JPH06741B2 - Method for producing indoles - Google Patents
Method for producing indolesInfo
- Publication number
- JPH06741B2 JPH06741B2 JP60296283A JP29628385A JPH06741B2 JP H06741 B2 JPH06741 B2 JP H06741B2 JP 60296283 A JP60296283 A JP 60296283A JP 29628385 A JP29628385 A JP 29628385A JP H06741 B2 JPH06741 B2 JP H06741B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- amino
- ethyl
- reaction
- bromo
- 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.)
- Expired - Lifetime
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 150000002475 indoles Chemical class 0.000 title claims description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical group C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- KYLUAQBYONVMCP-UHFFFAOYSA-N (2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P KYLUAQBYONVMCP-UHFFFAOYSA-N 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- -1 indole-3,4-dicarboxylic acid diester Chemical class 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 8
- VUIMBZIZZFSQEE-UHFFFAOYSA-N 1-(1h-indol-3-yl)ethanone Chemical compound C1=CC=C2C(C(=O)C)=CNC2=C1 VUIMBZIZZFSQEE-UHFFFAOYSA-N 0.000 description 6
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 125000005396 acrylic acid ester group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- XOUHVMVYFOXTMN-UHFFFAOYSA-N ethyl 1h-indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC)=CNC2=C1 XOUHVMVYFOXTMN-UHFFFAOYSA-N 0.000 description 2
- DWOHEEIRNZANTC-UHFFFAOYSA-N ethyl 5-chloro-1h-indole-3-carboxylate Chemical compound C1=C(Cl)C=C2C(C(=O)OCC)=CNC2=C1 DWOHEEIRNZANTC-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- HUCQPHINKBNKRU-UHFFFAOYSA-N (4-methylphenyl)phosphane Chemical compound CC1=CC=C(P)C=C1 HUCQPHINKBNKRU-UHFFFAOYSA-N 0.000 description 1
- GAIXPKAQNPGEGP-UHFFFAOYSA-N 1-(6-methoxy-1h-indol-3-yl)ethanone Chemical compound COC1=CC=C2C(C(C)=O)=CNC2=C1 GAIXPKAQNPGEGP-UHFFFAOYSA-N 0.000 description 1
- UAXNXOMKCGKNCI-UHFFFAOYSA-N 1-diphenylphosphanylethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 UAXNXOMKCGKNCI-UHFFFAOYSA-N 0.000 description 1
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 1
- UVRRJILIXQAAFK-UHFFFAOYSA-N 2-bromo-4-methylaniline Chemical compound CC1=CC=C(N)C(Br)=C1 UVRRJILIXQAAFK-UHFFFAOYSA-N 0.000 description 1
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- KURPPWHPIYBYBS-UHFFFAOYSA-N 2-ethenylaniline Chemical class NC1=CC=CC=C1C=C KURPPWHPIYBYBS-UHFFFAOYSA-N 0.000 description 1
- MYONYZHCIONNNA-UHFFFAOYSA-N 4-(2-bromoanilino)but-3-en-2-one Chemical compound CC(=O)C=CNC1=CC=CC=C1Br MYONYZHCIONNNA-UHFFFAOYSA-N 0.000 description 1
- XUDITEOFEQOSAK-UHFFFAOYSA-N 5-chloro-1h-indole-3-carboxylic acid Chemical compound C1=C(Cl)C=C2C(C(=O)O)=CNC2=C1 XUDITEOFEQOSAK-UHFFFAOYSA-N 0.000 description 1
- LPBGVZVDBKMWFS-UHFFFAOYSA-N 6-methoxy-1h-indole-3-carboxylic acid Chemical compound COC1=CC=C2C(C(O)=O)=CNC2=C1 LPBGVZVDBKMWFS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 238000001159 Fisher's combined probability test Methods 0.000 description 1
- 235000002597 Solanum melongena Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- YHDOEUDINHQBDO-UHFFFAOYSA-N ethyl 5-methyl-1h-indole-3-carboxylate Chemical compound C1=C(C)C=C2C(C(=O)OCC)=CNC2=C1 YHDOEUDINHQBDO-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 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
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 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
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Indole Compounds (AREA)
Description
【発明の詳細な説明】 産業上の利用分野 本発明は、一般式(I) （式中、Ｒ1は水素原子、アルコキシ基、低級アルキル
基、アルコキシカルボニル基、ニトロ基またはハロゲン
基を表し、Ｒ2はアセチル基、フェニルケトン基または
アルコキシカルボニル基を表す）で示されるインドール
類の製造方法に関するものである。DETAILED DESCRIPTION OF THE INVENTION Industrial Field of the Invention The present invention provides a compound of general formula (I) (Wherein R 1 represents a hydrogen atom, an alkoxy group, a lower alkyl group, an alkoxycarbonyl group, a nitro group or a halogen group, and R 2 represents an acetyl group, a phenylketone group or an alkoxycarbonyl group). The present invention relates to a manufacturing method of.
インドール類はそれ自体、香料や医薬品として利用され
るばかりでなく、農薬医薬の原料として有用な化合物で
ある。特に最近はアルカロイド類の合成原料として注目
されてきている。Indole itself is not only used as a fragrance and a medicine, but also a compound useful as a raw material for agrochemicals. In particular, it has recently attracted attention as a synthetic raw material for alkaloids.
従来の技術 従来、インドール類の合成方法としては、フィッシャー
法やライサート法をはじめとして数多くの反応方法が提
案されている。しかし、本発明に類似したパラジウム錯
体化合物を触媒とするインドール環合成反応は、ヘジダ
ス等による報告があるのみである。(Hegidus,etal,J.A
m.Chem.Soc.,100,5800,(1978)and J.Org.Chem.,49,265
7,(1984))ヘジダス等の方法はｏ−アリルアニリン類ま
たはｏ−ビニルアニリン類をパラジウム錯体触媒で環化
して、収率５０〜８０％でインドール類を得ている。2. Description of the Related Art Conventionally, as a method for synthesizing indoles, many reaction methods such as the Fisher method and the Lysate method have been proposed. However, the indole ring synthesis reaction using a palladium complex compound similar to the present invention as a catalyst has only been reported by Hedidas et al. (Hegidus, et al, JA
m.Chem.Soc., 100 , 5800, (1978) and J.Org.Chem., 49 , 265
7, (1984)) Hedidas et al. Obtained indoles with a yield of 50 to 80% by cyclizing o-allylanilines or o-vinylanilines with a palladium complex catalyst.
発明が解決しようとする問題点 ヘジダス等による方法は、原料の製造に手間がかかり、
また収率もあまり良くないので工業的に利用するのは問
題が多い。Problems to be Solved by the Invention The method by Hedidas or the like takes time and labor for manufacturing raw materials,
Moreover, since the yield is not so good, there are many problems in industrial use.
問題点を解決するための手段 本発明は、パラジウム錯体化合物を触媒とする新規なイ
ンドール類の製造方法を提供する。Means for Solving the Problems The present invention provides a novel method for producing indoles using a palladium complex compound as a catalyst.
すなわち、本発明は一般式(I) （式中、Ｒ1は水素原子、アルコキシ基、低級アルキル
基、アルコキシカルボニル基、ニトロ基またはハロゲン
基を表し、Ｒ2はアセチル基、フェニルケトン基または
アルコキシカルボニル基を表す）で示されるインドール
類を製造するに際し、一般式(II) （式中、Ｒ1，Ｒ2は前記に同じ）で示されるアミノオレ
フィン化合物を、酢酸パラジウムとトリフェニルホスフ
ィン類およびトリエチルアミンの存在下に溶媒中で加熱
環化することを特徴とする一般式(I)で示されるインド
ール類の製造方法である。That is, the present invention is represented by the general formula (I) (Wherein R 1 represents a hydrogen atom, an alkoxy group, a lower alkyl group, an alkoxycarbonyl group, a nitro group or a halogen group, and R 2 represents an acetyl group, a phenylketone group or an alkoxycarbonyl group). In the production of general formula (II) (In the formula, R 1 and R 2 are the same as above), the aminoolefin compound represented by the general formula (I) is heated and cyclized in a solvent in the presence of palladium acetate, triphenylphosphine and triethylamine. It is a method for producing indoles represented by I).
本発明で製造できるインドール類を具体的に列挙すれ
ば、例えば、３−アセチルインドール、インドール−３
−カルボン酸エステル、６−メトキシインドール−３−
カルボン酸エステル、３−アセチル−６−メトキシイン
ドール、インドール−３，４−ジカルボン酸ジエステ
ル、３−（５−メチルインドリル）メチルケトン、５−
クロロインドール−３−カルボン酸エステル、３−（５
−ニトロインドリル）メチルケトン等が挙げられる。Specific examples of the indoles that can be produced by the present invention include 3-acetylindole and indole-3.
-Carboxylic acid ester, 6-methoxyindole-3-
Carboxylic acid ester, 3-acetyl-6-methoxyindole, indole-3,4-dicarboxylic acid diester, 3- (5-methylindolyl) methyl ketone, 5-
Chloroindole-3-carboxylic acid ester, 3- (5
-Nitroindolyl) methyl ketone and the like.
本発明で出発原料となる一般式(II)で示されるアミノオ
レフィン化合物は、例えば、４−［（２−ブロモフェニ
ル）アミノ］−３−ブテン−２−オン、３−［（２−ブ
ロモ−５−メトキシフェニル）アミノ］−３−アクリル
酸エステル等が挙げられる。これらアミノオレフィン化
合物は通常考えられる合成方法の如何なる方法によつて
製造しても特に問題はない。例えば、ボーゼル等による
パラジウム錯体を利用したオレフィンのアミノ化反応
(J.J.Bozell,J.Org.Chem.,46,2561,(1981))を利用すれ
ば、ｏ−ブロムアニリンまたはその核置換誘導体とアク
リル酸エステルまたはメチルビニルケトンを原料として
かなりの好収率で本発明の出発化合物を得ることができ
る。ボーゼル等の方法を更に詳しく説明すれば、例え
ば、ジクロロビスアセトニトリルパラジウム錯体、ベン
ゾキノン、リチウムクロライドおよびオレフィン化合物
をテトラヒドロフラン（以下ＴＨＦとす）溶媒中室温で
混合し、これに後からＴＨＦに溶解したｏ−ブロムアニ
リン誘導体を加える。室温で２４時間ほど攪拌し、充分
に反応させた後溶媒を除去し、シリカゲルカラムクロマ
トグラフィーによって精製して、収率７０〜８０％でア
ミノオレフィン化合物を得ることができる。ただし、こ
の際利用できるオレフィン化合物は、アクリル酸エステ
ルやメチルビニルケトンのような共役オレフィン化合物
に限定され、ヘキセンやスチレン等の一般のオレフィン
化合物は反応しない。Examples of the amino olefin compound represented by the general formula (II) used as a starting material in the present invention include 4-[(2-bromophenyl) amino] -3-buten-2-one and 3-[(2-bromo- 5-methoxyphenyl) amino] -3-acrylic acid ester and the like can be mentioned. These amino olefin compounds can be produced by any of the generally considered synthetic methods without any problem. For example, amination reaction of olefin using palladium complex by Bozel etc.
(JJBozell, J.Org.Chem., 46 , 2561, (1981)), the o-bromoaniline or its nuclear substitution derivative and acrylic acid ester or methyl vinyl ketone can be used as raw materials in a fairly good yield. The starting compounds of the invention can be obtained. The method of Bozel et al. Will be described in more detail. For example, dichlorobisacetonitrile palladium complex, benzoquinone, lithium chloride and an olefin compound were mixed in a tetrahydrofuran (hereinafter referred to as THF) solvent at room temperature, and then dissolved in THF. -Add the bromaniline derivative. After stirring at room temperature for about 24 hours, allowing sufficient reaction, removing the solvent, and purifying by silica gel column chromatography, an amino olefin compound can be obtained in a yield of 70 to 80%. However, the olefin compounds that can be used at this time are limited to conjugated olefin compounds such as acrylic acid esters and methyl vinyl ketone, and general olefin compounds such as hexene and styrene do not react.
本発明における反応は、酢酸パラジウムとホスフィン化
合物より反応系内でゼロ価のパラジウム錯体が触媒とし
て作用して反応が進行するものである。したがって、酢
酸パラジウムの使用量は反応基質に対して０．５〜２０
モル％、好ましくは１〜１０モル％使用するのが好適で
ある。ゼロ価のパラジウムと錯体を形成するホスフィン
化合物としては、トリフェニルホスフィン、トリ−ｏ−
およびｐ−トリルホスフィンやビスジフェニルホスフィ
ノエタンの如き二座配位子を使用することができ、その
使用量は反応基質に対し１０〜５０モル％、好ましくは
１５〜３０モル％の範囲で使用する。また本反応では反
応に伴つて副生する臭化水素を捕捉する塩基性化合物を
添加するが、この塩基性化合物としては反応に関与しな
い三級のアミノ化合物が最も好適であり、その代表的化
合物はトリエチルアミンである。したがって、その使用
量は反応基質に対してほぼ等モル量添加すれば、本発明
の目的は十分達せられる。反応溶媒は本反応で形成され
るゼロ価のパラジウム錯体を溶解する物が良く、アルコ
ール類、アセトン、酢酸ＴＨＦ、ＤＭＦ、アセトニトリ
ル等が使用可能である。特に、アセトニトリルは本発明
では好適に使用することができる。また、本発明の反応
温度は１００℃以上が必要で、溶媒の種類によっては若
干の加圧下に行われる。In the reaction of the present invention, the zero-valent palladium complex acts as a catalyst in the reaction system from the palladium acetate and the phosphine compound to proceed the reaction. Therefore, the amount of palladium acetate used is 0.5 to 20 with respect to the reaction substrate.
It is suitable to use mol%, preferably 1 to 10 mol%. Examples of the phosphine compound that forms a complex with zero-valent palladium include triphenylphosphine and tri-o-
And bidentate ligands such as p-tolylphosphine and bisdiphenylphosphinoethane can be used, and the amount thereof is 10 to 50 mol%, preferably 15 to 30 mol% based on the reaction substrate. To do. In this reaction, a basic compound that traps hydrogen bromide produced as a by-product of the reaction is added, but as this basic compound, a tertiary amino compound that does not participate in the reaction is most suitable. Is triethylamine. Therefore, the object of the present invention can be sufficiently achieved if the amount used is approximately equimolar to the reaction substrate. The reaction solvent is preferably one that dissolves the zero-valent palladium complex formed in this reaction, and alcohols, acetone, THF acetate, DMF, acetonitrile and the like can be used. In particular, acetonitrile can be preferably used in the present invention. Further, the reaction temperature of the present invention is required to be 100 ° C. or higher, and the reaction is carried out under a slight pressure depending on the kind of the solvent.
反応終了後はパラジウムが析出しているので、これを濾
過回収し、濾液にはクロロホルムを加えてから塩酸、
水、飽和重曹水、水で洗浄し、無水硫酸マグネシュウム
で脱水乾燥すれば良い。溶媒を除去すれば粗生物を得る
ことができる。精製品が必要な場合は、カラムクロマト
グラフィーや再結晶で精製することができる。After the completion of the reaction, palladium was precipitated, so this was collected by filtration, and chloroform was added to the filtrate, followed by hydrochloric acid,
It may be washed with water, saturated sodium bicarbonate water, and water, and dehydrated and dried with anhydrous magnesium sulfate. The crude product can be obtained by removing the solvent. If a purified product is required, it can be purified by column chromatography or recrystallization.
以下、実施例および参考例により本発明を更に詳しく説
明する。Hereinafter, the present invention will be described in more detail with reference to Examples and Reference Examples.
参考例１ ３−［（２−ブロモ−４−メチルフェニル）アミノ］−
２−プロペノン酸エチルの合成 ５０mlナスフラスコに塩化パラジウム０．７６３ｇ
（４．３mmol）、無水アセトニトリル３０mlを入れ、湯
浴で３０〜４０℃に加熱して２時間攪拌した。減圧下で
アセトニトリルを追い出してジクロロビスアセトニトリ
ルパラジウム(II)を得た。次に３００ml丸底フラスコに
ジクロロビスアセトニトリルパラジウム(II)とベンゾキ
ノン４．６４ｇ（４３mmol）、塩化リチウム１８．２ｇ
（４３mmol）、アクリル酸エチル４．３０ｇ（４３mmo
l）、無水ＴＨＦ１５０mlを入れ、室温で１０分間かき
まぜた。そこへ２−ブロム−４−メチルアニリン８．０
ｇ（４３mmol）を無水ＴＨＦ２２mlに溶かしたものを加
え２４時間攪拌した。反応後ＴＨＦを追い出し、クロロ
ホルムを加え、塩を濾過した。母液を２０％苛性ソー
ダ、水の順に洗って無水硫酸マグネシュウムで脱水乾燥
した。クロロホルム除去後シリカゲルカラムクロマトグ
ラフィーにより分離精製を行い、表題の目的物を無色結
晶として６．６ｇ得た。（収率７４．１％） ＩＲ、Ｍ
ＡＳＳ、ＮＭＲ等の分析によって確認された。Reference Example 1 3-[(2-bromo-4-methylphenyl) amino]-
Synthesis of ethyl 2-propenate 0.763 g of palladium chloride in a 50 ml eggplant flask.
(4.3 mmol) and 30 ml of anhydrous acetonitrile were added, and the mixture was heated to 30 to 40 ° C. in a water bath and stirred for 2 hours. Acetonitrile was removed under reduced pressure to obtain dichlorobisacetonitrile palladium (II). Next, in a 300 ml round bottom flask, dichlorobisacetonitrile palladium (II) and benzoquinone 4.64 g (43 mmol), lithium chloride 18.2 g
(43 mmol), ethyl acrylate 4.30 g (43 mmo
l) and 150 ml of anhydrous THF were added, and the mixture was stirred at room temperature for 10 minutes. 2-Brom-4-methylaniline 8.0
What melt | dissolved g (43 mmol) in anhydrous THF22 ml was added, and it stirred for 24 hours. After the reaction, THF was driven off, chloroform was added, and salts were filtered. The mother liquor was washed with 20% caustic soda and water in that order, and dehydrated and dried over anhydrous magnesium sulfate. After removing chloroform, the product was separated and purified by silica gel column chromatography to obtain 6.6 g of the desired product as colorless crystals. (Yield 74.1%) IR, M
It was confirmed by analysis such as ASS and NMR.
ＩＲ(KBr)：3250(NH),2950,2900(CH),1660(C=0),1620,1
510,1460(C=C),1375(CH3),1200(C-O-C),865,810(CH)cm
-1 ＭＳ m/e:284[M+] ＮＭＲ δ(CDCl3):1.26(t,3H,J=7.0Hz),2.20(s,3H,C
H3),4.22(q,2H,J=7.0Hz),4.90(d,2H,J=8.0Hz),6.89-7.4
4(m,4H),10.3(brd,1H)ppm 実施例１ ５−メチルインドール−３−カルボン酸エチルの合成 封管の中に３−［（２−ブロモ−４−メチルフェニル）
アミノ］−２−プロペノン酸エチル４ｇ（１４．９mmo
l）、酢酸パラジウム０．１６７ｇ（０．７４５mmo
l）、トリ−ｏ−トリルホスフィン０．９０７ｇ（２．
９８mmol）、トリエチルアミン１．８８ｇ（１８．６mm
ol）を入れ、無水アセトニトリル１５mlを加えて溶かし
た。封管内を窒素で置換した後封管し、油浴で１００℃
に加熱して２０時間かきまぜた。反応終了後、クロロホ
ルムを加えてから、析出したパラジウムを濾過した。母
液を３％塩酸、水、飽和重曹水、水の順に洗浄した後、
無水硫酸マグネシュウムで脱水乾燥した。クロロホルム
を追い出した後、ベンゼン−シリカゲルカラムクロマト
グラフィーでメタノール−ベンゼン（１：１０）混合溶
媒で精製を行った。更にｎ−ヘキサン−ベンゼン（１：
１）溶媒より再結晶を行い白色の結晶２．５ｇを得た。
（収率８２．７％） 分析の結果、表題の化合物に相違
ないことが確認された。IR (KBr): 3250 (NH), 2950,2900 (CH), 1660 (C = 0), 1620,1
510,1460 (C = C), 1375 (CH 3 ), 1200 (COC), 865,810 (CH) cm
-1 MS m / e: 284 [M + ] NMR δ (CDCl 3 ): 1.26 (t, 3H, J = 7.0Hz), 2.20 (s, 3H, C
H 3 ), 4.22 (q, 2H, J = 7.0Hz), 4.90 (d, 2H, J = 8.0Hz), 6.89-7.4
4 (m, 4H), 10.3 (brd, 1H) ppm Example 1 Synthesis of ethyl 5-methylindole-3-carboxylate 3-[(2-bromo-4-methylphenyl) in a sealed tube.
Amino] -2-ethyl propenoate 4 g (14.9 mmo
l), 0.167 g of palladium acetate (0.745 mmo
l), 0.907 g of tri-o-tolylphosphine (2.
98 mmol), 1.88 g of triethylamine (18.6 mm)
ol) was added, and 15 ml of anhydrous acetonitrile was added and dissolved. After the inside of the sealed tube was replaced with nitrogen, the tube was sealed and heated in an oil bath at 100 ° C.
Heat to stir and stir for 20 hours. After the reaction was completed, chloroform was added, and the deposited palladium was filtered. After washing the mother liquor in this order with 3% hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate, and water,
It was dehydrated and dried with anhydrous magnesium sulfate. After removing chloroform, purification was carried out by a benzene-silica gel column chromatography with a mixed solvent of methanol-benzene (1:10). Furthermore, n-hexane-benzene (1:
1) Recrystallization from the solvent gave 2.5 g of white crystals.
(Yield 82.7%) As a result of analysis, it was confirmed that the title compound was the same.
融点 ：143-144℃ ＩＲ(KBr)：3225(NH),2970(CH),1660(C=0),1530,1440(C
=C),1375(CH3),1195,1050(C-O-C),875,800(CH)cm-1 ＭＳ m/e：203[M+] ＮＭＲ δCDCl3):1.36(t,3H,J=7.0Hz),2.41(s,3H,C
H3),4.40(q,2H,J=7.0Hz),7.04(d,1H,J=8.0Hz),7.26(d,1
H,J=8.0Hz),7.80(d,1H,J=3.0Hz),7.99(s,1H),9.10(brs,
1H)ppm 実施例２ インドール−３−カルボン酸エチルの合成 実施例１において３−［（２−ブロモ−４−メチルフェ
ニル）アミノ］−２−プロペノン酸エチルに代えて、３
−［（２−ブロモフェニル）アミノ］−２−プロペノン
酸エチルを使用した以外は実施例１とほぼ同様に行い、
白色結晶のインドール−３−カルボン酸エチルを収率９
６．０％で得た。Melting point: 143-144 ° C IR (KBr): 3225 (NH), 2970 (CH), 1660 (C = 0), 1530,1440 (C
= C), 1375 (CH 3 ), 1195,1050 (COC), 875,800 (CH) cm -1 MS m / e: 203 [M + ] NMR δCDCl 3 ): 1.36 (t, 3H, J = 7.0Hz) , 2.41 (s, 3H, C
H 3 ), 4.40 (q, 2H, J = 7.0Hz), 7.04 (d, 1H, J = 8.0Hz), 7.26 (d, 1
H, J = 8.0Hz), 7.80 (d, 1H, J = 3.0Hz), 7.99 (s, 1H), 9.10 (brs,
1H) ppm Example 2 Synthesis of ethyl indole-3-carboxylate Instead of ethyl 3-[(2-bromo-4-methylphenyl) amino] -2-propenoate in Example 1, 3
Substantially the same as in Example 1 except that ethyl-[(2-bromophenyl) amino] -2-propenate was used,
The yield of white crystalline ethyl indole-3-carboxylate was 9
Obtained at 6.0%.
融点 ：120-121℃ ＩＲ(KBr)：3225(NH),1660(C=0),1530,1440(C=C),1190,
1050(C-O-C),770,750,720(CH)cm-1 ＭＳ m/e：189[M+] ＮＭＲ δ(CDCl):1.37(t,3H,J=7.0Hz),4.40(q,2H,J=7.
0Hz),7.10-7.43(m,3H),7.84(d,1H,J=3.0Hz),8.13-8.27
(m,1H),9.31(brs,1H) 実施例３ ３−アセチルインドールの合成 実施例１において３−［（２−ブロモ−４−メチルフェ
ニル）アミノ］−２−プロペノン酸エチルに代えて、３
−［（２−ブロモフェニル）アミノ］−３−ブテン−２
−オンを使用した以外は実施例１とほぼ同様に行い、白
色結晶の３−アセチルインドールを収率９５．６％で得
た。Melting point: 120-121 ° C IR (KBr): 3225 (NH), 1660 (C = 0), 1530,1440 (C = C), 1190,
1050 (COC), 770,750,720 (CH) cm -1 MS m / e: 189 [M + ] NMR δ (CDCl): 1.37 (t, 3H, J = 7.0Hz), 4.40 (q, 2H, J = 7.
0Hz), 7.10-7.43 (m, 3H), 7.84 (d, 1H, J = 3.0Hz), 8.13-8.27
(m, 1H), 9.31 (brs, 1H) Example 3 Synthesis of 3-acetylindole In Example 1, instead of ethyl 3-[(2-bromo-4-methylphenyl) amino] -2-propenate, Three
-[(2-Bromophenyl) amino] -3-butene-2
The procedure of Example 1 was repeated except that -one was used to obtain 3-acetylindole as white crystals in a yield of 95.6%.
融点 ：189-190℃ ＩＲ(KBr)：3125(NH),1610(C=0),1575,1530,1440(C=C),
1245(C-CO-C),755(CH)cm-1 ＭＳ m/e：159[M+] ＮＭＲ δ(CDCl3):2.55(t,3H,J=7.0Hz),7.23-7.41(m,3
H),8.59-8.44(m,1H),8.59-8.81(m,1H)ppm 実施例４ ５−クロロインドール−３−カルボン酸エチルの合成 実施例１において３−［（２−ブロモ−４−メチルフェ
ニル）アミノ］−２−プロペノン酸エチルに代えて、３
−［（２−ブロモ−４−クロロフェニル）アミノ］−２
−プロペノン酸エチルを使用した以外は実施例１とほぼ
同様に行い、白色結晶の５−クロロインドール−３−カ
ルボン酸エチルを収率８１．７％で得た。Melting point: 189-190 ° C IR (KBr): 3125 (NH), 1610 (C = 0), 1575,1530,1440 (C = C),
1245 (C-CO-C), 755 (CH) cm -1 MS m / e: 159 [M + ] NMR δ (CDCl 3 ): 2.55 (t, 3H, J = 7.0Hz), 7.23-7.41 (m , 3
H), 8.59-8.44 (m, 1H), 8.59-8.81 (m, 1H) ppm Example 4 Synthesis of ethyl 5-chloroindole-3-carboxylate In Example 1, 3-[(2-bromo-4- Methylphenyl) amino] -2-propenate ethyl instead of 3
-[(2-Bromo-4-chlorophenyl) amino] -2
The procedure of Example 1 was repeated except that ethyl propenoate was used to obtain white crystals of ethyl 5-chloroindole-3-carboxylate in a yield of 81.7%.
融点 ：177-179℃ ＩＲ(KBr)：3200(NH),1650(C=0),1550,1520,1440(C=C),
1190,1030(C-O-C),890,800(CH),770(CH)cm-1 ＭＳ m/e：224[M+] ＮＭＲ δ(CDCl3):1.43(t,3H,J=7.0Hz),4.40(q,2H,J=
7.0Hz),7.20(d,1H,J=9.0Hz),7.34(d,1H,J=9.0Hz),7.92
(d,1H,J=3.0Hz),8.16(d,1H),8.63(brs,1H)ppm 実施例５ ３−（５−ニトロインドリル）フェニルケトンの合成 実施例１において３−［（２−ブロモ−４−メチルフェ
ニル）アミノ］−２−プロペノン酸エチルに代えて、Ｎ
−（２−ベンゾイルビニレン）−２−ブロモ−４−ニト
ロアニリンを使用した以外は実施例１とほぼ同様に行
い、褐色結晶状の３−（５−ニトロインドリル）フェニ
ルケトンを収率８３．９％で得た。Melting point: 177-179 ° C IR (KBr): 3200 (NH), 1650 (C = 0), 1550,1520,1440 (C = C),
1190,1030 (COC), 890,800 (CH), 770 (CH) cm -1 MS m / e: 224 [M + ] NMR δ (CDCl 3 ): 1.43 (t, 3H, J = 7.0Hz), 4.40 ( q, 2H, J =
7.0Hz), 7.20 (d, 1H, J = 9.0Hz), 7.34 (d, 1H, J = 9.0Hz), 7.92
(d, 1H, J = 3.0Hz), 8.16 (d, 1H), 8.63 (brs, 1H) ppm Example 5 Synthesis of 3- (5-nitroindolyl) phenyl ketone In Example 1, 3-[(2 N- instead of ethyl -bromo-4-methylphenyl) amino] -2-propenate
Substantially the same as in Example 1 except that-(2-benzoylvinylene) -2-bromo-4-nitroaniline was used, and the yield of 3- (5-nitroindolyl) phenyl ketone was 83. Obtained in 9%.
融点 ：234-236℃ ＩＲ(KBr)：3125(NH),1610(C=0),1590,1530,1480(C=C),
1570,1340(NO),1210(C-CO-C),890,830(CH),750,705(CH)
cm-1 ＭＳ m/e：266[M+] ＮＭＲ δ(d-アセトン):7.52-8.19(m,8H),9.24(d,1H,J=2.0
Hz),10.5(brs,1H,NH)ppm 実施例６ ４−メトキシカルボニルインドール−３−カルボン酸エ
チルの合成 実施例１において３−［（２−ブロモ−４−メチルフェ
ニル）アミノ］−２−プロペノン酸エチルに代えて、３
−［（２−ブロモ−４−メトキシカルボニル）アミノ］
−２−プロペノン酸エチルを使用した以外は実施例１と
ほぼ同様に行い、白色結晶の４−メトキシカルボニルイ
ンドール−３−カルボン酸エチルを収率９３．０％で得
た。Melting point: 234-236 ° C IR (KBr): 3125 (NH), 1610 (C = 0), 1590,1530,1480 (C = C),
1570,1340 (NO), 1210 (C-CO-C), 890,830 (CH), 750,705 (CH)
cm -1 MS m / e: 266 [M + ] NMR δ (d-acetone): 7.52-8.19 (m, 8H), 9.24 (d, 1H, J = 2.0
Hz), 10.5 (brs, 1H, NH) ppm Example 6 Synthesis of ethyl 4-methoxycarbonylindole-3-carboxylate In Example 1, 3-[(2-bromo-4-methylphenyl) amino] -2- 3 instead of ethyl propenoate
-[(2-Bromo-4-methoxycarbonyl) amino]
The procedure was substantially the same as in Example 1 except that ethyl-2-propenoate was used to obtain white crystals of ethyl 4-methoxycarbonylindole-3-carboxylate in a yield of 93.0%.
融点 ：93-94℃ ＩＲ(KBr)：3250(NH),1720,1670(C=0),1515,1430(C=C),
1200,1170(C-O-C),770,750(CH) ＭＳ m/e：247[M+] ＮＭＲ δ(CDCl3):1.33(t,3H,J=7.0Hz),3.97(s,3H),4.
36(q,2H,J=7.0Hz),7.13-7.51(m,3H 7.80(d,1H,J=2.0H
z),9.53(brs,1H)ppm 実施例７ ３−（６−メトキシカルボニルインドリル）フェニルケ
トンの合成 実施例１において３−［（２−ブロモ−４−メチルフェ
ニル）アミノ］−２−プロペノン酸エチルに代えて、Ｎ
−（２−ベンゾイルビニレン）−２−ブロモ−５−メト
キシカルボニルアニリンを使用した以外は実施例１とほ
ぼ同様に行い、淡黄色結晶の３−（６−メトキシカルボ
ニルインドリル）フェニルケトンを収率９６．８％で得
た。Melting point: 93-94 ° C IR (KBr): 3250 (NH), 1720,1670 (C = 0), 1515,1430 (C = C),
1200,1170 (COC), 770,750 (CH) MS m / e: 247 [M + ] NMR δ (CDCl 3 ): 1.33 (t, 3H, J = 7.0Hz), 3.97 (s, 3H), 4.
36 (q, 2H, J = 7.0Hz), 7.13-7.51 (m, 3H 7.80 (d, 1H, J = 2.0H
z), 9.53 (brs, 1H) ppm Example 7 Synthesis of 3- (6-methoxycarbonylindolyl) phenyl ketone In Example 1, 3-[(2-bromo-4-methylphenyl) amino] -2-propenone N instead of ethyl acid
The procedure was substantially the same as in Example 1 except that-(2-benzoylvinylene) -2-bromo-5-methoxycarbonylaniline was used, and a pale yellow crystalline 3- (6-methoxycarbonylindolyl) phenyl ketone was obtained. Obtained at 96.8%.
融点 ：360℃以上 ＩＲ(KBr)：3100(NH),1710,1600(C=0),1570,1500,1430
(C=C),1310(C-CO-C),1220,1090(C-O-C),890,830(CH),73
0,660(CH)cm-1 ＭＳ m/e：279[M+] 実施例８ ３−（６−メトキシインドリル）メチルケトンの合成 実施例１において３−［（２−ブロモ−４−メチルフェ
ニル）アミノ］−２−プロペノン酸エチルに代えて、４
−［（２−ブロモ−５−メトキシフェニル）アミノ］−
３−ブテン−２−オンを使用した以外は実施例１とほぼ
同様に行い、淡黄色結晶の３−（６−メトキシインドリ
ル）メチルケトンを収率８０．０％で得た。Melting point: 360 ° C or higher IR (KBr): 3100 (NH), 1710,1600 (C = 0), 1570,1500,1430
(C = C), 1310 (C-CO-C), 1220,1090 (COC), 890,830 (CH), 73
0,660 (CH) cm -1 MS m / e: 279 [M + ] Example 8 Synthesis of 3- (6-methoxyindolyl) methylketone In Example 1, 3-[(2-bromo-4-methylphenyl) amino was used. ] In place of ethyl-2-propenate, 4
-[(2-Bromo-5-methoxyphenyl) amino]-
The procedure of Example 1 was repeated, except that 3-buten-2-one was used, to obtain 3- (6-methoxyindolyl) methyl ketone as pale yellow crystals in a yield of 80.0%.
融点 ：208-209℃ ＩＲ(KBr)：3125(NH),1625(C=0),1580,1530,1450(C=C),
1280(C-CO-C),1230,11608C-O-C)890,830(CH)cm-1 ＭＳ m/e：189[M+] ＮＭＲ δ(d-DMSO):2.43(s,3H),3.78(s,3H),6.83(d,1
H,J=9.0Hz),6.98(d,1H,J=2.0Hz),7.99(s,1H),8.09-8.15
(m,1H),11.7(brs,1H)ppmMelting point: 208-209 ° C IR (KBr): 3125 (NH), 1625 (C = 0), 1580,1530,1450 (C = C),
1280 (C-CO-C), 1230,11608C-OC) 890,830 (CH) cm -1 MS m / e: 189 [M + ] NMR δ (d-DMSO): 2.43 (s, 3H), 3.78 (s , 3H), 6.83 (d, 1
H, J = 9.0Hz), 6.98 (d, 1H, J = 2.0Hz), 7.99 (s, 1H), 8.09-8.15
(m, 1H), 11.7 (brs, 1H) ppm
Claims (2)
基、アルコキシカルボニル基、ニトロ基またはハロゲン
基を表し、Ｒ2はアセチル基、フェニルケトン基または
アルコキシカルボニル基を表す）で示されるインドール
類を製造するに際し、一般式(II) （式中、Ｒ1，Ｒ2は前記に同じ）で示されるアミノオレ
フィン化合物を酢酸パラジウムとトリフェニルホスフィ
ン類およびトリエチルアミンの存在下に溶媒中で加熱環
化することを特徴とする一般式(I)で示されるインドー
ル類の製造方法。1. A general formula (I) (Wherein R 1 represents a hydrogen atom, a lower alkyl group, an alkoxy group, an alkoxycarbonyl group, a nitro group or a halogen group, and R 2 represents an acetyl group, a phenylketone group or an alkoxycarbonyl group). In the production of general formula (II) (In the formula, R 1 and R 2 are the same as above), the compound represented by the general formula (I) is characterized in that the compound is subjected to thermal cyclization in a solvent in the presence of palladium acetate, triphenylphosphine and triethylamine. ) The method for producing indoles represented by
−トリルホスフィンを使用することを特徴とする特許請
求の範囲第１項の製造方法。2. Tri-o as triphenylphosphine
-The process according to claim 1, characterized in that tolylphosphine is used.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60296283A JPH06741B2 (en) | 1985-12-26 | 1985-12-26 | Method for producing indoles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60296283A JPH06741B2 (en) | 1985-12-26 | 1985-12-26 | Method for producing indoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62153271A JPS62153271A (en) | 1987-07-08 |
| JPH06741B2 true JPH06741B2 (en) | 1994-01-05 |
Family
ID=17831555
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60296283A Expired - Lifetime JPH06741B2 (en) | 1985-12-26 | 1985-12-26 | Method for producing indoles |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06741B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4400597A (en) * | 1996-10-08 | 1998-05-05 | Fujisawa Pharmaceutical Co., Ltd. | Indole derivatives |
-
1985
- 1985-12-26 JP JP60296283A patent/JPH06741B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62153271A (en) | 1987-07-08 |
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