JPH04193856A - Production of triflouromethylphenol derivative - Google Patents
Production of triflouromethylphenol derivativeInfo
- Publication number
- JPH04193856A JPH04193856A JP2317730A JP31773090A JPH04193856A JP H04193856 A JPH04193856 A JP H04193856A JP 2317730 A JP2317730 A JP 2317730A JP 31773090 A JP31773090 A JP 31773090A JP H04193856 A JPH04193856 A JP H04193856A
- Authority
- JP
- Japan
- Prior art keywords
- trifluoromethyl
- producing
- derivative
- carbamate derivative
- alkyl
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 17
- -1 copper halide Chemical class 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 239000002798 polar solvent Substances 0.000 claims abstract description 9
- 229910052802 copper Inorganic materials 0.000 claims abstract description 7
- 239000010949 copper Substances 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- UYCAUPASBSROMS-AWQJXPNKSA-M sodium;2,2,2-trifluoroacetate Chemical compound [Na+].[O-][13C](=O)[13C](F)(F)F UYCAUPASBSROMS-AWQJXPNKSA-M 0.000 claims abstract description 7
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 6
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- 229910001508 alkali metal halide Inorganic materials 0.000 claims abstract 2
- 150000008045 alkali metal halides Chemical class 0.000 claims abstract 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 19
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 15
- RCBSEUPNIXQMME-UHFFFAOYSA-N trifluoromethyl carbamate Chemical class NC(=O)OC(F)(F)F RCBSEUPNIXQMME-UHFFFAOYSA-N 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 9
- ZOQOPXVJANRGJZ-UHFFFAOYSA-N 2-(trifluoromethyl)phenol Chemical class OC1=CC=CC=C1C(F)(F)F ZOQOPXVJANRGJZ-UHFFFAOYSA-N 0.000 claims description 8
- AKZWRTCWNXHHFR-PDIZUQLASA-N [(3S)-oxolan-3-yl] N-[(2S,3S)-4-[(5S)-5-benzyl-3-[(2R)-2-carbamoyloxy-2,3-dihydro-1H-inden-1-yl]-4-oxo-3H-pyrrol-5-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound NC(=O)O[C@@H]1Cc2ccccc2C1C1C=N[C@](C[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CCOC2)(Cc2ccccc2)C1=O AKZWRTCWNXHHFR-PDIZUQLASA-N 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 1
- 238000003756 stirring Methods 0.000 abstract description 4
- 239000003905 agrochemical Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 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 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- 230000009257 reactivity Effects 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical class COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- KCTVZKPLKCEUJF-UHFFFAOYSA-N methylcarbamothioic s-acid Chemical compound CNC(S)=O KCTVZKPLKCEUJF-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000020335 dealkylation Effects 0.000 description 2
- 238000006900 dealkylation reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- XEMRAKSQROQPBR-UHFFFAOYSA-N (trichloromethyl)benzene Chemical class ClC(Cl)(Cl)C1=CC=CC=C1 XEMRAKSQROQPBR-UHFFFAOYSA-N 0.000 description 1
- CUMCPOPFIHZRKZ-UHFFFAOYSA-N 2-propan-2-yl-4-(trifluoromethyl)phenol Chemical compound CC(C)C1=CC(C(F)(F)F)=CC=C1O CUMCPOPFIHZRKZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- RINRJHSRTCOBEI-UHFFFAOYSA-N 3-methyl-4-(trifluoromethyl)phenol Chemical compound CC1=CC(O)=CC=C1C(F)(F)F RINRJHSRTCOBEI-UHFFFAOYSA-N 0.000 description 1
- GXBPFHVMKLYJLC-UHFFFAOYSA-N 3-propan-2-yl-4-(trifluoromethyl)phenol Chemical compound CC(C)C1=CC(O)=CC=C1C(F)(F)F GXBPFHVMKLYJLC-UHFFFAOYSA-N 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- JDZCKJOXGCMJGS-UHFFFAOYSA-N [Li].[S] Chemical compound [Li].[S] JDZCKJOXGCMJGS-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- HXIRTSKHPFRRKO-UHFFFAOYSA-N o-methyl carbamothioate Chemical compound COC(N)=S HXIRTSKHPFRRKO-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- SFKTYEXKZXBQRQ-UHFFFAOYSA-J thorium(4+);tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Th+4] SFKTYEXKZXBQRQ-UHFFFAOYSA-J 0.000 description 1
- 238000006692 trifluoromethylation reaction Methods 0.000 description 1
- 150000005226 trifluoromethylbenzenes Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
トリフルオロメチルフェノール誘導体は医農薬中間体と
して有用なものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] Trifluoromethylphenol derivatives are useful as pharmaceutical and agricultural intermediates.
また、ある種のトリフルオロメチルフェノール誘導体の
あるものは優れた殺菌または除草活性を持つことが見い
だされている。Additionally, certain trifluoromethylphenol derivatives have been found to have excellent fungicidal or herbicidal activity.
［従来技術］
トリフルオロメチルベンゼン誘導体の製造方法としでは
、対応するトリクロロメチルベンゼン誘導体をフッ化水
素酸等のフッ素化剤と反応させる方法、ニトロソトリフ
ルオロメチル等のトリフルオロメチル化剤を用いて直接
ベンゼン環へトリフルオロメチル基を導入する方法等が
知られている。[Prior Art] Methods for producing trifluoromethylbenzene derivatives include a method in which a corresponding trichloromethylbenzene derivative is reacted with a fluorinating agent such as hydrofluoric acid, and a method in which a trifluoromethylating agent such as nitrosotrifluoromethyl is used. A method of directly introducing a trifluoromethyl group into a benzene ring is known.
トリフルオロメチルフェノールの製造方法としては、ハ
ロゲン化アニソール誘導体をハロゲン化第−銅存在下、
）・リフルオロ酢酸ナトリウムと反応させた後、三臭化
ホウ素等のルイス酸で処理することにより対応するトリ
フルオロメチルフェノールを製造する方法（ジャーナル
オブ ケミカル ソサイヤティー パーキンｌ、
Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｃａｌ ５ｏ
ｃｉｅｔｙＰａ ｒｋ ｉｎ Ｉ、Ｐ６６１ （１９８
０））等が知られている。As a method for producing trifluoromethylphenol, a halogenated anisole derivative is mixed in the presence of cupric halide,
)・A method for producing the corresponding trifluoromethylphenol by reacting it with sodium refluoroacetate and then treating it with a Lewis acid such as boron tribromide (Journal of Chemical Society Perkin I,
Journal of Chemical 5o
city Park in I, P661 (198
0)) etc. are known.
［従来技術の課題］
トリフルオロメチル法としては種々知られているが、フ
ェノール誘導体を位置選択的にトリフルオロメチル化す
る製造法としては上記ハロゲン化アニソール誘導体を用
いる方法のみである。しかし、ハロゲン化アニソール誘
導体を用いる方法では脱アルキル化工程にルイス酸を用
いるため脱アルキル化工程で条件により同時にベンゼン
環に置換しているアルキル基も脱離する等の欠点を有し
ており必ずしも好ましい方法ではない。[Problems with the Prior Art] Various trifluoromethyl methods are known, but the only production method for regioselectively trifluoromethylating a phenol derivative is a method using the above-mentioned halogenated anisole derivative. However, the method using a halogenated anisole derivative uses a Lewis acid in the dealkylation process, which has the disadvantage that the alkyl group substituted on the benzene ring may also be eliminated depending on the conditions in the dealkylation process. Not the preferred method.
［課題を解決するための手段］
本発明者らは、トリフルオロメチルを有するアルキルフ
ェノールの製造を行うためフェノール性水酸基の保護に
付いて種々検討を重ねた結果、カーバモイル基がトリフ
ルオロメチルを有するアルキルフェノールの製造に適し
た保護基であることを見いたし本発明を完成した。[Means for Solving the Problems] The present inventors have conducted various studies regarding the protection of phenolic hydroxyl groups in order to produce alkylphenols having trifluoromethyl, and as a result, the present inventors have discovered that alkylphenols having trifluoromethyl in the carbamoyl group have been developed. We found that this is a protecting group suitable for the production of , and completed the present invention.
すなわち、本発明は、一般式［Ｉ］
（但し、Ｒ１は直鎖または分岐したＣ −Ｃアルキル基
を示し、Ｒ２は直鎖または分岐したＣ〜Ｃ６アルキル基
を示し、Ｒは直鎖または分岐したＣ −０６アルキル基
、フェニル基、置換）ェニル基、ピリジル基または置換
ピリジル基を示し、Ｙは酸素原子または硫黄原子を示し
、Ｘは塩素原子、臭素原子またはヨウ素原子を示す。）
で表わされるカーバメート誘導体を非プロトン性極性溶
媒中、ハロゲン化銅、トリフルオロ酢酸ナトリウム及び
触媒存在下または触媒非存在下に加熱撹拌を行うことを
特徴とする一般式［ＩＩ］（但し、Ｒ、Ｒ、Ｒ３、Ｙは
前記に同じ。）で示されるトリフルオロメチルカーバメ
ート誘導体の製造法、および
一般式［Ｉ［］で表わされるトリフルオロメチルカーバ
メート誘導体を酸またはアルカリ存在下、極性溶媒また
はその混合溶媒中で加水分解することを特徴とする一般
式［エコ
（但し、Ｒ１は前記に同じ。）
で表わされるトリフルオロメチルフェノール誘導体の製
造方法を提供するものである。That is, the present invention is based on the general formula [I] (wherein R1 represents a straight chain or branched C-C alkyl group, R2 represents a straight chain or branched C-C6 alkyl group, and R represents a straight chain or branched C-C6 alkyl group). represents a C-06 alkyl group, phenyl group, substituted) phenyl group, pyridyl group or substituted pyridyl group, Y represents an oxygen atom or a sulfur atom, and X represents a chlorine atom, a bromine atom or an iodine atom. )
General formula [II] characterized in that a carbamate derivative represented by is heated and stirred in an aprotic polar solvent in the presence or absence of copper halide, sodium trifluoroacetate, and a catalyst (wherein R, R, R3, Y are the same as above.) and a method for producing a trifluoromethyl carbamate derivative represented by the general formula [I] in the presence of an acid or alkali in a polar solvent or a mixture thereof. The present invention provides a method for producing a trifluoromethylphenol derivative represented by the general formula [eco (where R1 is the same as above), which is characterized by hydrolysis in a solvent.
［作用］ 以下、本発明の詳細な説明する。[Effect] The present invention will be explained in detail below.
一般式［ＩＦ、［■コ、［ｍ］中のＲ１としては、メチ
ル基、エチル基、ｎ−プロピル基、１−プロピル基、ｎ
−ブチル基、Ｓ−ブチル基、１−ブチル基等の直鎖また
は分岐したＣ −０６のアルキル基を挙げることができ
る。R1 in the general formula [IF, [■co, [m]] is a methyl group, ethyl group, n-propyl group, 1-propyl group, n
Examples include linear or branched C-06 alkyl groups such as -butyl group, S-butyl group, and 1-butyl group.
一般式［Ｉ］、［Ｉ１１のＲ２としては、メチル基、エ
チルｕ、ｎ−プロピル基、１−プロピル基、ｎ−ブチル
基、Ｓ−ブチル基、ｔ−ブチル基等の直鎖または分岐し
たＣ −Ｃ６のアルキル県等を挙げることかでき Ｒ３
としては、メチル基、エチル基、ｎ−プロピル基、ｉ−
プロピル基、ｎ−ブチル基、Ｓ−ブチル基、ｔ−ブチル
基等の直鎖または分岐したＣ −０６の等のアルキル基
、）エニル基、トルイル基、キンリル基、ピリジル基等
の無置換または任意に置換されてよい芳香族置換基を挙
げることができる。R2 in general formulas [I] and [I11 is a linear or branched group such as methyl group, ethyl u, n-propyl group, 1-propyl group, n-butyl group, S-butyl group, t-butyl group, etc. Can you list the alkyl prefectures of C-C6? R3
Examples include methyl group, ethyl group, n-propyl group, i-
Straight chain or branched C-06 alkyl groups such as propyl group, n-butyl group, S-butyl group, t-butyl group, unsubstituted or Mention may be made of aromatic substituents which may be optionally substituted.
一般式［エコのＸとしては塩素原子、臭素原子、ヨウ素
原子性のハロゲン原子を挙げることができるが、反応性
から好ましくは臭素原子、ヨウ素原子である。X in the general formula [eco] can include chlorine atom, bromine atom, and iodine halogen atom, but from the viewpoint of reactivity, bromine atom and iodine atom are preferable.
一般式［エコ、［ｎ］のＹとしては酸素原子または硫黄
原子を挙げることができる。Y in the general formula [eco, [n] can include an oxygen atom or a sulfur atom.
本発明は、３−アルキル−４−ハロゲノフェノール誘導
体のように立体的の込み入った位置に置換基を有するハ
ロゲンをトリフルオロメチル基に置換でき対応する３−
アルキル−４−トリフルオロメチルフェノール誘導体を
製造することができる。The present invention provides a method for substituting a halogen having a substituent at a sterically complicated position, such as a 3-alkyl-4-halogenophenol derivative, with a trifluoromethyl group.
Alkyl-4-trifluoromethylphenol derivatives can be produced.
本発明の出発物質［Ｉ］は公知の方法により容易に製造
することができる。The starting material [I] of the present invention can be easily produced by a known method.
本発明は、トリフルオロメチル化を行う第一工程と第一
］−程で得られた生成物を加水分解する第二工程の２段
階からなる。The present invention consists of two steps: a first step of trifluoromethylation and a second step of hydrolyzing the product obtained in the first step.
第一工程に用いる非プロトン性極性溶媒としては、Ｎ、
Ｎ−ジメチルホルムアミド、Ｎ、Ｎ−ジメチルアセトア
ミド、Ｎ−メチルピロリドン、ヘキサメチルリン酸トリ
アミド、Ｎ、Ｎ−ジメチルイミダゾリトン、ジメチルス
ルホキシド等を挙げることができる、好ましくは、Ｎ−
メチルピロリドンである。その溶媒の使用量としては、
反応に供するカーバメート誘導体に対して、あらゆる量
で使用可能であるが、余りにも少量では撹拌が困難とな
る場合があり好ましくなく、また大量の使用は経済的で
はない。従って好ましくは５〜３０重量倍量である。The aprotic polar solvent used in the first step includes N,
N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoric triamide, N,N-dimethylimidazolitone, dimethylsulfoxide and the like can be mentioned, preferably N-
It is methylpyrrolidone. The amount of solvent used is
It can be used in any amount with respect to the carbamate derivative to be subjected to the reaction, but if it is too small, stirring may become difficult, which is not preferable, and if it is used in a large amount, it is not economical. Therefore, the amount is preferably 5 to 30 times by weight.
本工程は、触媒非存在下でも進行するが触媒を存在させ
ることによりより効率的に実施することができる。本工
程に用いる触媒としては、ヨウ化ナトリウム、臭化ナト
リウム、ヨウ化カリウム、臭化カリウム等のアルカリ金
属のハロゲン塩を挙げることができる。反応溶媒に対す
る溶解性から好ましくはヨウ化カリウム、臭化カリウム
であり、さらに反応性から好ましくはヨウ化カリウムで
ある。Although this step proceeds even in the absence of a catalyst, it can be carried out more efficiently in the presence of a catalyst. Examples of the catalyst used in this step include alkali metal halogen salts such as sodium iodide, sodium bromide, potassium iodide, and potassium bromide. Potassium iodide and potassium bromide are preferred from the viewpoint of solubility in the reaction solvent, and potassium iodide is further preferred from the viewpoint of reactivity.
本工程を触媒存在下実施する場合、触媒の使用量は反応
に供するカーバメート誘導体に対して、理論的には１．
０倍モル以上で可能であるが、好ましくは２倍モル以上
、］ｏ倍モル以下である。When this step is carried out in the presence of a catalyst, the amount of catalyst used is theoretically 1.
It is possible to use 0 times the mole or more, but preferably 2 times the mole or more and ]o times the mole or less.
本工程に使用する、Ｉ−リフルオロ酢酸すｌ・リウムの
使用量は、反応に供するカーバメ−１・誘導体に対して
、理論的には１．０倍モル以上で可能であるが、好まし
くは２倍モル以上、１０倍モル以下である。The amount of sulfur lithium I-lifluoroacetate used in this step can theoretically be at least 1.0 times the mole of the carbame-1 derivative to be subjected to the reaction, but preferably 2. It is at least twice the molar amount and no more than 10 times the molar amount.
本工程に使用するハロゲン化銅としては、臭化銅あるい
はヨウ化銅をあげることができるが、反応性から好まし
くはヨウ化銅である。As the copper halide used in this step, copper bromide or copper iodide can be mentioned, but copper iodide is preferable from the viewpoint of reactivity.
本工程に使用する、ハロゲン化銅の使用量は、反応に供
するカーバメート誘導体に対して、理論的には１．０倍
モル以上で可能であるが、好ましくは２倍モル以上、１
０倍モル以下である。The amount of copper halide used in this step can theoretically be at least 1.0 times the mole of the carbamate derivative to be subjected to the reaction, but preferably at least 2 times the mole and 1.
It is 0 times the mole or less.
本工程は、１５０〜１７０ ’Ｃの温度範囲で実施する
のが好ましく、１５０ ℃より低い温度では反応速度が
遅く好ましくない。This step is preferably carried out at a temperature in the range of 150 to 170'C, and temperatures lower than 150'C are undesirable because the reaction rate is slow.
本工程の反応時間は使用するカーバメート誘導体によっ
て異なるが６〜２４時間で完結する。The reaction time of this step varies depending on the carbamate derivative used, but it is completed in 6 to 24 hours.
本工程により得られた目的物は、溶媒を減圧留去後、不
溶物を濾別し、水洗、抽出、濃縮した後、蒸留、再結晶
、カラムクロマトグラフィー等で精製することによって
得ることができる。The target product obtained in this step can be obtained by distilling off the solvent under reduced pressure, filtering out insoluble materials, washing with water, extracting, concentrating, and then purifying by distillation, recrystallization, column chromatography, etc. .
第二工程に用いる極性溶媒としては、水、メタノール、
エタノール、プロパツール等のアルコール等またはこれ
らの混合溶媒が挙げられる。好ましくは、水−メタノー
ル混合溶媒または水−エタノール混合溶媒である。溶媒
の混合比はあらゆる比で可能であるが、好ましくは水に
対しアルコール１〜２０重量倍量である。混合溶媒の使
用量としては、反応に供するカーバメート誘導体に対し
て、あらゆる量で使用可能であるが、余りにも少量では
、撹拌が困難となる場合があり好ましくなく、また大量
の使用は経済的ではない。従って好ましくは５〜３０重
量倍量である。The polar solvent used in the second step includes water, methanol,
Examples include alcohols such as ethanol and propatool, and mixed solvents thereof. Preferred is a water-methanol mixed solvent or a water-ethanol mixed solvent. Although any mixing ratio of the solvent is possible, it is preferably 1 to 20 times the alcohol to water by weight. The mixed solvent can be used in any amount relative to the carbamate derivative to be subjected to the reaction, but if it is too small, stirring may become difficult and it is not preferable, and if it is used in a large amount, it is not economical. do not have. Therefore, the amount is preferably 5 to 30 times by weight.
本工程に用いる触媒としては、塩酸、臭化水素酸あるい
は硫酸等の酸または水酸化ナトリウム、水酸化カリウム
あるいは水酸化バリウム等のアルカリをあげることかて
ぎるが、反応性および経済＝ １２−
性から好ましくは水酸化すトリウムである。Examples of the catalyst used in this step include acids such as hydrochloric acid, hydrobromic acid, or sulfuric acid, or alkalis such as sodium hydroxide, potassium hydroxide, or barium hydroxide, but reactivity and economy = 12- Of these, thorium hydroxide is preferred.
本工程により得られた目的物は、抽出、蒸留、再結晶、
カラムクロマトグラフィー等の通常の精製操作により得
ることができる。The target product obtained through this process can be extracted, distilled, recrystallized,
It can be obtained by conventional purification operations such as column chromatography.
［発明の効果〕
本発明は、医農薬中間体として有用なトリフルオロメチ
ルを有するフェノール誘導体の簡便な製法を提供する。[Effects of the Invention] The present invention provides a simple method for producing a trifluoromethyl-containing phenol derivative useful as a pharmaceutical or agricultural intermediate.
［実施例コ
以下、実施例により本発明を具体的に説明するか本発明
はこれら具体例のみに限定されるものではない。[Examples] Hereinafter, the present invention will be specifically explained with reference to Examples, but the present invention is not limited to these specific examples.
実施例Ｉ
Ｎ−メチル−２−ピロリドン２０ｍ１に、３−イソプロ
ピル−４−ブロモフェニル Ｎ、Ｎ−ジメチルカーバメ
ート０．８２ｇ、ヨウ化カリウム２．１６ｇ、ｌ−リフ
ルオロ酢酸ナトリウム１．５６ｇ、ヨウ化銅２．１９ｇ
を入れ１６０℃で２０時間撹拌した。反応終了後、減圧
下Ｎ−メチルー２−ピロリドンを留去し、不溶物を濾別
した後、エーテルで抽出し、水洗、無水硫酸マグネシウ
ムで乾燥した後、溶媒を減圧留去した。シリカゲルカラ
ムクロマトグラフィー（展開溶媒；ベンゼン：ヘキサン
−１＝１）で精製し、３−イソプロピル−４−トリフル
オロメチルフェニル Ｎ、Ｎ−ジメチルカーバメ−１−
０，４０ｇ（収率５ｏ％）を得た。Example I To 20 ml of N-methyl-2-pyrrolidone, 0.82 g of 3-isopropyl-4-bromophenyl N,N-dimethylcarbamate, 2.16 g of potassium iodide, 1.56 g of sodium l-lifluoroacetate, and copper iodide. 2.19g
and stirred at 160°C for 20 hours. After the reaction was completed, N-methyl-2-pyrrolidone was distilled off under reduced pressure, insoluble materials were filtered off, extracted with ether, washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. It was purified by silica gel column chromatography (developing solvent: benzene:hexane-1=1), and 3-isopropyl-4-trifluoromethylphenyl N,N-dimethylcarbame-1-
0.40 g (yield 5o%) was obtained.
実施例２
エタノール１０ｍ１、水２ｍｌの混合溶媒中に、水酸化
すトリウム０．５ｇを溶解させ３−イソプロピル−４−
トリフルオロメチルフェニル Ｎ。Example 2 In a mixed solvent of 10 ml of ethanol and 2 ml of water, 0.5 g of sthorium hydroxide was dissolved and 3-isopropyl-4-
Trifluoromethylphenyl N.
Ｎ−ジメチルカーバメート０．３０ｇを添加し、８０℃
で２時間反応させた。反応物を室温まで冷却した後、減
圧下溶媒を留去し、生成物を水−エーテル系で抽出、水
層を希塩酸で酸性にした後、エーテルで抽出し、水洗し
た。無水硫酸マグネシウムで乾燥した後、溶媒を減圧留
去した。シリカゲルカラムクロマトグラフィー（展開溶
媒：ベンゼン：酢酸エチル−１０：１）で精製し、３−
イソプロピル−４−トリフルオロメチルフェノール＝
１４ −
０．１８ｇ（収率８３％）を冑だ。Add 0.30 g of N-dimethyl carbamate and heat to 80°C.
The mixture was allowed to react for 2 hours. After cooling the reaction mixture to room temperature, the solvent was distilled off under reduced pressure, and the product was extracted with a water-ether system. The aqueous layer was acidified with diluted hydrochloric acid, extracted with ether, and washed with water. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. Purified by silica gel column chromatography (developing solvent: benzene: ethyl acetate - 10:1),
Isopropyl-4-trifluoromethylphenol =
14 - Take 0.18 g (yield 83%).
実施例３
Ｎ−メチル−２−ピロリドン３０ｍ１に、３−メチル−
４−ブロモフェニル Ｎ−（３−メトキシ−２−ピリジ
ル）Ｎ−メチルチオカーバメート２．０ｇ、トリフルオ
ロ酢酸ナトリウム３．０ｇおよびヨウ化銅４．５ｇを添
加し１６０ ’Ｃで７時間撹拌した。反応終了後、減圧
下Ｎ−メチルー２−ピロリドンを留去し、不溶物を濾別
した後、エーテルで抽出し、水洗、無水硫酸マグネシウ
ムで乾燥した後、溶媒を減圧留去した。シリカゲルカラ
ムクロマトグラフィー（展開溶媒；ベンゼン・ヘキサジ
−］１）で精製し、３−メチル−４−トリフルオロメチ
ルフェニル Ｎ−（３−メＩ・キン−２−ピリジル）Ｎ
−メチルチオヵーバメ−１・０．１７ｇ（収率９％）を
得た。Example 3 To 30 ml of N-methyl-2-pyrrolidone, 3-methyl-
2.0 g of 4-bromophenyl N-(3-methoxy-2-pyridyl) N-methylthiocarbamate, 3.0 g of sodium trifluoroacetate and 4.5 g of copper iodide were added, and the mixture was stirred at 160'C for 7 hours. After the reaction was completed, N-methyl-2-pyrrolidone was distilled off under reduced pressure, and insoluble materials were filtered off, extracted with ether, washed with water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. Purified by silica gel column chromatography (developing solvent: benzene/hexadi-]1), and purified with 3-methyl-4-trifluoromethylphenyl N-(3-methylquin-2-pyridyl)N.
-Methylthiocarbame-1.0.17 g (yield 9%) was obtained.
融点 ７６〜７７°Ｃ
’Ｈ−ＮＭＲ（溶媒： ＣＤＣＩ 単位： δｐｐ
ｍ ）２．４５（ｓ、３１１）、３．７０（ｓ、３Ｈ）
、３．９０（ｓ、３１１）６．４５−７．７０（ｍ、６
１１）
１５ 一
実施例４
エタノール１０ｍ１、水２ｍｌの混合溶媒中に、水酸化
ナトリウム０．５ｇを溶解させ３−メチル−４−トリフ
ルオロメチルフェニル Ｎ−（３−メトキシ−２−ピリ
ジル）Ｎ−メチルチオカーバメート０．１７ｇを添加し
、８０℃で２時間反応させた。反応物を室温まで冷却し
た後、減圧下溶媒を留去し、生成物を水−エーテル系で
抽出、水層を希塩酸で酸性にした後、エーテルで抽出し
、水洗した。無水硫酸マグネシウムで乾燥した後、溶媒
を減圧留去した。シリカゲルカラムクロマトグラフィー
（展開溶媒；ベンゼン：酢酸エチル＝１、０ ： １．
）で精製し、３−メチル−４−トリフルオロメチルフ
ェノール０．０６ｇ （収率７６％）を得た。Melting point 76-77°C 'H-NMR (Solvent: CDCI Unit: δpp
m ) 2.45 (s, 311), 3.70 (s, 3H)
, 3.90 (s, 311) 6.45-7.70 (m, 6
11) 15 Example 4 0.5 g of sodium hydroxide was dissolved in a mixed solvent of 10 ml of ethanol and 2 ml of water to prepare 3-methyl-4-trifluoromethylphenyl N-(3-methoxy-2-pyridyl)N- 0.17 g of methylthiocarbamate was added and reacted at 80° C. for 2 hours. After cooling the reaction mixture to room temperature, the solvent was distilled off under reduced pressure, and the product was extracted with a water-ether system. The aqueous layer was acidified with diluted hydrochloric acid, extracted with ether, and washed with water. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. Silica gel column chromatography (developing solvent; benzene:ethyl acetate=1,0:1.
) to obtain 0.06 g (yield 76%) of 3-methyl-4-trifluoromethylphenol.
実施例５
Ｎ−メチル−２−ピロリドン２０ｍ１．３−イソプロピ
ル−４−ブロモフェニル Ｎ−（３−メトキシ−２−ピ
リジル）Ｎ−メチルチオカーバメート０．４０ｇ、
トリフルオロ酢酸ナトリウムＯ１８１ｇ、ヨウ化銅１．
２ｇを入れ１６０℃で２０時間撹拌した。反応終了後、
減圧下Ｎ−メチルー２−ピロリドンを留去し、不溶物を
濾別した後、エーテルで抽出し、水洗、無水硫酸マグネ
シウムで乾燥した後、溶媒を減圧留去した。シリカケル
カラムクロマトグラフィー（展開溶媒、ベンゼン。Example 5 N-methyl-2-pyrrolidone 20ml 1.3-isopropyl-4-bromophenyl N-(3-methoxy-2-pyridyl)N-methylthiocarbamate 0.40g,
Sodium trifluoroacetate O 181g, copper iodide 1.
2 g was added and stirred at 160°C for 20 hours. After the reaction is complete,
N-methyl-2-pyrrolidone was distilled off under reduced pressure, and insoluble matter was filtered off, followed by extraction with ether, washed with water, and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. Silica gel column chromatography (developing solvent, benzene.
ヘキサジ−１＝１）で精製し、３−イソプロピル−４−
１−リフルオロメチルフェニル Ｎ−３−メトキン−２
−ピリジル）Ｎ−メチルチオカーバメート０．０９ｇ
（収率］９％）を得た。3-isopropyl-4-
1-Lifluoromethylphenyl N-3-methquin-2
-pyridyl)N-methylthiocarbamate 0.09g
(Yield: 9%) was obtained.
融点 ７１〜７２°Ｃ
’Ｈ−ＮＭＲ（溶媒： ＣＤＣＩ 単位：δｐｐｍ
）］、、２３（ｄ、ａｌｌ、 Ｊ−７１１ｚ） 、３
．１．Ｏ−３，５０（ｍ、 ＩＩＩ）３．７７（ｓ、３
１１） 、３．９５（８，３１１） 、６．５５−７．
８０（ＩＮ、６１１）実施例６
エタノール１０ｍ１．水２ｍｌの混合溶媒中に、水酸化
ナトリウム０．５ｇを溶解させ３−イソプロピル−４−
トリフルオロメチルフェニル Ｎ−（３−メトキシ−２
−ピリジル）Ｎ−メチルチオカーバメート０．０９ｇを
添加し、８０℃で２時＝ １７−
間反応させた。反応物を室温まで冷却した後、減圧下溶
媒を留去し、生成物を水−エーテル系で抽出、水層を希
塩酸で酸性にした後、エーテルで抽出し、水洗した。無
水硫酸マグネシウムで乾燥した後、溶媒を減圧留去した
。シリカゲルカラムクロマトグラフィー（展開溶媒、ベ
ンゼン・酢酸エチル＝１０：］、）で精製し、３−イソ
プロピル−４−トリフルオロメチルフェノール０．０４
収率８１％）ｇを１！また。Melting point 71-72°C 'H-NMR (Solvent: CDCI Unit: δppm
)], 23(d, all, J-711z), 3
．． 1. O-3,50 (m, III) 3.77 (s, 3
11), 3.95 (8,311), 6.55-7.
80 (IN, 611) Example 6 Ethanol 10 ml. Dissolve 0.5 g of sodium hydroxide in a mixed solvent of 2 ml of water, and dissolve 3-isopropyl-4-
Trifluoromethylphenyl N-(3-methoxy-2
0.09 g of N-methylthiocarbamate (pyridyl) was added and reacted at 80° C. for 2 hours = 17 hours. After the reaction mixture was cooled to room temperature, the solvent was distilled off under reduced pressure, and the product was extracted with a water-ether system. The aqueous layer was acidified with diluted hydrochloric acid, extracted with ether, and washed with water. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. Purified by silica gel column chromatography (developing solvent: benzene/ethyl acetate = 10:), and 3-isopropyl-4-trifluoromethylphenol 0.04%
Yield 81%) g to 1! Also.
参考例Ｉ
Ｎ−メチル−２−ピロリドン５０ｍ１に、３−イソプロ
ピル−４−ブロモフェニル酢酸エステル１．１ｇ、
トリフルオロ酢酸ナトリウム２．３０ｇ１ヨウ化銅３．
２０ｇを入れ１６０°Ｃて２０時間撹拌した。その後、
ガスクロマトグラフィーにより分析を行ったか目的とす
る生成物は全く認められなかった。Reference Example I To 50 ml of N-methyl-2-pyrrolidone, 1.1 g of 3-isopropyl-4-bromophenyl acetate,
Sodium trifluoroacetate 2.30 g 1 Copper iodide 3.
20g was added and stirred at 160°C for 20 hours. after that,
Analysis by gas chromatography revealed no desired product at all.
参考例２
Ｎ−メチル−２−ピロリドン５０ｍ１に、３−メチル−
４−ブロモフェノール１．０ｇ、ｌ−リフ−］８−
ルオロ酢酸ナトリウム２．８０ｇ、ヨウ化銅１゜９６ｇ
を入れ１６０℃で２０時間撹拌した。その後、ガスクロ
マトグラフィーにより分析を行ったか目的とする生成物
は全く認められながった。Reference example 2 3-methyl-
1.0 g of 4-bromophenol, 2.80 g of sodium l-rif-]8-fluoroacetate, 1°96 g of copper iodide
and stirred at 160°C for 20 hours. Thereafter, analysis by gas chromatography revealed that the desired product was not observed at all.
参考例３
Ｎ−メチル−２−ピロリドン２０ｒｎｌ、３−イソプロ
ピル−４−ブロモフェニル Ｎ−（３−メトキシ−２−
ピリジル）Ｎ−メチルチオカーバメート０．４０ｇ、）
リフルオロ酢酸ナトリウム０゜８１ｇ１ヨウ化銅１．２
ｇを入れ１３０ ℃で２０時間撹拌した。その後、ガス
クロマトグラフィーにより分析を行ったが目的とする生
成物は全く認められなかった。Reference example 3 N-methyl-2-pyrrolidone 20rnl, 3-isopropyl-4-bromophenyl N-(3-methoxy-2-
pyridyl) N-methylthiocarbamate 0.40g,)
Sodium refluoroacetate 0°81g 1 copper iodide 1.2
g and stirred at 130°C for 20 hours. Thereafter, analysis was performed by gas chromatography, but the desired product was not observed at all.
Claims (10)
ルキル基を示し、Ｒ＾２は直鎖または分岐したＣ＿１〜
Ｃ＿６アルキル基を示し、Ｒ＾３は直鎖または分岐した
Ｃ＿１〜Ｃ＿６アルキル基、フェニル基、置換フェニル
基、ピリジル基または置換ピリジル基を示し、Ｙは酸素
原子または硫黄原子を示し、Ｘは塩素原子、臭素原子ま
たはヨウ素原子を示す。）で表わされるカーバメート誘
導体を非プロトン性極性溶媒中、ハロゲン化銅、トリフ
ルオロ酢酸ナトリウム及び触媒存在下または触媒非存在
下に加熱撹拌を行うことを特徴とする一般式［II］▲数
式、化学式、表等があります▼ （但し、Ｒ＾１、Ｒ＾２、Ｒ＾３、Ｙは前記に同じ。）
で示されるトリフルオロメチルカーバメート誘導体の製
造法。(1) General formula [I] ▲Mathematical formulas, chemical formulas, tables, etc.▼[I] (However, R^1 represents a straight chain or branched C_1-C_6 alkyl group, and R^2 represents a straight or branched C_1～
Represents a C_6 alkyl group, R^3 represents a linear or branched C_1 to C_6 alkyl group, phenyl group, substituted phenyl group, pyridyl group, or substituted pyridyl group, Y represents an oxygen atom or a sulfur atom, and X represents a chlorine atom. atom, bromine atom or iodine atom. ) is heated and stirred in an aprotic polar solvent in the presence or absence of a copper halide, sodium trifluoroacetate and a catalyst [II] ▲Mathematical formula, chemical formula , tables, etc.▼ (However, R^1, R^2, R^3, and Y are the same as above.)
A method for producing a trifluoromethyl carbamate derivative shown in
るトリフルオロメチルカーバメート誘導体の製造法。(2) A method for producing a trifluoromethyl carbamate derivative according to claim (1), wherein the copper halide is copper iodide.
ン塩であるトリフルオロメチルカーバメート誘導体の製
造法。(3) A method for producing a trifluoromethyl carbamate derivative, wherein the catalyst according to claim (1) is an alkali metal halide.
リウムであるトリフルオロメチルカーバメート誘導体の
製造法。(4) A method for producing a trifluoromethyl carbamate derivative, wherein the catalyst according to claim (1) or (3) is potassium iodide.
Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトア
ミド、Ｎ−メチルピロリドン、ヘキサメチルリン酸トリ
アミド、Ｎ，Ｎ−ジメチルイミダゾリドンまたはジメチ
ルスルホキシドであるトリフルオロメチルカーバメート
誘導体の製造法。(5) The aprotic polar solvent according to claim (1) is N,
A method for producing a trifluoromethyl carbamate derivative which is N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoric triamide, N,N-dimethylimidazolidone or dimethylsulfoxide.
子またはヨウ素原子であるトリフルオロメチルカーバメ
ート誘導体の製造方法。(6) A method for producing a trifluoromethyl carbamate derivative according to claim (1), wherein X in the general formula [I] is a bromine atom or an iodine atom.
記載のトリフルオロメチルカーバメート誘導体の製造法
。(7) Claim (1) wherein the reaction temperature is 150 to 170°C.
Process for producing the trifluoromethyl carbamate derivatives described.
カーバメート誘導体が３−アルキル−４−ハロゲノフェ
ニルカーバメート誘導体であり、一般式［II］で表わさ
れるトリフルオロメチルカーバメート誘導体が３−アル
キル−４−トリフルオロメチルフェニルカーバメート誘
導体であるトリフルオロメチルカーバメート誘導体の製
造法。(8) The carbamate derivative represented by the general formula [I] according to claim (1) is a 3-alkyl-4-halogenophenyl carbamate derivative, and the trifluoromethyl carbamate derivative represented by the general formula [II] is a 3-alkyl-4-halogenophenyl carbamate derivative. A method for producing a trifluoromethyl carbamate derivative, which is an alkyl-4-trifluoromethylphenyl carbamate derivative.
リフルオロメチルカーバメート誘導体を酸またはアルカ
リ存在下、極性溶媒またはその混合溶媒中で加水分解す
ることを特徴とする一般式［III］で表わされるトリフ
ルオロメチルフェノール誘導体の製造法。 ▲数式、化学式、表等があります▼［III］ （但し、Ｒ＾１は前記に同じ。）(9) The trifluoromethyl carbamate derivative represented by the general formula [II] according to claim (1) is hydrolyzed in the presence of an acid or an alkali in a polar solvent or a mixed solvent thereof. ] A method for producing a trifluoromethylphenol derivative represented by: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [III] (However, R^1 is the same as above.)
るトリフルオロメチルフェノール誘導体が３−アルキル
−４−トリフルオロメチルフェノール誘導体であるトリ
フルオロメチルフェノール誘導体の製造法。(10) A method for producing a trifluoromethylphenol derivative, wherein the trifluoromethylphenol derivative represented by the general formula [III] according to claim (9) is a 3-alkyl-4-trifluoromethylphenol derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2317730A JPH04193856A (en) | 1990-11-26 | 1990-11-26 | Production of triflouromethylphenol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2317730A JPH04193856A (en) | 1990-11-26 | 1990-11-26 | Production of triflouromethylphenol derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04193856A true JPH04193856A (en) | 1992-07-13 |
Family
ID=18091402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2317730A Pending JPH04193856A (en) | 1990-11-26 | 1990-11-26 | Production of triflouromethylphenol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04193856A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6464895B2 (en) * | 1995-03-24 | 2002-10-15 | Rhodia Chimie | Reagent and process which are useful for grafting a substituted difluoromethyl group onto a compound containing at least one electrophilic function |
| JP2012097082A (en) * | 2010-10-29 | 2012-05-24 | Saltigo Gmbh | Copper-catalyzed process for production of substituted or unsubstituted trifluoromethylated aryl and heteroaryl compound |
| JP2012224607A (en) * | 2011-04-22 | 2012-11-15 | Kyorin Pharmaceutical Co Ltd | Stabilized preparation |
-
1990
- 1990-11-26 JP JP2317730A patent/JPH04193856A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6464895B2 (en) * | 1995-03-24 | 2002-10-15 | Rhodia Chimie | Reagent and process which are useful for grafting a substituted difluoromethyl group onto a compound containing at least one electrophilic function |
| JP2012097082A (en) * | 2010-10-29 | 2012-05-24 | Saltigo Gmbh | Copper-catalyzed process for production of substituted or unsubstituted trifluoromethylated aryl and heteroaryl compound |
| JP2012224607A (en) * | 2011-04-22 | 2012-11-15 | Kyorin Pharmaceutical Co Ltd | Stabilized preparation |
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