JP4465674B2 - Method for producing benzyl (difluoromethyl) sulfide compound - Google Patents
Method for producing benzyl (difluoromethyl) sulfide compound Download PDFInfo
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- JP4465674B2 JP4465674B2 JP2003350882A JP2003350882A JP4465674B2 JP 4465674 B2 JP4465674 B2 JP 4465674B2 JP 2003350882 A JP2003350882 A JP 2003350882A JP 2003350882 A JP2003350882 A JP 2003350882A JP 4465674 B2 JP4465674 B2 JP 4465674B2
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- Prior art keywords
- benzyl
- difluoromethyl
- group
- salt
- sulfide
- Prior art date
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- -1 benzyl (difluoromethyl) sulfide compound Chemical class 0.000 title claims description 39
- 238000004519 manufacturing process Methods 0.000 title claims description 20
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 claims description 20
- 239000012044 organic layer Substances 0.000 claims description 19
- 229910052751 metal Inorganic materials 0.000 claims description 18
- 239000002184 metal Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 13
- RWRIWBAIICGTTQ-UHFFFAOYSA-N difluoromethane Chemical class FCF RWRIWBAIICGTTQ-UHFFFAOYSA-N 0.000 claims description 12
- 239000010410 layer Substances 0.000 claims description 12
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 11
- 229910052783 alkali metal Inorganic materials 0.000 claims description 8
- 150000001340 alkali metals Chemical class 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 38
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 28
- QMOWRNGLGDZHAF-UHFFFAOYSA-N difluoromethylsulfanylmethylbenzene Chemical class FC(F)SCC1=CC=CC=C1 QMOWRNGLGDZHAF-UHFFFAOYSA-N 0.000 description 23
- 238000000034 method Methods 0.000 description 21
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 239000002994 raw material Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 238000000926 separation method Methods 0.000 description 9
- QXGDJMRRBRQFBI-UHFFFAOYSA-N phenylmethanethiol;potassium Chemical compound [K].SCC1=CC=CC=C1 QXGDJMRRBRQFBI-UHFFFAOYSA-N 0.000 description 8
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 8
- 230000032683 aging Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 6
- JYQLKKNUGGVARY-UHFFFAOYSA-N difluoromethanesulfonyl chloride Chemical compound FC(F)S(Cl)(=O)=O JYQLKKNUGGVARY-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 159000000003 magnesium salts Chemical class 0.000 description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000002351 wastewater Substances 0.000 description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910003002 lithium salt Inorganic materials 0.000 description 2
- 159000000002 lithium salts Chemical class 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 238000004065 wastewater treatment Methods 0.000 description 2
- GKQXPTHQTXCXEV-UHFFFAOYSA-N (4-chlorophenyl)methanethiol Chemical compound SCC1=CC=C(Cl)C=C1 GKQXPTHQTXCXEV-UHFFFAOYSA-N 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- UKAZBNONDAVAKZ-UHFFFAOYSA-N [Li].CC1=CC=C(CS)C=C1 Chemical compound [Li].CC1=CC=C(CS)C=C1 UKAZBNONDAVAKZ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GRCDJFHYVYUNHM-UHFFFAOYSA-N bromodifluoromethane Chemical compound FC(F)Br GRCDJFHYVYUNHM-UHFFFAOYSA-N 0.000 description 1
- SXGBREZGMJVYRL-UHFFFAOYSA-N butan-1-amine;hydrobromide Chemical compound [Br-].CCCC[NH3+] SXGBREZGMJVYRL-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- YSLFMGDEEXOKHF-UHFFFAOYSA-N difluoro(iodo)methane Chemical compound FC(F)I YSLFMGDEEXOKHF-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- IUSOXUFUXZORBF-UHFFFAOYSA-N n,n-dioctyloctan-1-amine;hydrochloride Chemical compound [Cl-].CCCCCCCC[NH+](CCCCCCCC)CCCCCCCC IUSOXUFUXZORBF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004714 phosphonium salts Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- ZOCLAPYLSUCOGI-UHFFFAOYSA-M potassium hydrosulfide Chemical compound [SH-].[K+] ZOCLAPYLSUCOGI-UHFFFAOYSA-M 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000001577 simple distillation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004354 sulfur functional group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BRKFQVAOMSWFDU-UHFFFAOYSA-M tetraphenylphosphanium;bromide Chemical compound [Br-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BRKFQVAOMSWFDU-UHFFFAOYSA-M 0.000 description 1
- WAGFXJQAIZNSEQ-UHFFFAOYSA-M tetraphenylphosphonium chloride Chemical compound [Cl-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WAGFXJQAIZNSEQ-UHFFFAOYSA-M 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
ジフルオロメチルスルホニルアニリド誘導体のあるものは除草剤として有用であることが知られている。本発明はジフルオロメチルスルホニル基の導入に用いるジフルオロメチルスルフォニルクロライドを製造する際に、前駆体として有用なベンジル（ジフルオロメチル）スルフィド化合物を製造する方法に関するものである。 Certain difluoromethylsulfonylanilide derivatives are known to be useful as herbicides. The present invention relates to a method for producing a benzyl (difluoromethyl) sulfide compound useful as a precursor when producing difluoromethylsulfonyl chloride used for introduction of a difluoromethylsulfonyl group.
ベンジル（ジフルオロメチル）スルフィド化合物を得る方法として、ベンジルメルカプタンとクロロジフルオロメタンをＮ，Ｎ−ジメチルホルムアミド、ジオキサン、又はテトラヒドロフラン溶媒及び水酸化ナトリウムの存在下で反応させる方法は知られている（非特許文献１参照）。また、水とアルコールの混合溶媒を用いる方法が知られている。（特許文献１参照）。しかし、これらの方法は用いる溶媒が水と分液しないため、用いた溶媒が大量に廃水中に混入し、廃水処理負荷が大きくなり、環境に対してもやさしいものではなかった。これを避けるためには、溶媒回収といった工業的に煩雑な操作を必要とする。また、Ｎ，Ｎ−ジメチルホルムは皮膚、目、粘膜を刺激し、長期間の吸入により肝障害を起こすことが知られており、工業的実施には決して好ましいものではなかった。 As a method for obtaining a benzyl (difluoromethyl) sulfide compound, a method in which benzyl mercaptan and chlorodifluoromethane are reacted in the presence of N, N-dimethylformamide, dioxane, or tetrahydrofuran solvent and sodium hydroxide is known (non-patent document). Reference 1). Further, a method using a mixed solvent of water and alcohol is known. (See Patent Document 1). However, since the solvent used in these methods is not separated from water, a large amount of the solvent used is mixed into the wastewater, increasing the wastewater treatment load and not being environmentally friendly. In order to avoid this, an industrially complicated operation such as solvent recovery is required. In addition, N, N-dimethylform is known to irritate the skin, eyes and mucous membranes and cause liver damage by inhalation over a long period of time, which is not preferable for industrial practice.
また、有機層と水の二層系で反応することにより、ベンジル（ジフルオロメチル）スルフィド化合物を得る方法は知られていなかった。 Further, a method for obtaining a benzyl (difluoromethyl) sulfide compound by reacting in a two-layer system of an organic layer and water has not been known.
上記従来の技術の持つ欠点を解決した、廃水処理負荷が小さく環境にやさしい、ベンジル（ジフルオロメチル）スルフィド化合物を製造方法の開発が望まれていた。 It has been desired to develop a method for producing a benzyl (difluoromethyl) sulfide compound that solves the above-mentioned drawbacks of the prior art and has a small wastewater treatment load and is environmentally friendly.
上記のような状況に鑑み、本発明者がベンジル（ジフルオロメチル）スルフィド化合物を製造する方法について鋭意研究を重ねた結果、意外にも、水と有機層からなる二層系でベンジルメルカプタン金属塩とハロゲン化ジフルオロメタンとを反応させることにより、上記課題を解決できることを見出し、四級アンモニウム塩が存在すればなお好結果が得られやすいことを知得し、この知見に基づき本発明を完成するに至った。 In view of the above situation, as a result of the present inventor's extensive research on a method for producing a benzyl (difluoromethyl) sulfide compound, surprisingly, a benzyl mercaptan metal salt is formed in a two-layer system composed of water and an organic layer. The present inventors have found that the above-mentioned problems can be solved by reacting with halogenated difluoromethane, knowing that good results are still easily obtained if quaternary ammonium salts are present, and completing the present invention based on this finding. It came.
本発明方法により、ベンジル（ジフルオロメチル）スルフィド化合物の新規な工業的製造法が提供される。本発明方法によれば、原料として、入手容易なベンジルメルカプタン金属塩とハロゲン化ジフルオロメタンを用いてベンジル（ジフルオロメチル）スルフィド化合物を簡便な操作で製造できる。更に、本発明方法では溶媒回収といった操作が不要であり、従来の方法に比べて廃水の負荷も小さく環境にもやさしく、工業的な利用価値が高い。 The method of the present invention provides a novel industrial production method for benzyl (difluoromethyl) sulfide compounds. According to the method of the present invention, a benzyl (difluoromethyl) sulfide compound can be produced by a simple operation using a benzyl mercaptan metal salt and a halogenated difluoromethane as raw materials. Furthermore, the method of the present invention does not require an operation such as solvent recovery, has a smaller wastewater load than the conventional method, is environmentally friendly, and has high industrial utility value.
以下、本発明について詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明は、下記〔１〕乃至〔４〕項に記載の発明を提供する事により前記課題を解決したものである。
〔１〕一般式（１）
This invention solves the said subject by providing the invention as described in the following [1] thru | or [ 4 ] item.
[1] General formula (1)
（式中、Ｒは水素原子、アルキル基、ハロゲン原子、アルコキシ基、アルコキシアルキル基、ハロアルキル基、カルボキシル基、又はアルコキシカルボニル基を示し、ｎは１〜５を示し、Ｘ１はアルカリ金属又はアルカリ土類金属を示し、ｍはＸ１がアルカリ金属の場合は１を示し、Ｘ１がアルカリ土類金属の場合は２を示す。） (In the formula, R represents a hydrogen atom, an alkyl group, a halogen atom, an alkoxy group, an alkoxyalkyl group, a haloalkyl group, a carboxyl group, or an alkoxycarbonyl group, n represents 1 to 5, and X 1 represents an alkali metal or an alkali. An earth metal, and m represents 1 when X 1 is an alkali metal, and 2 when X 1 is an alkaline earth metal.
表されるベンジルメルカプタン金属塩と、一般式（２） Benzyl mercaptan metal salt represented by the general formula (2)
（式中、Ｘ２はハロゲン原子である。） (In the formula, X 2 is a halogen atom.)
で表されるハロゲン化ジフルオロメタンとを、水層と有機層からなる二層系で、四級アンモニウム塩存在下で反応させる事を特徴とする、一般式（４） Wherein the halogenated difluoromethane is reacted in the presence of a quaternary ammonium salt in a two-layer system consisting of an aqueous layer and an organic layer.
（式中、Ｒ、ｎは前記と同じ意味を示す。） (In the formula, R and n have the same meaning as described above.)
で表されるベンジル（ジフルオロメチル）スルフィド化合物の製造方法。 The manufacturing method of the benzyl (difluoromethyl) sulfide compound represented by these.
〔２〕有機層が、芳香族炭化水素溶媒層である、〔１〕記載のベンジル（ジフルオロメチル）スルフィド化合物の製造方法。 [2] The method for producing a benzyl (difluoromethyl) sulfide compound according to [1], wherein the organic layer is an aromatic hydrocarbon solvent layer .
〔３〕ベンジルメルカプタン金属塩を系内で調製するものである、〔１〕又は〔２〕のいずれか１項に記載のベンジル（ジフルオロメチル）スルフィド化合物の製造方法。 [3] The method for producing a benzyl (difluoromethyl) sulfide compound according to any one of [1] or [2], wherein a benzyl mercaptan metal salt is prepared in the system.
〔４〕Ｘ２が塩素原子である、〔１〕ないし〔３〕のいずれか１項に記載のベンジル（ジフルオロメチル）スルフィド化合物の製造方法。 [4] The method for producing a benzyl (difluoromethyl) sulfide compound according to any one of [1] to [ 3 ], wherein X 2 is a chlorine atom.
〔５〕Ｘ１がアルカリ金属である、〔１〕乃至〔４〕のいずれか１項に記載のベンジル（ジフルオロメチル）スルフィド化合物の製造方法。 [5] The method for producing a benzyl (difluoromethyl) sulfide compound according to any one of [1] to [ 4 ], wherein X 1 is an alkali metal.
以下、本発明方法について詳細に説明する。 Hereinafter, the method of the present invention will be described in detail.
本発明方法は、一般式（１）で表されるベンジルメルカプタン金属塩と、一般式（２）で表されるハロゲン化ジフルオロメタンとを、水と有機層よりなる二層系で、四級アンモニウム塩存在下で反応させる事を特徴とする、一般式（３）で表されるベンジル（ジフルオロメチル）スルフィド化合物の製造方法である。 The method of the present invention is a quaternary ammonium salt comprising a benzyl mercaptan metal salt represented by the general formula (1) and a halogenated difluoromethane represented by the general formula (2) in a two-layer system comprising water and an organic layer. A method for producing a benzyl (difluoromethyl) sulfide compound represented by the general formula (3) , wherein the reaction is performed in the presence of a salt .
まず、本発明方法の原料として用いる、一般式（１）で表される原料化合物について説明する。 First, the raw material compound represented by the general formula (1) used as a raw material of the method of the present invention will be described.
一般式（１）中のＲは、水素原子；例えばメチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｓｅｃ−ブチル基、ｔ−ブチル基、ｎ−ペンチル基、ｎ−ヘキシル基等の炭素数１乃至６（以下、炭素数については、炭素数が１乃至６である場合には、これを「Ｃ１〜Ｃ６」の様に略記する。）の直鎖又は分岐Ｃ１〜Ｃ６アルキル基；例えば塩素原子、臭素原子、ヨウ素原子、フッ素原子等のハロゲン原子；例えばメトキシ基、エトキシ基、ｎ−プロポキシ基、イソプロポキシ基等の直鎖又は分岐Ｃ１〜Ｃ６アルコキシ基；メトキシメチル基、メトキシエチル基、エトキシエチル基等の（直鎖又は分岐Ｃ１〜Ｃ６アルコキシ）−（直鎖又は分岐Ｃ１〜Ｃ６アルキレン）基として表現されるアルコキシアルキル基；フルオロメチル基、ジフルオロメチル基、トリフルオロメチル基等の直鎖又は分岐Ｃ１〜Ｃ６ハロアルキル基；カルボキシル基；メトキシカルボニル基、エトキシカルボニル基等の（直鎖又は分岐Ｃ１〜Ｃ６アルコキシ）カルボニル基として表現されるアルコキシカルボニル基であり、Ｘ１は例えばリチウム、ナトリウム、カリウムに代表されるアルカリ金属、又は例えばバリウム、カルシウム、マグネシウムに代表されるアルカリ土類金属を示す。 R in the general formula (1) is a hydrogen atom; for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, t-butyl group, n-pentyl group, n- Straight or branched C1-C6 having 1 to 6 carbon atoms such as a hexyl group (hereinafter, the carbon number is abbreviated as “C1 to C6” when the carbon number is 1 to 6). C6 alkyl group; for example, halogen atom such as chlorine atom, bromine atom, iodine atom, fluorine atom; linear or branched C1-C6 alkoxy group such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group; An alkoxyalkyl group represented as a (straight chain or branched C1-C6 alkoxy)-(straight chain or branched C1-C6 alkylene) group such as a methoxyethyl group, an ethoxyethyl group; A straight-chain or branched C1-C6 haloalkyl group such as a sulfur group, a difluoromethyl group, a trifluoromethyl group; a carboxyl group; a (linear or branched C1-C6 alkoxy) carbonyl group such as a methoxycarbonyl group or an ethoxycarbonyl group. that an alkoxycarbonyl group, X 1 is shown such as lithium, sodium, alkali metal typified by potassium, or such as barium, calcium, an alkaline earth metal typified by magnesium.
一般式（１）で表されるベンジルメルカプタン金属塩としては、具体的には例えばベンジルメルカプタンのリチウム塩、ナトリウム塩、カリウム塩、マグネシウム塩又はカルシウム塩、ｐ−クロロベンジルメルカプタンのリチウム塩、ナトリウム塩、カリウム塩、マグネシウム塩又はカルシウム塩、ｐ−メチルベンジルメルカプタンのリチウム塩、ナトリウム塩、カリウム塩、マグネシウム塩又はカルシウム塩、ｐ−メトキシベンジルメルカプタンのリチウム塩、ナトリウム塩、カリウム塩、マグネシウム塩又はカルシウム塩等を例示することができる。 Specific examples of the benzyl mercaptan metal salt represented by the general formula (1) include lithium salt, sodium salt, potassium salt, magnesium salt or calcium salt of benzyl mercaptan, lithium salt of sodium p-chlorobenzyl mercaptan, and sodium salt. , Potassium salt, magnesium salt or calcium salt, p-methylbenzyl mercaptan lithium salt, sodium salt, potassium salt, magnesium salt or calcium salt, p-methoxybenzyl mercaptan lithium salt, sodium salt, potassium salt, magnesium salt or calcium A salt etc. can be illustrated.
これらのベンジルメルカプタン金属塩は、相当する、一般式（１）で表されるベンジルメルカプタン化合物のＸ１に相当する基が水素である化合物、例えば、ベンジルメルカプタン、ｐ−クロロベンジルメルカプタン、ｐ−メチルベンジルメルカプタン等と、例えば水酸化リチウム、水酸化ナトリウム、水酸化カリウム等のアルカリ金属水酸化物、又は例えば水酸化カルシウム、水酸化マグネシウム等のアルカリ土類金属水酸化物を、一般式（１）で表されるベンジルメルカプタン金属塩のＸ１に相当する基が水素である化合物１モルに対して通常１．０〜１５．０当量、好ましくは１．０〜５．０当量の範囲で反応させることにより容易に得られる化合物である。なお、一般式（１）で表されるベンジルメルカプタン化合物のＸ１が水素である化合物は、例えば、ベンジルクロリド等に代表される、対応するベンジルハロゲン化物と、たとえば水硫化カリウムや水硫化ナトリウムに代表される水硫化アルカリ金属を反応させた後、反応液の液性を例えば塩酸等の酸を用いて酸性にする方法等により製造することができる。 These benzyl mercaptan metal salts are compounds in which the group corresponding to X 1 of the benzyl mercaptan compound represented by the general formula (1) is hydrogen, such as benzyl mercaptan, p-chlorobenzyl mercaptan, p-methyl. Benzyl mercaptan and the like and an alkali metal hydroxide such as lithium hydroxide, sodium hydroxide and potassium hydroxide, or an alkaline earth metal hydroxide such as calcium hydroxide and magnesium hydroxide are represented by the general formula (1) In general, the reaction is performed in the range of 1.0 to 15.0 equivalents, preferably 1.0 to 5.0 equivalents per 1 mol of the compound in which the group corresponding to X 1 of the benzyl mercaptan metal salt represented by formula (I) is hydrogen It is a compound easily obtained. A compound in which X 1 of the benzyl mercaptan compound represented by the general formula (1) is hydrogen includes, for example, a corresponding benzyl halide represented by benzyl chloride and the like, for example, potassium hydrosulfide and sodium hydrosulfide. After reacting a representative alkali metal hydrosulfide, it can be produced by a method in which the liquidity of the reaction solution is acidified using an acid such as hydrochloric acid.
本発明方法においては、一般式（１）で表されるベンジルメルカプタン金属塩は予め別途調製しておいたものを用いることもできるし、反応系内でベンジルメルカプタン金属塩を調製して使用することもできる。操作の簡便さの観点からは、反応系内でベンジルメルカプタン金属塩を調製する手法が好ましい。 In the method of the present invention, the benzyl mercaptan metal salt represented by the general formula (1) can be prepared separately in advance, or the benzyl mercaptan metal salt can be prepared and used in the reaction system. You can also. From the viewpoint of ease of operation, a method of preparing a benzyl mercaptan metal salt in the reaction system is preferable.
反応系内でベンジルメルカプタン金属塩を調製する方法としては、例えば上述のように、相当する一般式（１）で表されるベンジルメルカプタン金属塩のＸ１が金属ではなく水素である化合物と、アルカリ金属水酸化物、又はアルカリ土類金属水酸化物を反応させる事により、系内で一般式（１）で表されるベンジルメルカプタン金属塩を調製する方法や、例えば一般式（１）で表されるベンジルメルカプタン化合物のＸ１に相当する基が基−Ｃ（＝ＮＨ）ＮＨ２・ＨＸ（ここでＸは、フッ素原子、塩素原子、臭素原子、ヨウ素原子等のハロゲン原子を示すのであり、従ってＨＸでハロゲン化水素を表している。）である、例えばベンジルチオロニウム塩酸塩、ｐ−クロロベンジルチオロニウム塩酸塩、ｐ−メチルベンジルチオロニウム塩酸塩、ｐ−メトキシベンジルチオロニウム塩酸塩等のチオロニウム化合物１モルに対して、通常４．０〜１７．０当量、好ましくは４．０〜７．０当量の水酸化リチウム、水酸化ナトリウム、水酸化カリウム等のアルカリ金属水酸化物、又は水酸化カルシウムアルカリ土類金属水酸化物と反応させる方法を例示することができる。なお、上記チオロニウム化合物は、対応するベンジルハロゲン化物とチオ尿素とを反応させる方法で製造することができる。 As a method for preparing the benzyl mercaptan metal salt in the reaction system, for example, as described above, a compound in which X 1 of the corresponding benzyl mercaptan metal salt represented by the general formula (1) is not metal but hydrogen, A method of preparing a benzyl mercaptan metal salt represented by the general formula (1) in the system by reacting a metal hydroxide or an alkaline earth metal hydroxide, for example, represented by the general formula (1) The group corresponding to X 1 of the benzyl mercaptan compound is a group —C (═NH) NH 2 .HX (where X represents a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom, HX represents hydrogen halide.) For example, benzylthioronium hydrochloride, p-chlorobenzylthioronium hydrochloride, p-methylbenzylthioronium salt Salt, usually 1 to 4.0 equivalents, preferably 4.0 to 7.0 equivalents of lithium hydroxide, sodium hydroxide, and 1 mol of a thioronium compound such as p-methoxybenzylthioronium hydrochloride. The method of making it react with alkali metal hydroxides, such as potassium hydroxide, or a calcium hydroxide alkaline-earth metal hydroxide can be illustrated. In addition, the said thioronium compound can be manufactured by the method of making a corresponding benzyl halide and thiourea react.
続いて、一般式（２）で表されるハロゲン化ジフルオロメタンについて説明する。 Subsequently, the halogenated difluoromethane represented by the general formula (2) will be described.
一般式（２）中のＸ２はフッ素原子、塩素原子、臭素原子、ヨウ素原子等のハロゲン原子を示す。 X 2 in the general formula (2) represents a fluorine atom, a chlorine atom, a bromine atom, a halogen atom such as iodine atom.
従って、当反応に使用できる一般式（２）で表されるハロゲン化ジフルオロメタンとしては、具体的にはトリフルオロメタン、クロロジフルオロメタン、ブロモジフルオロメタン、ジフルオロヨードメタンを例示できるが、クロロジフルオロメタンが反応速度や副生物の少なさ、また比較的安価である点などから好ましいものとして例示できる。 Therefore, specific examples of the halogenated difluoromethane represented by the general formula (2) that can be used in this reaction include trifluoromethane, chlorodifluoromethane, bromodifluoromethane, and difluoroiodomethane. Preferred examples include the reaction rate, the number of by-products, and the relatively low cost.
これらの一般式（２）で表されるハロゲン化ジフルオロメタンは公知化合物である。 These halogenated difluoromethanes represented by the general formula (2) are known compounds.
当反応における、一般式（２）で表されるハロゲン化ジフルオロメタンの使用モル比は、一般式（１）で表される原料化合物に対して如何なるモル比でも反応が進行するが、一般式（１）で表されるベンジルメルカプタン化合物１モルに対して、一般式（２）で表されるハロゲン化ジフルオロメタンが、通常０.１〜１０.０モル、好ましくは１．０〜５．０モル、更に好ましくは１.４〜２.２モルの範囲を例示できる。 In this reaction, the reaction proceeds at any molar ratio of the halogenated difluoromethane represented by the general formula (2) to the raw material compound represented by the general formula (1). The halogenated difluoromethane represented by the general formula (2) is usually 0.1 to 10.0 moles, preferably 1.0 to 5.0 moles per mole of the benzyl mercaptan compound represented by 1). More preferably, the range of 1.4 to 2.2 mol can be exemplified.
当反応は四級アンモニウム塩を用いる。当反応に用いうる四級アンモニウム塩としては、例えば、テトラブチルアンモニウムブロミド、トリ−ｎ−オクチルメチルアンモニウムクロリド（株式会社 同仁科学研究所から「カプリコート」なる商品名で市販されている。）、テトラブチルアンモニウムクロリド等の四級アンモニウム塩；テトラフェニルホスホニウムブロミド、テトラフェニルホスホニウムクロリド等の四級ホスホニウム塩を例示することができるが、好ましくはテトラブチルアンモニウムブロミドを用いて行なうのがよい。 This reaction uses a quaternary ammonium salt . The quaternary ammonium salts used in those reactions, if example embodiment, tetrabutylammonium bromide, tri -n- octyl ammonium chloride (commercially available under the "Capri Court" is a trade name of Corporation Dojin Science.) , quaternary ammonium salts such as tetrabutylammonium chloride; tetraphenylphosphonium bromide, can be exemplified quaternary phosphonium salts such as tetraphenylphosphonium chloride, and it is preferably carried out using a Te tiger butyl ammonium bromide.
当反応における四級アンモニウム塩の使用量は、反応が充分に進行する量であれば何れでも良いが、一般式（１）で表される原料化合物１モルに対して０．００１〜１００モル、好ましくは０．０１〜１.０モルの範囲を例示できる。 The amount of the quaternary ammonium salt used in this reaction may be any amount as long as the reaction proceeds sufficiently, but 0.001 to 100 mol relative to 1 mol of the raw material compound represented by the general formula (1), Preferably the range of 0.01-1.0 mol can be illustrated.
当反応は、水溶媒及び原料のみからなる二層系でも行うことができるし、芳香族炭化水素溶媒及び水溶媒を用いて二層として行うことも好ましい態様として例示できる。当反応に用いうる芳香族炭化水素溶媒としては、例えば、トルエン、キシレン、クロロベンゼン等の芳香族炭化水素を例示できる。トルエン、キシレン、クロロベンゼン等の芳香族炭化水素が特に好ましい。該芳香族炭化水素溶媒は単独で、又は任意の混合割合の混合溶媒として用いることができる。 This reaction can also be carried out in a two-layer system consisting only of an aqueous solvent and a raw material, and can also be exemplified as a preferred embodiment by carrying out as a two-layer using an aromatic hydrocarbon solvent and an aqueous solvent. The aromatic hydrocarbon solvent which can be used in those reactions, if example embodiment, toluene, xylene, aromatic hydrocarbons such as chlorobenzene can be exemplified. Toluene, xylene, aromatic hydrocarbons such as chlorobenzene particularly preferred. The aromatic hydrocarbon solvent alone, or in any can be used as a mixed solvent mixing ratio.
芳香族炭化水素溶媒の使用量としては、一般式（１）で表される原料化合物１モルに対して通常０〜１０Ｌ（リットル）、好ましくは０．１〜２.０Ｌの範囲であれば良い。 The amount of the aromatic hydrocarbon solvent used is usually in the range of 0 to 10 L (liter), preferably 0.1 to 2.0 L, with respect to 1 mol of the raw material compound represented by the general formula (1). .
水の使用量としては、一般式（１）で表される原料化合物１モルに対して通常０.１〜１０Ｌ（リットル）、好ましくは０．１〜２.０Ｌの範囲であれば良い。 The amount of water used is usually in the range of 0.1 to 10 L (liter), preferably 0.1 to 2.0 L, relative to 1 mol of the raw material compound represented by the general formula (1).
当反応の反応温度は、溶媒の沸点以下の範囲を例示できるが、好ましくは１０℃〜６０℃の範囲が良い。 Although the reaction temperature of this reaction can illustrate the range below the boiling point of a solvent, Preferably the range of 10 to 60 degreeC is good.
当反応の反応時間は特に制限されないが、好ましくは４時間〜４０時間がよい。 Although the reaction time of this reaction is not particularly limited, it is preferably 4 hours to 40 hours.
反応器への原料等の添加順序及び反応方法は特に制限されないが、好適な例としては、水及び有機層中に四級アンモニウム塩を加え、これにベンジルメルカプタン化合物を加え溶解させる。次いで、ハロゲン化ジフルオロメタンを導入することにより反応を行い、ベンジル（ジフルオロメチル）フルフィド化合物を得る方法が挙げられる。 The order of addition of the raw materials and the like to the reactor and the reaction method are not particularly limited, but as a suitable example, a quaternary ammonium salt is added to water and the organic layer, and a benzyl mercaptan compound is added and dissolved therein. Next, there is a method in which a reaction is carried out by introducing a halogenated difluoromethane to obtain a benzyl (difluoromethyl) fluoride compound.
反応雰囲気は窒素やアルゴン等の不活性ガスで置換しておくことが望ましい。 The reaction atmosphere is preferably replaced with an inert gas such as nitrogen or argon.
反応終了後、有機層に抽出されている一般式（３）で表されるベンジル（ジフルオロメチル）フルフィド化合物は単離することなく溶液のままを他の反応に用いることもできるし、蒸留などにより一般式（３）で表されるベンジル（ジフルオロメチル）フルフィド化合物を単離することもできる。 After completion of the reaction, the benzyl (difluoromethyl) fluoride compound represented by the general formula (3) extracted in the organic layer can be used as it is for other reactions without isolation, or by distillation or the like. The benzyl (difluoromethyl) fluoride compound represented by the general formula (3) can also be isolated.
当反応によれば、四級アンモニウム塩存在下、有機層と水の二層系で反応し、一般式（３）で表されるベンジル（ジフルオロメチル）フルフィド化合物が生成する。得られる一般式（３）で表されるベンジル（ジフルオロメチル）フルフィド化合物は、ジフルオロメチルフルホニルクロライドの前駆体として有用な化合物である。 According to this reaction, in the presence of a quaternary ammonium salt , it reacts in a two-layer system of an organic layer and water to produce a benzyl (difluoromethyl) fluoride compound represented by the general formula (3). The resulting benzyl (difluoromethyl) fluoride compound represented by the general formula (3) is a useful compound as a precursor of difluoromethyl sulfonyl chloride.
次に、実施例を挙げて本発明化合物の製造方法を具体的に説明するが、本発明は、これら実施例によって何ら限定されるものではない。 Next, although the Example is given and the manufacturing method of this invention compound is demonstrated concretely, this invention is not limited at all by these Examples.
実施例１：ベンジル（ジフルオロメチル）スルフィドの合成
２００ｍｌの四径フラスコに水５０ｍｌ、クロロベンゼン５０ｍｌを加え、水酸化カリウム２８．１ｇ（０．５ｍｏｌ）、テトラブチルアンモニウムブロミド４．２２ｇを加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成した後、４０℃まで冷却し、ベンジルメルカプタンカリウム塩を系内で調製した。
Example 1: Synthesis of benzyl (difluoromethyl) sulfide 50 ml of water and 50 ml of chlorobenzene were added to a 200 ml four-diameter flask, and 28.1 g (0.5 mol) of potassium hydroxide and 4.22 g of tetrabutylammonium bromide were added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. After adding 20.4 g (0.1 mol) of benzylthioronium hydrochloride and aging for 40 minutes, the mixture was cooled to 40 ° C. to prepare benzyl mercaptan potassium salt in the system.
次いで、クロロジフルオロメタン１０．０ｇを２．５時間かけて導入し、４８％水酸化カリウム水溶液１１．６ｇ（０．１ｍｏｌ）を加えた。クロロジフルオロメタン２．７ｇを４０分かけて導入し反応した。反応終了後、水５０ｍｌを加え分液した。有機層を更に水２５ｍｌで洗浄した後、溶媒を留去することにより、ベンジル（ジフルオロメチル）スルフィドを１５.５ｇ（収率８９.７％）を得た。ここで得られたベンジル（ジフルオロメチル）スルフィドを単蒸留し、得られたガスクロマトグラフィーで全面積９８.６％のものを標品とし、以下内標分析法（内標物質；ｏ−ジクロロベンゼン）で収率を算出した。 Next, 10.0 g of chlorodifluoromethane was introduced over 2.5 hours, and 11.6 g (0.1 mol) of a 48% aqueous potassium hydroxide solution was added. 2.7 g of chlorodifluoromethane was introduced over 40 minutes to react. After completion of the reaction, 50 ml of water was added for liquid separation. The organic layer was further washed with 25 ml of water, and then the solvent was distilled off to obtain 15.5 g (yield 89.7%) of benzyl (difluoromethyl) sulfide. The benzyl (difluoromethyl) sulfide obtained here is subjected to simple distillation, and the obtained gas chromatography is used to prepare a sample having a total area of 98.6%. The internal standard analysis method (internal standard substance; o-dichlorobenzene) ) To calculate the yield.
１Ｈ−ＮＭＲ（ＣＨＣｌ３−ｄ１,４００ＭＨｚ）δ=４．０２（Ｓ，２Ｈ）、６．７４（ｔ，１Ｈ，Ｊ＝５６．４Ｈｚ）、７．２５−７．４２（ｍ，５Ｈ）
ＭＳ（ＧＣ−ＭＳ）ｍ／ｚ＝１７４（Ｍ＋）,９１（ｂａｓｅ）.
1 H-NMR (CHCl 3 -d 1 , 400 MHz) δ = 4.02 (S, 2H), 6.74 (t, 1H, J = 56.4 Hz), 7.25-7.42 (m, 5H) )
MS (GC-MS) m / z = 174 (M <+> ), 91 (base).
実施例２：ベンジル（ジフルオロメチル）スルフィドの合成
２００ｍｌの四径フラスコに水５０ｍｌ、トルエン５０ｍｌを加え、水酸化カリウム２８．１ｇ（０．５ｍｏｌ）、テトラブチルアンモニウムブロミド４．２２ｇを加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成した後、４０℃まで冷却し、ベンジルメルカプタンカリウム塩を系内で調製した。
Example 2: Synthesis of benzyl (difluoromethyl) sulfide 50 ml of water and 50 ml of toluene were added to a 200 ml four-diameter flask, and 28.1 g (0.5 mol) of potassium hydroxide and 4.22 g of tetrabutylammonium bromide were added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. After adding 20.4 g (0.1 mol) of benzylthioronium hydrochloride and aging for 40 minutes, the mixture was cooled to 40 ° C. to prepare benzyl mercaptan potassium salt in the system.
次いで、クロロジフルオロメタン１０．０ｇを４時間かけて導入し、４８％水酸化カリウム水溶液１１．６ｇ（０．１ｍｏｌ）を加えた。クロロジフルオロメタン２．７ｇを４０分かけて導入し反応した。反応終了後、水５０ｍｌを加え分液した。有機層を更に水２５ｍｌで洗浄し、ベンジル（ジフルオロメチル）スルフィドのトルエン溶液を５４.８ｇ（収率８８.４％）を得た。 Next, 10.0 g of chlorodifluoromethane was introduced over 4 hours, and 11.6 g (0.1 mol) of a 48% aqueous potassium hydroxide solution was added. 2.7 g of chlorodifluoromethane was introduced over 40 minutes to react. After completion of the reaction, 50 ml of water was added for liquid separation. The organic layer was further washed with 25 ml of water to obtain 54.8 g (yield: 88.4%) of a toluene solution of benzyl (difluoromethyl) sulfide.
実施例３：ベンジル（ジフルオロメチル）スルフィドの合成
２００ｍｌの四径フラスコに水５０ｍｌ、キシレン５０ｍｌを加え、水酸化カリウム２８．１ｇ（０．５ｍｏｌ）、テトラブチルアンモニウムブロミド４．２２ｇを加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成した後、４０℃まで冷却し、ベンジルメルカプタンカリウム塩を系内で調製した。
Example 3 Synthesis of benzyl (difluoromethyl) sulfide 50 ml of water and 50 ml of xylene were added to a 200 ml four-diameter flask, and 28.1 g (0.5 mol) of potassium hydroxide and 4.22 g of tetrabutylammonium bromide were added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. After adding 20.4 g (0.1 mol) of benzylthioronium hydrochloride and aging for 40 minutes, the mixture was cooled to 40 ° C. to prepare benzyl mercaptan potassium salt in the system.
次いで、クロロジフルオロメタン１０．０ｇを４．５時間かけて導入し、４８％水酸化カリウム水溶液１１．６ｇ（０．１ｍｏｌ）を加えた。クロロジフルオロメタン２．７ｇを１時間かけて導入し反応した。反応終了後、水５０ｍｌを加え分液した。有機層を更に水２５ｍｌで洗浄し、ベンジル（ジフルオロメチル）スルフィドのキシレン溶液を６２.４ｇ（収率８６.８％）を得た。 Next, 10.0 g of chlorodifluoromethane was introduced over 4.5 hours, and 11.6 g (0.1 mol) of a 48% aqueous potassium hydroxide solution was added. 2.7 g of chlorodifluoromethane was introduced and reacted over 1 hour. After completion of the reaction, 50 ml of water was added for liquid separation. The organic layer was further washed with 25 ml of water to obtain 62.4 g (yield 86.8%) of a xylene solution of benzyl (difluoromethyl) sulfide.
参考例１：クロロ（ジフルオロメチル）スルホンの合成
２００ｍｌ四径フラスコに、水４０ｍｌ、実施例３で得られたベンジル（ジフルオロメチル）スルフィドのキシレン溶液６２.４ｇを加え、攪拌しながら２０℃に冷却した。塩素ガス２０.１ｇを５時間かけて導入し、反応を行なった。反応終了後、分液を行い得られた有機層を精留することにより、クロロ（ジフルオロメチル）スルホン７.８ｇ（収率６０.４％）を得た。
Reference Example 1: Synthesis of chloro (difluoromethyl) sulfone 40 ml of water and 62.4 g of xylene solution of benzyl (difluoromethyl) sulfide obtained in Example 3 were added to a 200 ml four-diameter flask and cooled to 20 ° C. with stirring. did. A reaction was carried out by introducing 20.1 g of chlorine gas over 5 hours. After completion of the reaction, liquid separation was performed and the organic layer obtained was rectified to obtain 7.8 g of chloro (difluoromethyl) sulfone (yield 60.4%).
１Ｈ−ＮＭＲ（ＣＨＣｌ３−ｄ１，４００ＭＨｚ）δ＝６．４１（ｔ，１Ｈ，Ｊ＝５４．１Ｈｚ） 1 H-NMR (CHCl 3 -d 1 , 400 MHz) δ = 6.41 (t, 1H, J = 54.1 Hz)
実施例４：ベンジル（ジフルオロメチル）スルフィドの合成
２００ｍｌの四径フラスコに水５０ｍｌ、クロロベンゼン５０ｍｌを加え、水酸化カリウム２８．１ｇ（０．５ｍｏｌ）、テトラブチルアンモニウムブロミド４．２２ｇを加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成した後、４０℃まで冷却し、ベンジルメルカプタンカリウム塩を系内で調製した。
Example 4 Synthesis of benzyl (difluoromethyl) sulfide 50 ml of water and 50 ml of chlorobenzene were added to a 200 ml four-diameter flask, and 28.1 g (0.5 mol) of potassium hydroxide and 4.22 g of tetrabutylammonium bromide were added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. After adding 20.4 g (0.1 mol) of benzylthioronium hydrochloride and aging for 40 minutes, the mixture was cooled to 40 ° C. to prepare benzyl mercaptan potassium salt in the system.
次いでクロロジフルオロメタン１０．０ｇを２．５時間かけて導入し、４８％水酸化カリウム水溶液１１．６ｇ（０．１ｍｏｌ）を加えた。クロロジフルオロメタン２．７ｇを４０分かけて導入し反応した。反応終了後、水５０ｍｌを加え分液した。有機層を更に水２５ｍｌで洗浄し、ベンジル（ジフルオロメチル）スルフィドのクロロベンゼン溶液を７６.０ｇ（収率８２.９％）を得た。 Next, 10.0 g of chlorodifluoromethane was introduced over 2.5 hours, and 11.6 g (0.1 mol) of a 48% aqueous potassium hydroxide solution was added. 2.7 g of chlorodifluoromethane was introduced over 40 minutes to react. After completion of the reaction, 50 ml of water was added for liquid separation. The organic layer was further washed with 25 ml of water to obtain 76.0 g (yield 82.9%) of a chlorobenzene solution of benzyl (difluoromethyl) sulfide.
参考例２：クロロ（ジフルオロメチル）スルホンの合成
２００ｍｌ四径フラスコに、水４０ｍｌ、実施例４で得られたベンジル（ジフルオロメチル）スルフィドのクロロベンゼン溶液７６.０ｇを加え、攪拌しながら２０℃に冷却した。塩素ガス１９.２ｇを５時間かけて導入し、反応を行なった。反応終了後、分液を行い得られた有機層を精留することにより、クロロ（ジフルオロメチル）スルホン８.８ｇ（収率７０.４％）を得た。
Reference Example 2: Synthesis of chloro (difluoromethyl) sulfone To a 200 ml 4-diameter flask was added 40 ml of water and 76.0 g of the chlorobenzene solution of benzyl (difluoromethyl) sulfide obtained in Example 4 and cooled to 20 ° C. with stirring. did. 19.2 g of chlorine gas was introduced over 5 hours to carry out the reaction. After completion of the reaction, liquid separation was performed and the resulting organic layer was rectified to obtain 8.8 g (yield 70.4%) of chloro (difluoromethyl) sulfone.
実施例５：ベンジル（ジフルオロメチル）スルフィドの合成
２００ｍｌの四径フラスコに水５０ｍｌを加え、水酸化カリウム２８．１ｇ（０．５ｍｏｌ）、テトラブチルアンモニウムブロミド４.２２ｇを加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成した後、４０℃まで冷却し、ベンジルメルカプタンカリウム塩を系内で調製した。
Example 5 : Synthesis of benzyl (difluoromethyl) sulfide 50 ml of water was added to a 200 ml 4-diameter flask, and 28.1 g (0.5 mol) of potassium hydroxide and 4.22 g of tetrabutylammonium bromide were added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. After adding 20.4 g (0.1 mol) of benzylthioronium hydrochloride and aging for 40 minutes, the mixture was cooled to 40 ° C. to prepare benzyl mercaptan potassium salt in the system.
次いで、クロロジフルオロメタン１５．０ｇを１２時間かけて導入し、４８％水酸化カリウム水溶液１１．６ｇ（０．１ｍｏｌ）を加えた。クロロジフルオロメタン４.２ｇを６時間かけて導入し反応した。反応終了後、水５０ｍｌ、クロロベンゼン５０ｍｌを加え分液した。有機層を更に水２５ｍｌで洗浄し、ベンジル（ジフルオロメチル）スルフィドのクロロベンゼン溶液を７２．４ｇ（収率８４．４％）を得た。 Next, 15.0 g of chlorodifluoromethane was introduced over 12 hours, and 11.6 g (0.1 mol) of a 48% aqueous potassium hydroxide solution was added. The reaction was carried out by introducing 4.2 g of chlorodifluoromethane over 6 hours. After completion of the reaction, 50 ml of water and 50 ml of chlorobenzene were added for liquid separation. The organic layer was further washed with 25 ml of water to obtain 72.4 g (yield: 84.4%) of a chlorobenzene solution of benzyl (difluoromethyl) sulfide.
実施例６：ベンジル（ジフルオロメチル）スルフィドの合成Example 6: Synthesis of benzyl (difluoromethyl) sulfide
２００ｍｌの四径フラスコに水５０ｍｌ、クロロベンゼン５０ｍｌを加え、水酸化カリウム ２８．１ｇ（０．５ｍｏｌ）、テトラブチルアンモニウムブロミド４．２２ｇを加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成し、ベンジルメルカプタンカリウム塩を系内で調製した。 50 ml of water and 50 ml of chlorobenzene were added to a 200 ml four-diameter flask, and 28.1 g (0.5 mol) of potassium hydroxide and 4.22 g of tetrabutylammonium bromide were added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. 20.4 g (0.1 mol) of benzylthioronium hydrochloride was added and aged for 40 minutes to prepare benzyl mercaptan potassium salt in the system.
次いで、クロロジフルオロメタン１１.２ｇを４時間かけて導入し、４８％水酸化カリウム水溶液１１．６ｇ（０．１ｍｏｌ）を加えた。クロロジフルオロメタン４.１ｇを１時間かけて導入し反応した。反応終了後、水５０ｍｌを加え分液した。有機層を更に水２５ｍｌで洗浄し、ベンジル（ジフルオロメチル）スルフィドのクロロベンゼン溶液を６５.７ｇ（収率８２．４％）を得た。 Next, 11.2 g of chlorodifluoromethane was introduced over 4 hours, and 11.6 g (0.1 mol) of a 48% aqueous potassium hydroxide solution was added. The reaction was carried out by introducing 4.1 g of chlorodifluoromethane over 1 hour. After completion of the reaction, 50 ml of water was added for liquid separation. The organic layer was further washed with 25 ml of water to obtain 65.7 g (yield 82.4%) of a chlorobenzene solution of benzyl (difluoromethyl) sulfide.
比較参考例１：ベンジル（ジフルオロメチル）スルフィドの合成Comparative Reference Example 1: Synthesis of benzyl (difluoromethyl) sulfide
２００ｍｌの四径フラスコに水５０ｍｌ、クロロベンゼン５０ｍｌを加え、炭酸カリウム４４.５ｇ（０．２５ｍｏｌ）、テトラブチルアンモニウムブロミド４．２２ｇを加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成した。クロロジフルオロメタン５.２ｇを６時間かけて導入した。ガスクロマトグラフィーでの分析結果より、ベンジル（ジフルオロメチル）スルフィドが全面積で０.４％生成した。 50 ml of water and 50 ml of chlorobenzene were added to a 200 ml four-diameter flask, and 44.5 g (0.25 mol) of potassium carbonate and 4.22 g of tetrabutylammonium bromide were added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. 20.4 g (0.1 mol) of benzylthioronium hydrochloride was added and aged for 40 minutes. Chlorodifluoromethane (5.2 g) was introduced over 6 hours. As a result of analysis by gas chromatography, 0.4% of benzyl (difluoromethyl) sulfide was formed in the entire area.
比較参考例２（四級アンモニウム塩不使用例）：ベンジル（ジフルオロメチル）スルフィドの合成Comparative Reference Example 2 (Example of not using quaternary ammonium salt): Synthesis of benzyl (difluoromethyl) sulfide
２００ｍｌの四径フラスコに水５０ｍｌ、クロロベンゼン５０ｍｌを加え、水酸化カリウム２８．１ｇ（０．５ｍｏｌ）を加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成した後、４０℃まで冷却し、ベンジルメルカプタンカリウム塩を系内で調製した。 50 ml of water and 50 ml of chlorobenzene were added to a 200 ml four-diameter flask, and 28.1 g (0.5 mol) of potassium hydroxide was added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. After adding 20.4 g (0.1 mol) of benzylthioronium hydrochloride and aging for 40 minutes, the mixture was cooled to 40 ° C. to prepare benzyl mercaptan potassium salt in the system.
次いで、クロロジフルオロメタン１５．０ｇを５時間かけて導入し、４８％水酸化カリウム水溶液１１．６ｇ（０．１ｍｏｌ）を加えた。クロロジフルオロメタン７．７ｇを４時間かけて導入し反応した。反応終了後、水５０ｍｌを加え分液した。有機層を更に水２５ｍｌで洗浄し、ベンジル（ジフルオロメチル）スルフィドのクロロベンゼン溶液を６４.６ｇ（収率４５．０％）を得た。Next, 15.0 g of chlorodifluoromethane was introduced over 5 hours, and 11.6 g (0.1 mol) of a 48% aqueous potassium hydroxide solution was added. 7.7 g of chlorodifluoromethane was introduced over 4 hours to react. After completion of the reaction, 50 ml of water was added for liquid separation. The organic layer was further washed with 25 ml of water to obtain 64.6 g (yield 45.0%) of a chlorobenzene solution of benzyl (difluoromethyl) sulfide.
比較参考例３（ＰＥＧ−４００使用例）：ベンジル（ジフルオロメチル）スルフィドの合成Comparative Reference Example 3 (Example of using PEG-400): Synthesis of benzyl (difluoromethyl) sulfide
２００ｍｌの四径フラスコに水５０ｍｌ、クロロベンゼン５０ｍｌを加え、水酸化カリウム２８．１ｇ（０．５ｍｏｌ）、ＰＥＧ−４００を０.９０ｇ加えた。窒素雰囲気下、攪拌しながら６０℃まで昇温した。ベンジルチオロニウム塩酸塩２０．４ｇ（０．１ｍｏｌ）を加え、４０分熟成した後、４０℃まで冷却し、ベンジルメルカプタンカリウム塩を系内で調製した。 50 ml of water and 50 ml of chlorobenzene were added to a 200 ml quadrangular flask, and 28.1 g (0.5 mol) of potassium hydroxide and 0.90 g of PEG-400 were added. The temperature was raised to 60 ° C. with stirring in a nitrogen atmosphere. After adding 20.4 g (0.1 mol) of benzylthioronium hydrochloride and aging for 40 minutes, the mixture was cooled to 40 ° C. to prepare benzyl mercaptan potassium salt in the system.
次いで、クロロジフルオロメタン１５．０ｇを１２時間かけて導入した。ガスクロマトグラフィーでの分析結果より、ベンジル（ジフルオロメチル）スルフィドが全面積で４８.４％生成した。 Subsequently, 15.0 g of chlorodifluoromethane was introduced over 12 hours. As a result of analysis by gas chromatography, 48.4% of benzyl (difluoromethyl) sulfide was formed in the entire area.
ベンジル（ジフルオロメチル）スルフィドの新規な工業的製造法が提供される。本発明方法によれば、原料として、入手容易なベンジルメルカプタン化合物とハロゲン化ジフルオロメタンを用いてベンジル（ジフルオロメチル）スルフィド化合物を簡便な操作で製造できる。更に、本発明方法では溶媒回収といった操作が不要であり、従来の方法に比べて廃水の負荷も小さく、工業的な利用価値が高い。A new industrial process for the production of benzyl (difluoromethyl) sulfide is provided. According to the method of the present invention, a benzyl (difluoromethyl) sulfide compound can be produced by a simple operation using a readily available benzyl mercaptan compound and a halogenated difluoromethane as raw materials. Furthermore, the method of the present invention does not require an operation such as solvent recovery, has a smaller wastewater load than the conventional methods, and has high industrial utility value.
Claims (5)
表されるベンジルメルカプタン金属塩と、一般式（２）
で表されるハロゲン化ジフルオロメタンとを、水層と有機層からなる二層系で、四級アンモニウム塩存在下で反応させる事を特徴とする、一般式（３）
で表されるベンジル(ジフルオロメチル)スルフィド化合物の製造方法。 General formula (1)
Benzyl mercaptan metal salt represented by the general formula (2)
Wherein the halogenated difluoromethane is reacted in the presence of a quaternary ammonium salt in a two-layer system comprising an aqueous layer and an organic layer.
The manufacturing method of the benzyl (difluoromethyl) sulfide compound represented by these.
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