferably a phenyl group or a substituted phenyl group, and more preferably a phenyl group, a 4-chlorophenyl group, or a 4-methylphenyl group. The aralkyl group is preferably a benzyl group or a substituted benzyl group, and more preferably a benzyl group.
R 3 represents a hydrogen atom, an alkyl group, an aryl group, or a substituted amino group. In this case, the alkyl group is preferably a methyl group, an ethyl group, or a tertiary butyl group, and more preferably a methyl group. The aryl group is preferably a phenyl group. The substituted amino group is preferably a dimethylamino group, a monomethylamino group, or a phenylmethylamino group, and more preferably a dimethylamino group.
R 1 or R 2 and R 3 may form a cyclic structure. Examples of the cyclic structure include structures such as a piperidine ring, a pyrrolidine ring, an azacyclopentanone ring, a diazacyclopentanone ring, and a diazacyclohexanone ring.
代表的なアミド化合物を例示すると、Ｎ−メチルホルムアミド、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）、Ｎ，Ｎ−ジエチルホルムアミド、Ｎ，Ｎ−ジイソプロピルピバロイルアミド、１，３−ジメチル−２−イミダゾリジノン（ＤＭＩ）、Ｎ，Ｎ、Ｎ’，Ｎ’−テトラメチル尿素（ＴＭＵ）、Ｎ−メチルピロリドン（ＮＭＰ）、Ｎ−ホルミルピペリジン等が挙げられる。なかでも、Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジエチルホルムアミド、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチル尿素、Ｎ―ホルミルピペリジンまたは１，３−ジメチル−２−イミダゾリジノンが好ましい。 Examples of representative amide compounds include N-methylformamide, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N, N-diethylformamide, N, N-diisopropylpivaloylamide. 1,3-dimethyl-2-imidazolidinone (DMI), N, N, N ′, N′-tetramethylurea (TMU), N-methylpyrrolidone (NMP), N-formylpiperidine and the like. Among these, N, N-dimethylformamide, N, N-diethylformamide, N, N, N ′, N′-tetramethylurea, N-formylpiperidine or 1,3-dimethyl-2-imidazolidinone is preferable.
・反応温度等
フタル酸クロリド化合物とアミド化合物とを等モル量で混合すると、相当するイミドイルクロリド化合物と無水フタル酸誘導体（無水フタル酸化合物）を生成するように速やかに反応が進行する。その反応は基質により室温（約２０℃）〜１５０℃の範囲で行うことができる。Ｎ−メチルホルムアミド、Ｎ，Ｎ−ジメチルホルムアミド（ＤＭＦ）のようなホルムアミド化合物の場合には室温から５０℃の間で反応を行うことが好ましい。ＤＭＡＣ，ＤＭＩ，ＴＭＵのようなケトンタイプのアミド化合物では１００〜１５０℃で反応することが好ましい。
フタル酸クロリド化合物とアミド化合物との供給比率は特に限定されないが、実際的な条件を考慮すると、フタル酸クロリド化合物に対して、単離する場合にはアミド化合物を１〜１０当量とすることが好ましい。単離しない場合には０．０１〜１当量とすることが好ましい。
-Reaction temperature, etc. When the phthalic acid chloride compound and the amide compound are mixed in equimolar amounts, the reaction proceeds rapidly so as to produce a corresponding imidoyl chloride compound and a phthalic anhydride derivative (phthalic anhydride compound). The reaction can be carried out at room temperature (about 20 ° C.) to 150 ° C. depending on the substrate. In the case of a formamide compound such as N-methylformamide and N, N-dimethylformamide (DMF), the reaction is preferably carried out between room temperature and 50 ° C. For ketone type amide compounds such as DMAC, DMI, and TMU, it is preferable to react at 100 to 150 ° C.
The supply ratio of the phthalic acid chloride compound and the amide compound is not particularly limited, but considering practical conditions, the amide compound may be 1 to 10 equivalents in the case of isolation with respect to the phthalic acid chloride compound. preferable. When not isolated, it is preferably 0.01 to 1 equivalent.
・反応溶媒
イミドイルクロリド化合物は通常固体となるため、反応変化が目視で観測できる。後の反応に用いることを考慮して、イミドイルクロリド化合物の調製には溶媒を用いてもよいし、アミド化合物を溶媒と兼用したものとして用いてもよい。それらの場合、均一溶液あるいはスラリー状態となり、後の塩素化反応に好都合の形態となる。溶媒を用いる場合は特に制限はないが無水であることが好ましい。水があると、フタル酸クロリド化合物が加水分解されてしまう。それらの例として、ＤＭＦ，ＤＭＡＣ，ＤＭＩ、ＮＭＰ以外に、１，２−ジメトキシエタン、ジグライム、１，４−ジオキサン、エーテル、テトラヒドロフラン，テトラヒドロピラン、トルエン、キシレン、クロロトルエン、塩化ベンゾイル等が挙げられる。
-Reaction solvent Since imidoyl chloride compounds are usually solid, reaction changes can be observed visually. In consideration of use in the subsequent reaction, a solvent may be used for the preparation of the imidoyl chloride compound, or an amide compound may also be used as a solvent. In those cases, it becomes a homogeneous solution or a slurry state, and becomes a convenient form for the subsequent chlorination reaction. When a solvent is used, there is no particular limitation, but it is preferably anhydrous. If there is water, the phthalic acid chloride compound is hydrolyzed. Examples thereof include DMF, DMAC, DMI, NMP, 1,2-dimethoxyethane, diglyme, 1,4-dioxane, ether, tetrahydrofuran, tetrahydropyran, toluene, xylene, chlorotoluene, benzoyl chloride, and the like. .
［各種化合物の製造］
本発明の応用に係る実施態様として、上記の方法で調製したイミドイルクロリド化合物の合成反応場を、あるいはこれを単離したものを、従来知られている各種化合物の合成反応に提供することが挙げられる。その化学反応の例として、電子豊富なベンゼン核へのホルミル基の導入、カルボン酸から酸クロリドへの変換、アルコールから塩化物への変換、酸とアルコールからエステルの合成、アルデヒド基をジクロロメチル基へ変換などが挙げられ、幅広く適用できる。上記の公知の反応について説明された文献として、Ｍａｒｓｏｎ，Ｃ．Ｍ ，Ｔｅｔｒａｈｅｄｒｏｎ １９９２年，４８巻，３６５９頁 （前記非特許文献１）、Ｉｓｏｂｅ，Ｔ．＆Ｉｓｈｉｋａｗａ，Ｔ．Ｊ．Ｏｒｇ．Ｃｈｅｍ．１９９９年，６４巻，６９８４頁、６９８９頁、５８３２頁（前記非特許文献２）、Ｆｉｅｓｅｒ＆Ｆｉｅｓｅｒ、Ｒｅａｇｅｎｔ ｏｆ Ｏｒｇａｎｉｃ Ｓｙｎｔｈｅｓｉｓ（Ａ Ｗｉｌｅｙ Ｉｎｔｅｒｓｃｉｅｎｃｅ Ｐｕｂｌｉｃａｔｉｏｎ）４巻１８６頁，７巻４２２頁、Ｂｅｉｌｓｔｅｉｎ ４巻第ＩＶ増補版１７５頁、富岡清監訳、人名反応に学ぶ有機合成戦略（化学同人 ２００６年刊）４６８頁などが挙げられる。
ここで「電子豊富なベンゼン核」とは、電子供与基を置換基に持つベンゼン核という意味であり、その核をもつ芳香族に属する化合物を「電子豊富な芳香族化合物」という。電子豊富な芳香族化合物としては、例えばアニソール、ジメチルアミノベンゼン、１，２−ジメトキシベンゼン、１，３−ジメトキシベンゼン、１，２，３−トリメトキシベンゼン１，２―メチレンジオキシベンゼン等が挙げられる。
[Manufacture of various compounds]
As an embodiment according to the application of the present invention, a synthetic reaction field of imidoyl chloride compound prepared by the above method or an isolated one thereof can be provided for synthesis reactions of various known compounds. Can be mentioned. Examples of chemical reactions include the introduction of formyl groups into electron-rich benzene nuclei, conversion of carboxylic acids to acid chlorides, conversion of alcohols to chlorides, synthesis of esters from acids and alcohols, aldehyde groups to dichloromethyl groups Can be applied widely. References describing the above known reactions include Marson, C .; M, Tetrahedron 1992, 48, 3659 (Non-Patent Document 1), Isobe, T .; & Ishikawa, T .; J. et al. Org. Chem. 1999, 64, 6984, 6989, 5832 (Non-Patent Document 2), Fieser & Fieser, Reagent of Organic Synthesis (A Wiley Interscience Publication) 4 186, 7 422, Supplement to Beilstein 4 175 pages, translation by Kiyoshi Tomioka, organic synthesis strategy learned from personal name reaction (Chemical Doujin 2006), page 468.
Here, the “electron-rich benzene nucleus” means a benzene nucleus having an electron donating group as a substituent, and an aromatic compound having the nucleus is called an “electron-rich aromatic compound”. Examples of the electron-rich aromatic compound include anisole, dimethylaminobenzene, 1,2-dimethoxybenzene, 1,3-dimethoxybenzene, 1,2,3-trimethoxybenzene 1,2-methylenedioxybenzene and the like. It is done.
・イミドイルクロリド化合物の合成反応場をそのまま利用する態様
本実施態様においては、アミド化合物とフタル酸クロリド化合物とを用いてイミドイルクロリド化合物を合成する反応場を、そのまま各種化合物の生成等の反応に利用する。この場合、反応生成物中には無水フタル酸誘導体が副生し共存することとなるが、適当な溶媒を用いると溶解度の差により目的化合物を選択的に晶析させることができる。あるいは、目的化合物が液体の場合、蒸留により目的物を分離する方法を採用することが好ましい。また、目的化合物がアルカリ性水溶液により変化を受けない化合物である場合には、炭酸ナトリウム水溶液等のアルカリ水で処理すると無水フタル酸化合物が開環してナトリウム塩となり水層に溶解するので、目的化合物を有機溶媒で抽出する方法を採用することもできる。
分離した無水フタル酸誘導体は通常の有機化合物として廃棄することもできるし、既存の方法によってフタル酸クロリド誘導体に変換し再使用することもできる。このように、本実施態様の方法は、それ自体の安全性、有用性があるのみならず、副生物のリサイクルをも考慮した環境適合型のイミドイルクロリド化合物とそれらを用いる反応形態としても意義を有する。
A mode in which the synthesis reaction field of an imidoyl chloride compound is used as it is In this embodiment, a reaction field for synthesizing an imidoyl chloride compound by using an amide compound and a phthalic acid chloride compound is used as a reaction for generating various compounds. To use. In this case, the phthalic anhydride derivative is by-produced and coexists in the reaction product, but the target compound can be selectively crystallized by the difference in solubility when an appropriate solvent is used. Alternatively, when the target compound is a liquid, it is preferable to employ a method of separating the target product by distillation. In addition, when the target compound is a compound that is not affected by the alkaline aqueous solution, the phthalic anhydride compound opens to form a sodium salt and dissolves in the aqueous layer when treated with alkaline water such as an aqueous sodium carbonate solution. It is also possible to employ a method of extracting with an organic solvent.
The separated phthalic anhydride derivative can be discarded as a normal organic compound, or can be converted to a phthalic chloride derivative and reused by an existing method. As described above, the method of this embodiment is not only safe and useful in itself, but also significant as an environmentally compatible imidoyl chloride compound that takes into account recycling of by-products and a reaction form using them. Have
イミドイルクロリド化合物は次工程の反応（これを適用した各種化合物の合成反応）により元のアミド化合物に変化する。従って、フタル酸クロリド化合物と次工程で反応させる基質の中に触媒量のアミド化合物を加えると、反応系内でイミドイルクロリドに変化しながら次工程の反応を行うことができる。その場合、定法により無水フタル酸化合物を分離すれば目的の化合物が高収率で得られる。 The imidoyl chloride compound changes to the original amide compound by the reaction in the next step (synthesis reaction of various compounds to which this is applied). Therefore, when a catalytic amount of an amide compound is added to the substrate to be reacted with the phthalic acid chloride compound in the next step, the reaction in the next step can be performed while changing to imidoyl chloride in the reaction system. In that case, the target compound can be obtained in high yield by separating the phthalic anhydride compound by a conventional method.
すなわち、本発明においては、上記の手順で得たイミドイルクロリド化合物を単離し、または単離せずに、あるいは前記イミドイルクロリド化合物の生成の際に、酸素原子を含む有機化合物と接触させ、脱酸素クロル化反応を進行させる実施態様が好ましい。あるいは、上記の手順で得たイミドイルクロリド化合物を単離し、または単離せずに、あるいは前記イミドイルクロリド化合物の生成の際に、電子豊富な芳香族化合物と反応させ、加水分解し芳香核にホルミル基を導入する実施態様が好ましい。特に、上記イミドイルクロリドの生成を無溶媒で行うようなときには、これを単離することが難しい場合があり、本実施態様を好適に用いて所望の反応を行うことができる。 That is, in the present invention, the imidoyl chloride compound obtained by the above procedure is isolated or not isolated, or in the production of the imidoyl chloride compound, it is contacted with an organic compound containing an oxygen atom to remove it. Embodiments in which the oxygen chlorination reaction proceeds are preferred. Alternatively, the imidoyl chloride compound obtained by the above procedure is isolated or not isolated, or in the production of the imidoyl chloride compound, it is reacted with an electron-rich aromatic compound and hydrolyzed to form an aromatic nucleus. Embodiments in which formyl groups are introduced are preferred. In particular, when the above-mentioned imidoyl chloride is produced without a solvent, it may be difficult to isolate it, and this embodiment can be suitably used to carry out a desired reaction.
・イミドイルクロリド化合物を単離して利用する態様
本実施態様は、アミド化合物とフタル酸クロリド化合物から合成したイミドイルクロリド化合物と無水フタル酸化合物の混合物から、イミドイルクロリド化合物を単離する方法、並びにこれを目的の化合物の合成等の反応に適用することに関する。上記で述べたように無水フタル酸化合物は通常、次工程の塩素化反応に関与しないので、そのままの形で残るが生成物が固体である場合にはそれらの分離に手間がかかったり、収量ロスしたりする。そうした場合には、あらかじめ無水フタル酸化合物が混入していない純粋なイミドイルクロリド化合物を用いることが好ましい。
本実施態様によれば、イミドイルクロリド化合物と無水フタル酸化合物の混合物にエーテル系溶媒またはＢＴＸ化合物（ベンゼン、トルエン、キシレンのほか、そのハロゲン置換体を含む。）を用いると無水フタル酸化合物が溶媒に溶解するので、簡単なろ過操作で純粋なイミドイルクロリド化合物を結晶として単離することができる。エーテル系化合物の例としてジエチルエーテル、ジイソプロピルエーテル、テトラヒドロフラン、テトラヒドロピラン、１，４−ジオキサン、１，２−ジメトキシエタン、ジグライム、シクロペンチルメチルエーテルなどを挙げることができるが、中でもテトラヒドロフラン、１，４−ジオキサン、１，２−ジメトキシエタンが無水フタル酸を良く溶かすので好ましい。ＢＴＸ化合物としてはトルエン、パラクロロトルエン、オルトクロロトルエン、クロロベンゼン、キシレンなどが挙げられる。このとき、溶解度の調整のために一般式（１）で表されるアミド化合物を混合して用いることもできる。溶媒の選定に当たっては、無水フタル酸がよく溶解してイミドイルクロリドが不溶なものほど好ましい。溶解度で規定をするならば、２５℃で無水フタル酸を１０％以上溶解する溶媒が好ましく、１５％以上ならばより好ましく、２０％以上ならばさらに好ましい。
Embodiment in which an imidoyl chloride compound is isolated and used This embodiment is a method for isolating an imidoyl chloride compound from a mixture of an imidoyl chloride compound and a phthalic anhydride compound synthesized from an amide compound and a phthalic chloride compound, In addition, the present invention relates to application of the compound to a reaction such as synthesis of a target compound. As mentioned above, phthalic anhydride compounds usually do not participate in the chlorination reaction in the next step, so they remain as they are, but when the product is a solid, it takes time to separate them and yield loss. To do. In such a case, it is preferable to use a pure imidoyl chloride compound in which a phthalic anhydride compound is not mixed in advance.
According to this embodiment, when an ether solvent or a BTX compound (including benzene, toluene, xylene and its halogen substitution product) is used in a mixture of an imidoyl chloride compound and a phthalic anhydride compound, the phthalic anhydride compound is obtained. Since it dissolves in a solvent, a pure imidoyl chloride compound can be isolated as crystals by a simple filtration operation. Examples of ether compounds include diethyl ether, diisopropyl ether, tetrahydrofuran, tetrahydropyran, 1,4-dioxane, 1,2-dimethoxyethane, diglyme, cyclopentyl methyl ether, etc. Among them, tetrahydrofuran, 1,4- Dioxane and 1,2-dimethoxyethane are preferred because they dissolve phthalic anhydride well. Examples of the BTX compound include toluene, parachlorotoluene, orthochlorotoluene, chlorobenzene, xylene and the like. At this time, the amide compound represented by the general formula (1) can be mixed and used for adjusting the solubility. In selecting the solvent, it is preferable that phthalic anhydride dissolves well and imidoyl chloride is insoluble. If the solubility is specified, a solvent that dissolves 10% or more of phthalic anhydride at 25 ° C. is preferable, more preferably 15% or more, and still more preferably 20% or more.
具体例としていえば、その使用量は２５℃〜４０℃の間で４〜７重量倍用いると無水フタル酸化合物を完全に溶解できることを溶解度試験により明らかとした。また、その量におけるイミドイルクロリド化合物の溶解度は１％以下であることも併せて確認した。代表的な例を示すと、５重量倍の１，４−ジオキサン中ＤＭＦとフタル酸クロリドを等モル混合し室温〜４０℃で攪拌すると次第に結晶が析出してくる。析出した結晶はほぼ純粋なＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドであり、無水フタル酸は１，４−ジオキサンに溶解していた。イミドイルクロリド化合物は吸湿性であるので、空気を遮断しながら窒素で加圧ろ過する方法で単離することが好ましい。あるいは、オルトクロロトルエン４重量倍とＤＭＦ１重量倍の混合溶媒を用いると３５〜４０℃で無水フタル酸を完全に溶解することができるので、ほぼ純粋なＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドを簡単なろ過により結晶として単離することができる。
得られた結晶はそのまま用いることもできるし、乾燥して用いることもできる。このようにして得られたＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶はほぼ純品であるので、例えば、等モルの基質と適当な溶媒の中で室温（２０℃）〜６０℃で攪拌すると容易に次工程の塩素化反応が進行し、簡単なろ過により高純度の塩素化合物が高収率で得られる。
As a specific example, the solubility test revealed that the phthalic anhydride compound can be completely dissolved when used in an amount of 4 to 7 times by weight between 25 ° C. and 40 ° C. It was also confirmed that the solubility of the imidoyl chloride compound in that amount was 1% or less. As a typical example, when equimolar mixing of 5 times by weight of DMF and phthalic acid chloride in 1,4-dioxane and stirring at room temperature to 40 ° C., crystals gradually precipitate. The precipitated crystals were almost pure N, N-dimethylchloromethyleneiminium chloride, and phthalic anhydride was dissolved in 1,4-dioxane. Since the imidoyl chloride compound is hygroscopic, it is preferably isolated by a method of pressure filtration with nitrogen while blocking air. Alternatively, when a mixed solvent of 4 times by weight of orthochlorotoluene and 1 times by weight of DMF can be used to completely dissolve phthalic anhydride at 35 to 40 ° C., almost pure N, N-dimethylchloromethyleneiminium chloride can be obtained. It can be isolated as crystals by simple filtration.
The obtained crystal can be used as it is, or can be used after drying. Since the crystals of N, N-dimethylchloromethyleneiminium chloride thus obtained are almost pure, for example, they are stirred at room temperature (20 ° C.) to 60 ° C. in an equimolar substrate and an appropriate solvent. Then, the chlorination reaction in the next step proceeds easily, and a high purity chlorine compound can be obtained in a high yield by simple filtration.
本発明に関してその好ましい実施態様に基づき詳細に説明したが、その利点を繰り返すと下記のようになる。
アミド化合物にフタル酸クロリド類を作用させると、イミドイルクロリド化合物と無水フタル酸誘導体に変換されるが、多くの場合無水フタル酸誘導体は次工程の反応に直接関与せず未反応物として残るので、そのまま次工程の反応場に用いることができる。未反応の無水フタル酸誘導体は蒸留あるいは再結晶により容易に取り除くことができ、必要ならば回収しフタル酸クロリド類への再変換原料として用いることができる。従って、本発明の実施態様によれば、特殊な排水、廃棄物処理を必要としないクリーンなイミドイルクロリド化合物の製造方法を提供することができる。無水フタル酸誘導体からフタル酸クロリド類への変換反応は、本発明者らにより完成しており工業原料として安価に市場に供給されている（特開２０１０−５３１２６号、特開２０１０−１０５９２９号公報）。
また、必要ならばイミドイルクロリド化合物を簡単な操作で単離し用いることができる。即ち、イミドイルクロリド化合物と無水フタル酸誘導体の混合物をエーテル系溶媒またはＢＴＸ溶媒で処理すると無水フタル酸が溶媒に溶解するために、簡単なろ過操作で高純度のイミドイルクロリド化合物を結晶として得ることができ、様々な化合物の反応に適切な反応条件下で適用することができる。
Although the present invention has been described in detail based on its preferred embodiments, the advantages are repeated as follows.
When phthalic acid chlorides are allowed to act on amide compounds, they are converted into imidoyl chloride compounds and phthalic anhydride derivatives, but in many cases phthalic anhydride derivatives do not directly participate in the next step reaction and remain as unreacted products. It can be used as it is in the reaction field of the next step. Unreacted phthalic anhydride derivatives can be easily removed by distillation or recrystallization, and can be recovered and used as a raw material for reconversion to phthalic chlorides if necessary. Therefore, according to the embodiment of the present invention, it is possible to provide a method for producing a clean imidoyl chloride compound which does not require special waste water and waste treatment. The conversion reaction from phthalic anhydride derivatives to phthalic chlorides has been completed by the present inventors and is supplied to the market at low cost as an industrial raw material (Japanese Patent Laid-Open Nos. 2010-53126 and 2010-105929). ).
If necessary, the imidoyl chloride compound can be isolated and used by a simple operation. That is, when a mixture of an imidoyl chloride compound and a phthalic anhydride derivative is treated with an ether solvent or a BTX solvent, the phthalic anhydride is dissolved in the solvent, so that a highly pure imidoyl chloride compound is obtained as a crystal by a simple filtration operation. And can be applied under reaction conditions suitable for the reaction of various compounds.
以下に本発明について実施例に基づきさらに詳細に説明するが、本発明がこれに限定して解釈されるものではない。
（実施例Ｉ）イミドイルクロリド化合物の製造
（実施例１０１）
１，４−ジオキサン３０ｍＬ中、Ｎ，Ｎ−ジメチルホルムアミド３．０ｇ（４１．１ミリモル）とフタル酸クロリド８．３ｇ（４１．１ミリモル）を室温で混合した後、４０℃で３時間攪拌した。結晶をガラスフィルター上にあけて窒素加圧下でろ取し、１，４−ジオキサン８ｍＬで２回洗浄した。得られた結晶を真空乾燥し、５．２４ｇ（９９％収率）のＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドを得た。その融点は１２８℃（分解）であった（文献値 １３２℃、アルドリッチ社カタログ値）。
生成物のＮＭＲ測定から無水フタル酸はほとんど混入していないことを確認した。また、合成したＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドのＩＲ測定及びＮＭＲ測定を行った結果、アルドリッチ社から販売されている試薬とスペクトルがよく一致した。
ＩＲ（ＣＨＣｌ３） １６９９（Ｃ＝Ｎ）ｃｍ−１
３００Ｍｚ−１ＨＮＭＲ（ＣＤＣｌ３） δ＝３．９７８（ｓ、６Ｈ），１１．００２（ｓ、１Ｈ）
Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not construed as being limited thereto.
(Example I) Production of imidoyl chloride compound (Example 101)
In 30 mL of 1,4-dioxane, 3.0 g (41.1 mmol) of N, N-dimethylformamide and 8.3 g (41.1 mmol) of phthalic chloride were mixed at room temperature and then stirred at 40 ° C. for 3 hours. . The crystal was put on a glass filter, collected by filtration under nitrogen pressure, and washed twice with 8 mL of 1,4-dioxane. The obtained crystals were vacuum-dried to obtain 5.24 g (99% yield) of N, N-dimethylchloromethyleneiminium chloride. Its melting point was 128 ° C. (decomposition) (reference value 132 ° C., catalog value from Aldrich).
From the NMR measurement of the product, it was confirmed that phthalic anhydride was hardly mixed. Further, as a result of IR measurement and NMR measurement of the synthesized N, N-dimethylchloromethyleneiminium chloride, the spectrum was in good agreement with the reagent sold by Aldrich.
IR (CHCl 3 ) 1699 (C═N) cm −1
300Mz- 1 HNMR (CDCl 3 ) δ = 3.978 (s, 6H), 11.002 (s, 1H)
（実施例１０２）
１，２−ジメトキシエタン３０ｍＬ 中、Ｎ，Ｎ−ジメチルホルムアミド３．０６ｇ（４１．９ミリモル）とフタル酸クロリド８．４３ｇ（４１．７ミリモル）を４０℃で１時間攪拌した。結晶をガラスフィルター上にあけて窒素加圧下でろ取し、１，２−ジメトキシエタン１０ｍＬで２回洗浄した。得られた結晶を真空乾燥し、３．２０ｇ（６０％収率）のＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドを得た。その融点は１２７〜１２８℃（分解）であった。
(Example 102)
In 30 mL of 1,2-dimethoxyethane, 3.06 g (41.9 mmol) of N, N-dimethylformamide and 8.43 g (41.7 mmol) of phthalic chloride were stirred at 40 ° C. for 1 hour. The crystals were put on a glass filter, collected under nitrogen pressure, and washed twice with 10 mL of 1,2-dimethoxyethane. The obtained crystals were vacuum-dried to obtain 3.20 g (60% yield) of N, N-dimethylchloromethyleneiminium chloride. Its melting point was 127 to 128 ° C. (decomposition).
（実施例１０３）
１，３−ジメチル−２−イミダゾリジノン ３．５０ｇ（３０．７ミリモル）、フタル酸クロリド６．５４ｇ（３２．４ミリモル）の混合物を１４０℃で５時間加熱攪拌した。冷却後、１，４−ジオキサン２５ｍＬを加えると結晶が析出したので、ガラスフィルターにてろ過、１０ｍＬの１，４−ジオキサンで２回洗浄、５ｍＬのエーテルで１回洗浄後、真空乾燥した。２−クロロ−１，３−ジメチルイミダゾリュームクロリド ２．７２ｇ（収率５３％）を得た。このものの融点（分解点）は９４．６℃を示した（文献値融点： ９５〜１００℃ 非特許文献２）。
合成した２−クロロ−１，３−ジメチルイミダゾリュームクロリドのＩＲ測定及びＮＭＲ測定を行った結果、東京化成社から販売されている試薬とスペクトルがよく一致した。
ＩＲ（ＣＨＣｌ３） １６３６（Ｃ＝Ｎ）ｃｍ−１
３００Ｍｚ−１ＨＮＭＲ（ＣＤＣｌ３） δ＝３．３３７（６Ｈ），４．３１７（４Ｈ）
(Example 103)
A mixture of 1.50 g (30.7 mmol) of 1,3-dimethyl-2-imidazolidinone and 6.54 g (32.4 mmol) of phthalic chloride was heated and stirred at 140 ° C. for 5 hours. After cooling, when 25 mL of 1,4-dioxane was added, crystals were precipitated, which was filtered through a glass filter, washed twice with 10 mL of 1,4-dioxane, washed once with 5 mL of ether, and then dried in vacuo. 2.72 g (yield 53%) of 2-chloro-1,3-dimethylimidazolium chloride was obtained. The melting point (decomposition point) of this product was 94.6 ° C. (document value melting point: 95-100 ° C. Non-patent document 2).
As a result of performing IR measurement and NMR measurement of the synthesized 2-chloro-1,3-dimethylimidazole chloride, the spectrum was in good agreement with the reagent sold by Tokyo Chemical Industry.
IR (CHCl 3 ) 1636 (C═N) cm −1
300Mz- 1 HNMR (CDCl 3) δ = 3.337 (6H), 4.317 (4H)
（実施例１０４）
１，４−ジオキサン６ｍＬ、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチル尿素 ３．４９ｇ（３０．１ミリモル）、フタル酸クロリド６．２８ｇ（３１．１ミリモル）の混合物を１００℃で８時間加熱攪拌した。温かいうちに、１，４−ジオキサン１８ｍＬを反応液に追加し室温まで冷却した。析出した結晶をガラスフィルターにてろ過、５ｍＬの１，４−ジオキサン、５ｍＬのエーテルで洗浄、真空乾燥した。クロロ−Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルホルムアミジニウムクロリド２．８２ｇ（収率５５％）を得た。このものの融点は１５１−１５３℃を示した。
文献値融点：１５０−１５５℃ Ｊ．Ｍｅｄ．Ｃｈｅｍ．，１９６６年９巻９８０頁．
(Example 104)
A mixture of 6 mL of 1,4-dioxane, 3.49 g (30.1 mmol) of N, N, N ′, N′-tetramethylurea and 6.28 g (31.1 mmol) of phthalic chloride at 100 ° C. for 8 hours. Stir with heating. While warm, 18 mL of 1,4-dioxane was added to the reaction solution and cooled to room temperature. The precipitated crystals were filtered through a glass filter, washed with 5 mL of 1,4-dioxane, 5 mL of ether and dried in vacuo. 2.82 g (yield 55%) of chloro-N, N, N ′, N′-tetramethylformamidinium chloride was obtained. The melting point of this product was 151-153 ° C.
Literature value Melting point: 150-155 ° C. Med. Chem. 1966, 980, 980.
（実施例１０５）
１，４−ジオキサン７０ｍＬ中、Ｎ，Ｎ−ジエチルホルムアミド１０．１ｇ（０．１００モル）とフタル酸クロリド２１．１ｇ（０．１０４モル）を室温で混合した後、４０℃で３時間攪拌した。結晶をガラスフィルター上にあけて窒素加圧下でろ過し、１，４−ジオキサン２０ｍＬで２回洗浄した。得られた結晶を真空乾燥し、１４．４ｇ（９２％収率）のＮ，Ｎ−ジエチルクロロメチレンイミニウムクロリドを得た。ｍｐ１１４．８−１１５．３℃（分解）。
(Example 105)
In 70 mL of 1,4-dioxane, 10.1 g (0.100 mol) of N, N-diethylformamide and 21.1 g (0.104 mol) of phthalic chloride were mixed at room temperature and then stirred at 40 ° C. for 3 hours. . The crystals were opened on a glass filter, filtered under nitrogen pressure, and washed twice with 20 mL of 1,4-dioxane. The obtained crystals were vacuum-dried to obtain 14.4 g (92% yield) of N, N-diethylchloromethyleneiminium chloride. mp 114.8-115.3 ° C. (decomposition).
（実施例１０６）
１，４−ジオキサン２０ｍＬ中、Ｎ−ホルミルピペリジン３ｇ（２６．５ミリモル）とフタル酸クロリド６ｇ（２９．７ミリモル）を４０℃、２．５時間攪拌した。室温に冷却すると結晶が析出したのでろ過、１，４−ジオキサン洗、エーテル洗を行い真空乾燥し、１−（クロロメチレン）ピペリジニウムクロリドを３．６８ｇ（収率８２．５％）得た。融点は１１１−１１３℃であった。
(Example 106)
In 20 mL of 1,4-dioxane, 3 g (26.5 mmol) of N-formylpiperidine and 6 g (29.7 mmol) of phthalic acid chloride were stirred at 40 ° C. for 2.5 hours. Crystals precipitated when cooled to room temperature, and were filtered, washed with 1,4-dioxane, washed with ether and dried in vacuo to give 3.68 g (yield 82.5%) of 1- (chloromethylene) piperidinium chloride. . The melting point was 111-113 ° C.
（実施例ＩＩ）単離試薬を用いた例
（実施例２０１）
実施例Ｉ−１０１と同様にして合成したＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶を１．０５ｇ（８．２ミリモル）測り取った。そこに、１，４−ジオキサン６ｍＬと４，４’−スチルベンジカルボン酸１．０８ｇ（４．０３ミリモル）を加え６０℃にて１時間攪拌した。５０℃にてろ過し１，４−ジオキサンで洗浄、真空乾燥し１．１１ｇ（収率９０％）の４，４’−スチルベンジカルボン酸クロリドを得た。ＨＰＬＣ分析は９９．５％の純度を示した。無水フタル酸は含まれていなかった。得られた４，４’−スチルベンジカルボン酸クロリドの融点は２３４℃であった。
文献値融点：２２７〜２３０℃：Ｊ．Ａｍ．Ｃｈｅｍ．Ｓｏｃ．，１９４７年，６９巻、５０３頁
文献値融点：２３８℃：Ｊ．Ｏｒｇ．Ｃｈｅｍ．，１９９０年，５５巻、２８６４頁。
ＩＲ（ＫＢｒ）１７４８，１５９１ｃｍ−１
３００ＭＨｚ−１ＨＮＭＲ（ＣＤＣｌ３） δ＝７．５０（ｓ，２Ｈ），７．７７（ｄ，Ｊ＝８．４Ｈｚ，４Ｈ），７．９７（ｄ，Ｊ＝８．４Ｈｚ，４Ｈ）
(Example II) Example using an isolation reagent (Example 201)
1.05 g (8.2 mmol) of N, N-dimethylchloromethyleneiminium chloride crystals synthesized in the same manner as in Example I-101 was measured. Thereto, 6 mL of 1,4-dioxane and 1.08 g (4.03 mmol) of 4,4′-stilbene dicarboxylic acid were added and stirred at 60 ° C. for 1 hour. Filtration at 50 ° C., washing with 1,4-dioxane, and vacuum drying gave 1.11 g (yield 90%) of 4,4′-stilbene dicarboxylic acid chloride. HPLC analysis showed a purity of 99.5%. No phthalic anhydride was included. The resulting 4,4′-stilbene dicarboxylic acid chloride had a melting point of 234 ° C.
Literature value Melting point: 227-230 ° C. Am. Chem. Soc. 1947, 69, 503 Literature value Melting point: 238 ° C. Org. Chem. 1990, 55, 2864.
IR (KBr) 1748, 1591 cm −1
300 MHz- 1 H NMR (CDCl 3 ) δ = 7.50 (s, 2H), 7.77 (d, J = 8.4 Hz, 4H), 7.97 (d, J = 8.4 Hz, 4H)
（実施例２０２）
実施例Ｉ−１０１と同様にして合成したＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶を１．１５ｇ（９．０ミリモル）測り取った。そこに１，４−ジオキサン５ｍＬと４，４‘−ビフェニルジカルボン酸１．０４ｇ（４．２８ミリモル）を加え、６０℃にて１時間攪拌した。冷却後、析出した結晶をろ取し、４，４‘−ビフェニルジカルボン酸クロリド０．９８ｇ（収率８２％）を得た。
得られた４，４‘−ビフェニルジカルボン酸クロリドの融点は１８８℃であった。
文献値融点：１８４℃：Ｊ．Ｃｈｅｍ．Ｓｏｃ．，１９４０年１３１５頁、 ＵＳＰ２８５６４２５）。
ジエチルアミン処理によるＨＰＬＣ内標純度は９９．５％であった。
ＧＣ−ＭＳ（ジエチルアミン処理後）ｍ／ｚ３５２（Ｍ＋）
(Example 202)
1.15 g (9.0 mmol) of N, N-dimethylchloromethyleneiminium chloride crystals synthesized in the same manner as in Example I-101 was measured. Thereto were added 5 mL of 1,4-dioxane and 1.04 g (4.28 mmol) of 4,4′-biphenyldicarboxylic acid, and the mixture was stirred at 60 ° C. for 1 hour. After cooling, the precipitated crystals were collected by filtration to obtain 0.98 g (yield 82%) of 4,4′-biphenyldicarboxylic acid chloride.
The resulting 4,4′-biphenyldicarboxylic acid chloride had a melting point of 188 ° C.
Literature value Melting point: 184 ° C. Chem. Soc. 1940, page 1315, USP 2856425).
The internal standard purity of the HPLC by diethylamine treatment was 99.5%.
GC-MS (after diethylamine treatment) m / z 352 (M + )
（実施例２０３）
実施例Ｉ−１０１と同様にして合成したＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶を１．１１ｇ（８．７ミリモル）測り取った。そこに１，４−ジオキサン５ｍＬと２，６−ナフタレンジカルボン酸０．９３ｇ（４．３ミリモル）を加え６０℃にて１時間攪拌した。室温まで冷却し２，６−ナフタレンジカルボン酸クロリドの結晶を０．９１ｇ（収率８４％）得た。この生成物の融点は１８８−１９０℃であった。
文献値融点１８６℃：日本化学会誌 １９７４年，６０３頁。
文献値融点１８９−１９０℃：Ｊ．Ａｍ．Ｃｈｅｍ．Ｓｏｃ．，１９９６年，１１８巻、８７８２頁．
ＧＣ−ＭＳ（ジエチルアミン処理後）ｍ／ｚ３２６（Ｍ＋）
(Example 203)
1.11 g (8.7 mmol) of N, N-dimethylchloromethyleneiminium chloride crystals synthesized in the same manner as in Example I-101 was weighed. Thereto, 5 mL of 1,4-dioxane and 0.93 g (4.3 mmol) of 2,6-naphthalenedicarboxylic acid were added and stirred at 60 ° C. for 1 hour. After cooling to room temperature, 0.91 g (yield 84%) of 2,6-naphthalenedicarboxylic acid chloride crystals was obtained. The melting point of this product was 188-190 ° C.
Literature value Melting point 186 ° C: Journal of the Chemical Society of Japan, 1974, p.
Literature value Melting point 189-190 ° C. Am. Chem. Soc. 1996, 118, 8782.
GC-MS (after diethylamine treatment) m / z 326 (M + )
（実施例２０４）
実施例Ｉ−１０１と同様にしてＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶を１．８０ｇ（１４．１ミリモル）得た。そこにオクタン酸２．０８ｇ（１４．４ミリモル）とＤＭＦ２．５ｍＬを加え室温で１時間攪拌した。ＧＣ−ＭＳを測定するとオクタノイルクロリドが９０％と原料のオクタン酸が１０％の混合物であった。
ＧＣ−ＭＳ：ｍ／ｚ１２７（Ｍ−３５＋）
(Example 204)
In the same manner as in Example I-101, 1.80 g (14.1 mmol) of N, N-dimethylchloromethyleneiminium chloride crystals were obtained. Thereto were added 2.08 g (14.4 mmol) of octanoic acid and 2.5 mL of DMF, and the mixture was stirred at room temperature for 1 hour. When GC-MS was measured, it was a mixture of 90% octanoyl chloride and 10% raw material octanoic acid.
GC-MS: m / z 127 (M-35 + )
（実施例２０５）
実施例Ｉ−１０１と同様にして合成したＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶０．２１ｇ（１．６４ミリモル）にベンジルアルコール０．１６ｇ（１．４８ミリモル）を加え室温にて１時間攪拌した。ＧＣ−ＭＳを測定するとベンジルクロリドが９５．５％の収率で得られていた。
ｍ／ｚ＝１２６（Ｍ＋），１２８（Ｍ＋２＋）＝約３：１
(Example 205)
0.16 g (1.48 mmol) of benzyl alcohol was added to 0.21 g (1.64 mmol) of N, N-dimethylchloromethyleneiminium chloride crystals synthesized in the same manner as in Example I-101, and the mixture was stirred at room temperature. Stir for hours. As measured by GC-MS, benzyl chloride was obtained in a yield of 95.5%.
m / z = 126 (M + ), 128 (M + 2 + ) = about 3: 1
（実施例２０６）
実施例Ｉ−１０１と同様にして合成したＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶０．６０ｇ（４．７ミリモル）にジクロロメタン１５ｍＬを加え攪拌したが、スラリー状態であった。そこに２−ヘキサノール（ラセミ体）０．４１ｇ（４．０ミリモル）のジクロロメタン溶液４ｍＬを加えると直ちに均一溶液となった。室温にて攪拌し１５分後に飽和重曹水でクエンチしＧＣ分析すると、２−ヘキサノールは完全に消失し、９９％以上の変換率で２−ヘキシルホルメートに変化していた。ＧＣ−ＭＳは親ピークが観測されず、ｍ／ｚ１０１（Ｍ−２９＋）及び８５、８４が観測された。２−クロロヘキサンの標品ＧＣＭＳと保持時間とスペクトルが異なっていた。さらに構造を確認するために１ＭＮａＯＨ水溶液３ｍＬを加え室温で１時間攪拌後、ＧＣ−ＭＳを測定すると２−ヘキサノールに完全に変化していた。そのスペクトルは試薬標品のそれと完全に一致した。
別途、同じ反応を１，４−ジオキサン溶媒にて８０℃で１時間行い、重曹処理後ＧＣＭＳを測定すると２−クロロヘキサンの標品スペクトルと一致した。変換率は９９％以上であった。
(Example 206)
To 0.60 g (4.7 mmol) of N, N-dimethylchloromethyleneiminium chloride crystals synthesized in the same manner as in Example I-101, 15 mL of dichloromethane was added and stirred, but in a slurry state. When 4 mL of a dichloromethane solution of 0.41 g (4.0 mmol) of 2-hexanol (racemate) was added thereto, a homogeneous solution was immediately formed. After stirring at room temperature and quenching with saturated aqueous sodium bicarbonate after 15 minutes and GC analysis, 2-hexanol completely disappeared and changed to 2-hexyl formate with a conversion rate of 99% or more. In GC-MS, no parent peak was observed, and m / z 101 (M-29 + ) and 85 and 84 were observed. The retention time and spectrum differed from the standard GCMS of 2-chlorohexane. Further, in order to confirm the structure, 3 mL of 1 M NaOH aqueous solution was added and stirred at room temperature for 1 hour, and when GC-MS was measured, it was completely changed to 2-hexanol. The spectrum was completely consistent with that of the reagent preparation.
Separately, the same reaction was carried out in a 1,4-dioxane solvent at 80 ° C. for 1 hour, and GCMS was measured after treatment with sodium bicarbonate, which was consistent with the standard spectrum of 2-chlorohexane. The conversion rate was 99% or more.
（実施例２０７）
実施例Ｉ−１０５に合成したＮ，Ｎ−ジエチルクロロメチレンイミニウムクロリドの結晶を１０．５ｇ（０．０６７モル）測り取った。そこに、１，４−ジオキサン４０ｍＬと４，４’−ビフェニルジカルボン酸７．８ｇ（０．０３２モル）を加え６０℃にて１時間攪拌した。４０℃にてろ過し１，４−ジオキサンで洗浄、真空乾燥し７．１ｇ（収率７８％）の４，４’−ビフェニルジカルボン酸クロリドを得た。ＨＰＬＣ分析は９９．４％の純度を示した。無水フタル酸は含まれていなかった。
(Example 207)
10.5 g (0.067 mol) of N, N-diethylchloromethyleneiminium chloride crystals synthesized in Example I-105 were weighed. Thereto were added 40 mL of 1,4-dioxane and 7.8 g (0.032 mol) of 4,4′-biphenyldicarboxylic acid, and the mixture was stirred at 60 ° C. for 1 hour. The mixture was filtered at 40 ° C., washed with 1,4-dioxane, and vacuum-dried to obtain 7.1 g (yield 78%) of 4,4′-biphenyldicarboxylic acid chloride. HPLC analysis showed a purity of 99.4%. No phthalic anhydride was included.
（実施例２０８）
実施例Ｉ−１０１と同様にしてＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドを合成した。即ち、３００ｍＬ４つ口フラスコにＤＭＦ１０ｇ（１３．７ミリモル）、１，４−ジオキサン１００ｍＬ（缶出し）を入れ、攪拌下フタル酸クロリド３０ｇ（１４．８ミリモル）を室温で５分かかって滴下した。４０℃の油浴にて３時間攪拌した。ガラスフィルターにて窒素での加圧ろ過を行ってＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶をろ取、乾燥１，４−ジオキサン３０ｍＬで２回洗浄した。
上記のガラスフィルターでろ取したＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの全量を乾燥せずに３００ｍＬ４つ口フラスコに移し、乾燥ジクロロメタン７０ｍＬを加え攪拌した。４，４‘−オキシビス安息香酸１１．３ｇ（４３．８ミリモル）を加え、３０ｍＬのジクロロメタンを追加した。４０℃の油浴中、攪拌を続けると次第に均一溶液となり２時間で反応終了とし、ガラスフイルターで微量の不溶物を取り除いた。エバポレーターで約１／４になるまで濃縮した。この状態でフラスコ内に結晶が析出し始めていた。５℃まで冷却し、結晶をろ取、乾燥シクロヘキサン５ｍＬで２回結晶を洗浄した。室温真空乾燥１時間で４，４‘−オキシビス安息香酸クロリドの白色結晶９．７ｇ（収率７５％）を得た。ろ液から２番晶を２．７ｇ（２１％収率）を得た。
ＨＰＬＣ分析１番晶：９９．８６％、２番晶：９９．８０％
Ｍｐ ８９．６−８９．８℃。（１番晶）
ＩＲ（ＫＢｒ）：１７４８ｃｍ−１．
(Example 208)
N, N-dimethylchloromethyleneiminium chloride was synthesized in the same manner as in Example I-101. That is, 10 g of DMF (13.7 mmol) and 100 mL of 1,4-dioxane (canned) were placed in a 300 mL four-necked flask, and 30 g (14.8 mmol) of phthalic chloride was added dropwise at room temperature over 5 minutes with stirring. The mixture was stirred for 3 hours in an oil bath at 40 ° C. Pressure filtration with nitrogen was performed with a glass filter, and crystals of N, N-dimethylchloromethyleneiminium chloride were collected by filtration and washed twice with 30 mL of dry 1,4-dioxane.
The entire amount of N, N-dimethylchloromethyleneiminium chloride collected by filtration with the above glass filter was transferred to a 300 mL four-necked flask without drying, and 70 mL of dry dichloromethane was added and stirred. 11.4 g (43.8 mmol) of 4,4′-oxybisbenzoic acid was added and 30 mL of dichloromethane was added. When stirring was continued in a 40 ° C. oil bath, the solution gradually became a homogeneous solution, and the reaction was completed in 2 hours. A trace amount of insoluble matter was removed with a glass filter. It concentrated to about 1/4 with the evaporator. In this state, crystals began to precipitate in the flask. After cooling to 5 ° C., the crystals were collected by filtration and washed twice with 5 mL of dry cyclohexane. 9.7 g (yield 75%) of white crystals of 4,4′-oxybisbenzoic acid chloride was obtained at room temperature under vacuum drying for 1 hour. 2.7 g (21% yield) of second crystal was obtained from the filtrate.
HPLC analysis 1st crystal: 99.86%, 2nd crystal: 99.80%
Mp 89.6-89.8 ° C. (1st crystal)
IR (KBr): 1748 cm < -1 >.
文献値融点：ｍｐ ８９．２―８９．８℃：Ｄｏｋｌ．Ｃｈｅｍ． （ｅｎｇｌ． Ｔｒａｎｓｌ．） １９８４年， ２７９巻， ３８８頁
文献値融点：ｍｐ８８℃：工業化学雑誌１９６７年， ７０巻， １６０７頁．
ＧＣ−ＭＳ（ジエチルアミドとして）：ｍ／ｚ＝３６８（Ｍ＋、９％）、３６７（２４％）、２９６（ベースピーク）、１９６（５０％）
Literature value Melting point: mp 89.2-89.8 ° C: Dokl. Chem. (Engl. Transl.) 1984, 279, 388 Literature value Melting point: mp 88 ° C: Industrial Chemical Journal 1967, 70, 1607.
GC-MS (as diethylamide): m / z = 368 (M + , 9%), 367 (24%), 296 (base peak), 196 (50%)
（実施例２０９）
実施例ＩＩ−２０８のジクロロメタンを４−クロロトリフルオロメチルベンゼンに代えて同じように実施した。結晶が出るまで濃縮し収率６９％で４，４‘−オキシビス安息香酸クロリドの白色結晶を得た。
ＨＰＬＣ純度９９．７２％
(Example 209)
The same procedure was followed as in Example II-208, except that 4-chlorotrifluoromethylbenzene was used instead of dichloromethane. Concentration until crystals appeared, yielding white crystals of 4,4'-oxybisbenzoic acid chloride in 69% yield.
HPLC purity 99.72%
（実施例２１０）
実施例Ｉ−１０１の溶媒１，４−ジオキサンをオルトクロロトルエンに代えて同じようにＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドを合成した。即ち、１Ｌ４つ口フラスコにＮ，Ｎ−ジメチルホルムアミド９０ｇ（１．２３モル）、オルトクロロトルエン３１０ｍＬ（缶出し）を入れ、攪拌下フタル酸クロリド８４．５ｇ（０．４１８モル）を室温で５分かかって滴下した。５０℃の油浴にて３時間半攪拌を続け、ガラスフィルターにて、窒素での加圧ろ過を行ってＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリド結晶をろ取、オルトクロロトルエン１５０ｍＬで２回洗浄した。
上記のＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶全量を乾燥せずに１Ｌ４つ口フラスコに移し、オルトクロロトルエン３００ｍＬと４，４‘−オキシビス安息香酸４５ｇ（０．１７４モル）を加え、７０℃の油浴中、攪拌を続けると次第に均一溶液となった。４時間で反応終了とし、底に褐色の液体層（主に未反応のＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドとＮ，Ｎ−ジメチルホルムアミド）が２５ｍＬをデカンテーションで取り除いた。
反応液をエバポレーターで７０ｍＬになるまで濃縮した。１０℃まで冷却し、結晶をろ取、ヘキサン３０ｍＬで結晶を洗浄した。室温真空乾燥１時間で４，４‘−オキシビス安息香酸クロリドの白色結晶３５．８ｇ（収率７０％）を得た。
ＨＰＬＣ分析：９９．７０％
Ｍｐ ８９．８℃。
(Example 210)
N, N-dimethylchloromethyleneiminium chloride was synthesized in the same manner by replacing the solvent 1,4-dioxane of Example I-101 with orthochlorotoluene. That is, N, N-dimethylformamide 90 g (1.23 mol) and orthochlorotoluene 310 mL (canned) are placed in a 1 L four-necked flask, and 84.5 g (0.418 mol) of phthalic acid chloride is stirred at room temperature for 5 hours. It took a minute and dropped. Stirring was continued in an oil bath at 50 ° C. for 3 hours and a half, followed by pressure filtration with nitrogen through a glass filter to filter out N, N-dimethylchloromethyleneiminium chloride crystals, twice with 150 mL of orthochlorotoluene. Washed.
Transfer the entire amount of the above N, N-dimethylchloromethyleneiminium chloride crystals to a 1 L four-necked flask without drying, add 300 mL of orthochlorotoluene and 45 g (0.174 mol) of 4,4′-oxybisbenzoic acid, When stirring was continued in an oil bath at 70 ° C., a homogeneous solution gradually formed. The reaction was completed in 4 hours, and 25 mL of a brown liquid layer (mainly unreacted N, N-dimethylchloromethyleneiminium chloride and N, N-dimethylformamide) was removed by decantation at the bottom.
The reaction solution was concentrated to 70 mL with an evaporator. The mixture was cooled to 10 ° C., the crystals were collected by filtration, and washed with 30 mL of hexane. The white crystal | crystallization 35.8g (70% of yield) of 4,4'- oxybisbenzoic acid chloride was obtained at room temperature vacuum drying for 1 hour.
HPLC analysis: 99.70%
Mp 89.8 ° C.
（実施例２１１）
実施例Ｉ−１０６で得た１−（クロロメチレン）ピペリジニウムクロリド２．６ｇ（１５．５ミリモル）とアニソール３．７ｇ（３４．２ミリモル）を１００℃で４時間攪拌したのち、酢酸エチルと１モル濃度の塩酸を加え酢酸エチル層を分離した。飽和重曹水で洗ったのち、無水硫酸ナトリウムで乾燥後、溶媒を減圧留去した。残渣は５．２ｇあり、ＧＣ分析の結果、１．７５ミリモルの４−メトキシベンズアルデヒドが得られていることがわかった。１−（クロロメチレン）ピペリジニウムクロリド基準で１１％の収率であった。
ＧＣ−ＭＳ：ｍ／ｚ＝１３６（Ｍ＋）、１３５（ベースピーク）、１０７，９２，７７。
(Example 211)
After stirring 2.6 g (15.5 mmol) of 1- (chloromethylene) piperidinium chloride obtained in Example I-106 and 3.7 g (34.2 mmol) of anisole at 100 ° C. for 4 hours, ethyl acetate was added. And 1 molar hydrochloric acid were added, and the ethyl acetate layer was separated. The extract was washed with saturated aqueous sodium hydrogen carbonate and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was 5.2 g, and as a result of GC analysis, it was found that 1.75 mmol of 4-methoxybenzaldehyde was obtained. The yield was 11% based on 1- (chloromethylene) piperidinium chloride.
GC-MS: m / z = 136 (M <+> ), 135 (base peak), 107, 92, 77.
（実施例２１２）
実施例Ｉ−１０１に合成したＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶０．４４ｇ（３．４ミリモル）を１，４−ジオキサン１０ｍＬに懸濁させ、トリフェニルメタノール０．７２ｇ（２．８ミリモル）の１，４−ジオキサン４ｍＬ溶液を室温で滴下した。８０℃にて３０分間攪拌すると均一溶液となった。重曹水とジクロロメタンを加え、有機相を分離、溶媒を留去すると０．７８ｇのトリフェニルメチルクロリドが定量的収率で得られた。
融点１１２−１１３℃
文献値融点：１１１−１１２℃：Ｏｒｇ．Ｓｙｎｔｈｅｓｉｓ Ｃｏｌｌ．ＶｏｌＩＩＩ，８４１頁。
ＧＣ−ＭＳは試薬標品のそれと一致した。ｍ／ｚ＝２４３（Ｍ−３５＋）。
(Example 212)
0.44 g (3.4 mmol) of N, N-dimethylchloromethyleneiminium chloride crystals synthesized in Example I-101 was suspended in 10 mL of 1,4-dioxane, and 0.72 g (2. 8 mmol) in 1,4-dioxane (4 mL) was added dropwise at room temperature. When stirred at 80 ° C. for 30 minutes, a homogeneous solution was obtained. Sodium bicarbonate water and dichloromethane were added, the organic phase was separated, and the solvent was distilled off to obtain 0.78 g of triphenylmethyl chloride in a quantitative yield.
Melting point 112-113 ° C
Literature value Melting point: 111-112 ° C: Org. Synthesis Coll. Vol III, page 841.
GC-MS was consistent with that of the reagent preparation. m / z = 243 (M-35 <+> ).
（実施例ＩＩＩ）単離せずに所定の反応を行う例
（実施例３０１）
フタル酸クロリド１．０９ｇ（５．４ミリモル）と４−フルオロベンズアルデヒド０．５２ｇ（４．１９ミリモル）の混合物にＮ，Ｎ−ジメチルホルムアミドを０．１ｇ（１．３７ミリモル）加え、５０℃で３時間攪拌した。反応液のＧＣ−ＭＳを測定すると主生成物のマススペクトルは標品の１−ジクロロメチル−４−フルオロベンゼンのマススペクトルと完全に一致した。
ｍ／ｚ＝１７８（Ｍ＋）：１８０（Ｍ＋２＋）＝約３：２（二塩素化物）
別途ＧＣ分析では１−ジクロロメチル−４−フルオロベンゼンが９５％生成していることが明らかとなった。なお、反応後のフタル酸無水物は蒸留残渣から容易に単離して回収することができた。
(Example III) Example of carrying out a predetermined reaction without isolation (Example 301)
0.1 g (1.37 mmol) of N, N-dimethylformamide was added to a mixture of 1.09 g (5.4 mmol) of phthalic acid chloride and 0.52 g (4.19 mmol) of 4-fluorobenzaldehyde, and the mixture was heated at 50 ° C. Stir for 3 hours. When the GC-MS of the reaction solution was measured, the mass spectrum of the main product completely coincided with the mass spectrum of the standard 1-dichloromethyl-4-fluorobenzene.
m / z = 178 (M + ): 180 (M + 2 + ) = about 3: 2 (dichlorinated product)
Separate GC analysis revealed that 95% of 1-dichloromethyl-4-fluorobenzene was produced. In addition, the phthalic anhydride after the reaction could be easily isolated and recovered from the distillation residue.
（実施例３０２）
塩化ベンゾイル８ｍＬにＮ，Ｎ−ジメチルホルムアミド０．３６ｇ（４．９ミリモル）、フタル酸クロリド１．１２ｇ（５．５ミリモル）を順次加え攪拌した。そこに、４−フルオロベンズアルデヒド０．５０ｇ（４．０ミリモル）を加え室温で３．５時間攪拌した。反応液のＧＣ−ＭＳ分析は標品の１−ジクロロメチル−４−フルオロベンゼンのマススペクトルと完全に一致し、その変換率（収率）は９５％であった。
(Example 302)
To 8 mL of benzoyl chloride, 0.36 g (4.9 mmol) of N, N-dimethylformamide and 1.12 g (5.5 mmol) of phthalic chloride were sequentially added and stirred. 4-fluorobenzaldehyde 0.50g (4.0 mmol) was added there, and it stirred at room temperature for 3.5 hours. GC-MS analysis of the reaction solution completely matched the mass spectrum of the standard 1-dichloromethyl-4-fluorobenzene, and the conversion rate (yield) was 95%.
（実施例３０３）
Ｎ，Ｎ−ジメチルホルムアミド１．１９ｇ（１６．３ミリモル）にフタル酸クロリド０．２７ｇ（１．３４ミリモル）を室温で加え３０分間攪拌した。反応液はスラリー状態となった。そこにベンジルアルコール０．１２ｇ（１．１１ミリモル）を加えると直ちに均一溶液となった。室温で１時間攪拌後、一部をエーテルと水の中に入れ、よく攪拌したのち有機層のＧＣ−ＭＳを測定した。ベンジルアルコールは完全に消失しており、全てベンジルクロリドに変化していた。そのＧＣ−ＭＳのピークは標品のそれと完全に一致した。
ｍ／ｚ １２６（Ｍ＋）、１２８（Ｍ＋２＋）。１２６：１２８＝ｃａ３：１、９１（ベースピーク）。
Example 303
To 1.19 g (16.3 mmol) of N, N-dimethylformamide was added 0.27 g (1.34 mmol) of phthalic chloride at room temperature and stirred for 30 minutes. The reaction solution became a slurry. When 0.12 g (1.11 mmol) of benzyl alcohol was added thereto, a homogeneous solution was immediately formed. After stirring at room temperature for 1 hour, a part was put into ether and water, and after stirring well, GC-MS of the organic layer was measured. Benzyl alcohol had completely disappeared and all changed to benzyl chloride. The GC-MS peak was completely consistent with that of the standard.
m / z 126 (M <+> ), 128 (M + 2 < + > ). 126: 128 = ca 3: 1, 91 (base peak).
（実施例３０４）
１，３−ジメチル−２−イミダジリジノン（ＤＭＩ）０．１４ｇ（１．２３ミリモル）とフタル酸クロリド０．２５ｇ（１．２４ミリモル）を室温で加え攪拌しながらオイルバス中で３０分かかって１３０℃まで温度を上げた。さらに１４０℃で１時間攪拌したのち室温まで冷却すると固化した。そこにＤＭＩを１ｍＬ加え全体を均一溶液としたのち、ベンジルアルコールを室温で加え１時間攪拌した。反応液の一部をとり、エーテルと水の中に入れ、よく攪拌しその有機層のＧＣ−ＭＳを測定した。その結果、ベンジルアルコールが４０％残っており、ベンジルクロリドが６０％生成していることがわかった。反応液を室温でさらに１５時間攪拌し同様にＧＣ−ＭＳを測定するとベンジルクロリドの生成率（収率）が８４％で１６％のベンジルアルコールが残っていた。
(Example 304)
Add 0.14 g (1.23 mmol) of 1,3-dimethyl-2-imidazolidinone (DMI) and 0.25 g (1.24 mmol) of phthalic chloride at room temperature and stir in an oil bath for 30 minutes with stirring. The temperature was raised to ° C. The mixture was further stirred at 140 ° C. for 1 hour and then cooled to room temperature to solidify. 1 mL of DMI was added thereto to make a uniform solution, and then benzyl alcohol was added at room temperature and stirred for 1 hour. A part of the reaction solution was taken, put in ether and water, stirred well, and GC-MS of the organic layer was measured. As a result, it was found that 40% of benzyl alcohol remained and 60% of benzyl chloride was produced. The reaction solution was further stirred at room temperature for 15 hours, and GC-MS was measured in the same manner. As a result, the yield (yield) of benzyl chloride was 84% and 16% of benzyl alcohol remained.
（実施例３０５）
Ｎ，Ｎ−ジメチルホルムアミド６．７ｇ（９１．８ミリモル）とフタル酸クロリド３．０ｇ（１４．８ミリモル）を室温で３０分間攪拌した。反応液はスラリー状態であったが、４−メトキシベンジルアルコール１．４０ｇ（１０．２ミリモル）を加えると直ちに均一溶液となった。そのまま３０分間攪拌を続け、ＧＣでモニターすると原料の４−メトキシベンジルアルコールは完全に消失し、４−メトキシベンジルクロリドに変化していた。反応液にジクロロメタンと炭酸ナトリウム水溶液を加え、よく振り混ぜジクロロメタン層を分離し、炭酸ナトリウム水溶液でもう一度洗浄した。この操作を２回繰り返しジクロロメタン層を無水硫酸ナトリウムで乾燥した。溶媒を留去すると無色の液体が得られ、ＧＣ−ＭＳでほぼ純品の４−メトキシベンジルクロリドであることが判明した。
得量１．４６ｇ（収率９２％）
ｍ／ｚ＝１５６（Ｍ＋），１５８（Ｍ＋２＋）．
(Example 305)
6.7 g (91.8 mmol) of N, N-dimethylformamide and 3.0 g (14.8 mmol) of phthalic chloride were stirred at room temperature for 30 minutes. The reaction solution was in a slurry state, but when 1.40 g (10.2 mmol) of 4-methoxybenzyl alcohol was added, it immediately became a homogeneous solution. Stirring was continued for 30 minutes, and when monitored by GC, the raw material 4-methoxybenzyl alcohol completely disappeared and changed to 4-methoxybenzyl chloride. Dichloromethane and an aqueous sodium carbonate solution were added to the reaction solution, shaken well, the dichloromethane layer was separated, and washed once more with an aqueous sodium carbonate solution. This operation was repeated twice, and the dichloromethane layer was dried over anhydrous sodium sulfate. When the solvent was distilled off, a colorless liquid was obtained, which was found to be almost pure 4-methoxybenzyl chloride by GC-MS.
1.46 g yield (92% yield)
m / z = 156 (M <+> ), 158 (M + 2 < + > ).
（実施例３０６）
Ｎ，Ｎ−ジメチルホルムアミド９．０４ｇ（０．１２モル）とＮ、Ｎ―ジメチルアニリン５．０ｇ（０．０４１モル）を混合し、フタル酸クロリド８．４ｇ（０．０４２モル）を室温で滴下した。反応混合液を７０℃まで上昇させ１時間攪拌した。反応液の一部を取りジクロロメタンと水を加え、ジクロロメタン層のＧＣ分析を行うと９４％の変換率（収率）で４−（Ｎ、Ｎ―ジメチルアミノ）ベンズアルデヒドが生成していた。
(Example 306)
9.04 g (0.12 mol) of N, N-dimethylformamide and 5.0 g (0.041 mol) of N, N-dimethylaniline are mixed, and 8.4 g (0.042 mol) of phthalic acid chloride is mixed at room temperature. It was dripped. The reaction mixture was raised to 70 ° C. and stirred for 1 hour. A portion of the reaction solution was taken, dichloromethane and water were added, and GC analysis of the dichloromethane layer revealed that 4- (N, N-dimethylamino) benzaldehyde was produced at a conversion rate (yield) of 94%.
（実施例３０７）
２，６−ナフタレンジカルボン酸 １２，１ｇ（５６ミリモル）を１，４−ジオキサン１６０ｍＬに懸濁した。室温で撹拝しながらフタル酸クロリド３０ｇ（１４８ミリモル）を滴下、さらにＮ，Ｎ−ジメチルホルムアミド３ｍＬを加えたのち、７０℃で３．５時間撹絆した。微量の不溶物を除去するためにＧ２ガラスフィルターでろ過し、室温で２時間静置した。
析出した結晶をろ取し、エーテル２５ｍＬで洗浄後、デシケーター中で２時間真空乾燥した。１０．６ｇ（７８％収率）の２，６−ナフタレンジカルボン酸クロリドを得た。
ｍｐ１９０．３−１９０．６℃。ＨＰＬＣ純度９８．５％。
ＧＣ−ＭＳ：ｍ／ｚ＝２５２（Ｍ＋）：２５４（Ｍ十２＋）＝３：２
ジエチルアミン処理 ｍ／ｚ＝３０４（Ｍ＋）
(Example 307)
12,1 g (56 mmol) of 2,6-naphthalenedicarboxylic acid was suspended in 160 mL of 1,4-dioxane. While stirring at room temperature, 30 g (148 mmol) of phthalic acid chloride was added dropwise, 3 mL of N, N-dimethylformamide was further added, and the mixture was stirred at 70 ° C. for 3.5 hours. In order to remove a trace amount of insoluble matter, the solution was filtered with a G2 glass filter and allowed to stand at room temperature for 2 hours.
The precipitated crystals were collected by filtration, washed with 25 mL of ether, and then vacuum-dried in a desiccator for 2 hours. 10.6 g (78% yield) of 2,6-naphthalenedicarboxylic acid chloride was obtained.
mp 190.3-190.6 ° C. HPLC purity 98.5%.
GC-MS: m / z = 252 (M + ): 254 (M + 2 + ) = 3: 2
Diethylamine treatment m / z = 304 (M + )
（実施例３０８）
２，６−ナフタレンジカルボン酸 ５４ｇ（０．２５モル）を１，２−ジメトキシエタン４６５ｍＬに懸濁、Ｎ，Ｎ−ジメチルホルムアミド５ｍＬを加えたのちフタル酸クロリド１２５ｇ（０．６２モル）を室温で滴下後、７５℃で２時間攪拌した。微量の不溶物を除去するためにＧ２ガラスフィルターでろ過し、室温で１４時間静置した。析出した結晶をろ取し、１，２−ジメトキシエタン１００ｍＬ、ヘキサン２００ｍＬで洗浄後、デシケーター中で２時間真空乾燥した。４５ｇ（７１％収率）の２，６−ナフタレンジカルボン酸クロリドを得た。
ｍｐ１９１℃。ＨＰＬＣ純度９９．９６％。無水フタル酸は含まれていなかった。
(Example 308)
Suspend 54 g (0.25 mol) of 2,6-naphthalenedicarboxylic acid in 465 mL of 1,2-dimethoxyethane, add 5 mL of N, N-dimethylformamide, and then add 125 g (0.62 mol) of phthalic acid chloride at room temperature. After dropping, the mixture was stirred at 75 ° C. for 2 hours. In order to remove a trace amount of insoluble matter, the solution was filtered with a G2 glass filter and allowed to stand at room temperature for 14 hours. The precipitated crystals were collected by filtration, washed with 100 mL of 1,2-dimethoxyethane and 200 mL of hexane, and then vacuum dried in a desiccator for 2 hours. 45 g (71% yield) of 2,6-naphthalenedicarboxylic acid chloride was obtained.
mp 191 ° C. HPLC purity 99.96%. No phthalic anhydride was included.
（実施例３０９）
１，４−ジオキサン２ｍＬ中、Ｎ−メチルホルムアミド０．６１ｇ（１０．３ミリモル）とフタル酸クロリド２．０ｇ（９．９ミリモル）を４０℃で２時間攪拌した。室温まで冷却したが相当するイミドイルクロリドの結晶は析出しなかったので、ベンジルアルコール０．９５ｇ（９．８ミリモル）を加え５０℃で３時間反応し、水を加えて反応を停止した。エーテルで有機物を抽出しＧＣ−ＭＳ分析を行った結果、ベンジルアルコールが１２％残存し、ベンジルクロリド７９％、ベンジルホーメート９％の混合物であった。
(Example 309)
In 2 mL of 1,4-dioxane, 0.61 g (10.3 mmol) of N-methylformamide and 2.0 g (9.9 mmol) of phthalic chloride were stirred at 40 ° C. for 2 hours. After cooling to room temperature, no corresponding imidoyl chloride crystals were precipitated, so 0.95 g (9.8 mmol) of benzyl alcohol was added and reacted at 50 ° C. for 3 hours, and water was added to stop the reaction. The organic substance was extracted with ether and subjected to GC-MS analysis. As a result, 12% of benzyl alcohol remained, and a mixture of 79% benzyl chloride and 9% benzylformate was obtained.
（実施例３１０）
Ｎ−メチルホルムアニリド１．３ｇ（０．９６ミリモル）とフタル酸クロリド２．２ｇ（１．０９ミリモル）を無溶媒にて５０℃で４時間、さらに８０℃で１時間反応させた。室温まで冷却すると全体が固化したが、１，４−ジオキサン４ｍＬを加えると完全に溶解してしまった。相当するイミドイルクロリドを結晶として単離することができなかったので、ベンジルアルコール１ｇ（０．９３ミリモル）を加え室温で３時間、さらに７０℃で１時間攪拌した。ＧＣ−ＭＳ分析の結果、ベンジルアルコールは完全に消失し、ベンジルクロリド４０％とベンジルホーメート６０％が生成していた。
(Example 310)
N-methylformanilide 1.3 g (0.96 mmol) and phthalic chloride 2.2 g (1.09 mmol) were reacted in the absence of solvent at 50 ° C. for 4 hours and further at 80 ° C. for 1 hour. Although the whole solidified when cooled to room temperature, it completely dissolved when 4 mL of 1,4-dioxane was added. Since the corresponding imidoyl chloride could not be isolated as crystals, 1 g (0.93 mmol) of benzyl alcohol was added and the mixture was stirred at room temperature for 3 hours and further at 70 ° C. for 1 hour. As a result of GC-MS analysis, benzyl alcohol completely disappeared, and 40% benzyl chloride and 60% benzylformate were formed.
（実施例３１１）
Ｎ，Ｎ−ジメチルベンズアミド６ｇ（４０ミリモル）とフタル酸クロリド９ｇ（４４．６ミリモル）を無溶媒にて１００℃で３時間攪拌した。室温まで冷却すると全体が固化したが、１，４−ジオキサン１０ｍＬを加えると全体が均一となり、相当するイミドイルクロリドを結晶として単離できなかった。ベンジルアルコール２．６ｇ（２４ミリモル）を加え室温で１時間攪拌するとベンジルアルコールは消失しベンジルクロリドに完全に変換していた。
(Example 311)
6 g (40 mmol) of N, N-dimethylbenzamide and 9 g (44.6 mmol) of phthalic chloride were stirred at 100 ° C. for 3 hours without solvent. Although the whole solidified when cooled to room temperature, the whole became uniform when 10 mL of 1,4-dioxane was added, and the corresponding imidoyl chloride could not be isolated as crystals. When 2.6 g (24 mmol) of benzyl alcohol was added and stirred at room temperature for 1 hour, the benzyl alcohol disappeared and was completely converted to benzyl chloride.
（実施例３１２）
Ｎ，Ｎ−ジメチルアセトアミド ４．３ｇ（４９ミリモル）とフタル酸クロリド１０．４（５１．５ミリモル）を３０℃で攪拌した。反応液は直ちに茶褐色に変化し固化し攪拌が不能になった。１，４−ジオキサン５０ｍＬを加えると全体が均一となった。２，６−ナフタレンジカルボン酸４．３ｇ（２０ミリモル）を加え懸濁状態で７０℃３時間攪拌すると均一溶液となった。室温まで冷却して析出した固体をろ取し、１，４−ジオキサンとヘキサンで洗浄後乾燥すると４．５ｇの２，６−ナフタレンジカルボン酸クロリドが得られた。収率は８９％であった。
(Example 312)
4.3 g (49 mmol) of N, N-dimethylacetamide and 10.4 (51.5 mmol) of phthalic acid chloride were stirred at 30 ° C. The reaction solution immediately turned brown and solidified, making stirring impossible. The whole became uniform when 50 mL of 1,4-dioxane was added. When 4.3 g (20 mmol) of 2,6-naphthalenedicarboxylic acid was added and stirred in a suspended state at 70 ° C. for 3 hours, a homogeneous solution was obtained. After cooling to room temperature, the precipitated solid was collected by filtration, washed with 1,4-dioxane and hexane and dried to obtain 4.5 g of 2,6-naphthalenedicarboxylic acid chloride. The yield was 89%.
（比較例ｃ３１）
ベンゾイルクロリド１０ｇ中、４，４’−スチルベンジカルボン酸１．０ｇ（３．７３ミリモル）とフタル酸クロリド１．５１ｇ（７．４８ミリモル）の混合物を７０℃で５時間攪拌した。ＧＣ分析をすると４，４’−スチルベンジカルボン酸クロリドの収率は１％以下であり、大半の原料を回収した。
(Comparative Example c31)
A mixture of 1.0 g (3.73 mmol) of 4,4′-stilbene dicarboxylic acid and 1.51 g (7.48 mmol) of phthalic chloride in 10 g of benzoyl chloride was stirred at 70 ° C. for 5 hours. According to GC analysis, the yield of 4,4′-stilbene dicarboxylic acid chloride was 1% or less, and most of the raw material was recovered.
（比較例ｃ３２）
４，４’−スチルベンジカルボン酸３０．１ｇ（０．１１モル）とフタル酸クロリド４７．５ｇ（０．２３モル）をベンゾイルクロリド３００ｇを溶媒として１４０℃で５時間攪拌した。冷却後、結晶をろ取、真空乾燥し３３．４ｇの薄緑色の結晶を得た。ＨＰＬＣ分析により、４，４’−スチルベンジカルボン酸クロリドの純度は９８．５％であり、無水フタル酸が０．３９％混入していた。ＨＰＬＣ感度補正。
(Comparative Example c32)
3,4'-stilbene dicarboxylic acid 30.1 g (0.11 mol) and phthalic acid chloride 47.5 g (0.23 mol) were stirred at 140 ° C. for 5 hours using 300 g of benzoyl chloride as a solvent. After cooling, the crystals were collected by filtration and dried under vacuum to obtain 33.4 g of light green crystals. According to HPLC analysis, the purity of 4,4′-stilbene dicarboxylic acid chloride was 98.5% and phthalic anhydride was mixed in 0.39%. HPLC sensitivity correction.
（比較例ｃ３３）
塩化ベンゾイル７３．１ｇ（０．５２０モル）中、２，６−ナフタレンジカルボン酸５．０ｇ（０．０２３モル）とフタル酸クロリド１０．０ｇ（０．０４９モル）の混合物を１４０℃で４時間攪拌した。ＨＰＬＣで反応をモニターすると２，６−ナフタレンジカルボン酸は完全に消失していたが、さらに２時間攪拌を続けた。室温まで冷却し５．３ｇの２，６−ナフタレンジカルボン酸クロリドの結晶をろ取した。この結晶を４−クロロ安息香酸を内部標準にしてＨＰＬＣ分析すると混入している無水フタル酸は３１ｗｔ％も含まれていた。
(Comparative Example c33)
In 73.1 g (0.520 mol) of benzoyl chloride, a mixture of 5.0 g (0.023 mol) of 2,6-naphthalenedicarboxylic acid and 10.0 g (0.049 mol) of phthalic acid chloride at 140 ° C. for 4 hours. Stir. When the reaction was monitored by HPLC, 2,6-naphthalenedicarboxylic acid was completely disappeared, but stirring was further continued for 2 hours. After cooling to room temperature, 5.3 g of 2,6-naphthalenedicarboxylic acid chloride crystals were collected by filtration. When this crystal was analyzed by HPLC using 4-chlorobenzoic acid as an internal standard, 31 wt% of phthalic anhydride contained was contained.
（実施例ＩＶ）
回転子が入った１０ｍＬの試験管に温度計を取り付け、無水フタル酸１．０ｇと１，４−ジオキサン、ＴＨＦ、または１，２−ジメトキシエタン（ＤＭＥ）３ｍＬを入れた。攪拌しながら温めると６０〜８０℃で無水フタル酸が溶解した。そのままゆっくりと冷却し無水フタル酸の結晶が析出し始める温度を調べた。結晶が析出し始めると、１ｍＬずつ１，４−ジオキサン、ＴＨＦまたは１，２−ジメトキシエタンを加え、結晶が析出する温度と溶媒量を詳細に調べた。
そのようにして３０℃、２５℃、２０℃での無水フタル酸が１，４−ジオキサン、ＴＨＦ、ジメトキシエタンに溶解する量を求めた。無水フタル酸１ｇを溶解できる１，４−ジオキサンの量をＶ、テトラヒドロフランの量をＲ、１，２−ジメトキシエタンの量をＹとすると、以下のようになった。
30℃ 5mL<V<4mL 4mL<R<3.5mL 5mL~Y
25℃ 6mL<V<5mL 5mL<R<4.5mL 5.5mL<Y<5mL
20℃ 7mL~V 5.5mL~R 6mL~Y
Example IV
A thermometer was attached to a 10 mL test tube containing a rotor, and 1.0 g of phthalic anhydride and 3 mL of 1,4-dioxane, THF, or 1,2-dimethoxyethane (DME) were added. When warmed with stirring, phthalic anhydride dissolved at 60-80 ° C. The temperature was slowly cooled as it was, and the temperature at which phthalic anhydride crystals began to precipitate was examined. When crystals began to precipitate, 1-mL each of 1,4-dioxane, THF, or 1,2-dimethoxyethane was added, and the temperature and amount of solvent at which crystals were precipitated were examined in detail.
Thus, the amount of phthalic anhydride dissolved in 1,4-dioxane, THF, and dimethoxyethane at 30 ° C., 25 ° C., and 20 ° C. was determined. When the amount of 1,4-dioxane capable of dissolving 1 g of phthalic anhydride is V, the amount of tetrahydrofuran is R, and the amount of 1,2-dimethoxyethane is Y, the following results are obtained.
30 ℃ 5mL <V <4mL 4mL <R <3.5mL 5mL ~ Y
25 ° C 6mL <V <5mL 5mL <R <4.5mL 5.5mL <Y <5mL
20 ℃ 7mL ~ V 5.5mL ~ R 6mL ~ Y
一方、Ｎ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの１，４−ジオキサン、ＴＨＦ、ＤＭＥへの溶解度を調べた。その結果、３０℃でＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリド１ｇを溶解するのに必要な１，４−ジオキサンの量は約４００〜５００ｍＬ，ＴＨＦは４００〜４５０ｍＬ、１，２−ジメトキシエタンは３５０ｍＬ以上であった。
この結果から明らかなとおり、本発明の単離方法によれば、目的のイミドイルクロリド化合物を純度よくエーテル系溶媒から単離して得ることができることが分かる。
On the other hand, the solubility of N, N-dimethylchloromethyleneiminium chloride in 1,4-dioxane, THF, and DME was examined. As a result, the amount of 1,4-dioxane required to dissolve 1 g of N, N-dimethylchloromethyleneiminium chloride at 30 ° C. is about 400 to 500 mL, THF is 400 to 450 mL, and 1,2-dimethoxyethane is It was 350 mL or more.
As is apparent from the results, according to the isolation method of the present invention, it can be seen that the target imidoyl chloride compound can be obtained with high purity from an ether solvent.
（実施例Ｖ）非特許文献３との対比
（比較例ｃ５１）
以下のようにして非特許文献３のエントリー１２に記載された反応の追試を行った。
ピバロイルクロリド１．３９ｇ（１１．５４ミリモル）とＤＭＦ５ｍＬを室温で１時間攪拌した。特に変化は見られなかった。そこにジクロロメタン３５ｍＬと２−オクチルアルコール０．９４ｇ（７．２３ミリモル）を加え１時間攪拌した。反応液に水２０ｍＬを加え有機相を分液、飽和炭酸ナトリウム溶液１５ｍＬで２回洗浄、続いて１ＮＨＣｌ、ブラインで洗浄した。無水硫酸ナトリウムで乾燥後、溶媒を減圧留去し、１．１ｇの残渣を得た。これをキャピラリーＧＣで分析した。（分析値は全面積％）
ＤＭＦ １８％、２−オクチルホルメート３１％、２−オクタノール ２８％、２−ピバロイルオクタノエート３３％の混合物であった。それぞれの化学構造はＧＣ−ＭＳで分析確認した。
Example V Comparison with Non-Patent Document 3 (Comparative Example c51)
The reaction described in entry 12 of Non-Patent Document 3 was added as follows.
1.39 g (11.54 mmol) of pivaloyl chloride and 5 mL of DMF were stirred at room temperature for 1 hour. There was no particular change. Thereto, 35 mL of dichloromethane and 0.94 g (7.23 mmol) of 2-octyl alcohol were added and stirred for 1 hour. 20 mL of water was added to the reaction solution, and the organic phase was separated and washed twice with 15 mL of saturated sodium carbonate solution, followed by 1N HCl and brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain 1.1 g of residue. This was analyzed by capillary GC. (Analysis value is total area%)
It was a mixture of 18% DMF, 31% 2-octyl formate, 28% 2-octanol, and 33% 2-pivaloyl octanoate. Each chemical structure was analyzed and confirmed by GC-MS.
非特許文献３は、上記エントリー１２の反応の結果について、塩素化生成物の収率を６０％と示している。上記結果と相違する理由は不明であるが、本発明者らの追試によると塩素化生成物はトレース程度しか確認されなかった。２−オクチルホルメートを塩素化生成物として評価してしまったことが示唆される。 Non-Patent Document 3 shows that the yield of the chlorinated product is 60% for the result of the reaction of entry 12 above. The reason for the difference from the above results is unclear, but according to the inventors' additional test, only a trace of chlorinated products was confirmed. It is suggested that 2-octyl formate has been evaluated as a chlorinated product.
（実施例５０１）
上記比較例ｃ５１との対比を考慮して、本発明の好ましい条件を適用した。
まず、ピバロイルクロリドをフタル酸クロリドに代えることが考慮されるが、そうすると、結晶が生成し、Ｎ，Ｎ−ジメチルクロロメチレンイミニウムクロリドを単離することができることは実施例１０１に示したとおりである。
そこで、さらに、実施例２０６と同様にＮ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶０．７１ｇ（５．６ミリモル）にジクロロメタン１５ｍＬを加え５−７℃に冷却した。そこに２−オクタノール（ラセミ体）０．６０ｇ（４．６ミリモル）のジクロロメタン溶液５ｍＬを加え、氷浴を取り除き室温で１５分攪拌した。反応液をそのままＧＣ−ＭＳに導入し２−オクタノールが完全に消費されていることを確認した。ＧＣ−ＭＳによる主成分は２−オクチルクロリドであった。また、反応液の一滴を取り飽和炭酸水素ナトリウム溶液とジクロロメタンの混合物に入れてよく振り混ぜＧＣＭＳを測定した場合の主生成物は２−オクチルホルメートであった。また、反応液の一部を試験管に取り少量の１，４−ジオキサンを加え８０℃のオイルバスに１時間漬けたのち、飽和炭酸水素ナトリウム溶液を加えよく振り混ぜジクロロメタン層をＧＣＭＳ分析すると２−オクチルクロリドが主生成物であった。
反応液全体を飽和炭酸水素ナトリウム溶液で洗浄後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し０．５６ｇの残渣を得、ＧＣ−ＭＳで分析すると２−オクチルクロリドではなく、２−オクチルホルメートが単一成分として得られた。単離収率７７％。純度９９％以上。なお、単離収率は単離に係るロスを含み上記の値であったが、反応基質が残っていないこと、副生物の生成が見られないことからほぼ１００％の反応収率で２−オクチルホルメートが得られていると判断された。下記スキーム２は、このときの反応スキームを整理して示したものである。
(Example 501)
In consideration of the comparison with the comparative example c51, preferable conditions of the present invention were applied.
First, consideration is given to replacing pivaloyl chloride with phthalic acid chloride, but in that case, crystals are formed and N, N-dimethylchloromethyleneiminium chloride can be isolated as shown in Example 101. It is as follows.
Therefore, in the same manner as in Example 206, 15 mL of dichloromethane was added to 0.71 g (5.6 mmol) of N, N-dimethylchloromethyleneiminium chloride crystals and cooled to 5-7 ° C. Thereto was added 5 mL of a solution of 0.60 g (4.6 mmol) of 2-octanol (racemate) in dichloromethane, the ice bath was removed, and the mixture was stirred at room temperature for 15 minutes. The reaction solution was introduced into GC-MS as it was, and it was confirmed that 2-octanol was completely consumed. The main component by GC-MS was 2-octyl chloride. Further, when a drop of the reaction solution was taken and placed in a mixture of saturated sodium hydrogen carbonate solution and dichloromethane and shaken well, and GCMS was measured, the main product was 2-octyl formate. A portion of the reaction solution is taken into a test tube, a small amount of 1,4-dioxane is added, and the mixture is immersed in an oil bath at 80 ° C. for 1 hour. Then, a saturated sodium hydrogen carbonate solution is added and shaken well. -Octyl chloride was the main product.
The entire reaction solution was washed with a saturated sodium bicarbonate solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.56 g of residue, which was analyzed by GC-MS, and 2-octyl formate was obtained as a single component instead of 2-octyl chloride. Isolated yield 77%. Purity 99% or more. Although the isolation yield was the above value including the loss related to isolation, there was no reaction substrate left and no by-product was produced. It was judged that octyl formate was obtained. The following scheme 2 shows a summary of the reaction scheme at this time.
（実施例５０２）
次に、前記比較例ｃ５１と基質をそろえ、前記実施例３０１の条件と同様にして、イミドイルクロリド化合物を単離せずに所定の反応を行った結果を示す。
ジクロロメタン２５ｍＬにフタル酸クロリド１．０９ｇ（５．４ミリモル）とＮ，Ｎ−ジメチルホルムアミド０．３９ｇ（５．４ミリモル）を加え、４０℃にて２時間攪拌するとスラリー状態となった。そこに２−オクタノール０．６５ｇ（５ミリモル）を加え、室温で０．５時間攪拌した。反応液の一部を取り飽和炭酸水素ナトリウムとよく振り混ぜ、ジクロロメタン層をＧＣＭＳで分析した。その結果は２−オクチルホルメートと無水フタル酸のほぼ１：１混合物であった。このとき、反応基質が残っていないこと、副生物の生成が見られないことからほぼ１００％の反応収率で２−オクチルホルメートが得られていると判断された。
(Example 502)
Next, the results of performing the predetermined reaction without isolating the imidoyl chloride compound in the same manner as in Example 301, with the substrate of Comparative Example c51 aligned.
To 25 mL of dichloromethane, 1.09 g (5.4 mmol) of phthalic acid chloride and 0.39 g (5.4 mmol) of N, N-dimethylformamide were added and stirred at 40 ° C. for 2 hours to obtain a slurry state. 2-octanol 0.65g (5 mmol) was added there, and it stirred at room temperature for 0.5 hour. A part of the reaction solution was taken and mixed well with saturated sodium bicarbonate, and the dichloromethane layer was analyzed by GCMS. The result was an approximately 1: 1 mixture of 2-octyl formate and phthalic anhydride. At this time, it was judged that 2-octyl formate was obtained with a reaction yield of almost 100% because no reaction substrate remained and no by-product was observed.
（実施例５０３）
さらに、脂肪族１級アルコールとの反応についても下記に示しておく。
Ｎ，Ｎ−ジメチルクロロメチレンイミニウムクロリドの結晶０．６８ｇ（５．３ミリモル）にジクロロメタン１５ｍＬを加え、５−７℃に冷却した。そこに１−オクタノール０．５４ｇ（４．２ミリモル）のジクロロメタン溶液５ｍＬを加え、室温にて１０分間攪拌した。反応液を直接ＧＣ分析すると原料の１−オクタノールは完全に消費されており、１−クロロオクタンが９９％以上の選択率で観測された。反応液を飽和炭酸水素ナトリウム溶液で洗い、無水硫酸ナトリウムで乾燥、溶媒を留去し０．６ｇの残渣を得た。ＧＣ−ＭＳで分析すると１−オクチルホルメート９０％と１−クロロオクタン１０％の混合物であった。
(Example 503)
Furthermore, the reaction with the aliphatic primary alcohol is also shown below.
To 0.68 g (5.3 mmol) of crystals of N, N-dimethylchloromethyleneiminium chloride, 15 mL of dichloromethane was added and cooled to 5-7 ° C. Thereto was added 5 mL of a dichloromethane solution of 0.54 g (4.2 mmol) of 1-octanol, and the mixture was stirred at room temperature for 10 minutes. When the reaction solution was directly analyzed by GC, the starting material 1-octanol was completely consumed, and 1-chlorooctane was observed at a selectivity of 99% or more. The reaction solution was washed with a saturated sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 0.6 g of a residue. When analyzed by GC-MS, it was a mixture of 90% 1-octylformate and 10% 1-chlorooctane.
上記実施例Ｖの結果を下記表にまとめて示す。 The results of Example V are summarized in the following table.
＊２：１−オクチルホルメート及び１−オクチルクロリドの収率である。
Claims (7)
前記酸素原子を含む有機化合物が、カルボン酸化合物、アルコール化合物、又はアルデヒド化合物である製造方法。 An organic compound containing an oxygen atom, isolated or without isolation of the imidoyl chloride compound obtained by the production method according to any one of claims 1 to 5, or when the imidoyl chloride compound is produced. A method for producing a deoxygenated chlorinated product, wherein the deoxygenated chlorinated product is brought into contact with a compound to cause a deoxygenated chlorination reaction
The manufacturing method whose organic compound containing the said oxygen atom is a carboxylic acid compound, an alcohol compound, or an aldehyde compound.
Electron-rich aromatics isolated or not isolated from the imidoyl chloride compound obtained by the production method according to any one of claims 1 to 5 or when the imidoyl chloride compound is produced. A process for producing an aromatic compound having a formyl group, which is reacted with a compound and hydrolyzed to introduce a formyl group into an aromatic nucleus.
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