JPH013157A - 2-aminobenzyl alcohol derivative - Google Patents
2-aminobenzyl alcohol derivativeInfo
- Publication number
- JPH013157A JPH013157A JP62-158510A JP15851087A JPH013157A JP H013157 A JPH013157 A JP H013157A JP 15851087 A JP15851087 A JP 15851087A JP H013157 A JPH013157 A JP H013157A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- formula
- general formula
- represents hydrogen
- alcohol derivative
- 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.)
- Granted
Links
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical class NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 title claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 238000006722 reduction reaction Methods 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 10
- -1 2-(2-substituted aminobenzylsulfinyl)benzimidazole Chemical class 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000007126 N-alkylation reaction Methods 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 150000001556 benzimidazoles Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000000767 anti-ulcer Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000010446 mirabilite Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical compound C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- FGJMERWOCACHCQ-UHFFFAOYSA-N 2-(chloromethyl)-n-methyl-n-(2-methylpropyl)aniline;hydrochloride Chemical compound Cl.CC(C)CN(C)C1=CC=CC=C1CCl FGJMERWOCACHCQ-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-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
- 230000006181 N-acylation Effects 0.000 description 1
- 108091027881 NEAT1 Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- QTQUJRIHTSIVOF-UHFFFAOYSA-N amino(phenyl)methanol Chemical class NC(O)C1=CC=CC=C1 QTQUJRIHTSIVOF-UHFFFAOYSA-N 0.000 description 1
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940125900 compound 59 Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- XCMVSUPUUQDGTL-UHFFFAOYSA-N methyl 2-(2-methylpropylamino)benzoate Chemical compound COC(=O)C1=CC=CC=C1NCC(C)C XCMVSUPUUQDGTL-UHFFFAOYSA-N 0.000 description 1
- 229940102398 methyl anthranilate Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
本発明は、２−アミノベンジルアルコール誘導体に関し
、更に詳細には、次の一般式（Ｉ）（式中、Ｒは水素、
アルキル、アルコキシ、ハロゲン又はトリフルオロメチ
ルを示し、Ｒは水素又はアルキルを示す）
で表わされる２−アミノベンジルアルコール誘導体に関
する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 2-aminobenzyl alcohol derivatives, more specifically, the following general formula (I) (wherein R is hydrogen,
2-aminobenzyl alcohol derivative represented by: alkyl, alkoxy, halogen or trifluoromethyl, and R represents hydrogen or alkyl.
上記一般式（Ｉ）で表ねされる２−アミノベンジルアル
コール誘導体は、医薬、農薬等の合成中間体として広く
使用することができ、殊に本発明者らに見い出された抗
潰瘍作用及び胃腸の細胞保（式中、Ｙ及びＹは水素、ハ
ロゲン、アルコキシ、アルキル、トリフルオロメチル、
アミノ等を示し、Ｒ及びＲは前記と同じ）
で表ねきれる２−（２−置換アミノベンジルスルフィニ
ル）ベンズイミダゾール誘導体（西独公開Ｐ３５３１４
８７、特願昭６１−”８２２６８他）の重要な合成中間
体である。The 2-aminobenzyl alcohol derivative represented by the above general formula (I) can be widely used as a synthetic intermediate for medicines, agricultural chemicals, etc., and in particular has an anti-ulcer effect and a gastrointestinal effect discovered by the present inventors. cell retention (wherein Y and Y are hydrogen, halogen, alkoxy, alkyl, trifluoromethyl,
2-(2-substituted aminobenzylsulfinyl)benzimidazole derivative (West German Publication P35314)
87, Japanese Patent Application No. 1987-82268, etc.).
本発明者らは、前記一般式（Ｘ）で表わされるベンズイ
ミダゾール誘導体の工業的規模の合成法に関する鋭意研
究を行った結果、上記一般式ＣＩ）で表わきれる２−ア
ミノベンジルアルコール誘導体を経由した合成法を用い
ることにより、■ｎ便な操作で、しかも高収率で、上記
一般式（×）で表ねされるベンズイミダゾール誘導体を
得ることを見い出し、本発明を完成した。The present inventors conducted intensive research on an industrial scale synthesis method for the benzimidazole derivative represented by the general formula (X), and found that The present inventors have discovered that by using the above synthetic method, a benzimidazole derivative represented by the above general formula (x) can be obtained in a convenient operation and in high yield, and have completed the present invention.
本発明の目的は、上記一般式（Ｉ）で表わされる２−ア
ミノベンジルアルコール誘導体を提供するにある。An object of the present invention is to provide a 2-aminobenzyl alcohol derivative represented by the above general formula (I).
更に、上記一般式（１）で表ねされる２−アミノベンジ
ルアルコール誘導体の製造方法を提供することも、本発
明の目的である。Furthermore, it is also an object of the present invention to provide a method for producing a 2-aminobenzyl alcohol derivative represented by the above general formula (1).
本発明は、次の一般式（Ｉ）
（式中、Ｒは水素、アルキル、アルコキシ、ハロゲン又
はトリフルオロメチルを示し、Ｒば水素又はアルキルを
示す）
で表わされる２−アミノベンジルアルコール誘導体に関
する。The present invention relates to a 2-aminobenzyl alcohol derivative represented by the following general formula (I) (wherein R represents hydrogen, alkyl, alkoxy, halogen or trifluoromethyl, and R represents hydrogen or alkyl).
上記−数式（Ｉ）のＲ及びＲのアルキルとしては、メチ
ル、エチル、プロピル等のＣｌ−Ｃｒの低級アルキルを
、Ｒのアルコキシとしては、メトキシ、エトキシ、プロ
ポキシ等のＣ１〜Ｃ５のアルコキシを、Ｒのハロゲンと
しては、塩素、フッ素等が挙げられる。As the alkyl for R and R in the above formula (I), Cl-Cr lower alkyl such as methyl, ethyl, propyl, etc., and as the alkoxy for R, C1 to C5 alkoxy such as methoxy, ethoxy, propoxy, etc. Examples of the halogen for R include chlorine and fluorine.
上記−数式（Ｉ）で表わされる２−アミノベンジルアル
コール誘導体は、以下に示す方法等により得ることがで
きる。すなわち、
（Ａ法） −数式（＋１ ）
（式中、Ｒは水素、アルキル、アルコキシ、ハロゲン又
はトリフルオロメチルを示し Ｒ３は水素、アルキル又
はアラルキルを示す）で表わされる化合物を還元反応に
付し、−数式（Ｉｌｌ ）（式中、Ｒ１は前記と同じ）
で表わされる化合物を得、次いでこれをＮ−アルキル化
反応に付すことにより、−数式（ＩＶ）（式中、Ｒ１は
アルキルを示し、Ｒ１は前記と同じ）
で表わされる２−アミノベンジルアルコール誘導。The 2-aminobenzyl alcohol derivative represented by formula (I) above can be obtained by the method shown below. That is, (Method A) - A compound represented by the formula (+1) (wherein R represents hydrogen, alkyl, alkoxy, halogen or trifluoromethyl, and R3 represents hydrogen, alkyl or aralkyl) is subjected to a reduction reaction. , - By obtaining a compound represented by the formula (Ill) (wherein R1 is the same as above) and then subjecting this to an N-alkylation reaction, - a compound represented by the formula (IV) (wherein R1 represents alkyl) is obtained. , R1 is the same as above).
体を得ることができる。又、
（Ｂ法） −数式（Ｖ）
（式中、Ｒは水素、アルキル、アルコキシ、ハロゲン又
はトリフルオロメチルを示し、Ｒｔｋ水素又はアルキル
を示し、モしてＲ５はアルキル又はアラルキルを示す）
で表わされる化合物にアシル化剤を作用させ、−数式（
ＶＩ）
（式中、Ｒ，Ｒ及びＲは前記と同じ）
で表わされる化合物を得、次いでこれを還元反応に付す
ことにより、上記−数式（Ｉ）で表わされる２−アミノ
ヘンシルアルコール誘導体を得ることができる。You can get a body. Also, (Method B) - Formula (V) (wherein R represents hydrogen, alkyl, alkoxy, halogen or trifluoromethyl, Rtk represents hydrogen or alkyl, and R5 represents alkyl or aralkyl) An acylating agent is allowed to act on the compound represented by the formula (
VI) (wherein R, R and R are the same as above) By obtaining the compound represented by and then subjecting it to a reduction reaction, the 2-aminohensyl alcohol derivative represented by the above-mentioned formula (I) can be obtained. Obtainable.
一般式（ＴＩ）のＲ３、−数式（ＴＶ）の計、−数式（
Ｖ）のＲゞて示されるアルキルとしては、メチル、エチ
ル、プロピル等の０１〜Ｃ５の低級アルキルが挙げられ
、−数式（ＩＴ ）のＲ３、−数式（Ｖ）のＲゞで示さ
れるアラルキルとしては、ベンジル、ベンズヒドリル等
が挙げられる。R3 of general formula (TI), - total of formula (TV), - formula (
Examples of the alkyl represented by R in V) include 01 to C5 lower alkyl such as methyl, ethyl, propyl, etc. -R3 in formula (IT), and aralkyl represented by R in formula (V) Examples include benzyl and benzhydryl.
Ａ法及びＢ法で示す還元反応に用いる反応試薬としては
、アミド及びエステル又はカルボン酸をそれぞれアミン
及びアルコールに還元可能な反応用いられる。還元反応
における反応溶媒としては、メタノール、エタノール等
のアルコール類、テトラヒドロフラン、ジエチルエーテ
ル等のエーテル類が挙げられ、反応温度は一り℃〜還流
温度で行われる。Reaction reagents used in the reduction reactions shown in Methods A and B are those capable of reducing amide and ester or carboxylic acid to amine and alcohol, respectively. Examples of the reaction solvent in the reduction reaction include alcohols such as methanol and ethanol, and ethers such as tetrahydrofuran and diethyl ether, and the reaction temperature is 1° C. to reflux temperature.
Ａ法のＮ−アルキル化反応としては、公知のＮ−アルキ
ル化方法、例えばアルキルハライド、ジアルキル硫酸等
を用いる方法、あるいはＮ−アシル化後、還元反応に付
す方法などが挙げられる。Examples of the N-alkylation reaction in Method A include known N-alkylation methods, such as a method using an alkyl halide, dialkyl sulfuric acid, etc., or a method in which N-acylation is followed by a reduction reaction.
Ｂ法のアシル化剤としては、公知のアシル化反応に用い
られる試薬、例えばイソ酪酸、イソ酪酸無水物、イソ酪
酸クロライド等が用いられる。As the acylating agent in method B, reagents used in known acylation reactions, such as isobutyric acid, isobutyric anhydride, isobutyric acid chloride, and the like are used.
Ａ法の原料である一般式（ＩＩ ）の化合物は、例えば
次式で示される方法により得られる。（Ｂｕｌｌ。The compound of general formula (II), which is a raw material in Method A, can be obtained, for example, by the method shown by the following formula. (Bull.
Ｓｏｃ、Ｃｈｉｍ、Ｆｒａｎｃｅ ’６０，３３７）
他の化合物も同様な方法により得られる。Soc, Chim, France '60, 337)
Other compounds can be obtained by similar methods.
又、）３法の原料でＲがアルキルの場合は、一般式（Ｖ
ｌ＋ ）
（式中、Ｒ及びＲは前記と同じ）
の化合物に、公知のＮ−アルキル化方法を用いることに
より得られる。In addition, when R is alkyl in the raw material of method 3), general formula (V
l+ ) (wherein R and R are the same as above) using a known N-alkylation method.
かくして得られた、一般式ＣＩ）で表わさ°れる２−ア
ミノベンジルアルコール誘導体を用いることで、例えば
以下で示される合成工程により、上記一般式（Ｘ）で表
わされる２−（２−置換アミノベンジルスルフィニル）
ベンズイミダゾール誘導体を得ることができる。By using the thus obtained 2-aminobenzyl alcohol derivative represented by general formula CI), 2-(2-substituted aminobenzyl alcohol derivative represented by general formula sulfinyl)
Benzimidazole derivatives can be obtained.
一般式（Ｘ）で表わされる他の化合物も、上記と同様な
方法により得ることができる。Other compounds represented by general formula (X) can also be obtained by the same method as above.
以上、本発明化合物である一般式（Ｉ）で表わきれる２
−アミノベンジルアルコール誘導体を経由することで、
抗潰瘍及び胃腸の細胞保護作用を有する、一般式（×）
で表わきれる２−（２−置換アミノベンジルスルフィニ
ル）ベンズイミダゾール誘導体を簡便な操作で、しかも
高収率で、得ることができる。更に、一般式（Ｉ）で表
わきれる２−アミノベンジルアルコール誘導体は、一般
式（Ｘ）で表わきれる２−（２−置換アミノベンジルス
ルフィニル）ベンズイミダゾール誘導体の合成中間体以
外にも、他の医薬、農薬の合成中間体としても有用であ
る。As mentioned above, 2 represented by the general formula (I) which is the compound of the present invention
-via aminobenzyl alcohol derivative,
General formula (×) with anti-ulcer and gastrointestinal cytoprotective effects
The 2-(2-substituted aminobenzylsulfinyl)benzimidazole derivative represented by can be obtained by a simple operation and in high yield. Furthermore, the 2-aminobenzyl alcohol derivative represented by the general formula (I) may be used as a synthetic intermediate for the 2-(2-substituted aminobenzylsulfinyl)benzimidazole derivative represented by the general formula (X). It is also useful as a synthetic intermediate for pharmaceuticals and agricultural chemicals.
次に実施例、参考例を挙げて、本発明を更に詳細に説明
する。Next, the present invention will be explained in more detail by giving examples and reference examples.
参考例１
２−イソブチルアミノ 患 酸メチルエステルアントラ
ニル酸メチル５８ｇ、イソ酪酸クロライド４１ｇ、炭酸
カリウム５３ｇ及びベンゼン１．２１の混合物を、１時
間加熱還流する。２０ｔまで冷却後、反応液を水、ｌＮ
−ＨＣｌ、飽和食塩水の順に洗浄し、芒硝乾燥後、溶媒
を減圧下留去して無色油状物を得た。Reference Example 1 2-Isobutylamino Acid Methyl Ester A mixture of 58 g of methyl anthranilate, 41 g of isobutyric acid chloride, 53 g of potassium carbonate, and 1.21 g of benzene was heated under reflux for 1 hour. After cooling to 20t, the reaction solution was diluted with water and lN.
-HCl and saturated brine, and after drying with Glauber's salt, the solvent was distilled off under reduced pressure to obtain a colorless oil.
実施例１
２−イソブチルアミノペンシルアルコール水素化リチウ
ムアルミニウム４０．９ｇの乾燥エーテル１．３１懸濁
液に、参考例１で得た２−イソブチルアミノ安息香酸メ
チルエステルの乾燥エーテル０．４１の溶液を、水冷下
３０分かけて滴下する。室温で２０分、更に１時間加熱
還流後冷却する。反応液に飽和芒硝水を氷冷しながら加
えて、過剰の水素化リチウムアルミニウムを分解する。Example 1 2-isobutylaminopencyl alcohol To a suspension of 40.9 g of lithium aluminum hydride in 1.31 g of dry ether, a solution of 0.41 g of dry ether of 2-isobutylaminobenzoic acid methyl ester obtained in Reference Example 1 was added. , dropwise over 30 minutes under water cooling. The mixture was heated under reflux for 20 minutes at room temperature and for an additional hour, and then cooled. Saturated sodium sulfate solution is added to the reaction solution while cooling with ice to decompose excess lithium aluminum hydride.
不溶物を濾別し、濾液を芒硝乾燥する。溶媒を減圧上留
去し、目的物を淡黄色油状物として６４ｇ（９３％）得
た。Insoluble matter is filtered off, and the filtrate is dried over sodium sulfate. The solvent was distilled off under reduced pressure to obtain 64 g (93%) of the desired product as a pale yellow oil.
’ＨＮＭＲ（ＣＤＣＩ３）
δ： ０．９６（ｄ、６Ｈ，Ｊ＝８Ｈ２）１．６−２．
１（ｍ、ＬＨ）
２．９２（ｄ、２Ｈ，Ｊ＝８Ｈｚ）
３．１６（ｂｒ、２Ｈ）
４．５６（ｓ、２Ｈ）
６．４−７．３（ｍ、４Ｈ）
ｎｅａｔ 刊。'HNMR (CDCI3) δ: 0.96 (d, 6H, J=8H2) 1.6-2.
1 (m, LH) 2.92 (d, 2H, J=8Hz) 3.16 (br, 2H) 4.56 (s, 2H) 6.4-7.3 (m, 4H) Published by neat.
ＩＲνｍａＸ Ｃｍ ・
３３８０．２９５０．２８６０．１６００゜１５８０．
１５１０．１４６０，１３１０゜９９０．７４０
実施例２
２−イソブチルアミノベンジルアルコール６４ｇ、ジメ
チル硫酸９０ｇ、炭酸カルシウム７９ｇ及び水３２０ｍ
１の混合物を、室温で２時間攪拌する。反応液にエーテ
ル０．５１を加え、不溶物を濾別する。濾液を水洗した
後１０％塩酸（０，７１）で抽出し、エーテルで洗浄す
る。次に、水層に炭酸カリウムを加えアルカリ性とし、
析出してくる油状物をエーテル抽出して飽和食塩水で洗
浄、芒硝乾燥後溶媒を減圧上留去して、目的物を黄色油
状物として６３．３ｇ（９２％）得た。IRνmaX Cm ・3380.2950.2860.1600°1580.
1510.1460, 1310°990.740 Example 2 64 g of 2-isobutylaminobenzyl alcohol, 90 g of dimethyl sulfate, 79 g of calcium carbonate, and 320 m of water
The mixture of 1 is stirred at room temperature for 2 hours. Add 0.51 g of ether to the reaction solution, and filter off insoluble matter. The filtrate is washed with water, extracted with 10% hydrochloric acid (0.71), and washed with ether. Next, add potassium carbonate to the water layer to make it alkaline.
The precipitated oil was extracted with ether, washed with saturated brine, dried with sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 63.3 g (92%) of the desired product as a yellow oil.
’ＨＮＭＲ（ＣＤＣ１３）
δ： ０．９６（ｄ、６Ｈ，Ｊ＝７Ｈｚ）１．６−２．
１（ｍ、ＬＨ）
２．６４（ｓ、３Ｈ）
２．７０（ｃｌ、２Ｈ，Ｊ＝８Ｈｚ）
４．７８（ｓ、２Ｈ）
５．４０ （ｓ 、 Ｌ Ｈ）
７．０−７．４（ｍ、４Ｈ）
ｎｅａｔ −１。'HNMR (CDC13) δ: 0.96 (d, 6H, J=7Hz) 1.6-2.
1 (m, LH) 2.64 (s, 3H) 2.70 (cl, 2H, J=8Hz) 4.78 (s, 2H) 5.40 (s, LH) 7.0-7.4 (m, 4H) neat -1.
ＩＲνｍａｘ Ｃｍ ・
３３７０．２９５０，１５９０，１４５０゜１０２０．
７６０
参考例２
実施例２で得たベンジルアルコール６３．３ ｇを乾燥
ベンゼン１１に溶解し、油上塩化チオニル４９ｇの乾燥
ベンゼン０．２１溶液を、２０分かけて滴下する。室温
で１時間、更に５０〜５５℃で２０分間ｆｆｊ拌する。IRνmax Cm ・3370.2950,1590,1450°1020.
760 Reference Example 2 63.3 g of benzyl alcohol obtained in Example 2 is dissolved in 11 parts of dry benzene, and a solution of 49 g of thionyl chloride in 0.21 parts of dry benzene on oil is added dropwise over 20 minutes. Stir at room temperature for 1 hour and then at 50-55°C for 20 minutes.
５０℃以下で過剰の塩化チオニル及びベンゼンを減圧上
留去し、析出する結晶を濾過し、ベンゼンで洗浄後、減
圧上乾燥して標題化合物を白色結晶として６４．４ｇ
（７９％）得た。Excess thionyl chloride and benzene were distilled off under reduced pressure at 50°C or below, and the precipitated crystals were filtered, washed with benzene, and dried under reduced pressure to obtain 64.4 g of the title compound as white crystals.
(79%) obtained.
’ＨＮＭＲ（ＣＤＣＩ３）
δ： １．００（ｄ、６Ｈ，Ｊ＝８Ｈｚ）１．７−２．
２（ｍ、ＩＨ）
３．３２（ｓ、３Ｈ）
２．４８（ｄ、２Ｈ，Ｊ＝８Ｈｚ）
５．３２（ｓ、２Ｈ）
７．３−７．８（ｍ、４Ｈ）
参考例３
２−メルカプトベンズイミダゾール３９ｇ１エタノール
６４０ｍＩ、２−（Ｎ−イソブチル−Ｎ−メチルアミノ
）ベンジルクロライド塩酸塩６４．４ｇの混合物を室温
で２０分攪拌する。析出しノ；沈殿物を濾取し、クロロ
ポルム１１及び炭酸カリウム１００ｇの水ＩＩ水溶液の
混合液に得られた固体を加え、よく攪拌し分液する。ク
ロロホルム層を芒硝乾燥後、溶媒を減圧上留去し油状物
８４．５ｇを得る。これにエーテルを少量加え結晶化さ
せ、析出した結晶な濾別後、減圧上乾燥し、目的物を白
色粉末として７４．８ｇ（８９％）を得た。'HNMR (CDCI3) δ: 1.00 (d, 6H, J=8Hz) 1.7-2.
2 (m, IH) 3.32 (s, 3H) 2.48 (d, 2H, J=8Hz) 5.32 (s, 2H) 7.3-7.8 (m, 4H) Reference example 3 2 - A mixture of 39 g of mercaptobenzimidazole, 640 ml of ethanol, and 64.4 g of 2-(N-isobutyl-N-methylamino)benzyl chloride hydrochloride is stirred at room temperature for 20 minutes. Precipitation: The precipitate is collected by filtration, and the obtained solid is added to a mixed solution of chloroporm 11 and 100 g of potassium carbonate in Water II aqueous solution, and the mixture is thoroughly stirred and separated. After drying the chloroform layer over Glauber's salt, the solvent was distilled off under reduced pressure to obtain 84.5 g of an oily substance. A small amount of ether was added to this to cause crystallization, and the precipitated crystals were filtered off and dried under reduced pressure to obtain 74.8 g (89%) of the desired product as a white powder.
ＮＭＲ（ＣＤＣ］３）
δ：０．９８（ｄ、６Ｈ，Ｊ＝７Ｈｚ）１．８−２．２
（ｍ、Ｌ Ｈ）
２．６８（ｄ、２Ｈ，Ｊ＝８ ト＋ｚ）２．８０（ｓ
、３ｌ−（）
４．４８ （ｓ 、 ２ Ｈ）
６．９−７．８（ｍ、８Ｈ）
参考例４
２−１２−（Ｎ−イソブチル−Ｎ−メチルアミノ）ベン
ジルチオ］ベンズイミダゾール７６．１ｇをクロロホル
ム１．１１に溶解し、水冷する。これに、５℃以下でｍ
−クロロ過安息香酸５０．２ ｇ （純度８０％）を徐
々に加える。更に５℃以下で３０分攪拌後、反応液に飽
和重曹水を加え、分液する。り００ホルム層を更に飽和
重曹水、１０％ヂオ硫酸ナトリウム水溶液、飽和食塩水
の順で洗浄し、芒硝乾燥後、溶媒を減圧上留去する。析
出してくる結晶にアセトニトリル１００ｍ ｌを加え、
濾取する。アセトニトリルで洗浄し、標題化合物７０．
５ｇ（８８％）を得た。このものを更に塩化メチレン−
アセトニトリルで再結晶し、１票題化合物の純品５９．
７ｇを得た。NMR (CDC) 3) δ: 0.98 (d, 6H, J=7Hz) 1.8-2.2
(m, L H) 2.68 (d, 2H, J=8 + z) 2.80 (s
, 3l-() 4.48 (s, 2H) 6.9-7.8(m, 8H) Reference Example 4 2-12-(N-isobutyl-N-methylamino)benzylthio]benzimidazole 76.1g Dissolve in 1.11 parts of chloroform and cool with water. In addition, m
- Gradually add 50.2 g of chloroperbenzoic acid (80% purity). After further stirring for 30 minutes at 5° C. or lower, saturated aqueous sodium bicarbonate solution was added to the reaction solution and the mixture was separated. The 00 form layer is further washed in the order of saturated sodium bicarbonate solution, 10% sodium diosulfate solution, and saturated saline solution, and after drying with sodium sulfate, the solvent is distilled off under reduced pressure. Add 100ml of acetonitrile to the precipitated crystals,
Filter. Wash with acetonitrile to obtain the title compound 70.
5g (88%) was obtained. Add this to methylene chloride
Recrystallized from acetonitrile to obtain 1 pure product of the title compound 59.
7g was obtained.
ＮＭＲ（ＣＤＣＩ３）
δ：０．９２（ｄ、６Ｈ，Ｊ＝７Ｈｚ）１．５−２．０
（ｍ、 Ｉ Ｈ）
２．６２（ｃｌ、２Ｈ，Ｊ＝８Ｈｚ）
２．６４（ｓ、３Ｈ）
４．５２（ｄ、２Ｈ，Ｊ＝１４Ｈｚ）
４．９０（ｄ、２Ｈ，Ｊ＝１４Ｈｚ）
６．８−７．９（ｍ、８Ｈ）
ｍ、ｐ、１２６〜１２６．５℃
特許出願人 日本ケミファ株式会社NMR (CDCI3) δ: 0.92 (d, 6H, J=7Hz) 1.5-2.0
(m, I H) 2.62 (cl, 2H, J=8Hz) 2.64 (s, 3H) 4.52 (d, 2H, J=14Hz) 4.90 (d, 2H, J=14Hz) 6.8-7.9 (m, 8H) m, p, 126-126.5°C Patent applicant Nippon Chemifa Co., Ltd.
Claims (3)
ン又はトリフルオロメチルを 示し、Ｒ＾２は水素又はアルキルを示す） で表わされる２−アミノベンジルアルコー ル誘導体。(1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 represents hydrogen, alkyl, alkoxy, halogen, or trifluoromethyl, and R^2 represents hydrogen or alkyl.) 2-Aminobenzyl alcohol derivative.
ン又はトリフルオロメチルを示し、 Ｒ＾３は水素、アルキル又はアラルキルを示す） で表わされる化合物を還元反応に付し、一 般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＾１は前記と同じ） で表わされる化合物を得、次いでこれをＮ −アルキル化反応に付すことを特徴とする、一般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＾４はアルキルを示し、Ｒ＾１は前記と同じ
） で表わされる２−アミノベンジルアルコー ル誘導体の製造方法。(2) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1 represents hydrogen, alkyl, alkoxy, halogen, or trifluoromethyl, and R^3 represents hydrogen, alkyl, or aralkyl.) The represented compound is subjected to a reduction reaction to obtain a compound represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. Production of a 2-aminobenzyl alcohol derivative represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^4 represents alkyl, and R^1 is the same as above) Method.
ン又はトリフルオロメチルを示し、 Ｒ＾２は水素又はアルキルを示し、そしてＲ＾５はアル
キル又はアラルキルを示す） で表わされる化合物にアシル化剤を作用さ せ、一般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＾１、Ｒ＾２及びＲ＾５は前記と同じ）で表
わされる化合物を得、次いでこれを還 元反応に付すことを特徴とする、一般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＾１及びＲ＾２は前記と同じ） で表わされる２−アミノベンジルアルコー ル誘導体の製造方法。(3) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1 represents hydrogen, alkyl, alkoxy, halogen, or trifluoromethyl, R^2 represents hydrogen or alkyl, and R^ 5 represents alkyl or aralkyl) An acylating agent is applied to the compound represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1, R^2 and R^5 are as above) There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by obtaining a compound represented by A method for producing a 2-aminobenzyl alcohol derivative represented by:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15851087A JPH07107026B2 (en) | 1987-06-25 | 1987-06-25 | 2-aminobenzyl alcohol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15851087A JPH07107026B2 (en) | 1987-06-25 | 1987-06-25 | 2-aminobenzyl alcohol derivative |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JPH013157A true JPH013157A (en) | 1989-01-06 |
| JPS643157A JPS643157A (en) | 1989-01-06 |
| JPH07107026B2 JPH07107026B2 (en) | 1995-11-15 |
Family
ID=15673310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15851087A Expired - Lifetime JPH07107026B2 (en) | 1987-06-25 | 1987-06-25 | 2-aminobenzyl alcohol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07107026B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102011013366B4 (en) | 2011-03-08 | 2014-10-02 | Federal-Mogul Burscheid Gmbh | Mechanical seal |
-
1987
- 1987-06-25 JP JP15851087A patent/JPH07107026B2/en not_active Expired - Lifetime
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