JPH07247267A - Production of phenyl ethers - Google Patents
Production of phenyl ethersInfo
- Publication number
- JPH07247267A JPH07247267A JP6066651A JP6665194A JPH07247267A JP H07247267 A JPH07247267 A JP H07247267A JP 6066651 A JP6066651 A JP 6066651A JP 6665194 A JP6665194 A JP 6665194A JP H07247267 A JPH07247267 A JP H07247267A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- alkyl
- reaction
- added
- 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 abstract description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical class C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 21
- 238000006243 chemical reaction Methods 0.000 abstract description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 abstract description 9
- 239000002585 base Substances 0.000 abstract description 5
- 238000006266 etherification reaction Methods 0.000 abstract description 5
- -1 phenyl ether compound Chemical class 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000005991 sulfenylation reaction Methods 0.000 abstract description 4
- OEKPXLAHJWRJFR-UHFFFAOYSA-N 4-hydroxycyclohexa-2,4-diene-1-thione Chemical compound OC1=CCC(=S)C=C1 OEKPXLAHJWRJFR-UHFFFAOYSA-N 0.000 abstract description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 abstract description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract description 2
- 239000004009 herbicide Substances 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 abstract 2
- 239000003905 agrochemical Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 239000013462 industrial intermediate Substances 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
- 239000012043 crude product Substances 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000001577 simple distillation Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- MRCQDFNEMYBGIV-UHFFFAOYSA-N 2-methyl-6-methylsulfanylphenol Chemical compound CSC1=CC=CC(C)=C1O MRCQDFNEMYBGIV-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- LXUNZSDDXMPKLP-UHFFFAOYSA-N 2-Methylbenzenethiol Chemical compound CC1=CC=CC=C1S LXUNZSDDXMPKLP-UHFFFAOYSA-N 0.000 description 1
- HPXOTHKSLCMBPG-UHFFFAOYSA-N 2-methoxy-1-methyl-3-methylsulfanylbenzene Chemical compound COc1c(C)cccc1SC HPXOTHKSLCMBPG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- WLHCBQAPPJAULW-UHFFFAOYSA-N 4-methylbenzenethiol Chemical class CC1=CC=C(S)C=C1 WLHCBQAPPJAULW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- OFQPKKGMNWASPN-UHFFFAOYSA-N Benzyl methyl sulfide Chemical compound CSCC1=CC=CC=C1 OFQPKKGMNWASPN-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 238000006956 Pummerer reaction Methods 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-O butylazanium Chemical compound CCCC[NH3+] HQABUPZFAYXKJW-UHFFFAOYSA-O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 150000004707 phenolate Chemical class 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000013076 target substance Substances 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は農医薬中間体、特に除草
剤の中間体として有用なフェニルエーテル類の製造方法
に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing phenyl ethers useful as intermediates for agricultural and pharmaceutical products, especially as intermediates for herbicides.
【０００２】[0002]
【従来の技術】一般式〔III 〕2. Description of the Related Art General formula [III]
【化４】 （式中、Ｒ1 はアルキル基を、Ｒ2 はアルキル基又はア
ラルキル基を示す。）で表わされる化合物は一般式〔I
V〕[Chemical 4] (In the formula, R 1 represents an alkyl group and R 2 represents an alkyl group or an aralkyl group.) Is a compound represented by the general formula [I
V)
【化５】 （式中、Ｒ1 は前記と同じ意味を示す。）で表わされる
フェノール類をＵＳＰ２，９２３，７４３あるいはＵＳ
Ｐ４，３２４，９２０に記載された方法に従ってスルフ
ェニル化し、一般式〔Ｉ〕[Chemical 5] (In the formula, R 1 has the same meaning as described above.) The phenols represented by USP 2,923,743 or US
Sulfenylation according to the method described in P4,324,920, the general formula [I]
【化６】 （式中、Ｒ1 は前記と同じ意味を示す。）で表わされる
化合物とした後、エーテル化することによって得ること
ができる。しかしながら、これらの方法ではスルフェニ
ル化で副生するｐ−スルフェニルフェノール及び未反応
原料を分離しなければならないこと、２，６−置換フェ
ノールのエーテル化反応が置換基の立体障害により一般
的な工業的なエーテル化反応ではスムースに進行しない
等の問題点を有していた。[Chemical 6] (In the formula, R 1 has the same meaning as described above.) The compound can be obtained by etherification. However, in these methods, p-sulfenylphenol, which is a by-product of sulfenylation, and unreacted raw materials must be separated, and the etherification reaction of 2,6-substituted phenol is generally caused by steric hindrance of substituents. The industrial etherification reaction has a problem that it does not proceed smoothly.
【０００３】[0003]
【課題を解決するための手段】本発明者等は一般式〔II
I 〕Means for Solving the Problems The present inventors have proposed the general formula [II
I]
【化７】 （式中、Ｒ1 及びＲ2 は前記と同じ意味を示す。）で表
わされる化合物の工業的な製造方法について鋭意研究し
た結果、スルフェニル化した後、副生するｐ−スルフェ
ニルフェノール及び未反応原料はアルカリ処理すること
により、容易に分離ができること、及び、エーテル化の
際、固液相間反応されることにより目的物を高収率で得
られることを見い出し、本発明を完成した。即ち、本発
明は一般式〔Ｉ〕[Chemical 7] (In the formula, R 1 and R 2 have the same meanings as described above.) As a result of earnest research on an industrial production method of the compound, p-sulfenylphenol and a non-produced by-product after sulfenylation The present invention has been completed by finding that the reaction raw material can be easily separated by treating with an alkali, and that the target product can be obtained in a high yield by the solid-liquid phase reaction during etherification. That is, the present invention has the general formula [I]
【化８】 （式中、Ｒ1 は前記と同じ意味を示す。）で表わされる
化合物を塩基及び４級アンモニウム塩の存在下、一般式
〔II−１〕あるいは〔II−２〕[Chemical 8] (In the formula, R 1 has the same meaning as described above.) The compound represented by the general formula [II-1] or [II-2] in the presence of a base and a quaternary ammonium salt is used.
【化９】 （式中、Ｒ2 は前記と同じ意味を示し、Ｒ2 ′は低級ア
ルキル基を示す。）で表わされる化合物と固液相間反応
させることを特徴とする一般式〔III 〕[Chemical 9] (In the formula, R 2 has the same meaning as described above and R 2 ′ represents a lower alkyl group.) The compound represented by the general formula [III] is characterized in that the solid-liquid phase reaction is carried out.
【化１０】 （式中、Ｒ1 及びＲ2 は前記と同じ意味を示す。）で表
わされる化合物の製造方法である。[Chemical 10] (Wherein R 1 and R 2 have the same meanings as described above).
【０００４】反応はベンゼン、トルエン等の不活性溶媒
に、一般式〔Ｉ〕で表されるｏ−メチルチオフェノール
類及びこれと等モルの塩基水溶液を加え、共沸脱水しフ
ェノラート塩の結晶を析出させ、この塩のスラリー溶液
に相間反応条件下で０．９〜１．１モル、好ましくは等
モルの〔II−１〕あるいは〔II−２〕で表わされる化合
物を加えることによって行なわれる。〔II−１〕で表わ
されるハロゲン化物としては塩化物、臭化物等が挙げら
れるが、Ｒ2 がメチル基等の低級アルキル基の場合、
〔II−２〕で表わされる硫酸エステルの方が有利の場合
がある。塩基としては、水酸化ナトリウム、水酸化カリ
ウム等が挙げられ、触媒としては、一般の四級アンモニ
ウム塩が使用でき、その量は０．０１〜０．１当量程度
で良い。反応温度は室温〜４０℃程度であり、反応時間
は１〜３時間程度である。In the reaction, an o-methylthiophenol represented by the general formula [I] and an aqueous base solution equimolar thereto are added to an inert solvent such as benzene or toluene, and azeotropic dehydration is performed to precipitate crystals of a phenolate salt. Then, 0.9 to 1.1 mol, preferably an equimolar amount of the compound represented by [II-1] or [II-2] is added to the slurry solution of this salt under the interphase reaction condition. Examples of the halide represented by [II-1] include chloride and bromide. When R 2 is a lower alkyl group such as a methyl group,
In some cases, the sulfate ester represented by [II-2] is more advantageous. Examples of the base include sodium hydroxide and potassium hydroxide, and as the catalyst, a general quaternary ammonium salt can be used, and the amount thereof may be about 0.01 to 0.1 equivalent. The reaction temperature is room temperature to about 40 ° C., and the reaction time is about 1 to 3 hours.
【０００５】本発明の原料化合物である一般式〔Ｉ〕で
表わされる化合物は例えば一般式〔IV〕で表わされるフ
ェノール類を１，２−ジクロロエタン等の有機溶媒中、
塩化アルミニウムの存在下、ジメチルスルフィドと反応
させることにより得られる。反応終了後、酸性にした
後、有機層を分離し、溶媒をペンタン、ヘキサン等のパ
ラフィン系溶媒、ベンゼン、トルエン等の芳香族系溶媒
等に適宜置換し、塩基性水溶液で洗浄する。これによ
り、未反応原料及び副生したｐ−メチルチオフェノール
類は水層に移行し、有機層に目的物が残る。この溶液を
濃縮した後、単蒸留することにより、目的物を得ること
ができる。洗浄する塩基としては水酸化ナトリウム、水
酸化カリウム、炭酸ナトリウム、炭酸カリウムなどが挙
げられ、０．１〜１．０当量程度用いる。The compound represented by the general formula [I] which is the starting material compound of the present invention is obtained by, for example, adding the phenol represented by the general formula [IV] to an organic solvent such as 1,2-dichloroethane.
It is obtained by reacting with dimethyl sulfide in the presence of aluminum chloride. After completion of the reaction, the reaction mixture is acidified, the organic layer is separated, the solvent is appropriately replaced with a paraffinic solvent such as pentane and hexane, an aromatic solvent such as benzene and toluene, and washed with a basic aqueous solution. As a result, the unreacted raw materials and the by-produced p-methylthiophenols move to the aqueous layer, and the target substance remains in the organic layer. The target product can be obtained by concentrating this solution and then subjecting it to simple distillation. Examples of the base to be washed include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like, and are used in an amount of about 0.1 to 1.0 equivalent.
【０００６】一般式〔III 〕で表わされる化合物は例え
ば下記反応式に従ってメチル基を目的の置換基に変換す
ることもできる。In the compound represented by the general formula [III], for example, a methyl group can be converted into a desired substituent according to the following reaction formula.
【化１１】 （式中、Ｒ3 はアルコキシカルボニル基、アルケニルオ
キシカルボニル基もしくはオキソ基で置換されていても
よいアルキル基、アルケニル基、又はアラルキル基を示
す。）[Chemical 11] (In the formula, R 3 represents an alkyl group, an alkenyl group or an aralkyl group which may be substituted with an alkoxycarbonyl group, an alkenyloxycarbonyl group or an oxo group.)
【０００７】[0007]
【実施例】次に実施例を挙げ、本発明を更に詳細に説明
する。 実施例１ ２−メチル−６−（メチルチオ）アニソール
の合成：２−メチル−６−（メチルチオ）フェノール
８．６２ｇ（５６．０ｍｍｏｌ）をトルエン１００ｍｌ
に溶解し、そこに水酸化ナトリウム２．４６ｇ（６１．
６ｍｍｏｌ）の水溶液１０ｍｌを加え、常圧で共沸脱水
を行い、結晶を析出させた。冷却後、臭化テトラ−ｎ−
ブチルアンモニウム０．５ｇ（１．６ｍｍｏｌ）及びジ
メチル硫酸７．７６ｇ（６１．６ｍｍｏｌ）を加え、室
温で３時間攪拌した。次いで反応溶液を濾過し、濾液を
飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥
した。減圧下で溶媒を留去することにより粗物を得、こ
れを減圧蒸留することにより目的物６．６０ｇを得た。
沸点９７〜９８℃／５ｍｍＨｇEXAMPLES The present invention will be described in more detail with reference to examples. Example 1 Synthesis of 2-methyl-6- (methylthio) anisole: 8.62 g (56.0 mmol) of 2-methyl-6- (methylthio) phenol was added to 100 ml of toluene.
2.46 g of sodium hydroxide (61.
10 ml of an aqueous solution of 6 mmol) was added, and azeotropic dehydration was performed under normal pressure to precipitate crystals. After cooling, tetra-n-bromide
Butyl ammonium (0.5 g, 1.6 mmol) and dimethyl sulfate (7.76 g, 61.6 mmol) were added, and the mixture was stirred at room temperature for 3 hours. Then, the reaction solution was filtered, the filtrate was washed with saturated saline and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product, which was distilled under reduced pressure to obtain 6.60 g of the desired product.
Boiling point 97-98 ° C / 5mmHg
【０００８】参考例１ ２−メチル−６−（メチルチ
オ）フェノールの合成：ｏ−クレゾール７３．７ｇ
（０．６７６ｍｏｌ）を１，２−ジクロロエタン７３０
ｍｌに溶解し、ジメチルジスルフィド４５．０ｇ（０．
４７０ｍｏｌ）及び塩化アルミニウム４５．０ｇ（０．
３４０ｍｏｌ）を加え、１２時間加熱還流を行った。冷
却後、冷水１Ｌ、濃塩酸１００ｍｌを加え有機層を分取
した。飽和食塩水で洗浄し、無水硫酸マグネシウムで乾
燥した後、溶媒を減圧下で留去し、粗物を得た。この粗
物を改めてヘキサン１Ｌに溶解させ、水酸化ナトリウム
１％水溶液１Ｌで洗浄した。無水硫酸マグネシウムで乾
燥した後、減圧下で溶媒を留去することにより粗物を得
た。この粗物を減圧単蒸留することにより目的物２８．
５ｇを得た。 沸点１０１〜１０２℃／１４ｍｍＨｇ なお、洗浄液である１％水酸化ナトリウム水溶液に濃塩
酸を加え酸性化した後、酢酸エチル１Ｌを加え有機層を
分取した。無水マグネシウムで乾燥した後、減圧下で溶
媒を留去し粗物を得た。この粗物を減圧単蒸留すること
によってｏ−クレゾール３３．３ｇを回収した。Reference Example 1 Synthesis of 2-methyl-6- (methylthio) phenol: 73.7 g of o-cresol
(0.676 mol) of 1,2-dichloroethane 730
It was dissolved in 4 ml of dimethyl disulfide (0.
470 mol) and aluminum chloride 45.0 g (0.
(340 mol) was added, and the mixture was heated under reflux for 12 hours. After cooling, 1 L of cold water and 100 ml of concentrated hydrochloric acid were added to separate the organic layer. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give a crude product. This crude product was dissolved again in 1 L of hexane and washed with 1 L of a 1% aqueous sodium hydroxide solution. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain a crude product. By subjecting this crude product to simple distillation under reduced pressure, the desired product 28.
5 g was obtained. Boiling point 101-102 ° C / 14 mmHg In addition, 1% sodium hydroxide aqueous solution as a washing solution was acidified by adding concentrated hydrochloric acid, and then 1 L of ethyl acetate was added to separate an organic layer. After drying over anhydrous magnesium, the solvent was distilled off under reduced pressure to obtain a crude product. By subjecting this crude product to simple distillation under reduced pressure, 33.3 g of o-cresol was recovered.
【０００９】参考例２ ２−ベンジルオキシ−３−メチ
ルベンゼンチオールの合成：２−ベンジルオキシ−３−
（メチルチオ）トルエン２．３７ｇ（９．７ｍｍｏｌ）
をメタノール２０ｍｌに溶解し、タングステン酸ナトリ
ウム５％水溶液５ｍｌ及び過酸化水素３０％水溶液１．
１ｇ（９．７ｍｍｏｌ）を加え、４０℃で２時間攪拌し
た。冷却後、水及び酢酸エチルを加え有機層を分取し、
チオ硫酸ナトリウム５％水溶液及び飽和食塩水で洗浄し
た。次いで無水硫酸マグネシウムで乾燥し、減圧下で溶
媒を留去した。次いで、得られた粗物を無水酢酸１０ｍ
ｌに溶解し、１２０℃で４時間攪拌した。冷却後、減圧
下で無水酢酸を留去し、粗Ｐｕｍｍｅｒｅｒ反応生成物
を得た。この粗物をメタノール３０ｍｌに溶解し、水酸
化ナトリウム３％水溶液４５ｍｌを加え室温で３０分間
攪拌した。その後希塩酸を加え酸性化し、塩化メチレン
を加え有機層を分取した。飽和食塩水で洗浄した後、無
水硫酸マグネシウムで乾燥し、減圧下で溶媒を留去し
た。得られた粗物をシリカゲルカラムクロマトグラフィ
ー（溶出液；ヘキサン）で精製し目的物０．６３ｇを得
た。 1Ｈ−ＮＭＲ（ＣＤＣｌ3 ）δ ２．３（ｓ，３
Ｈ，ＣＨ3 ），３．７（ｓ，１Ｈ，ＳＨ），４．９
（ｓ，２Ｈ，ＣＨ2 ），６．９−７．５（ｍ，８Ｈ，ａ
ｒｏｍａｔｉｃ ｐｒｏｔｏｎｓ）ｐｐｍ．Reference Example 2 Synthesis of 2-benzyloxy-3-methylbenzenethiol: 2-benzyloxy-3-
2.37 g (9.7 mmol) of (methylthio) toluene
Is dissolved in 20 ml of methanol, 5 ml of a 5% aqueous solution of sodium tungstate and a 30% aqueous solution of hydrogen peroxide 1.
1 g (9.7 mmol) was added, and the mixture was stirred at 40 ° C. for 2 hours. After cooling, water and ethyl acetate were added to separate the organic layer,
It was washed with a 5% aqueous solution of sodium thiosulfate and saturated saline. Then, it was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Then, the obtained crude product was treated with acetic anhydride 10 m.
It was dissolved in 1 and stirred at 120 ° C. for 4 hours. After cooling, acetic anhydride was distilled off under reduced pressure to obtain a crude Pummerer reaction product. This crude product was dissolved in 30 ml of methanol, 45 ml of a 3% aqueous sodium hydroxide solution was added, and the mixture was stirred at room temperature for 30 minutes. After that, dilute hydrochloric acid was added to acidify, methylene chloride was added to separate the organic layer. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (eluent: hexane) to obtain 0.63 g of the desired product. 1 H-NMR (CDCl 3 ) δ 2.3 (s, 3
H, CH 3 ), 3.7 (s, 1H, SH), 4.9
(S, 2H, CH 2 ), 6.9-7.5 (m, 8H, a
romantic protons) ppm.
【００１０】参考例３ アリル［（２−ベンジルオキシ
−３−メチル）フェニルチオ］アセテートの合成：２−
ベンジルオキシ−３−メチルベンゼンチオール０．６３
ｇ（２．７ｍｍｏｌ）をＤＭＦ１０ｍｌに溶解し、６０
％水素化ナトリウム０．１０８ｇ（２．７ｍｍｏｌ）を
添加し３０分間室温でかくはんした。この溶液に臭化酢
酸アリル０．４８ｇ（２．７ｍｍｏｌ）を加えさらに３
時間攪拌した後、反応溶液を冷水中にあけ、酢酸エチル
で抽出した。有機層を分離し、水及び飽和食塩水で洗浄
した後、無水硫酸マグネシウムで乾燥した。減圧下で溶
媒を留去し、得られた粗物をシリカゲルカラムクロマト
グラフィー（溶出液；塩化メチレン）で精製し、目的物
０．４７ｇ（１．４ｍｍｏｌ）を得た。 ＮＭＲ：δ 1Ｈ（ＣＤＣｌ3 ）７．６−６．９（ｍ，８
Ｈ），５．８（ｍ，１Ｈ），５．３（ｂｒｄ，Ｊ＝１７
Ｈｚ，１Ｈ），５．２（ｂｒｄ，Ｊ＝１３Ｈｚ，１
Ｈ），４．９（ｓ，２Ｈ），４．５（ｂｒｄ，Ｊ＝６Ｈ
ｚ，２Ｈ），３．７（ｓ，２Ｈ），２．３（ｓ，３Ｈ）Reference Example 3 Synthesis of allyl [(2-benzyloxy-3-methyl) phenylthio] acetate: 2-
Benzyloxy-3-methylbenzenethiol 0.63
g (2.7 mmol) was dissolved in 10 ml of DMF, and 60
% Sodium hydride (0.108 g, 2.7 mmol) was added, and the mixture was stirred for 30 minutes at room temperature. To this solution, 0.48 g (2.7 mmol) of allyl bromide acetate was added and further 3
After stirring for an hour, the reaction solution was poured into cold water and extracted with ethyl acetate. The organic layer was separated, washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: methylene chloride) to obtain 0.47 g (1.4 mmol) of the desired product. NMR: δ 1 H (CDCl 3 ) 7.6-6.9 (m, 8
H), 5.8 (m, 1H), 5.3 (brd, J = 17)
Hz, 1H), 5.2 (brd, J = 13 Hz, 1
H), 4.9 (s, 2H), 4.5 (brd, J = 6H
z, 2H), 3.7 (s, 2H), 2.3 (s, 3H)
【００１１】[0011]
【発明の効果】本発明の製造方法は固液相間反応させる
ことにより高収率で目的物を得ることができ、また、原
料化合物を容易に得られるので、工業的に優れた製造方
法である。INDUSTRIAL APPLICABILITY According to the production method of the present invention, the target product can be obtained in a high yield by the solid-liquid phase reaction, and the starting compound can be easily obtained. is there.
Claims (1)
物を塩基及び４級アンモニウム塩の存在下、一般式〔II
−１〕又は〔II−２〕 【化２】 （式中、Ｒ2 はアルキル基又はアラルキル基を、Ｈａｌ
はハロゲン原子を、Ｒ2′は低級アルキル基を示す。）
で表わされる化合物と固液相間反応させることを特徴と
する一般式〔III 〕 【化３】 （式中、Ｒ1 及びＲ2 は前記と同じ意味を示す。）で表
わされる化合物の製造方法。1. A compound represented by the general formula [I]: (In the formula, R 1 represents an alkyl group.) The compound represented by the general formula [II
-1] or [II-2] (In the formula, R 2 represents an alkyl group or an aralkyl group;
Represents a halogen atom, and R 2 ′ represents a lower alkyl group. )
A compound represented by the general formula [III] (Wherein R 1 and R 2 have the same meanings as described above).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6066651A JPH07247267A (en) | 1994-03-10 | 1994-03-10 | Production of phenyl ethers |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6066651A JPH07247267A (en) | 1994-03-10 | 1994-03-10 | Production of phenyl ethers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07247267A true JPH07247267A (en) | 1995-09-26 |
Family
ID=13322026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6066651A Pending JPH07247267A (en) | 1994-03-10 | 1994-03-10 | Production of phenyl ethers |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07247267A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013526557A (en) * | 2010-05-17 | 2013-06-24 | ジェヌフィト | Improved production of chalcone derivatives |
| WO2015122396A1 (en) * | 2014-02-13 | 2015-08-20 | イハラケミカル工業株式会社 | Method for producing harmful-organism control agent, and intermediate thereof |
-
1994
- 1994-03-10 JP JP6066651A patent/JPH07247267A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013526557A (en) * | 2010-05-17 | 2013-06-24 | ジェヌフィト | Improved production of chalcone derivatives |
| WO2015122396A1 (en) * | 2014-02-13 | 2015-08-20 | イハラケミカル工業株式会社 | Method for producing harmful-organism control agent, and intermediate thereof |
| CN105980354A (en) * | 2014-02-13 | 2016-09-28 | 庵原化学工业株式会社 | Method for producing harmful-organism control agent, and intermediate thereof |
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