JPS63290856A - 5-alkoxyanthranilic ester - Google Patents
5-alkoxyanthranilic esterInfo
- Publication number
- JPS63290856A JPS63290856A JP12433087A JP12433087A JPS63290856A JP S63290856 A JPS63290856 A JP S63290856A JP 12433087 A JP12433087 A JP 12433087A JP 12433087 A JP12433087 A JP 12433087A JP S63290856 A JPS63290856 A JP S63290856A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- general formula
- added
- alkoxyanthranilic
- solution
- 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
- 150000002148 esters Chemical class 0.000 title claims description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 14
- 239000002904 solvent Substances 0.000 abstract description 9
- -1 5-Methoxyanthranilic acid methyl ester Chemical class 0.000 abstract description 6
- 238000007126 N-alkylation reaction Methods 0.000 abstract description 4
- 230000002496 gastric effect Effects 0.000 abstract description 4
- 230000000767 anti-ulcer Effects 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 150000001350 alkyl halides Chemical class 0.000 abstract description 2
- 150000008050 dialkyl sulfates Chemical class 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000002633 protecting effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- 239000010446 mirabilite Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 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 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 150000001556 benzimidazoles Chemical class 0.000 description 5
- 150000001989 diazonium salts Chemical class 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 239000012954 diazonium Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- WQGBLANNDGKZCM-UHFFFAOYSA-N 2-(1h-benzimidazol-2-ylsulfanylmethyl)-4-methoxy-n,n-dimethylaniline Chemical compound COC1=CC=C(N(C)C)C(CSC=2NC3=CC=CC=C3N=2)=C1 WQGBLANNDGKZCM-UHFFFAOYSA-N 0.000 description 2
- DNUYOWCKBJFOGS-UHFFFAOYSA-N 2-[[10-(2,2-dicarboxyethyl)anthracen-9-yl]methyl]propanedioic acid Chemical compound C1=CC=C2C(CC(C(=O)O)C(O)=O)=C(C=CC=C3)C3=C(CC(C(O)=O)C(O)=O)C2=C1 DNUYOWCKBJFOGS-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- IJFXRHURBJZNAO-UHFFFAOYSA-N meta--hydroxybenzoic acid Natural products OC(=O)C1=CC=CC(O)=C1 IJFXRHURBJZNAO-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- OLIIUOPPLGCSDK-UHFFFAOYSA-N methyl 2-(dimethylamino)-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1N(C)C OLIIUOPPLGCSDK-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical compound C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 101150034533 ATIC gene Proteins 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- UNTBPXHCXVWYOI-UHFFFAOYSA-O azanium;oxido(dioxo)vanadium Chemical compound [NH4+].[O-][V](=O)=O UNTBPXHCXVWYOI-UHFFFAOYSA-O 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- DWBKSTKVIIRFHL-UHFFFAOYSA-N methyl 2-amino-5-hydroxybenzoate Chemical compound COC(=O)C1=CC(O)=CC=C1N DWBKSTKVIIRFHL-UHFFFAOYSA-N 0.000 description 1
- MOVBJUGHBJJKOW-UHFFFAOYSA-N methyl 2-amino-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1N MOVBJUGHBJJKOW-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000010288 sodium nitrite Nutrition 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
- 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は、５−アルコキシアントラニル酸エステルに関
し、更に詳細には、次の一般式（Ｉ）（式中 Ｒ１及び
Ｒはアルキル基を示し Ｒ３及びＲ＋は水素、鎖状又は
環状アルキル基を示す。ただし Ｒ３及びＲ＋が共に水
素の場合を除く）
で表わされる５−アルコキシアントラニル酸エステルに
関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 5-alkoxyanthranilic acid esters, and more particularly, the present invention relates to 5-alkoxyanthranilic acid esters, and more particularly, the following general formula (I) (wherein R1 and R represent an alkyl group, R3 and R+ are hydrogen, linear or a cyclic alkyl group (except when both R3 and R+ are hydrogen).
本発明者らは、先に次の一般式（■）
ゝに′−′
（式中、Ｙｌ及びＹ２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３′
ン等を示し、Ｒ及びＲ４′はそれぞれ水素、鎖状又は環
状アルキル、アリール、アラルキールを示し、Ｒは前記
と同じ）
で表わきれるベンズイミダゾール誘導体が、抗潰瘍作用
及び胃腸の細胞保護作用を有することを見い出し、特許
出願している。（特開昭６１−２２１１７５、特願昭６
ｌ−８２２６８）本発明者らは、前記一般式（Ｉｆ ）
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（Ｉ
）で表わされる５−アルコキシアントラニル酸エステル
を経由した合成法を用いることにより、簡便な操作で、
しかも高収率で上記一般式（Ｉりで表わされるベンズイ
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 previously proposed the following general formula (■) ゝ′−′ (wherein Yl and Y2 are hydrogen, halogen, alkoxy,
alkyl, trifluoromethyl, amine, etc., R and R4' each represent hydrogen, chain or cyclic alkyl, aryl, aralkyl, and R is the same as above). It was discovered that it has an ulcer effect and a gastrointestinal cell protective effect, and a patent application has been filed. (Unexamined Japanese Patent Publication No. 61-221175, Patent Application No. 6
l-82268) The present inventors have determined that the general formula (If)
As a result of intensive research on an industrial scale synthesis method for the benzimidazole derivative represented by the general formula (I
) By using a synthetic method via a 5-alkoxyanthranilate ester represented by
Furthermore, they have discovered that a benzimidazole derivative represented by the above general formula (I) can be obtained 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５−ア
ルコキシアントラニル酸エステルを提供するにある。An object of the present invention is to provide a 5-alkoxyanthranilic acid ester represented by the above general formula (I).
更に、上記一般式（Ｉ）で表わきれる５−アルコキシア
ントラニル酸エステル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 5-alkoxyanthranilic acid ester represented by the above general formula (I).
（式中、Ｒ１及びＲ２はアルキル基を示し、Ｒ３及びＲ
１は水素、鎖状または環状アルキル基を示す。ただし、
Ｒ及びＲが共に水素の場合を除く）
で表わされる５−アルコキシアントラニル酸エステルに
関する。(In the formula, R1 and R2 represent an alkyl group, R3 and R
1 represents hydrogen, a chain or cyclic alkyl group. however,
5-alkoxyanthranilic acid esters (excluding cases where R and R are both hydrogen)
上記一般式（Ｉ）のＲ１及びＲ２で示されるアルキル基
としては、メチル、エチル等の０１〜Ｃ５−の低級アル
キル基を示し Ｒ３及びＲ４で示されるアルキル基とし
ては、メチル、エチル、プロピル、ブチル、イソプロピ
ル、イソブチル等の０１〜ｃ６の鎖状アルキル基又はシ
クロヘキシル、シクロペンチル等の環状アルキル基が挙
げられる。The alkyl groups represented by R1 and R2 in the above general formula (I) include 01-C5- lower alkyl groups such as methyl and ethyl; the alkyl groups represented by R3 and R4 include methyl, ethyl, propyl, Examples include chain alkyl groups of 01 to c6 such as butyl, isopropyl, and isobutyl, and cyclic alkyl groups such as cyclohexyl and cyclopentyl.
上記一般式（１）で表わされる５−アルコキシアントラ
ニル酸エステルは、一般式（ＩＩＩ ）（式中、Ｒは前
記と同じ）
で表わされる化合物に、一般式（Ｒ）２ＳＯ４（式中、
Ｒは前記と同じ）で表わされる化合物を反応させ、一般
式（ＩＶ）
（式中、Ｒ及びＲは前記と同じ）
で表わされる化合物を得、次いでＮ−アルキル化反応に
付すことにより得られる。The 5-alkoxyanthranilic acid ester represented by the above general formula (1) is added to the compound represented by the general formula (III) (wherein R is the same as above).
R is the same as above) to obtain a compound represented by general formula (IV) (wherein R and R are the same as above), and then subjected to N-alkylation reaction. .
一般式（ＩＩＩ ）で表わされる化合物とジアルキル硫
酸（（Ｒ）２Ｓ Ｏ＋）との反応は、エタノール、メタ
ノール、メチルエチルケトン、アセトン等の有機溶媒中
、好ましくは、アセトン中、水酸化カリウム、水酸化ナ
トリウム等の塩基の存在下、０〜４０℃で行なわれる。The reaction between the compound represented by the general formula (III) and dialkyl sulfate ((R)2SO+) is carried out in an organic solvent such as ethanol, methanol, methyl ethyl ketone, acetone, etc., preferably in acetone, using potassium hydroxide, sodium hydroxide, etc. The reaction is carried out at 0 to 40°C in the presence of a base such as.
一般式（ＩＶ）で表わされる化合物のＮ−アルキル化反
応は、公知方法、例えばアルキルハライド、ジアルキル
硫酸等を用いて行なわれる。The N-alkylation reaction of the compound represented by the general formula (IV) is carried out using a known method, for example, using an alkyl halide, dialkyl sulfuric acid, or the like.
また、上記一般式（ＩＩＩ ）の化合物から中間体を単
離せず、０−アルコキシ化、Ｎ−アルキル化により一般
式（Ｉ）の５−アルコキシアントラニル酸エステルを得
ることができる。Furthermore, the 5-alkoxyanthranilic acid ester of the general formula (I) can be obtained by O-alkoxylation or N-alkylation without isolating the intermediate from the compound of the general formula (III).
原料である一般式（ＩＩＩ）の化合物は、例えば以下の
反応工程′で示される方法により、得ることがゲン、ア
ルコキシ等の置換基を示し、）（Ｌｔｃｉ。The compound of general formula (III) which is a raw material can be obtained, for example, by the method shown in the following reaction step', and has a substituent such as gen, alkoxy, etc.) (Ltci.
Ｈｓｏ： 、ＢＦ； 等を示し、Ｒ１は前記と同じ）す
なわち、式（Ｖ）で表わされるｍ−ヒドロキシ安息香酸
に一般式（Ｖｌ）で表わされるジアゾニウム塩を水系溶
媒中で反応きせ、一般式（■）で表わされるジアゾニウ
ム化合物を得、ここで一般式（Ｖｌ）で表わされ化合物
におけるＱは、水素又はニトロ、へロゲン、アルコキシ
等の一般式（■）で表わきれる化合物がジアゾニウム塩
となりうる置換基であればよい。Hso: , BF; etc., and R1 is the same as above) That is, m-hydroxybenzoic acid represented by formula (V) is reacted with a diazonium salt represented by general formula (Vl) in an aqueous solvent, and the general formula A diazonium compound represented by (■) is obtained, where Q in the compound represented by the general formula (Vl) is hydrogen or nitro, halogen, alkoxy, etc. The compound represented by the general formula (■) is a diazonium salt. Any substituent that can be used may be used.
一般式（■）で表わされる化合物のエステル化反応は、
触媒として塩酸、硫酸、ｐ−トルエンスルホン酸、メタ
ンスルホン酸等の酸の存在下、−１０°Ｃから用いる溶
媒の沸点、好ましくは、２、Ｏ’Ｃ〜５０’Ｃで３０分
〜５０時間、好マシ＜は、２時間から１２時間で行うこ
とができる。反応溶媒としては、一般式ＲＯＨ（式中、
Ｒは前記と同じ）で表わされる反応に関与するアルコー
ル体を大過剰用いることにより行うのが好ましい。The esterification reaction of the compound represented by the general formula (■) is
In the presence of an acid such as hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid, etc. as a catalyst, from -10°C to the boiling point of the solvent used, preferably from 2.0°C to 50°C, for 30 minutes to 50 hours. , preferably, can be carried out in 2 to 12 hours. As a reaction solvent, the general formula ROH (in the formula,
It is preferable to use a large excess of the alcohol participating in the reaction represented by (R is the same as above).
次いで、一般式（■）で表わされる化合物の還元反応は
、アンモニア、ヒドラジン、ハイドロサルファイドナト
リウムなどの還元剤、好ましくは、ハイドロサルファイ
ドナトリウムを用い、水又はメタノール、エタノール、
プロシマノールなどのアルコール性溶媒、あるいはアセ
トン、テトラヒドロフラン、ジメチルホルムアミド、ジ
メチルスルホキサイドなどのような氷と混合する溶媒中
で、好ましくは、水やアルコール性溶媒中、０℃〜。Next, the reduction reaction of the compound represented by the general formula (■) is carried out using a reducing agent such as ammonia, hydrazine, sodium hydrosulfide, preferably sodium hydrosulfide, and water, methanol, ethanol,
in an alcoholic solvent such as procimanol, or a solvent mixed with ice such as acetone, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, etc., preferably in water or an alcoholic solvent, from 0°C.
１００℃、好まシくハ、２０℃〜６０℃で、１０分〜２
４時間、好ましくは、３０分〜２時間で反応は行なわれ
る。100°C, preferably 20°C to 60°C, 10 minutes to 2
The reaction is carried out for 4 hours, preferably 30 minutes to 2 hours.
また、一般式°（１）で示きれる化合物は、例えば以下
の反応工程により得ることもできる。Further, the compound represented by the general formula (1) can also be obtained, for example, by the following reaction steps.
かくして得られた一般式（Ｉ’ ）で表わされる５−ア
ルコキシアントラニル酸エステルを用いることで、例え
ば以下で示きれる合成工程により、上記一般式（ＩＩ
）で表ねきれる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 5-alkoxyanthranilic acid ester represented by the general formula (I'), the above general formula (II
) A benzimidazole derivative can be obtained.
以上、本発明化合物である一般式（Ｉ）で表わされ゛る
５−アルコキシアントラニル酸エステルを経由すること
で、抗潰瘍及び胃腸の細胞保護作用を有する゛、一般式
（ｎ）で表わされる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営る。 更に、一
般式（Ｉ）で表ねされる５−アルコキシアントラニル酸
エステルは、一般式（ＩＩ）で表わされるベンズイミダ
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 described above, the compound of the present invention, which has antiulcer and gastrointestinal cell protective effects, has anti-ulcer and gastrointestinal cytoprotective effects via the 5-alkoxyanthranilic acid ester represented by general formula (I), which is a compound of the present invention. A benzimidazole derivative can be obtained by a simple operation and in high yield. Furthermore, the 5-alkoxyanthranilic acid ester represented by the general formula (I) can be used not only as a synthetic intermediate for the benzimidazole derivative represented by the general formula (II) but also as a synthetic intermediate for other pharmaceuticals and agricultural chemicals. Useful.
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.
５−メトキシアントラニ？メチル
アセトン２９０ｍ１を氷水で冷却し粉砕した水酸え攪拌
下、ジメチル硫ａ１３．４ｇのアセトン３０ｍ１溶液を
５℃前後に保ち３０分かけて滴下した。5-Methoxyantrani? 290 ml of methyl acetone was cooled with ice water and pulverized with water. While stirring, a solution of 13.4 g of dimethyl sulfur a in 30 ml of acetone was added dropwise over 30 minutes while keeping the temperature around 5°C.
ざらにこの温度で１５分攪拌後酢酸３．６ｍｌを加え１
５分同温度で攪拌した。不溶物を濾過して除営、アセト
ンを４０℃以下で減圧留去し浅漬にｒｌｆＦ４エチル１
５０ｍ１を加えて飽和炭酸水素ナトリウム溶液１５０ｍ
１で２回洗浄した。有機層をＩＮ−塩ｆｉ１５０ｍｌで
２回抽出し、この塩酸溶液を冷却下２０％水酸化ナトリ
ウムでＰＨ７，０！で中和しｔ４析出した油状物をエー
テル１５０ｍ１で抽出し冷却し゛た０、５Ｎ水酸化ナト
リウム及び飽和食塩水で洗浄した。エーテル層を芒硝乾
燥後、減圧留去し１２．７５ｇ＄緑色油状物を得た。After stirring at this temperature for 15 minutes, add 3.6 ml of acetic acid.
The mixture was stirred at the same temperature for 5 minutes. Insoluble matter was filtered and removed, acetone was distilled off under reduced pressure at 40°C or less, and rlfF4 ethyl 1
Add 50ml of saturated sodium bicarbonate solution to 150ml
Washed twice with 1. The organic layer was extracted twice with 150 ml of IN-salt fi, and the hydrochloric acid solution was diluted with 20% sodium hydroxide under cooling to pH 7.0! The precipitated oil was extracted with 150 ml of ether and washed with cooled 0.5N sodium hydroxide and saturated brine. After drying the ether layer with Glauber's salt, it was distilled off under reduced pressure to obtain 12.75 g of green oil.
ＮＭＲ，ＣＣＤＣｌ３ ）
δ： ３．７４ （ｓ、３Ｈ）
３．８６ （ｓ、３Ｈ）
６．４８−７．４０ （ｍ、３Ｈ）
５゜１６ （ｂｒ ｓ 、２Ｈ）
実Ｍ！例２
５−メトキシアントラニル酸メチル１１．８ｇにジメチ
ル硫酸６．２ｇを加え、しばらく室温で攪拌し、更に約
１００℃で１時間攪拌して冷却後、酢酸エチル１００ｍ
１とＩＮ−水酸化ナトリウム７０ｍ１を加えて油状物を
溶解した。酢酸エチル層を飽和食塩水で洗浄し、芒硝乾
燥した。芒硝を濾別後溶媒を減圧留去し、１１．８ｇの
褐色油状物を得た。NMR, CCDCl3) δ: 3.74 (s, 3H) 3.86 (s, 3H) 6.48-7.40 (m, 3H) 5°16 (br s, 2H) Real M! Example 2 6.2 g of dimethyl sulfuric acid was added to 11.8 g of methyl 5-methoxyanthranilate, stirred at room temperature for a while, further stirred at about 100°C for 1 hour, cooled, and then added 100 ml of ethyl acetate.
1 and 70 ml of IN-sodium hydroxide were added to dissolve the oil. The ethyl acetate layer was washed with saturated brine and dried over sodium sulfate. After filtering out the Glauber's salt, the solvent was distilled off under reduced pressure to obtain 11.8 g of a brown oil.
この油状物にジメチル硫酸８．２ｇ （６５，２ｍｍｏ
ｌ）を加え、しばらく室温で攪拌後、更に約１００℃で
１時間攪拌した。冷却後粘調油状物に３Ｎ−塩ｗｉ６０
ｍｌ及びエーテル６０ｍ１を加え溶解した。水層を分取
し、エーテル６０ｍ１で再度洗浄後、冷却下３Ｎ−水酸
化ナトリウム８０ｍ１を少しずつ加え中和した。水層が
アルカリ性であることを確認し、析出した油状物をエー
テル１００ｍ３で抽出し、飽和食塩水で洗浄後、芒硝乾
燥した。芒硝を濾別後エーテルを減圧留去し、１１．６
ｇのＮ、Ｎ−ジメチル−５メトキシアントラニル酸メチ
ルを褐色油状物として得た。To this oil, 8.2 g of dimethyl sulfate (65.2 mmo
1) was added, and the mixture was stirred for a while at room temperature, and then further stirred at about 100°C for 1 hour. After cooling, add 3N salt to the viscous oil.
ml and 60 ml of ether were added and dissolved. The aqueous layer was separated, washed again with 60 ml of ether, and neutralized by adding 80 ml of 3N sodium hydroxide little by little while cooling. After confirming that the aqueous layer was alkaline, the precipitated oil was extracted with 100 m3 of ether, washed with saturated brine, and dried with sodium sulfate. After filtering out the Glauber's salt, the ether was distilled off under reduced pressure, and 11.6
g of methyl N,N-dimethyl-5methoxyanthranilate was obtained as a brown oil.
’ＨＮＭＲ（ＣＤＣＩ３ ）
δ＝２．７６ （ｓ、６Ｈ，ＮＭｅ２ ）３．７６
（ｓ、３Ｈ，−ＯＭｅ ）３．８８ （ｓ、３Ｈ，−
Ｃ○２Ｍｅ）６．８−７．３ （ｍ、３Ｈ，ａｒｏ−ｍ
ａｔｉｃ ｐｒｏｔｏｎｓ）
ＩＲ（ｎｅａｔ） ａｍ−’
２８７０．１７２０，１４９０゜
１２８０．１２２０．１０６５
参考例１
５−ヒドロキシ−２−フェニルアゾ 。'HNMR (CDCI3) δ=2.76 (s,6H,NMe2)3.76
(s, 3H, -OMe)3.88 (s, 3H, -
C○2Me) 6.8-7.3 (m, 3H, aro-m
atic protons) IR(neat) am-' 2870.1720,1490°1280.1220.1065 Reference Example 1 5-Hydroxy-2-phenylazo.
水３６０ｍ１に濃塩酸１５１ｍ１を加えざらにアニリン
６７．４を加え内温を０℃以下に冷却した。亜硝酸ナト
リウム５０ｇの水１４５ｍ１溶液を内温５℃以下に保ち
約１５分かけて滴下した。ざらに同温度で１５分攪拌し
てジアゾニウム塩を調整した。151 ml of concentrated hydrochloric acid was added to 360 ml of water, 67.4 ml of aniline was added, and the internal temperature was cooled to below 0°C. A solution of 50 g of sodium nitrite in 145 ml of water was added dropwise over about 15 minutes while keeping the internal temperature below 5°C. The mixture was roughly stirred at the same temperature for 15 minutes to prepare a diazonium salt.
水酸化ナトリウム９１．６ｇ （純度９５％）の水４５
０ｍ１溶液にｍ−ヒドロキシ安息香酸１００ｇを加えて
溶解した溶液に攪拌下、内温２５℃でジアゾニウム塩溶
液を５分ですばやく滴下した。ざらに３０分攪拌後不溶
物を濾別し濾液を氷冷した。濃塩酸１２０ｍ１を内温的
１０℃で滴下後析出した結晶を濾取し水で洗浄し乾燥さ
せ１７０ｇのｔＸＵ化合物を参考例２
５−ヒドロキシアントラニル メチル
（１）５−ヒドロキシ−２−フェニルアゾ安息香酸４８
．４ｇ（０，２ｍｏ ｌ）をメタノール４８０ｍ ｌに
！！濁きせて水冷し、濃硫酸２０ｍ１を内温１０’〜２
０°Ｃで約３０分かけて滴下した。その後室温で１０時
間撹拌し、溶媒を４００Ｃ以下で減圧留去した。残渣に
水３００ｍ ｌを加えクロロホルムで抽出し、水、飽和
食塩水で洗浄後、芒硝乾燥した。芒硝を濾別し、溶媒を
減圧留去することにより５７ｇの５−ヒドロキシ−２−
フェニルアゾ安息香酸メチルを濃赤色油状物として得た
。91.6g of sodium hydroxide (95% purity) 45g of water
The diazonium salt solution was quickly added dropwise over 5 minutes to a solution prepared by adding 100 g of m-hydroxybenzoic acid to a 0 ml solution while stirring at an internal temperature of 25°C. After roughly stirring for 30 minutes, insoluble matter was filtered off, and the filtrate was cooled on ice. After dropping 120 ml of concentrated hydrochloric acid at an internal temperature of 10°C, the precipitated crystals were collected by filtration, washed with water, and dried to obtain 170 g of the tXU compound. 48
．． 4g (0.2mol) to 480ml of methanol! ! Make it cloudy, cool it with water, and add 20ml of concentrated sulfuric acid to an internal temperature of 10'~2.
The mixture was added dropwise at 0°C over about 30 minutes. Thereafter, the mixture was stirred at room temperature for 10 hours, and the solvent was distilled off under reduced pressure at 400C or less. 300 ml of water was added to the residue, extracted with chloroform, washed with water and saturated brine, and dried with Glauber's salt. 57 g of 5-hydroxy-2-
Methyl phenylazobenzoate was obtained as a dark red oil.
’ＨＮＭＲ（ＣＤＣＩ、）δ： ３．９４（ｓ、３Ｈ）。'HNMR (CDCI,) δ: 3.94 (s, 3H).
６．８４＝８．ＯＯ（ｍ、８Ｈ）
（２）上記で得た油状物をエタノール２５６ｍ１に溶解
し５０°Ｃに加温後、Ｎ ａ ｚ Ｓ ｚ Ｏ＋１０２
ｇの水３００ｍ１溶液を約１５分かけて加えた。１．５
時間撹拌後、更に粉末のＮａｚｓｚｏ今１０．２ｇを加
えてからエタノールを減圧留去し、析出した油状物を酢
酸エチルで抽出した。抽出液を飽和食塩水で洗浄後芒硝
乾燥した。芒硝を濾別後、溶媒を減圧留去し、析出した
結晶をエーテルを加えて濾取し、２１．５ｇ（６４，４
，％）の５−ヒドロキシアントラニル酸メチルを褐色粉
末として得た。6.84=8. OO (m, 8H) (2) Dissolve the oil obtained above in 256 ml of ethanol and heat to 50°C, then N a z S z O+102
A solution of 50 g in 300 ml of water was added over about 15 minutes. 1.5
After stirring for an hour, 10.2 g of Nazszo powder was further added, the ethanol was distilled off under reduced pressure, and the precipitated oil was extracted with ethyl acetate. The extract was washed with saturated saline and dried with mirabilite. After filtering out the Glauber's salt, the solvent was distilled off under reduced pressure, and the precipitated crystals were collected by filtration after adding ether to give 21.5 g (64,4
,%) of methyl 5-hydroxyanthranilate was obtained as a brown powder.
’ＨＮＭＲ・（ＣＤ３０Ｄ）δ：
３．８２（ｓ、３Ｈ）
６．５４〜７．２４（ｍ、３Ｈ）
参考例３
一ゝ 々ノー −ぐべゝジノ
コール
水素化アルミニウムリチウム３．６ｇを無水エーテル８
０ｍ１に懸濁させ、氷冷下Ｎ、Ｎ−ジメチルー５−メト
キシアントラニル酸メチル１１．６ｇのエーテル４０ｍ
ｌ溶液を１５℃以下で約３０分で滴下した。この温度
でざらに１５分撹拌した後、飽和芒硝水を加えて過剰の
水素化アルミニウムリチウムを分解した。不溶物を濾別
し、ａｔ液を芒硝乾燥後減圧留去して７．４３ｇの２−
ジメチルアミノ−５−メトキシベンジルアルコールを淡
黄色油状物として得た。'HNMR・(CD30D)δ: 3.82 (s, 3H) 6.54-7.24 (m, 3H) Reference Example 3 One by one, 3.6 g of lithium aluminum hydride was added to 8 g of anhydrous ether.
11.6 g of methyl N,N-dimethyl-5-methoxyanthranilate in 40 ml of ether under ice cooling.
1 solution was added dropwise over about 30 minutes at a temperature below 15°C. After roughly stirring for 15 minutes at this temperature, excess lithium aluminum hydride was decomposed by adding saturated sodium sulfate solution. Insoluble materials were filtered off, and the at solution was dried with sodium sulfate and then distilled off under reduced pressure to obtain 7.43 g of 2-
Dimethylamino-5-methoxybenzyl alcohol was obtained as a pale yellow oil.
’Ｈ−ＮＭＲ（ＣＤＣＩＢ ） ざ：２．６４
（ｓ、６Ｈ）、３．７４ （ｓ。'H-NMR (CDCIB) Z: 2.64
(s, 6H), 3.74 (s.
３Ｈ）、４．７５ （ｓ、２Ｈ）、５．８０ （ｂｒ
ｓ、ＬＨ）、６．５−７．２（ｍ、３Ｈ）
参考例４
塩化チオニル５．５ｇのベンゼン２８ｍ１溶液を氷冷し
２−ジメチルアミノ−５−メトキシベンジルアル、コー
ル７．０ｇのベンゼン７ｍｌ溶液を１５〜２０℃で約３
０分かけて滴下した。室温で１５分撹拌後ベンゼンを減
圧留去し、得られた淡褐色油状物を冷却した後、エタノ
ール３０ｍ１及び２−メルカプトベンズイミダゾール５
．５ｇを加えて室温で撹拌した。エーテル３０ｍ１をす
こしずつ加え結晶を析出させ１時間撹拌する。結晶を濾
取後エタノール／エーテル（１／１）溶液、エーテルで
洗浄し、１１．３ｇの二塩酸塩を淡黄色結晶として得た
。ざらに酢酸エチル６００ｍ１に！！濁し、飽和炭酸水
素ナトリウムで中和し、処理することにより８．３ｇの
２−（２−ジメチルアミノ−５−メトキシベンジルチオ
）−ベンズイミダゾールを淡褐色結晶として得た。3H), 4.75 (s, 2H), 5.80 (br
s, LH), 6.5-7.2 (m, 3H) Reference Example 4 A solution of 5.5 g of thionyl chloride in 28 ml of benzene was cooled with ice, and 7.0 g of benzene was added to 2-dimethylamino-5-methoxybenzyl alcohol. 7ml solution at 15-20℃ for approx.
It was added dropwise over 0 minutes. After stirring at room temperature for 15 minutes, benzene was distilled off under reduced pressure, and the obtained light brown oil was cooled, and then 30 ml of ethanol and 5 ml of 2-mercaptobenzimidazole were added.
．． 5 g was added and stirred at room temperature. Add 30 ml of ether little by little to precipitate crystals, and stir for 1 hour. The crystals were collected by filtration and washed with an ethanol/ether (1/1) solution and ether to obtain 11.3 g of dihydrochloride as pale yellow crystals. Roughly 600ml of ethyl acetate! ! The mixture was clouded, neutralized with saturated sodium bicarbonate, and treated to give 8.3 g of 2-(2-dimethylamino-5-methoxybenzylthio)-benzimidazole as pale brown crystals.
参考例５
２−（２−ジメチルアミノ−５−メトキシベンジルチオ
）ベンズイミダゾール４０ｇを塩化メチレン１２０ｍ
ｌ及びメタノール１２０ｍ ｌに溶解し冷却下酢酸３０
ｍ１，３５％過酸化水素水３５ｍ１を加え２℃以下でメ
タバナジン酸アンモン２．４ｇを加え２〜５℃で３〜４
時間撹拌した。飽和重曹水１６０ｍ１を少しずつ加えて
酢酸を中和し１５分撹拌した。有機層を分取し１０％チ
オ硫酸ナトリウム溶液１００ｍ１で洗浄後Ｉ Ｎ −Ｎ
ａ ＯＨ１２８ｍ ｌで２回抽出した。水層を２０％
塩化アンモニウム溶液１００ｍ ｌを加え析出する油状
物を塩化メチレンで抽出し芒硝乾燥した。芒硝を濾別し
濾液に市販の２８％Ｎ ａ ＯＭ ｅ ／ Ｍ ｅ Ｏ
Ｈ溶液１７．２８ｇを加え、塩化メチレンを減圧留去し
、残渣に酢酸エチル１２０ｍ１を加えて１時間撹拌した
。析出した結晶を濾取し酢酸エチルで洗浄して３０．８
ｇの標題化合物のナトリウム塩を淡黄色結晶として得た
。Reference Example 5 40 g of 2-(2-dimethylamino-5-methoxybenzylthio)benzimidazole was dissolved in 120 m of methylene chloride.
120 ml of methanol and 30 ml of acetic acid under cooling.
ml, add 35ml of 35% hydrogen peroxide solution, add 2.4g of ammonium metavanadate at 2°C or below, and boil at 2-5°C for 3-4 hours.
Stir for hours. 160 ml of saturated sodium bicarbonate solution was added little by little to neutralize the acetic acid, and the mixture was stirred for 15 minutes. The organic layer was separated and washed with 100 ml of 10% sodium thiosulfate solution.
a Extracted twice with 128 ml of OH. 20% water layer
100 ml of ammonium chloride solution was added, and the precipitated oil was extracted with methylene chloride and dried with mirabilite. The mirabilite was separated by filtration and the filtrate was mixed with commercially available 28% NaOMe/MeO.
17.28 g of H solution was added, methylene chloride was distilled off under reduced pressure, 120 ml of ethyl acetate was added to the residue, and the mixture was stirred for 1 hour. The precipitated crystals were collected by filtration and washed with ethyl acetate to give 30.8
The sodium salt of the title compound of g was obtained as pale yellow crystals.
ざらにこの結晶をメタノール／酢酸エチルで精製し、純
粋なナトリウム塩２２ｇを得た。これを塩化メチレン９
０ｍ１に！！濁し、１０％塩化アンモニウム溶液９０ｍ
１を加えて中和し有機層を芒硝乾燥した。芒硝を濾別し
溶媒を減圧留去し、ただちに酢酸エチル９０ｍ１を加え
水冷下２時間静置した。析出した結晶を濾取し冷酢酸エ
チルで洗浄し減圧乾燥し１３．３ｇの標題化合物の白色
結晶を得た。The crystals were roughly purified with methanol/ethyl acetate to obtain 22 g of pure sodium salt. Add this to methylene chloride 9
To 0m1! ! Cloudy, 90ml of 10% ammonium chloride solution
1 was added to neutralize the mixture, and the organic layer was dried with mirabilite. Glauber's salt was filtered off and the solvent was distilled off under reduced pressure. Immediately, 90 ml of ethyl acetate was added and the mixture was allowed to stand for 2 hours under water cooling. The precipitated crystals were collected by filtration, washed with cold ethyl acetate, and dried under reduced pressure to obtain 13.3 g of the title compound as white crystals.
Claims (2)
及びＲ＾４は水素、鎖状又は環状アルキル基を示す。た
だし、Ｒ＾３及びＲ＾４が共に水素の場合を除く） で表わされる５−アルコキシアントラニル酸エステル。(1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 and R^2 represent an alkyl group, and R^3
and R^4 represents hydrogen, a chain or cyclic alkyl group. 5-alkoxyanthranilic acid ester represented by the following formula (excluding the case where both R^3 and R^4 are hydrogen).
（式中、Ｒ＾２はアルキル基を示す）で表わされる化合
物を反応させ、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） で表わされる化合物を得、次いで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＾３及び
Ｒ＾４はそれぞれ鎖状又は環状アルキル基を示し、Ｒ＾
１及びＲ＾２は前記と同じ。ただし、Ｒ＾３及びＲ＾４
が共に水素の場合を除く） で表わされる５−アルコキシアントラニル酸エステルの
製造方法。(2) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 represents an alkyl group) In the compound represented by the general formula (R^2)_2SO_4
(In the formula, R^2 represents an alkyl group) is reacted with the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 and R^2 are the same as above) There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (wherein R^3 and R^4 are each a chain or cyclic alkyl Indicates the group, R^
1 and R^2 are the same as above. However, R^3 and R^4
(except when both are hydrogen).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62124330A JP2536756B2 (en) | 1987-05-21 | 1987-05-21 | 5-alkoxyanthranilic acid ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62124330A JP2536756B2 (en) | 1987-05-21 | 1987-05-21 | 5-alkoxyanthranilic acid ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63290856A true JPS63290856A (en) | 1988-11-28 |
| JP2536756B2 JP2536756B2 (en) | 1996-09-18 |
Family
ID=14882666
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62124330A Expired - Lifetime JP2536756B2 (en) | 1987-05-21 | 1987-05-21 | 5-alkoxyanthranilic acid ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2536756B2 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4935360A (en) * | 1972-07-31 | 1974-04-01 | ||
| JPS5632441A (en) * | 1979-07-13 | 1981-04-01 | Thomae Gmbh Dr K | Carboxylic acid amide |
-
1987
- 1987-05-21 JP JP62124330A patent/JP2536756B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4935360A (en) * | 1972-07-31 | 1974-04-01 | ||
| JPS5632441A (en) * | 1979-07-13 | 1981-04-01 | Thomae Gmbh Dr K | Carboxylic acid amide |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2536756B2 (en) | 1996-09-18 |
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