CA2048001A1 - 2-substituted-1-hydroxyindoles - Google Patents
2-substituted-1-hydroxyindolesInfo
- Publication number
- CA2048001A1 CA2048001A1 CA 2048001 CA2048001A CA2048001A1 CA 2048001 A1 CA2048001 A1 CA 2048001A1 CA 2048001 CA2048001 CA 2048001 CA 2048001 A CA2048001 A CA 2048001A CA 2048001 A1 CA2048001 A1 CA 2048001A1
- Authority
- CA
- Canada
- Prior art keywords
- cyano
- hydroxy
- indole
- group
- compound
- 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.)
- Abandoned
Links
- -1 2-substituted-1-hydroxyindoles Chemical class 0.000 title claims abstract description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 125000001424 substituent group Chemical group 0.000 claims abstract description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims abstract description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 29
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 8
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- MNBZUVGXWZGKRD-UHFFFAOYSA-N 6-chloro-1-hydroxy-2-(4-nitrophenyl)indole-3-carbonitrile Chemical compound N#CC=1C2=CC=C(Cl)C=C2N(O)C=1C1=CC=C([N+]([O-])=O)C=C1 MNBZUVGXWZGKRD-UHFFFAOYSA-N 0.000 claims description 3
- KUTKNBCXXRYTMC-UHFFFAOYSA-N 6-chloro-1-hydroxy-2-phenylindole-3-carbonitrile Chemical compound N#CC=1C2=CC=C(Cl)C=C2N(O)C=1C1=CC=CC=C1 KUTKNBCXXRYTMC-UHFFFAOYSA-N 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 229920002554 vinyl polymer Chemical group 0.000 claims description 3
- QCQKGTFNCCMAIV-UHFFFAOYSA-N 1-hydroxy-2-[3-(trifluoromethyl)phenyl]indole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C1=CC=CC(C(F)(F)F)=C1 QCQKGTFNCCMAIV-UHFFFAOYSA-N 0.000 claims description 2
- COSOGHVVOHLZEM-UHFFFAOYSA-N 1-hydroxy-2-pyridin-2-ylindole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C1=CC=CC=N1 COSOGHVVOHLZEM-UHFFFAOYSA-N 0.000 claims description 2
- WVTOSADCDDJFEY-UHFFFAOYSA-N 1-hydroxy-2-pyridin-4-ylindole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C1=CC=NC=C1 WVTOSADCDDJFEY-UHFFFAOYSA-N 0.000 claims description 2
- NTNCOGFJGUSLDN-UHFFFAOYSA-N 2-(2-formylphenyl)-1-hydroxyindole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C1=CC=CC=C1C=O NTNCOGFJGUSLDN-UHFFFAOYSA-N 0.000 claims description 2
- JDBSZSREIBLLNQ-UHFFFAOYSA-N 2-(furan-2-yl)-1-hydroxyindole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C1=CC=CO1 JDBSZSREIBLLNQ-UHFFFAOYSA-N 0.000 claims description 2
- JQQPXHBGNLBSCD-UHFFFAOYSA-N 2-ethenyl-1-hydroxyindole-3-carbonitrile Chemical compound C1=CC=C2N(O)C(C=C)=C(C#N)C2=C1 JQQPXHBGNLBSCD-UHFFFAOYSA-N 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- ZXSPLEOWPRDGSI-UHFFFAOYSA-N 5,6-dichloro-1-hydroxy-2-phenylindole-3-carbonitrile Chemical compound N#CC=1C2=CC(Cl)=C(Cl)C=C2N(O)C=1C1=CC=CC=C1 ZXSPLEOWPRDGSI-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- TXDKDAKBQCOQDD-UHFFFAOYSA-N 1-hydroxy-2-[4-(hydroxyiminomethyl)phenyl]indole-3-carbonitrile Chemical compound C1=CC(C=NO)=CC=C1C1=C(C#N)C2=CC=CC=C2N1O TXDKDAKBQCOQDD-UHFFFAOYSA-N 0.000 claims 1
- CCMKUQNCUXZGLI-UHFFFAOYSA-N 2-(3,4-dimethoxybenzoyl)-1-hydroxyindole-3-carbonitrile Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)C1=C(C#N)C2=CC=CC=C2N1O CCMKUQNCUXZGLI-UHFFFAOYSA-N 0.000 claims 1
- UXWLFODUOVHWHX-UHFFFAOYSA-N 2-(4-fluorophenyl)-1-hydroxyindole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C1=CC=C(F)C=C1 UXWLFODUOVHWHX-UHFFFAOYSA-N 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 125000006575 electron-withdrawing group Chemical group 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 6
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 6
- 239000000417 fungicide Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- JUGQARWTQZEZRI-UHFFFAOYSA-N ethyl 2-cyano-2-(2-nitrophenyl)acetate Chemical compound CCOC(=O)C(C#N)C1=CC=CC=C1[N+]([O-])=O JUGQARWTQZEZRI-UHFFFAOYSA-N 0.000 description 3
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 2
- FSEVOXNEAYNPRA-UHFFFAOYSA-N 1-hydroxy-2-phenylindole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C1=CC=CC=C1 FSEVOXNEAYNPRA-UHFFFAOYSA-N 0.000 description 2
- IJLKADPQWIRZCU-UHFFFAOYSA-N 2-benzoyl-1-hydroxyindole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C(=O)C1=CC=CC=C1 IJLKADPQWIRZCU-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 2
- 229940067157 phenylhydrazine Drugs 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IKSNDOVDVVPSMA-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CBr)C=C1 IKSNDOVDVVPSMA-UHFFFAOYSA-N 0.000 description 1
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 1
- QSIOIOLLRSZDFF-UHFFFAOYSA-N 1-hydroxy-2-[4-(trifluoromethyl)phenyl]indole-3-carbonitrile Chemical compound N#CC=1C2=CC=CC=C2N(O)C=1C1=CC=C(C(F)(F)F)C=C1 QSIOIOLLRSZDFF-UHFFFAOYSA-N 0.000 description 1
- WAKHLWOJMHVUJC-UHFFFAOYSA-N 2-hydroxyimino-1,2-diphenylethanol Chemical class C=1C=CC=CC=1C(=NO)C(O)C1=CC=CC=C1 WAKHLWOJMHVUJC-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 241000123650 Botrytis cinerea Species 0.000 description 1
- 241000222235 Colletotrichum orbiculare Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000009849 Cucumis sativus Nutrition 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 241000221785 Erysiphales Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 241000233614 Phytophthora Species 0.000 description 1
- 241000233629 Phytophthora parasitica Species 0.000 description 1
- 240000004713 Pisum sativum Species 0.000 description 1
- 235000010582 Pisum sativum Nutrition 0.000 description 1
- 241000221300 Puccinia Species 0.000 description 1
- 241001123569 Puccinia recondita Species 0.000 description 1
- 241001385948 Pythium sp. Species 0.000 description 1
- 241001361634 Rhizoctonia Species 0.000 description 1
- 241000813090 Rhizoctonia solani Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- OCWHMJVGSFIXBJ-UHFFFAOYSA-N ethyl 2-(6-cyano-6-nitrocyclohexa-2,4-dien-1-yl)acetate Chemical compound CCOC(=O)CC1C=CC=CC1(C#N)[N+]([O-])=O OCWHMJVGSFIXBJ-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000003032 phytopathogenic effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Landscapes
- Indole Compounds (AREA)
Abstract
Abstract of the Disclosure The present invention relates to 2-substituted-1-hydroxyindoles of the following formula:
Description
2 ~ 3 ~3 ~
2-SUBSTITUTED-l-~YDROX~I~DOLES
Field of the Invention The present invention relates to compounds useful as fungicides.
Background of the Invention In view of world hunger, it is useful to provide the public with a variety of fungicides for use in food agriculture.
The general structure of l-hydroxy-2-indoles is known in the art. Use of l-hydroxy indoles as fungicides is not known in the art. Although a number of N-substituted indoles have been described as active fungicides, none listed as active fungicides had an oxygen substituent, as found in l-hydroxy indoles.
US-A-3,296,277 discloses 3-cyano-1-hydroxy-2-phenylindole in which the phenyl group at the 2-position of the indole nucleus bears a nitro lower alkoxy substituent at either the ortho, meta, or para position. These compounds are disclosed as having pharmacological activity9 not as fungicides.-Loudon, et al., Journal of the ChemicalSociety, 3466 (1960) disclose the preparation of 3-cyano-1-hydroxy-2-phenylindole. Only phenyl, however, is discussed as a substituent in the 2-position of l-hydroxyindole. Other substituents in the 2-position are not disclosed.
. : :
-2~ 2 ~
Summary of the Invention The present invention relates to novel 2-substitu.ted-1-hydroxyindoles having the following formula:
R
I
R3 - ~ o ~ ._R2 wherein, Rl is an electron withdrawing group, R2 is selected from the group consisting of alkenyl having 2-10 carbon atoms, an N-substituted a-iminobenzyl group wherein the substituents are selected from the group consisting of phenyl, anilino and dimethylamino, and an unsubstituted or substituted aromatic group having meta or para substituents selected from the group consisting of nitro, trifluoromethyl, fluoro, formyl, hydroxyiminomethyl and carbamoyl, R is selected from the group consisting of halogen atoms, and n is 0, 1 or 2 provided that when R2 is either phenyl or nitro substituted phenyl and n is 0, then Rl is not cyano.
In one aspeet of the invention, a l-hydroxyindole is provided comprising the structure as shown above wherein Rl is cyano, and R2, R3, and n are defined as above.
Detailed Description of the Preferred Embodiments The compounds of the present invention are useful in controlling foliar phytopathogenic fungi.
The fungi are controlled by applying a fungicidally .
:
effective amount of one or more of the inventive compounds having the following formula:
Rl I
Rn - ~ ~ ~_R2 OH
wherein, Rl is an electron withdrawing group, such as carbamoyl, for example, carbamoyl, t-butylcarbamoyl, and dimethylcarbamoyl, carboxy, cyano and nitro;
R2 is selected from the group consisting of alkenyl having 2-10 carbon atoms, such as vinyl, allyl or butenyl, an N-substituted a-iminobenzyl group wherein the substituents are attached to said imino group and are selected from the group consisting of phenyl, anilino and dimethylamino, such as ~-(phenylimino)benzyl, ~-(N'-phenylazino)benzyl and a-(N', N'-dimethylazino)ben~yl, and an unsubstituted or substituted aromatic group having meta or para substituents selected from the group consisting of nitro, trifluoromethyl, fluoro, formyl, hydroxyiminomethyl and carbamoyl, such as phenyl, 4-nitrophenyl, 3-nitrophenyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 4-formylphenyl, 4-carbamoylphenyl and 4-hydroxyiminomethylphenyl;
R is a halogen atom, such as chloro, bromo, iodo or fluoro; and n is 0, 1 or 2.
In the compounds of this invention, when R2 is either phenyl or nitro substituted phenyl and n is O, then Rl is not cyano.
Preferred compounds of the invention h~ve the above structure wherein Rl is cyano and ~2, R3 and n are as described above.
Other preferred compounds of the invention have the above structure wherein, Rl is cyano;
R2 is 3-trifluoromethylphenyl, 4-fluorophenyl, 4-formylphenyl, 4-carbamoylphenyl, phenyl, 2-furyl, vinyl, 4-pyridyl, 2-pyridyl, a-(phenylimino)benzyl or hydroxyiminomethylphenyl;
and n is O and represents no substituents at R3.
Even more preferred compounds of the invention have the above structure wherein Rl is cyano;
R2 is phenyl, 4-nitrophenyl or methyl; and R3 is chloro and n is 1 or 2 so that R3 represents 5,6-dichloro or 6-chloro.
n Even further preferred compounds of the invention have the above structure wherein Rl is cyano;
R is phenyl, 3-nitrophenyl, or 4-nitrophenyl;
R3 is 6-chloro; and n is 1.
The most preferred compounds of the invention are compounds wherein R is 3-nitrophenyl or 4-nitrophenyl.
Compounds representative of the present invention include:
3-cyano-1-hydroxy-2-(3-trifluoromethylphenyl)indole, 3-cyano-1-hydroxy-2-(4-fluorophenyl~indole, 3-cyano-1-hydroxy-2-(formylphenyl)indole, 3-cyano-1-hydroxy-2-(4-hydroxyiminome-thylphenyl)indole, 3-cyano-6-chloro-1-hydroxy-2-(4-nitrophenyl)indole, 3-cyano-5,6-dichloro-1-hydroxy-2-phenylindole, ~, ,; :
, ,; :
'~ '-' ~
, _5_ 2 ~ 3 3-cyano-6-chloro-1-hydroxy-2-phenylindole, 3-cyano-2-(2-furyl)-1-hydroxyindole, 3-cyano-1-hydroxy-2-vinylindole, 3-cyano-1-hydroxy-2-(4-pyridyl)indole, 3-cyano-1-hydroxy-2-(2-pyridyl)indole, 3-cyano-2-(3,4-dimethoxybenzoyl)-~-hydroxyindole, 3-cyano-1-hydroxy-2-[a-~phenylimino)benzyl]indole, 3-cyano-1-hydroxy-2-[a-(phenylazino)benzyl]indole and 3-cyano-2-[~-(dimethylazino)benzyl]-1-hydroxyindole.
The 2-substituted l-hydroxyindoles are generally obtainable as colorless to yellow crystalline materials having characteristic melting points and absorption spectra and which may be purified by recrystallization from common organic solvents. They are appreciably soluble in many organic solvents such as methanol, ethanol, acetone, chloroform, benzene, dioxane, dimethyl sulfoxide and N,N-dimethyl~ormamide, but are relatively insoluble in water.
The compounds of the invention can be prepared in general through minor modifications of literature procedures.
The synthesis of l-hydroxy-3-cyano-2-phenylindole was first described by Loudon and Tennant in 1~ Ç~Lem. ~Q~, 3466(1960). This preparation is represented by the ~ollowing reaction scheme:
:CN
lNo2 ~ /CN CN
I O l I
~. Ph ~ Ph ~!~ ,!~ 1H
I O i ~./ Ph :CN
The preparation involved the cyanide induced cyclization of either of two 2-nitrophenyl-substituted cyanostilbenes.
Further development towards the preparation of l-hydroxyindoles is seen in the work of F.J.
Petracek shown in US-A-3,296,277 which discloses the preparation of indoles containing substituted phenyls in the 2-position as seen in the following reaction scheme:
NO CN NO CN
1 2 1 ¦ 2 ¦/C02Et I `o \C02Er ArCH2Br > ~ \ ~ \CH Ar I~ 0~. - Ar < ~Na2C3 OE
This synthesis involves the condensation of ethyl 2-nitrophenylcyano acetate with various benzyl halides under basic conditions followed by aqueous alkaline rearrangement providing 2-aryl-3-cyano-1-hydroxyindoles. The free hydroxyl group is preferred for activity. Other compounds can be prepared by the acid rearrangement of the well known benzoin oximes through the method described by E. Fischer in Chemische Berichte, 28,585 (1985~.
The compounds of the invention can be prepared by using a slight modification of the method of Petracek as discussed hereinabove in reference to US-A-3,296,277. 2-Halonitrobenzene can be condensed with ethyl cyanoacetate in the presence of excess potassium hydroxide affording a good yield of the 2 ~
ethyl 2-cyano-2-nitrophenylacetate as can be seen by the following reaction scheme:
Cl /CN l2 IN
2-SUBSTITUTED-l-~YDROX~I~DOLES
Field of the Invention The present invention relates to compounds useful as fungicides.
Background of the Invention In view of world hunger, it is useful to provide the public with a variety of fungicides for use in food agriculture.
The general structure of l-hydroxy-2-indoles is known in the art. Use of l-hydroxy indoles as fungicides is not known in the art. Although a number of N-substituted indoles have been described as active fungicides, none listed as active fungicides had an oxygen substituent, as found in l-hydroxy indoles.
US-A-3,296,277 discloses 3-cyano-1-hydroxy-2-phenylindole in which the phenyl group at the 2-position of the indole nucleus bears a nitro lower alkoxy substituent at either the ortho, meta, or para position. These compounds are disclosed as having pharmacological activity9 not as fungicides.-Loudon, et al., Journal of the ChemicalSociety, 3466 (1960) disclose the preparation of 3-cyano-1-hydroxy-2-phenylindole. Only phenyl, however, is discussed as a substituent in the 2-position of l-hydroxyindole. Other substituents in the 2-position are not disclosed.
. : :
-2~ 2 ~
Summary of the Invention The present invention relates to novel 2-substitu.ted-1-hydroxyindoles having the following formula:
R
I
R3 - ~ o ~ ._R2 wherein, Rl is an electron withdrawing group, R2 is selected from the group consisting of alkenyl having 2-10 carbon atoms, an N-substituted a-iminobenzyl group wherein the substituents are selected from the group consisting of phenyl, anilino and dimethylamino, and an unsubstituted or substituted aromatic group having meta or para substituents selected from the group consisting of nitro, trifluoromethyl, fluoro, formyl, hydroxyiminomethyl and carbamoyl, R is selected from the group consisting of halogen atoms, and n is 0, 1 or 2 provided that when R2 is either phenyl or nitro substituted phenyl and n is 0, then Rl is not cyano.
In one aspeet of the invention, a l-hydroxyindole is provided comprising the structure as shown above wherein Rl is cyano, and R2, R3, and n are defined as above.
Detailed Description of the Preferred Embodiments The compounds of the present invention are useful in controlling foliar phytopathogenic fungi.
The fungi are controlled by applying a fungicidally .
:
effective amount of one or more of the inventive compounds having the following formula:
Rl I
Rn - ~ ~ ~_R2 OH
wherein, Rl is an electron withdrawing group, such as carbamoyl, for example, carbamoyl, t-butylcarbamoyl, and dimethylcarbamoyl, carboxy, cyano and nitro;
R2 is selected from the group consisting of alkenyl having 2-10 carbon atoms, such as vinyl, allyl or butenyl, an N-substituted a-iminobenzyl group wherein the substituents are attached to said imino group and are selected from the group consisting of phenyl, anilino and dimethylamino, such as ~-(phenylimino)benzyl, ~-(N'-phenylazino)benzyl and a-(N', N'-dimethylazino)ben~yl, and an unsubstituted or substituted aromatic group having meta or para substituents selected from the group consisting of nitro, trifluoromethyl, fluoro, formyl, hydroxyiminomethyl and carbamoyl, such as phenyl, 4-nitrophenyl, 3-nitrophenyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 4-formylphenyl, 4-carbamoylphenyl and 4-hydroxyiminomethylphenyl;
R is a halogen atom, such as chloro, bromo, iodo or fluoro; and n is 0, 1 or 2.
In the compounds of this invention, when R2 is either phenyl or nitro substituted phenyl and n is O, then Rl is not cyano.
Preferred compounds of the invention h~ve the above structure wherein Rl is cyano and ~2, R3 and n are as described above.
Other preferred compounds of the invention have the above structure wherein, Rl is cyano;
R2 is 3-trifluoromethylphenyl, 4-fluorophenyl, 4-formylphenyl, 4-carbamoylphenyl, phenyl, 2-furyl, vinyl, 4-pyridyl, 2-pyridyl, a-(phenylimino)benzyl or hydroxyiminomethylphenyl;
and n is O and represents no substituents at R3.
Even more preferred compounds of the invention have the above structure wherein Rl is cyano;
R2 is phenyl, 4-nitrophenyl or methyl; and R3 is chloro and n is 1 or 2 so that R3 represents 5,6-dichloro or 6-chloro.
n Even further preferred compounds of the invention have the above structure wherein Rl is cyano;
R is phenyl, 3-nitrophenyl, or 4-nitrophenyl;
R3 is 6-chloro; and n is 1.
The most preferred compounds of the invention are compounds wherein R is 3-nitrophenyl or 4-nitrophenyl.
Compounds representative of the present invention include:
3-cyano-1-hydroxy-2-(3-trifluoromethylphenyl)indole, 3-cyano-1-hydroxy-2-(4-fluorophenyl~indole, 3-cyano-1-hydroxy-2-(formylphenyl)indole, 3-cyano-1-hydroxy-2-(4-hydroxyiminome-thylphenyl)indole, 3-cyano-6-chloro-1-hydroxy-2-(4-nitrophenyl)indole, 3-cyano-5,6-dichloro-1-hydroxy-2-phenylindole, ~, ,; :
, ,; :
'~ '-' ~
, _5_ 2 ~ 3 3-cyano-6-chloro-1-hydroxy-2-phenylindole, 3-cyano-2-(2-furyl)-1-hydroxyindole, 3-cyano-1-hydroxy-2-vinylindole, 3-cyano-1-hydroxy-2-(4-pyridyl)indole, 3-cyano-1-hydroxy-2-(2-pyridyl)indole, 3-cyano-2-(3,4-dimethoxybenzoyl)-~-hydroxyindole, 3-cyano-1-hydroxy-2-[a-~phenylimino)benzyl]indole, 3-cyano-1-hydroxy-2-[a-(phenylazino)benzyl]indole and 3-cyano-2-[~-(dimethylazino)benzyl]-1-hydroxyindole.
The 2-substituted l-hydroxyindoles are generally obtainable as colorless to yellow crystalline materials having characteristic melting points and absorption spectra and which may be purified by recrystallization from common organic solvents. They are appreciably soluble in many organic solvents such as methanol, ethanol, acetone, chloroform, benzene, dioxane, dimethyl sulfoxide and N,N-dimethyl~ormamide, but are relatively insoluble in water.
The compounds of the invention can be prepared in general through minor modifications of literature procedures.
The synthesis of l-hydroxy-3-cyano-2-phenylindole was first described by Loudon and Tennant in 1~ Ç~Lem. ~Q~, 3466(1960). This preparation is represented by the ~ollowing reaction scheme:
:CN
lNo2 ~ /CN CN
I O l I
~. Ph ~ Ph ~!~ ,!~ 1H
I O i ~./ Ph :CN
The preparation involved the cyanide induced cyclization of either of two 2-nitrophenyl-substituted cyanostilbenes.
Further development towards the preparation of l-hydroxyindoles is seen in the work of F.J.
Petracek shown in US-A-3,296,277 which discloses the preparation of indoles containing substituted phenyls in the 2-position as seen in the following reaction scheme:
NO CN NO CN
1 2 1 ¦ 2 ¦/C02Et I `o \C02Er ArCH2Br > ~ \ ~ \CH Ar I~ 0~. - Ar < ~Na2C3 OE
This synthesis involves the condensation of ethyl 2-nitrophenylcyano acetate with various benzyl halides under basic conditions followed by aqueous alkaline rearrangement providing 2-aryl-3-cyano-1-hydroxyindoles. The free hydroxyl group is preferred for activity. Other compounds can be prepared by the acid rearrangement of the well known benzoin oximes through the method described by E. Fischer in Chemische Berichte, 28,585 (1985~.
The compounds of the invention can be prepared by using a slight modification of the method of Petracek as discussed hereinabove in reference to US-A-3,296,277. 2-Halonitrobenzene can be condensed with ethyl cyanoacetate in the presence of excess potassium hydroxide affording a good yield of the 2 ~
ethyl 2-cyano-2-nitrophenylacetate as can be seen by the following reaction scheme:
Cl /CN l2 IN
5~ \ ~ 2 Co2Et ~.\ /.
./ KOH DMA ~ /
¦2 CN TMG*,DMA*
loNa2C3 1 I~ ~o~I~o2Et <
MeOH ¦ ~ / Ar H20 \o/
CN
I
*ArCH2X where X is halo I~ ,O~o - Ar preferably chloro or bromo I *TMG=1,1,3,3,-tetramethylguanidine OH *DMA=N,N-dimethylacetamide Various benzyl halides can then be condensed with the acetate ester followed by cyclization to the aryl-substituted indole as shown. Bromides are preferred.
The compounds of the invention were particularly tested for activity against Colletotrichum lagenarium (Anthracnose on cucumbers), Puccinia xecondit_ (wheat leaf rust), Erisiphe polygoni (powdery mildew on beans), Phytophthora in~estans (late blight on tomatoes), Rhizoctonia solani (Rhizoctonia on cotton), Pythium sp. (damping off on peas) and Botrytis Cinerea (gray mold). They showed particularly enhanced activity against rust disease, including Puccinia recondita (wheat leaf rust).
The introduction of highly hydrophilic groups such as carboxylate or sulfamoyl was found to decrease activity. Further, the introduction of highly hydrophobic groups such as 4-phenylsulfonylphenyl, benzophenonyl, t-butylphenyl were also found to decrease activity.
"
-8- ~ ~L~8 Preparation of Ethyl Cyano-2-nitrophenvl-acetate A mixture of 2-chloronitrobenzene (47.2 g, 0.300 mole) and ethyl cyanoacetate (40 ml, 0.38 mol) in N,N-dimethylacetamide (DMA, 250 ml) was treat~d at once with potassium hydroxide pellets (120 g, 2.14 mole). The mixture was mechanically stirred and heated for ten minutes at 110 - 120C (caution:
minimal heat `application may be needed, exothermic reaction) then poured into ice-cold dilute hydrochloric acid. Ether extractive workup gave an oil. The oil was passed through silica gel eluting with toluene to provide a yellow oil, which was dissolved in 100 ml methanol then chilled. The solid was filtered to afford ethyl cyano-2-nitrophenylacetate as a yellow solid (51.4 g, 73.2%) mp 57-61C (literature 59-60C).
~xample 1: Preparation of l-~ydroxy-3-cyano-2-(4-tri-fluoromethylphenyl)indole A mixture of ethyl cyano-2-nitrophenylacetate (4.68 g, 20.0 mmole), 4-trifluoromethylbenzyl bromide (4.77 g, 20.0 mmole), 1,1,3,3-tetramethylguanidine (TMG, 2.81 ml, 22.4 mmole) in DMA (50 ml) was heated to 100C. Two additional 0.2 ml portions of the benzyl bromide were added at 15 min intervals. After a final 15 min the mixture was poured into water.
Ethyl acetate extractive workup afforded the alkylated product as an oil. This oil in methanol ~80 ml) with aqueous sodium carbonate (20 ml, 1.0 M) was heated at reflux for 5 h then poured into ice-cold dilute hydrochloric acid. The solid was filtered, air dried then recrystallized twice from toluene to afford N-hydroxy-3-cyano-2-(4-trifluoromethylphenyl)indole as a cream solid (3.81 g, 63.1%) mp 202-203C (at which temperature it decomposed.).
2 ~
Examples 2 to ll:
The compounds described in the following Tabes I and II, which also contain the melting points and elemental analyses for these compounds, were prepared by the procedure of Example l and the hereinabove described modified procedures of Petracek, except using the appropriate starting materials in equivalent amounts.
2 ~
TABLE I
CN
I
X ~ =. ~ Y
OH
(% Found~
Elemental Analysis (%Calculated~
Example X Y ~p(oc~a N C H
3 H 3-CF3 187-188 9.2 63.6 3.0 9.3 63.6 3.0 4 H 4-F 208-209 10.5b 72.4 3.9 10.7 72.1 3.8 H 4-CH0 207-209 ll.lC 72.5 4.0 11.8 72.5 4.0 6 H 4-CH=NOH 200-205 15.668.9 4.1 15.2 69.3 4.0 7 6-C1 4-No2 252 13.2d 56.7 2.6 13.2 56.6 2.3 8 5,6-C12 H 223-224 lo.oe 59.3 2.9 10.1 59.4 2.8 9 6-Cl H 225-227 10.5 67.1 3.5 10.4 67.0 3.4 - . i , , . .
. . .~ ,... ' .
. ~ ' :.
TABLE II
CN
., I
t ~ ~ - R
~ / \N /
I
OE
(% Fo~nd) Elemental Analysis (%Calculated~
10 Example R mp(C)a N C E
-CH=C~2 182-183 14.9 71.4 4.5 15.2 71.7 4.4 ~ 219-220 12.8f 69.0 3.8 15-- ~ 12.9 69.4 3.7 Key to Table I and II footnotes:
a) All compounds melted with decomposition.
b) through f): Although all samples were dried in vacuo, certain samples retained solvent of crystallization. Therefore, the calculated values of the elements (N, C and H) for certain examples were based on retentions of specific molar ratios of solvent as follows:
Molar Ratio of Footno~e Example _~olventCompound/Solvent b 4 Toluene 15/2 c 5 Acetonitrile 3/1 d 7 Water 4/1 e 8 Acetonitrile 4/1 30 f 11 Acetonitrile 10/1 : . :
~.
- -.
, 2 ~
Example 12: Preparation of 3-cyano-1-hydroxy-2-~a-(phenylimino)-benzylJindole CN
I~,O~ N~
~ ~
A mixture of 3-cyano-2-benzoyl-1-hydroxy-indole (2.62 g, 10.0 mmole) and aniline (1.0 g, 10.8 mmole) were heated at reflux in toluene (50 ml) undex a trap for 16 hours. Concentration in vacuQ
afforded a solid. Recrystallization from methylcyclohexane provided dark crystals, m.p. 188-190C. Analysis (dry 25C): Fd(calculated) N, 12.2 (12.4), C, 78.2 (78.3) H, 4.7 (4.5).
Example 13: Preparation of 3-cyano-1-hydroxy-2-[a-(phenylazino)-benzyl]indo~e CN
I~ ,O~ /~ N NHPh OH
A mixture of 3-cyano-2-benzoyl-1 hydroxy-indole (2.62 , 10.0 mmole) and phenylhydrazine (1.1 ml, 11.1 mmole) was heated at reflux in ethanol (35 ml) for fifteen minut.es. The mixture was treated with additional phenylhydrazine (0.25 ml, 2.5 mmole) and stirred at ambient temperature for 16 hours. The mixture was concentrated in vacuo then triturated , ! ' , .-:' ': '' ' ' ~ ~'' ,` ,~ ''' ' .
, -13- 2 ~ Q ~
with ether-ligroin mixture to give a yellow solid.
Recrystallization from acetic acid yielded a bright yellow solid which was dried in vacuo at 800C, mp 154-158C. Analysis (dry 25C): Fd(calculated 12.5 mole % acetic acid) N, 15.7 (15.5), C, 74.2 (74.2), H, 4.6 (4.7).
Example 14: Preparation of 3-cyano-2-[a-(dimethylazino)benzyl]-l-hydroxyindole.
CN
I
I~ ,0~ ~N-N(CE3)2 OH
This compound was prepared as described for Example 13. A yellow solid, mp 164-165C, was obtained. Analysis (dry 25C): Fd (Calculated 11 mole % methanol) N, 18.2 (18.2), C, 70.5 (70.6), H, 5.3 (5.4)
./ KOH DMA ~ /
¦2 CN TMG*,DMA*
loNa2C3 1 I~ ~o~I~o2Et <
MeOH ¦ ~ / Ar H20 \o/
CN
I
*ArCH2X where X is halo I~ ,O~o - Ar preferably chloro or bromo I *TMG=1,1,3,3,-tetramethylguanidine OH *DMA=N,N-dimethylacetamide Various benzyl halides can then be condensed with the acetate ester followed by cyclization to the aryl-substituted indole as shown. Bromides are preferred.
The compounds of the invention were particularly tested for activity against Colletotrichum lagenarium (Anthracnose on cucumbers), Puccinia xecondit_ (wheat leaf rust), Erisiphe polygoni (powdery mildew on beans), Phytophthora in~estans (late blight on tomatoes), Rhizoctonia solani (Rhizoctonia on cotton), Pythium sp. (damping off on peas) and Botrytis Cinerea (gray mold). They showed particularly enhanced activity against rust disease, including Puccinia recondita (wheat leaf rust).
The introduction of highly hydrophilic groups such as carboxylate or sulfamoyl was found to decrease activity. Further, the introduction of highly hydrophobic groups such as 4-phenylsulfonylphenyl, benzophenonyl, t-butylphenyl were also found to decrease activity.
"
-8- ~ ~L~8 Preparation of Ethyl Cyano-2-nitrophenvl-acetate A mixture of 2-chloronitrobenzene (47.2 g, 0.300 mole) and ethyl cyanoacetate (40 ml, 0.38 mol) in N,N-dimethylacetamide (DMA, 250 ml) was treat~d at once with potassium hydroxide pellets (120 g, 2.14 mole). The mixture was mechanically stirred and heated for ten minutes at 110 - 120C (caution:
minimal heat `application may be needed, exothermic reaction) then poured into ice-cold dilute hydrochloric acid. Ether extractive workup gave an oil. The oil was passed through silica gel eluting with toluene to provide a yellow oil, which was dissolved in 100 ml methanol then chilled. The solid was filtered to afford ethyl cyano-2-nitrophenylacetate as a yellow solid (51.4 g, 73.2%) mp 57-61C (literature 59-60C).
~xample 1: Preparation of l-~ydroxy-3-cyano-2-(4-tri-fluoromethylphenyl)indole A mixture of ethyl cyano-2-nitrophenylacetate (4.68 g, 20.0 mmole), 4-trifluoromethylbenzyl bromide (4.77 g, 20.0 mmole), 1,1,3,3-tetramethylguanidine (TMG, 2.81 ml, 22.4 mmole) in DMA (50 ml) was heated to 100C. Two additional 0.2 ml portions of the benzyl bromide were added at 15 min intervals. After a final 15 min the mixture was poured into water.
Ethyl acetate extractive workup afforded the alkylated product as an oil. This oil in methanol ~80 ml) with aqueous sodium carbonate (20 ml, 1.0 M) was heated at reflux for 5 h then poured into ice-cold dilute hydrochloric acid. The solid was filtered, air dried then recrystallized twice from toluene to afford N-hydroxy-3-cyano-2-(4-trifluoromethylphenyl)indole as a cream solid (3.81 g, 63.1%) mp 202-203C (at which temperature it decomposed.).
2 ~
Examples 2 to ll:
The compounds described in the following Tabes I and II, which also contain the melting points and elemental analyses for these compounds, were prepared by the procedure of Example l and the hereinabove described modified procedures of Petracek, except using the appropriate starting materials in equivalent amounts.
2 ~
TABLE I
CN
I
X ~ =. ~ Y
OH
(% Found~
Elemental Analysis (%Calculated~
Example X Y ~p(oc~a N C H
3 H 3-CF3 187-188 9.2 63.6 3.0 9.3 63.6 3.0 4 H 4-F 208-209 10.5b 72.4 3.9 10.7 72.1 3.8 H 4-CH0 207-209 ll.lC 72.5 4.0 11.8 72.5 4.0 6 H 4-CH=NOH 200-205 15.668.9 4.1 15.2 69.3 4.0 7 6-C1 4-No2 252 13.2d 56.7 2.6 13.2 56.6 2.3 8 5,6-C12 H 223-224 lo.oe 59.3 2.9 10.1 59.4 2.8 9 6-Cl H 225-227 10.5 67.1 3.5 10.4 67.0 3.4 - . i , , . .
. . .~ ,... ' .
. ~ ' :.
TABLE II
CN
., I
t ~ ~ - R
~ / \N /
I
OE
(% Fo~nd) Elemental Analysis (%Calculated~
10 Example R mp(C)a N C E
-CH=C~2 182-183 14.9 71.4 4.5 15.2 71.7 4.4 ~ 219-220 12.8f 69.0 3.8 15-- ~ 12.9 69.4 3.7 Key to Table I and II footnotes:
a) All compounds melted with decomposition.
b) through f): Although all samples were dried in vacuo, certain samples retained solvent of crystallization. Therefore, the calculated values of the elements (N, C and H) for certain examples were based on retentions of specific molar ratios of solvent as follows:
Molar Ratio of Footno~e Example _~olventCompound/Solvent b 4 Toluene 15/2 c 5 Acetonitrile 3/1 d 7 Water 4/1 e 8 Acetonitrile 4/1 30 f 11 Acetonitrile 10/1 : . :
~.
- -.
, 2 ~
Example 12: Preparation of 3-cyano-1-hydroxy-2-~a-(phenylimino)-benzylJindole CN
I~,O~ N~
~ ~
A mixture of 3-cyano-2-benzoyl-1-hydroxy-indole (2.62 g, 10.0 mmole) and aniline (1.0 g, 10.8 mmole) were heated at reflux in toluene (50 ml) undex a trap for 16 hours. Concentration in vacuQ
afforded a solid. Recrystallization from methylcyclohexane provided dark crystals, m.p. 188-190C. Analysis (dry 25C): Fd(calculated) N, 12.2 (12.4), C, 78.2 (78.3) H, 4.7 (4.5).
Example 13: Preparation of 3-cyano-1-hydroxy-2-[a-(phenylazino)-benzyl]indo~e CN
I~ ,O~ /~ N NHPh OH
A mixture of 3-cyano-2-benzoyl-1 hydroxy-indole (2.62 , 10.0 mmole) and phenylhydrazine (1.1 ml, 11.1 mmole) was heated at reflux in ethanol (35 ml) for fifteen minut.es. The mixture was treated with additional phenylhydrazine (0.25 ml, 2.5 mmole) and stirred at ambient temperature for 16 hours. The mixture was concentrated in vacuo then triturated , ! ' , .-:' ': '' ' ' ~ ~'' ,` ,~ ''' ' .
, -13- 2 ~ Q ~
with ether-ligroin mixture to give a yellow solid.
Recrystallization from acetic acid yielded a bright yellow solid which was dried in vacuo at 800C, mp 154-158C. Analysis (dry 25C): Fd(calculated 12.5 mole % acetic acid) N, 15.7 (15.5), C, 74.2 (74.2), H, 4.6 (4.7).
Example 14: Preparation of 3-cyano-2-[a-(dimethylazino)benzyl]-l-hydroxyindole.
CN
I
I~ ,0~ ~N-N(CE3)2 OH
This compound was prepared as described for Example 13. A yellow solid, mp 164-165C, was obtained. Analysis (dry 25C): Fd (Calculated 11 mole % methanol) N, 18.2 (18.2), C, 70.5 (70.6), H, 5.3 (5.4)
Claims (9)
1. A compound having the following formula:
wherein, R1 is carbamoyl, t-butylcarbamoyl, dimethylcarbamoyl, carboxy, nitro or cyano;
R2 is an alkenyl having 2-10 carbon atoms, an N-substituted .alpha.-iminobenzyl group wherein the substituents are selected from the group consisting of phenyl, anilino and dimethylamino, an unsubstituted aromatic group or an aromatic group having meta or para substituents selected from the group consisting of nitro, trifluoromethyl, fluoro, formyl, hydroxyiminomethyl and carbamoyl;
R3 is a halogen atom; and n is 0, 1 or 2 provided that when R2 is either phenyl or nitro substituted phenyl and n is 0, then R1 is not cyano.
wherein, R1 is carbamoyl, t-butylcarbamoyl, dimethylcarbamoyl, carboxy, nitro or cyano;
R2 is an alkenyl having 2-10 carbon atoms, an N-substituted .alpha.-iminobenzyl group wherein the substituents are selected from the group consisting of phenyl, anilino and dimethylamino, an unsubstituted aromatic group or an aromatic group having meta or para substituents selected from the group consisting of nitro, trifluoromethyl, fluoro, formyl, hydroxyiminomethyl and carbamoyl;
R3 is a halogen atom; and n is 0, 1 or 2 provided that when R2 is either phenyl or nitro substituted phenyl and n is 0, then R1 is not cyano.
2. The compound of claim 1 wherein R1 is cyano; and R2 is alkenyl, the unsubstituted aromatic group or the aromatic group with meta or para substituents.
3. The compound of claim 1 wherein R1 is cyano, R2 is 3-trifluoromethylphenyl,
4-methoxyphenyl, 4-fluorophenyl, 4-formylphenyl, 4-carbamoylphenyl, 2-furyl, vinyl, 4-pyridyl, 2-pyridyl, and .alpha.-(phenylimino)benzyl; and n is 0.
4. The compound of claim 1 wherein R1 is cyano, R2 is phenyl, 4-nitrophenyl, 3-nitrophenyl or methyl;
R3 is chloro and n is 1 or 2.
4. The compound of claim 1 wherein R1 is cyano, R2 is phenyl, 4-nitrophenyl, 3-nitrophenyl or methyl;
R3 is chloro and n is 1 or 2.
5. The compound of claim 4 wherein R3 is 6-chloro and n is 1.
6. The compound of claim 5 wherein R2 is 4-nitrophenyl.
7. The compound of claim 5 wherein R2 is 3-nitrophenyl.
8. The compound of claim 1 selected from the group consisting of:
3-cyano-1-hydroxy-2-(3-trifluoromethylphenyl)indole, 3-cyano-1-hydroxy-2-(4-fluorophenyl)indole, 3-cyano-1-hydroxy-2-(formylphenyl)indole, 3-cyano-1-hydroxy-2-(4-hydroxyiminomethylphenyl)indole, 3-cyano-6-chloro-1-hydroxy-2-(4-nitrophenyl)indole, 3-cyano-5,6-dichloro-1-hydroxy-2-phenylindole, 3-cyano-6-chloro-1-hydroxy-2-phenylindole, 3-cyano-2-(2-furyl)-1-hydroxyindole, 3-cyano-1-hydroxy-2-vinylindole, 3-cyano-1-hydroxy-2-(4-pyridyl)indole, 3-cyano-1-hydroxy-2-(2-pyridyl)indole, 3-cyano-2-(3,4-dimethoxybenzoyl)-1-hydroxyindole, 3-cyano-1-hydroxy-2-[.alpha.-(phenylimino)benzyl]indole, 3-cyano-1-hydroxy-2-[.alpha.-(phenylazino)benzyl]indole and 3-cyano-2-[.alpha.-(dimethylazino)benzyl]-1-hydroxyindole.
3-cyano-1-hydroxy-2-(3-trifluoromethylphenyl)indole, 3-cyano-1-hydroxy-2-(4-fluorophenyl)indole, 3-cyano-1-hydroxy-2-(formylphenyl)indole, 3-cyano-1-hydroxy-2-(4-hydroxyiminomethylphenyl)indole, 3-cyano-6-chloro-1-hydroxy-2-(4-nitrophenyl)indole, 3-cyano-5,6-dichloro-1-hydroxy-2-phenylindole, 3-cyano-6-chloro-1-hydroxy-2-phenylindole, 3-cyano-2-(2-furyl)-1-hydroxyindole, 3-cyano-1-hydroxy-2-vinylindole, 3-cyano-1-hydroxy-2-(4-pyridyl)indole, 3-cyano-1-hydroxy-2-(2-pyridyl)indole, 3-cyano-2-(3,4-dimethoxybenzoyl)-1-hydroxyindole, 3-cyano-1-hydroxy-2-[.alpha.-(phenylimino)benzyl]indole, 3-cyano-1-hydroxy-2-[.alpha.-(phenylazino)benzyl]indole and 3-cyano-2-[.alpha.-(dimethylazino)benzyl]-1-hydroxyindole.
9. The compound of claim 8 is 3-cyano-6-chloro-1-hydroxy-2-(4-nitrophenyl) indole or 3-cyano-6-chloro-1-hydroxy-2-phenylindole.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US56299790A | 1990-08-06 | 1990-08-06 | |
US562,997 | 1990-08-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2048001A1 true CA2048001A1 (en) | 1992-02-07 |
Family
ID=24248653
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA 2048001 Abandoned CA2048001A1 (en) | 1990-08-06 | 1991-07-26 | 2-substituted-1-hydroxyindoles |
Country Status (1)
Country | Link |
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CA (1) | CA2048001A1 (en) |
-
1991
- 1991-07-26 CA CA 2048001 patent/CA2048001A1/en not_active Abandoned
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