CN110759913B - Indolylhydrazone derivatives, preparation method thereof and application thereof in plant virus prevention and control, sterilization and disinsection - Google Patents
Indolylhydrazone derivatives, preparation method thereof and application thereof in plant virus prevention and control, sterilization and disinsection Download PDFInfo
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- CN110759913B CN110759913B CN201810852990.XA CN201810852990A CN110759913B CN 110759913 B CN110759913 B CN 110759913B CN 201810852990 A CN201810852990 A CN 201810852990A CN 110759913 B CN110759913 B CN 110759913B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
Abstract
The invention relates to tetrahydroazepinesAnd [4, 5-b ]]The indole acylhydrazone derivatives, the preparation method and the application in the aspects of preventing and treating plant viruses, sterilizing and killing pests, and the meanings of all groups in the general formula are shown in the specification. Tetrahydroazepine of the inventionAnd [4, 5-b ]]The indole acylhydrazone derivatives have excellent plant virus resisting activity, broad-spectrum bactericidal activity and insecticidal activity.
Description
Technical Field
Background
Aza derivativesAnd [4, 5-b ]]Indole-like structures are important heterocyclic building blocks found in a range of biologically active molecules and natural products. For example, PNU-22394 is a potent 5-HT2cAgonists, which may have some effect in the treatment of obsessive compulsive disorder, anxiety, obesity; dopamine receiver: the human brain can secrete a dopamine receptor, and the human body lacks the dopamine receptor, so that the reaction is slowed, and obesity is easily caused. Natural products such as subencanadine F, ngoniensis, ibogamine and the like have obvious pharmaceutical properties, and show certain anti-cancer and Cyclin Dependent Kinase (CDK) inhibitors and glycogen synthase kinase inhibitors. Thus efficiently synthesizing azaAnd [4, 5-b ]]Indole backbones and structural derivations are essential in order to find highly active compounds.
With respect to aza ringsAnd [4, 5-b ]]Construction of indole skeleton: in 2009 plum loyalty et al reported that the seven-step method realizes the total synthesis of subencanadine F, the method is simple, efficient and good in protection, and moreover, the chemically selective Dieckmann condensation constructs bicyclo [4.3.1 ]]The skeleton should be used in synthetic and natural products, with many more applications (j. org. chem., 2009, 7)4(19): 7533-7535.). In 2010 Waters et al, in turn, achieved the total synthesis of subencanadine F by a different approach (J.org. chem., 2010, 75 (20): 7026-. Both are similar in the method of constructing the seven-membered ring: direct ring-closing rearrangement of tryptamine analogue and halogenated pyruvate to obtain aza-heptatomic ring [4, 5-b ]]An indole skeleton. 2017 Longwu et al report that the regioselectivity of aromatic hydrocarbon-methylene amide cyclization reaction catalyzed by copper represents that methylene of a first catalytic pi system comprises cyclization with regioselectivity reversion, and realize high-efficiency acquisition of nitrogen heterocycles [4, 5-b ] with diversified structures under mild conditions]Indole. Under the action of a catalyst Cu, lone pair electrons on the indole attack alkyne 2 position, and then cyclization is carried out to obtain azaAnd [4, 5-b ]]Indole (ACS.Catal., 2017, 7 (6): 4004-. Boominathan et al report 2017 that aza is efficiently realized under the catalysis of catalytic amount of TfOHAnd [4, 5-b ]]The synthesis of indole substances (org.biomol.chem., 2017, 15 (8): 1872-1875), but no report on the biological activity thereof is available.
Disclosure of Invention
It is an object of the present invention to provide tetrahydroazepinesAnd [4, 5-b ]]Indole acylhydrazone derivatives, a preparation method thereof and application thereof in the aspects of plant virus prevention and control, sterilization and disinsection. The tetrahydroazepine of this patentAnd [4, 5-b ]]The indole acylhydrazone derivatives show good plant virus resistance activity, bactericidal activity and insecticidal activity.
Tetrahydroazepine of the inventionAnd [4, 5-b ]]IndoloylHydrazone derivatives are compounds having the structure shown by the following general formula:
wherein R is1Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthryl group, a substituted or unsubstituted phenanthryl group, a nitrogen-containing heterocyclic ring having 2 to 10 carbon atoms, an oxygen-containing heterocyclic ring having 2 to 10 carbon atoms, a sulfur-containing heterocyclic ring having 2 to 10 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from one or more of hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene;
R2、R3respectively represent hydrogen, alkyl of C1-C10, alkenyl of C2-C10, alkynyl of C2-C10, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted anthryl, substituted or unsubstituted phenanthryl, nitrogen-containing heterocycle containing 2-10 carbon atoms, oxygen-containing heterocycle containing 2-10 carbon atoms, sulfur-containing heterocycle containing 2-10 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from one or more of hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene.
Tetrahydroazepine of the inventionAnd [4, 5-b ]]A process for preparing an indole acylhydrazone compound, comprising: first, L-tryptophan in SOCl2Esterification reaction is carried out on the L-tryptophan methyl ester and methanol under catalysis to generate L-tryptophan methyl ester (I), Ts protecting group on the L-tryptophan methyl ester forms II under the alkaline condition of triethylamine, the II respectively carries out nucleophilic substitution on the II and alpha-bromoacetophenone to generate III, and then trifluoromethanesulfonic acid is carried outThe dehydration condensation cyclization rearrangement generates corresponding IV under the catalytic action, the IV is hydrazinolyzed to generate corresponding hydrazide V, and the intermediate V is respectively subjected to aldehyde condensation to form the tetrahydroazepine shown in the general formulaAnd [4, 5-b ]]Indole acylhydrazone compounds.
The tetrahydroazepines of the general formulaAnd [4, 5-b ]]The indoxyl hydrazone compound has excellent plant virus activity resistance, can well inhibit tobacco mosaic virus, pepper virus, rice virus, tomato virus, sweet potato virus, melon virus, maize dwarf mosaic virus and the like, can effectively prevent and treat virus diseases of various crops such as tobacco, pepper, rice, tomato, melon and vegetable, grain, vegetable, bean and the like, and is particularly suitable for preventing and treating the tobacco mosaic virus. Tetrahydroazepines of general formulaAnd [4, 5-b ]]The indolylhydrazone derivative has good activity of resisting Tobacco Mosaic Virus (TMV).
The tetrahydroazepines of the general formulaAnd [4, 5-b ]]The indolylhydrazone compound can be used as a plant virus inhibitor directly or together with an agriculturally acceptable carrier, or can be used with other plant virus resisting agents such as diazosulfide (BTH), Tiadinil (TDL), 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid (TDLA), DL-beta-aminobutyric acid (BABA), ribavirin, ningnanmycin, phenanthroindolizidine alkaloid antofine, bitriazole compounds XY-13 and XY-30, virus A, salicylic acid, polyhydroxy dinaphthalene and amino-oligosaccharin to form an interactive composition, and the compositions have the performance synergismSome of them showed additive effects.
The tetrahydroazepines of the general formulaAnd [4, 5-b ]]The indole acylhydrazone compounds exhibit bactericidal activity against 14 pathogenic bacteria, among which 14: cucumber wilt, peanut brown spot, apple ring rot, tomato early blight, wheat scab, potato late blight, rape sclerotium, cucumber gray mold, rice sheath blight, phytophthora capsici, rice bakanae, wheat sheath blight, corn speck and watermelon anthrax.
The tetrahydroazepines of the general formulaAnd [4, 5-b ]]The indole acylhydrazone compound has the activity of killing adult mites, diamondback moths, armyworms, mosquito larvae, cotton bollworms and corn borers.
The tetrahydroazepines of the general formulaAnd [4, 5-b ]]The indoxyl hydrazone compound can be directly used as an insecticidal bactericide, can also be used by adding an agriculturally acceptable carrier, and can also be used in combination with other insecticidal and acaricidal bactericides such as tebufenpyrad, chlorfenapyr, etoxazole, fenpyroximate and the like, and the compositions have synergistic effects and additive effects.
Detailed Description
The invention provides tetrahydroazepineAnd [4, 5-b ]]Indolylhydrazone derivatives, the tetrahydroazepineAnd [4, 5-b ]]The indole acylhydrazone derivative is a compound shown as a general formula:
wherein R is1Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthryl group, a substituted or unsubstituted phenanthryl group, a nitrogen-containing heterocyclic ring having 2 to 10 carbon atoms, an oxygen-containing heterocyclic ring having 2 to 10 carbon atoms, a sulfur-containing heterocyclic ring having 2 to 10 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from one or more of hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene;
R2、R3respectively represent hydrogen, alkyl of C1-C10, alkenyl of C2-C10, alkynyl of C2-C10, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted anthryl, substituted or unsubstituted phenanthryl, nitrogen-containing heterocycle containing 2-10 carbon atoms, oxygen-containing heterocycle containing 2-10 carbon atoms, sulfur-containing heterocycle containing 2-10 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from one or more of hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene.
In the present invention, specific examples of the alkyl group of C1 to C10 may be, for example: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, and the like.
The hydrocarbon group of C1 to C6 may be selected from the specific examples of the alkyl group mentioned above and satisfy the respective limitations.
The alkylamino group of C1-C6 may be an alkylamino group formed by the above-mentioned specific examples satisfying the alkyl group defined by 1-6 carbon atoms.
The alkoxy group having C1 to C6 may be an alkoxy group formed by the above-mentioned specific examples of the alkyl group satisfying the definition of 1 to 6 carbon atoms.
The nitrogen-containing heterocyclic ring having 2 to 10 carbon atoms may be an unsaturated nitrogen heterocyclic ring or a saturated nitrogen heterocyclic ring as long as the nitrogen is a structural atom in the ring structure of the heterocyclic ring and the number of carbon atoms of the heterocyclic ring is 2 to 10, and may be, for example, unsubstituted or C1-C6 alkyl-substituted pyrrole, unsubstituted or C1-C6 alkyl-substituted hydrogenated pyrrole, unsubstituted or C1-C7 alkyl-substituted imidazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated imidazole, unsubstituted or C1-C5 alkyl-substituted pyridine, unsubstituted or C1-C5 alkyl-substituted hydrogenated pyridine, unsubstituted or C1-C7 alkyl-substituted pyrazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated pyrazole, unsubstituted or C1-C7 alkyl-substituted thiazole, Unsubstituted or C1-C7 alkyl substituted hydrogenated thiazoles, unsubstituted or C1-C7 alkyl substituted oxazoles, unsubstituted or C1-C7 alkyl substituted hydrogenated oxazoles, and the like. The alkyl group as the substituent may be selected from the specific examples of the alkyl group described above, and the substitution of the alkyl group may be single-point or multi-point, and the present invention is not particularly limited thereto.
The oxygen-containing heterocyclic ring having 2 to 10 carbon atoms may be an unsaturated heterocyclic ring or a saturated heterocyclic ring as long as the ring structure of the heterocyclic ring has oxygen as a structural atom and the number of carbon atoms of the heterocyclic ring is 2 to 10, and may be, for example, unsubstituted or C1-C6 alkyl-substituted furan, unsubstituted or C1-C6 alkyl-substituted hydrogenated furan, unsubstituted or C1-C7 alkyl-substituted oxazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated oxazole, unsubstituted or C1-C3 alkyl-substituted 1, 3-benzodioxole, unsubstituted or C1-C2 alkyl-substituted 1, 4-benzodioxole, or the like.
The sulfur-containing heterocyclic ring having 2 to 10 carbon atoms may be an unsaturated sulfur heterocyclic ring or a saturated sulfur heterocyclic ring, as long as sulfur is a structural atom in the ring structure of the heterocyclic ring and the number of carbon atoms of the heterocyclic ring is 2 to 10, and for example, it may be unsubstituted or C1-C6 alkyl-substituted thiophene, unsubstituted or C1-C6 alkyl-substituted hydrogenated thiophene, unsubstituted or C1-C7 alkyl-substituted thiazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated thiazole, or the like.
Wherein R in the formula2、R3They may be the same or different and may be selected independently of each other.
Preferably, R1Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthryl group, a substituted or unsubstituted phenanthryl group, a nitrogen-containing heterocyclic ring having 2 to 8 carbon atoms, an oxygen-containing heterocyclic ring having 2 to 8 carbon atoms, a sulfur-containing heterocyclic ring having 2 to 8 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is respectively and independently selected from one or more of hydroxyl, F, Cl, Br, I, cyano, nitro, trifluoromethyl, trifluoromethoxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy and n-pentoxy C1-C5 alkylamino;
R2、R3is independently selected from alkyl of C1-C8, alkenyl of C2-C8, alkynyl of C2-C8, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted anthryl, substituted or unsubstituted phenanthryl, nitrogen-containing heterocycle containing 2-8 carbon atoms, oxygen-containing heterocycle containing 2-8 carbon atoms, sulfur-containing heterocycle containing 2-8 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from one or more of hydroxyl, F, C1, Br, I, cyano, nitro, trifluoromethyl, trifluoromethoxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy and alkylamino of C1-C5.
In a preferred embodiment of the present invention, the compound represented by the general formula (xxxv) is one selected from the group consisting of compounds represented by the following formulae:
(S, E) -N' - (4-chlorobenzylidene) -5-phenyl-3-p-tolueneSulfonyl-1, 2, 3, 6-tetrahydroazepinesAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-1);
(S, E) -N' - (4-Chlorobenzylidene) -5- (4-methoxyphenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-2);
(S, E) -N' - (4-Chlorobenzylidene) -5- (4-chlorophenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-3);
(S, E) -N' -benzylidene-5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-4);
(S, E) -N' - (4-Nitrophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-5);
(S, E) -N' - (4-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-6);
(S, E) -N' - (3-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-7);
(S,E) -N' - (2-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-8);
(S, E) -N' - (3-nitrophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-9);
(S, E) -N' - (4-cyanophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-10);
(S, E) -N' - (4-tert-butylbenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-11);
(S, E) -N' - (4-dimethylaminobenzenemethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-12);
(S, E) -N '- (1, 1' -biphenyl-4-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-13);
(S, E) -N' - (3-Chlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-14);
(S, E) -N' - (2-Chlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-15);
(S, E) -N' - (2, 4-dichlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-16);
(S, E) -N' - (3, 4-dichlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-17);
(S, E) -N' - (3, 4-dimethoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-18);
(S, E) -N' - (benzo [ d ]][1,3]Dioxymethylene-5-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-19);
(S, E) -N' - (2, 3-dihydrobenzo [ b ]][1,4]Dioxin-6-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-20);
(S, E) -N' - (3, 5-di-tert-butyl-4-hydroxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-21);
(S, E) -N' - (2, 2-dimethylpropenyl) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-22);
(S, E) -N' - (4-bromo-2, 6-difluorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-23);
(S, E) -5-phenyl-N' - (pyridine-3-methylene) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-24);
(S, E) -5-phenyl-N' - (thiophene-2-methylene) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-25);
(S, E) -N' - (pyrrole-2-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-26);
(S, E) -N' -octenyl-5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-27).
The invention provides a tetrahydroazepine as defined aboveAnd [4, 5-b ]]A process for the preparation of an indolylhydrazone derivative which comprises: first, L-tryptophan in SOCl2Esterification reaction is carried out on the L-tryptophan methyl ester and methanol under catalysis to generate L-tryptophan methyl ester (I), Ts protecting group on the L-tryptophan methyl ester forms II under the alkaline condition of triethylamine, the II respectively carries out nucleophilic substitution on the L-tryptophan methyl ester and alpha-bromoacetophenone to generate III, then dehydration condensation cyclization rearrangement is carried out under the catalysis of trifluoromethanesulfonic acid to generate corresponding IV, hydrazinolysis is carried out on the IV to generate corresponding hydrazide V, and the intermediate V respectively carries out aldehyde condensation to obtain tetrahydroazepine shown in the general formulaAnd [4, 5-b ]]Indole acylhydrazone compounds;
wherein R is1、R2、R3As described above, the present invention is not described in detail herein.
The present invention provides the above tetrahydroazepineAnd [4, 5-b ]]The application of indole acylhydrazone derivatives in the aspect of anti-plant virus activity.
The invention provides tetrahydroazepineAnd [4, 5-b ]]The indoxyl hydrazone derivative has excellent plant virus resisting activity, can well inhibit tobacco mosaic virus, pepper virus, rice virus, tomato virus, sweet potato virus, melon virus, corn dwarf mosaic virus and the like, can effectively prevent and treat virus diseases of various crops such as tobacco, pepper, rice, tomato, melon and vegetable, grain, vegetable, bean and the like, and is particularly suitable for preventing and treating the tobacco mosaic virus. Tetrahydroazepines of general formulaAnd [4, 5-b ]]The indolylhydrazone derivative has good activity of resisting Tobacco Mosaic Virus (TMV).
The invention provides tetrahydroazepineAnd [4, 5-b ]]The indolylhydrazone derivative can be directly used as a plant virus inhibitor, can be added with an agriculturally acceptable carrier for use, and can also be used together with other plant virus resisting agents, such as diazosulfide (BTH), Tiadinil (TDL), 4-methyl-1, 2, 3-thiadiazole-5-formic acid (TDLA), DL-beta-aminobutyric acid (BABA), ribavirin, ningnanmycin, phenanthroindolizidine alkaloid antofine, bitriazole compounds XY-13 and XY-30, virus A, salicylic acid, polyhydroxy dinaphthalene aldehyde and amino-oligosaccharin to form an interactive composition, and the compositions have synergistic effect and have additive effect.
The tetrahydroazepine of the present invention is useful for obtaining a high activity against plant virusesAnd [4, 5-b ]]The indole acylhydrazone derivative is preferably selected from one or more of the following compounds:
(S, E) -N' - (3-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-7);
(S, E) -N' - (2-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-8);
(S, E) -N '- (1, 1' -biphenyl-4-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-13);
(S, E) -N' - (2, 3-dihydrobenzo [ b ]][1,4]Dioxin-6-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-20);
(S, E) -N' - (4-bromo-2, 6-difluorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-23).
The invention also provides a method for preparing the tetrahydroazepineAnd [4, 5-b ]]Indole acylhydrazone derivatives as plant virus inhibitors are useful in methods for combating plant viruses.
The present invention provides the above tetrahydroazepineAnd [4, 5-b ]]The indole acylhydrazone derivatives are applied to sterilization.
The invention provides tetrahydroazepineAnd [4, 5-b ]]The indole acylhydrazone derivatives have high bactericidal activity, and particularly aim at one or more of pathogenic bacteria causing cucumber wilt, peanut brown spot, apple ring spot, tomato early blight, wheat scab, potato late blight, rape sclerotium, cucumber gray mold, rice sheath blight, phytophthora capsici, rice bakanae, wheat sheath blight, corn speckles and watermelon anthracnose.
In particular, the tetrahydroazepines of the inventionAnd [4, 5-b ]]The indole acylhydrazone derivative shows broad-spectrum bactericidal activity, the inhibition rates of part of target compounds on peanut brown spots, wheat sharp eyedrops, rice seedlings and rape sclerotia are higher, the inhibition rates of the compound VI-20 on peanut brown spots, wheat sharp eyedrops and rice seedlings are respectively 73.7%, 77.8% and 81.8% inhibition rates (50 mg/L), and the inhibition effect on the rice seedlings is stronger than that of control sample chlorothalonil; the inhibition rates of the compounds VI-4, VI-13 and VI-24 on wheat sharp eyespot are 72.2%, 87.0% and 70.4% respectively; inhibition of rape sclerotia by compounds VI-18 and VI-27 at a concentration of 50 mg/L: 70.7 percent and 65.9 percent.
The invention provides tetrahydroazepineAnd [4, 5-b ]]The indole acylhydrazone derivatives have high insecticidal activity, and particularly have high insecticidal activity on one or more of tetranychus cinnabarinus, diamondback moth, armyworm, mosquito larvae, cotton bollworm and corn borer.
In particular, the tetrahydroazepines of the inventionAnd [4, 5-b ]]The indoxyl hydrazone derivative has excellent insecticidal activity on diamondback moths, particularly, the lethality rates of VI-22, VI-13 and VI-11 to the diamondback moths are respectively 85 percent, 80 percent and 80 percent even under the condition of low concentration of 100mg/L, but no obvious activity rule exists. Some compounds have higher activity on armyworm, such as VI-26, the lethality rate of which to armyworm is 50% at 200 mg/L.
The tetrahydroazepine provided by the inventionAnd [4, 5-b ]]The indoxyl hydrazone derivative can be directly used as an insecticidal bactericide, can be added with an agriculturally acceptable carrier for use, and can also be used in combination with other insecticidal and acaricidal bactericides such as tebufenpyrad, chlorfenapyr, etoxazole, fenpyroximate and the like, and the compositions have synergistic effects and additive effects.
The invention also provides a method for preparing the tetrahydroazepineAnd [4, 5-b ]]Indole acylhydrazone derivatives are useful as pesticides for pesticidal methods.
The invention also provides a method for preparing the tetrahydroazepineAnd [4, 5-b ]]Indole acylhydrazone derivatives are used as bactericide for sterilization.
The following examples and biological test results are provided to further illustrate the invention and are not meant to limit the invention.
L-Tryptophan methyl ester (I)
A250 mL round-bottom flask was charged with 10.31g (50mmol) of L-tryptophan, 150mL of anhydrous methanol, and 10mL of thionyl chloride was slowly added under ice-water bath conditions. After the dripping is finished, the solution is clarified, heated and refluxed for 5h, and is desolventized after TLC detection reaction is completed, a saturated sodium carbonate solution is washed, ethyl acetate (50mL multiplied by 3) is used for extraction, saturated saline solution is washed for three times, anhydrous sodium sulfate is dried, suction filtration is carried out, rotary evaporation is carried out, 10.51g of brown solid is obtained, and the yield is 96%. Melting point: 90-91 ℃.1H NMR(400MHz,CDCl3)δ8.65 (s,1H,Ar-NH),7.60(d,J=8.0Hz,1H,Ar-H),7.29(d,J=8.0Hz,1H,Ar-H),7.16(t,J=7.2Hz, 1H,Ar-H),7.10(t,J=7.2Hz,1H,Ar-H),6.95(d,J=2.4Hz,1H,C=CH),3.84(dd,J=8.0,4.8Hz, 1H,-CH-NH2),3.70(s,3H,-OCH3),3.27(dd,J=14.4,4.8Hz,1H,-CH-CH2),3.04(dd,J=14.4,4.8Hz,1H,-CH-CH2),1.58(s,2H,NH2).13C NMR(100MHz,CDCl3)δ175.9,136.4,127.4, 123.2,122.1,119.4,118.7,111.4,110.8,54.9,52.1,30.8.
N-Ts protected L-tryptophan methyl ester (II)
Adding 8.63g (39.5mmol) of L-tryptophan methyl ester, 120mL of anhydrous dichloromethane, 11mL (79mmol) of triethylamine and 7.69g (59.3mmol) of p-toluenesulfonyl chloride into a 500mL round-bottom flask, reacting at room temperature for 1.5h-2h, adding water to quench the reaction after the TLC detection reaction is finished, extracting with ethyl acetate for multiple times, and performing reduced-pressure desolventizing column chromatography to obtain 9.63g of a white solid, wherein the yield is 66%, and the melting point: 100-101 ℃.1H NMR(400MHz,CDCl3)δ8.09(s,1H,Ar-NH),7.60(d,J=8.4Hz,2H,Ar-H), 7.43(d,J=8.0Hz,1H,Ar-H),7.32(d,J=8.0Hz,1H,Ar-H),7.22-7.14(m,3H,Ar-H),7.06(t,J =7.2Hz,1H,Ar-H),7.02(d,J=2.4Hz,1H,C=CH),5.12(d,J=9.2Hz,1H,NH-Ts),4.29-4.17 (m,1H,-CH-CH2),3.43(s,3H,-OCH3),3.23(d,J=5.6Hz,2H,-CH-CH2),2.37(s,3H,-CH3).13C NMR(100MHz,CDCl3)δ171.8,143.5,136.4,136.1,129.5,127.1,123.6,122.1,119.6, 118.4,111.4,108.8,56.0,52.5,29.2,21.5.
III-1 Synthesis method
Synthesis example of III-1: adding 1.86g (5mmol) of II, 10mL of DMF, adding 1.04g (7.5mmol) of anhydrous potassium carbonate into a 100mL round-bottom flask, stirring for 0.5h under the condition of ice-water bath, adding 1.19g (6mmol) of alpha-bromoacetophenone, reacting for 1.5-2h, quenching with water, extracting with ethyl acetate (50mL multiplied by 3), washing with saturated ammonium chloride solution, drying with anhydrous sodium sulfate, desolventizing under reduced pressure, and performing column chromatography: PE: EA system gave III-1.
(S) -methyl 3- (1H-indole-3) -2- (4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide) propionate (III-1)
Yellow solid, yield 80%, melting point: : 118 ℃ and 120 ℃.1H NMR(400MHz,CDCl3)δ7.99-7.93(m,3H),7.84 (d,J=8.4Hz,2H),7.60(t,J=7.6Hz,1H),7.50(t,J=7.6Hz,2H),7.41(d,J=8.0Hz,1H),7.31 (d,J=8.0Hz,1H),7.24(d,J=8.0Hz,2H),7.17(t,J=7.2Hz,1H),7.10-7.05(m,1H),6.95(d,J=2.4Hz,1H),5.11(d,J=1.6Hz,2H),4.65(dd,J=9.7,5.3Hz,1H),3.42(s,3H),3.24(dd,J= 14.0,9.6Hz,1H),3.14(dd,J=14.0,5.2Hz,1H),2.41(s,3H).13C NMR(100MHz,DMSO)δ 189.1,166.1,138.5,131.3,130.9,129.8,128.4,124.1,123.6,122.9,122.8,121.7,118.1,116.8, 114.3,113.1,106.1,104.3,54.0,46.8,44.8,21.6,16.4.
Compounds III-2 to III-3 were prepared by repeating the procedure of III-1.
The characterization results of the obtained compounds are shown below:
(S) -methyl 3- (1H-indole-3) -2- (N-2- (4-methoxyphenyl) -2-oxoethyl) -4-methylbenzenesulfonamide) propionate (III-2)
Yellow solid, yield 67%, melting point: 100-102 ℃.1H NMR(400MHz,CDCl3)δ8.12(s,1H),7.94(d,J =8.0Hz,2H),7.83(d,J=7.6Hz,2H),7.39(d,J=7.6Hz,1H),7.28(d,J=8.0Hz,1H),7.21(d,J =8.0Hz,2H),7.14(t,J=7.6Hz,1H),7.05(t,J=7.6Hz,1H),6.96-6.90(m,3H),5.06(s,2H), 4.64(dd,J=9.6,5.2Hz,1H),3.87(s,3H),3.39(s,3H),3.23(dd,J=14.0,9.6Hz,1H),3.13(dd,J =14.0,5.2Hz,1H),2.38(s,3H).13C NMR(100MHz,CDCl3)δ192.7,171.3,163.9,143.6,136.6, 136.1,130.3,129.3,128.1,128.1,127.0,123.4,122.0,119.5,118.4,114.0,111.2,109.8,59.3,55.6, 52.0,49.7,26.8,21.6.
(S) -2- (N-2- (4-chlorophenyl) -2-oxoethyl) -4-methylbenzenesulfonamide) -3- (1H-indole-3) -propionic acid methyl ester (III-3)
White solid, yield 62%, melting point: 80-81 ℃.1H NMR(400MHz,CDCl3)δ7.96(s,1H),7.90(d,J=8.8 Hz,2H),7.82(d,J=8.4Hz,2H),7.46(d,J=8.8Hz,2H),7.40(d,J=8.0Hz,1H),7.31(d,J=8.4 Hz,1H),7.24(d,J=8.0Hz,2H),7.17(t,J=7.2Hz,1H),7.08(t,J=7.2Hz,1H),6.95(d,J=2.4 Hz,1H),5.05(s,2H),4.64(dd,J=9.6,5.6Hz,1H),3.42(s,3H),3.23(dd,J=14.0,9.6Hz,1H), 3.13(dd,J=14.0,5.2Hz,1H),2.41(s,3H).13C NMR(100MHz,CDCl3)δ193.2,171.3,143.7, 140.1,136.4,136.1,133.4,129.4,129.4,129.1,128.1,127.0,123.2,122.1,119.6,118.4,111.2, 109.7,59.1,52.1,49.9,26.8,21.6.
(S) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Synthesis method of indole-2-methyl formate (IV-1)
Adding 4.03g of III-1 crude product and 100mL of 1, 2-dichloroethane into a 100mL round-bottom flask, adding 0.2 equivalent of trifluoromethanesulfonic acid, reacting for 2 hours at room temperature, detecting the reaction, performing desolventization under reduced pressure, adding water and dichloromethane, extracting for three times, washing with saturated saline solution for three times, drying with anhydrous sodium sulfate, and performing vacuum filtration, desolventization and column chromatography. Yellow solid, yield 84%, melting point: 88-90 ℃.1H NMR (400MHz,CDCl3)δ7.75(d,J=8.4Hz,2H),7.52(s,1H),7.48-7.38(m,6H),7.32(d,J=8.0Hz, 2H),7.15-7.03(m,3H),6.98(d,J=0.4Hz,1H),5.57(t,J=3.6Hz,1H),3.92(dd,J=16.0,4.8 Hz,1H),3.28(s,3H),2.79(dd,J=16.0,3.2Hz,1H),2.42(s,3H).13C NMR(100MHz,CDCl3)δ 168.0,144.4,138.7,135.6,135.1,131.2,130.0,129.7,129.0,128.4,128.0,127.3,124.4,122.4,119.7,117.7,116.5,110.7,110.6,57.6,52.2,28.3,21.7.
Compounds IV-2 to IV-3 were prepared by repeating the procedure of IV-1.
The characterization results of the obtained compounds are shown below:
(S) -5- (4-methoxyphenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid methyl ester (IV-2)
Yellow solid, yield 65%, melting point: 95-97 ℃.1H NMR(400MHz,CDCl3)δ7.74(d,J=8.0Hz,2H),7.56 (s,1H),7.46(d,J=7.6Hz,1H),7.31(t,J=8.4Hz,4H),7.14-7.03(m,3H),6.96(d,J=8.4Hz, 2H),6.93(s,1H),5.56(s,1H),3.90(dd,J=16.0,4.8Hz,1H),3.86(s,3H),3.27(s,3H),2.77(dd,J =16.0,2.4Hz,1H),2.40(s,3H).13C NMR(100MHz,CDCl3)δ168.1,159.5,144.3,135.7,135.1, 131.6,130.9,130.9,129.9,128.5,127.3,124.0,122.3,119.7,117.7,116.3,114.3,110.7,110.5,57.7, 55.4,52.2,28.2,21.6.
(S) -5- (4-chlorophenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid methyl ester (IV-3)
Yellow solid, yield 68%, melting point: 94-96 ℃.1H NMR(400MHz,CDCl3)δ7.73(d,J=8.4Hz,2H),7.52 (s,1H),7.46(d,J=7.2Hz,1H),7.44-7.38(m,2H),7.37-7.29(m,4H),7.16-7.04(m,3H), 6.97(s,1H),5.59-5.51(m,1H),3.91(dd,J=16.0,5.2Hz,1H),3.24(s,3H),2.76(dd,J=16.0, 2.8Hz,1H),2.41(s,3H).13C NMR(100MHz,CDCl3)δ167.9,144.6,137.2,135.4,135.2,134.0, 131.0,130.9,130.0,129.2,128.4,127.3,124.5,122.5,119.9,117.7,115.0,110.9,110.8,57.7,52.2, 28.3,21.7.
(S) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Synthesis method of indole-2-formylhydrazine (V-1)
Adding IV-10.5 g, 8mL of absolute ethyl alcohol and 20mL of hydrazine hydrate at room temperature, reacting for 4-5h to generate white precipitate, filtering and drying to obtain 0.4g of white solid, wherein the yield is 80%, and the melting point is as follows: 135 ℃ and 137 ℃.1H NMR(400MHz,DMSO-d6)δ10.04(s,1H), 9.12(s,1H),7.73(d,J=7.2Hz,2H),7.54-7.34(m,8H),7.24(d,J=7.6Hz,1H),7.05-6.82(m, 3H),5.27(s,1H),3.98(s,2H),3.79(d,J=11.2Hz,1H),2.36(s,3H),2.29(d,J=15.6Hz,1H). 13C NMR(100MHz,DMSO-d6)δ166.1,144.3,139.2,135.8,134.7,131.1,130.1,129.1,128.6, 127.9,127.5,127.0,124.2,121.2,118.6,117.4,111.5,110.3,58.9,26.9,21.0.HRMS(ESI)calcd for C26H24N4O3S(M+H)+473.1647,found 473.1639.
Compounds V-2 to V-3 were prepared by repeating the procedure for V-1.
The characterization results of the obtained compounds are shown below:
(S) -5- (4-methoxyphenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (V-2)
Yellow solid, yield 35%, melting point: 150 ℃ and 152 ℃.1H NMR(400MHz,DMSO-d6)δ10.00(s,1H),9.09(s, 1H),7.70(d,J=8.0Hz,2H),7.39(d,J=7.6Hz,3H),7.34(d,J=8.0Hz,2H),7.22(d,J=7.6Hz, 1H),7.04(d,J=8.4Hz,2H),6.95(dt,J=14.8,6.8Hz,2H),6.84(s,1H),5.26(s,1H),4.00(s,2H), 3.82(s,3H),3.74(dd,J=15.6,5.2Hz,1H),2.35(s,3H),2.28(d,J=14.8Hz,1H).13C NMR(100 MHz,DMSO-d6)δ166.2,158.8,144.2,135.8,134.8,131.5,131.3,130.3,130.,127.8,126.9,123.4, 121.2,118.6,117.6,117.4,114.0,111.5,110.1,59.2,55.2,26.8,21.0.HRMS(ESI)calcd for C27H26N4O4S(M+H)+503.1753,found 503.1746.
(S) -5- (4-chlorophenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd 24,5-b]Indole-2-formyl hydrazine (V-3)
Yellow solid, yield 32%, melting point: 144 ℃ and 145 ℃.1H NMR(400MHz,DMSO-d6)δ10.07(s,1H),9.09(s, 1H),7.74(d,J=8.4Hz,2H),7.54(d,J=8.8Hz,2H),7.43(d,J=8.4Hz,4H),7.37(d,J=8.0Hz, 1H),7.19(d,J=7.6Hz,1H),7.01-6.90(m,2H),6.89(s,1H),5.24(d,J=2.8Hz,1H),3.95(s, 2H),3.78(dd,J=16.0,5.2Hz,1H),2.37(s,3H),2.21(dd,J=16.0,2.8Hz,1H).13C NMR(100 MHz,DMSO-d6)δ165.9,144.4,138.0,135.8,134.5,132.2,131.1,130.8,130.2,128.6,127.9, 127.1,124.3,121.3,118.7,117.4,115.5,111.4,110.3,58.4,26.9,21.0.HRMS(ESI)calcd for C26H23ClN4O3S(M+H)+507.1257,found 507.1251.
Target compound (S, E) -N' - (4-chlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Synthesis of indole-2-formylhydrazine (VI-1)
0.4g V-1, 30mL of absolute ethyl alcohol and 1.5 equivalent of p-chlorobenzaldehyde are added into a 100mL round-bottom flask, the mixture is heated to 100 ℃ for reflux reaction for 12 hours, and after the reaction is completely monitored by TLC, decompression, desolventization and column chromatography are carried out. Pale yellow solid 0.42g, yield 83%, melting point: 147 ℃ and 149 ℃.1H NMR(400MHz,DMSO-d6)δ11.42,11.19(s,1H),10.27,10.15(s,1H), 8.19,7.89(s,1H),7.88-6.76(m,18H),6.07-6.01,5.45-5.40(m,1H),4.12,3.87(dd,J=15.6, 5.6Hz,1H),2.75-2.67,2.46-2.42(m,1H),2.40,2.37(s,3H).13C NMR(100MHz,DMSO-d6)δ 168.0,163.9,146.4,145.0,144.8,142.8,140.0,139.6,136.5,136.4,135.7,135.2,135.0,134.9, 133.5,133.4,132.8,131.9,130.7,129.7,129.5,129.3,129.1,129.0,128.2,128.1,127.9,127.8, 127.6,127.5,125.2,124.6,121.8,121.5,119.2,119.1,117.5,116.7,115.3,112.1,110.4,109.9,59.9, 27.6,27.3,21.6.HRMS(ESI)calcd for C33H27ClN4O3S(M+H)+595.1570,found 595.1564.
Compounds VI-2 to VI-27 were prepared by repeating the procedure of VI-1.
The characterization results of the obtained compounds are shown below:
(S, E) -N' - (4-Chlorobenzylidene) -5- (4-methoxyphenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-6 ]]Indole-2-formyl hydrazine (VI-2)
Light brown solid 0.30g, yield 60%, melting point: 240 ℃ and 242 ℃.1HNMR(400MHz,DMSO-d6)δ11.44,11.21 (s,1H),10.26,10.14(s,1H),8.22,7.91(s,1H),7.89-6.77(m,17H),6.07,5.44(s,1H),4.12(dd,J =15.2,5.6Hz,1H),3.83(s,3H),2.72,2.45(d,J=14.8Hz,1H),2.40,2.37(s,3H).13C NMR(100 MHz,DMSO-d6)δ168.1,164.0,163.2,159.4,159.2,144.7,142.7,136.42,136.37,135.8,135.0, 134.9,133.5,133.4,133.2,132.3,132.2,131.7,130.7,130.6,130.5,129.7,129.3,129.1,129.0, 128.1,127.8,127.5,127.4,124.3,123.8,121.7,121.4,119.2,119.1,117.9,117.58,117.56,116.7, 115.5,114.7,112.1,110.2,109.7,60.1,59.7,56.5,55.7,27.5,27.3,21.6,19.1.HRMS(ESI)calcd for C34H29ClN4O4S(M+H)+625.1676,found 625.1674.
(S, E) -N' - (4-Chlorobenzylidene) -5- (4-chlorophenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-3)
Pale yellow solid 0.39g, yield 79%, melting point: 153-155 ℃.1H NMR(400MHz,DMSO-d6)δ11.42,11.19 (s,1H),10.33,10.21(s,1H),8.25-6.76(m,18H),6.05(d,J=2.8Hz,0.6H),5.44(s,0.4H),4.15, 3.91(dd,J=15.6,5.6Hz,1H),2.70(d,J=14.0Hz,1H),2.41(s,2H),2.38(s,1H).13C NMR(100 MHz,DMSO-d6)δ167.8,163.7,146.5,145.1,144.9,142.8,138.9,138.5,136.5,136.4,135.6,135.04,134.98,133.5,133.4,132.8,132.5,131.7,131.5,131.1,130.7,129.7,129.3,129.2,129.1, 129.0,128.2,127.8,127.6,127.5,125.3,124.7,121.9,121.6,119.3,119.2,117.6,116.7,115.8, 113.8,112.0,110.4,109.9,59.5,59.4,27.7,27.4,21.6.HRMS(ESI)calcd for C33H26ClN4O3S (M+H)+629.1181,found 629.1171.
(S, E) -N' -benzylidene-5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-4)
Yellow solid 0.41g, yield 88%, melting point: 222 ℃ and 224 ℃.1H NMR(400MHz,DMSO-d6)δ11.35,11.12 (s,1H,Ar-NH),10.28,10.15(s,1H,-NH-N),8.21-6.72(m,20H,Ar-H),6.04,5.42(m,1H, -CH-CH2),4.14,3.88(dd,J=15.6,5.6Hz,1H,-CH-CH2),2.70,2.39(dd,J=15.6,5.6Hz,1H, -CH-CH2),2.40,2.38(s,3H,CH3).13C NMR(100MHz,DMSO-d6)δ167.9,163.7,147.7,145.0, 144.8,144.0,140.0,139.6,136.5,136.4,135.7,135.2,134.6,134.4,133.4,132.8,131.9,130.7, 130.6,130.5,129.7,129.6,129.5,129.3,129.2,129.1,128.2,128.1,127.9,127.8,127.6,127.49, 127.45,127.4,125.2,124.6,121.7,121.5,119.2,119.1,117.5,117.4,116.6,115.2,112.1,110.3, 109.9,59.9,59.8,27.6,27.2,22.7,21.6.HRMS(ESI)calcd for C33H28N4O3S(M+H)+561.1960, found 561.1954.
(S, E) -N' - (4-Nitrophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-5)
Yellow solid 0.43g, yield 84%, melting point: 155 ℃ and 157 ℃.1H NMR(400MHz,DMSO-d6)δ11.69,11.44(s, 1H),10.29,10.16(s,1H),8.42-6.74(m,19H),6.08,5.45(dd,J=4.8,2.4Hz,1H),4.13,3.89(dd, J=16.0,5.6Hz,1H),2.72(dd,J=16.0,2.4Hz,1H),2.40,2.38(s,3H).13C NMR(100MHz, DMSO-d6)δ167.7,163.7,147.9,147.8,144.7,144.5,144.4,141.3,140.2,139.5,139.1,136.0, 135.9,135.1,134.6,132.2,131.4,130.2,129.0,128.8,127.9,127.8,127.6,127.4,127.2,127.0, 126.9,124.6,124.3,124.0,123.9,121.3,121.0,118.71,118.67,117.04,117.01,116.2,114.8,111.6, 109.8,109.3,59.4,59.3,27.1,26.9,21.1.HRMS(ESI)calcd for C33H27N5O5S(M+H)+606.1811, found 606.1809.
(S, E) -N' - (4-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-6)
Pale yellow solid 0.46g, yield 92%, melting point: 232 ℃ and 234 ℃.1H NMR(400MHz,DMSO-d6)δ11.20,10.99 (s,1H),10.28,10.15(s,1H),8.11,7.82(s,1H),7.77(t,J=8.8Hz,3H),7.52-6.75(m,15H),6.01,5.39(s,1H),4.14(dd,J=15.6,5.6Hz,1H),3.86(s,2H),3.76(s,1H),2.67(d,J=14.8Hz,1H), 2.40,2.38(s,3H).13C NMR(100MHz,DMSO-d6)δ167.2,163.04,163.01,160.9,160.8,147.2, 144.5,144.4,143.4,139.6,139.2,136.0,135.3,134.7,132.3,131.5,130.3,129.6,129.1,128.8, 128.6,128.5,127.7,127.6,127.6,127.4,127.4,127.1,127.0,126.7,126.5,126.5,124.8,124.2, 121.3,121.0,118.74,118.66,117.11,117.08,116.9,116.2,114.7,114.6,114.2,111.7,110.0,109.5, 59.5,59.3,55.4,55.3,27.2,26.8,21.1.HRMS(ESI)calcd for C34H30N4O4S(M+H)+591.2066, found 591.2066.
(S, E) -N' - (3-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-7)
Yellow solid 0.40g, yield 80%, melting point: 230 ℃ and 232 ℃.1H NMR(400MHz,DMSO-d6)δ11.38,11.19(s,1H),10.30,10.17(s,1H),8.18,7.89(s,1H),7.84-6.75(m,18H),6.04,5.45(s,1H),4.10,3.92(dd, J=15.2,5.2Hz,1H),3.86,3.73(s,3H),2.70,2.45 (d,J=15.2Hz,1H),2.38(d,J=6.0Hz,3H).13C NMR(100MHz,DMSO-d6)δ168.0,163.7, 160.2,159.9,147.6,145.0,144.8,143.7,140.0,139.7,136.5,136.4,136.0,135.9,135.6,135.2, 132.8,132.0,130.7,130.7,130.3,129.6,129.2,128.2,128.1,127.9,127.8,127.6,127.5,125.2, 124.6,121.8,121.5,120.6,119.9,119.1,117.5,117.3,116.9,116.7,116.4,115.7,112.2,112.1, 111.2,110.3,110.0,60.1,59.7,55.6,55.5,27.7,27.1,21.6.HRMS(ESI)calcd for C34H30N4O4S (M+H)+591.2066,found 591.2063.
(S, E) -N' - (2-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-8)
Yellow solid 0.42g, yield 84%, melting point: 134 ℃ and 136 ℃.1H NMR(400MHz,DMSO-d6)δ11.38,11.10 (s,1H),10.29,10.16(s,1H),8.57,8.24(s,1H),8.06-6.75(m,18H),6.05,5.40(d,J=3.0Hz,1H), 4.16(dd,J=15.6,5.6Hz,0.6H),3.91(dd,J=9.6,5.6Hz,0.4H),3.86,3.85(s,3H),2.71,2.42(dd, J=15.2,2.0Hz,1H),2.39,2.37(s,3H).13C NMR(100MHz,DMSO-d6)δ167.8,163.6,158.2,158.1,144.8,143.2,140.0,139.8,139.6,136.5,136.4,135.7,135.2,132.8,132.0,131.9,130.8, 130.7,129.6,129.3,128.2,128.1,127.9,127.8,127.6,127.5,125.9,125.8,125.2,124.7,122.6, 122.4,121.8,121.54,121.49,121.1,119.2,119.1,117.6,117.5,116.7,115.3,112.5,112.2,112.1, 110.5,109.9,59.9,59.8,56.2,56.1,27.5,27.2,21.6.HRMS(ESI)calcd for C34H30N4O4S(M+H)+ 591.2066,found 591.2063.
(S, E) -N' - (3-nitrophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-9)
Dark yellow solid 0.43g, yield 84%, melting point: 249 ℃ and 252 ℃.1H NMR(400MHz,DMSO-d6)δ11.66,11.43 (s,1H),10.31,10.18(s,1H),8.68-6.73(m,19H),6.11,5.49(s,1H),4.08,3.92(d,J=12.0Hz, 1H),2.70,2.45(d,J=15.2Hz,1H),2.40,2.38(s,3H).13C NMR(100MHz,DMSO-d6)δ168.3, 164.2,148.9,148.6,145.3,145.0,144.9,141.8,139.9,139.6,136.5,136.4,136.3,136.2,135.5, 135.2,133.7,133.4,132.8,132.0,131.1,130.8,130.7,129.5,129.3,128.1,127.9,127.8,127.5, 127.4,125.1,124.8,124.7,124.6,121.8,121.7,121.5,121.4,119.2,117.5,116.7,115.7,112.1, 110.3,109.9,59.9,27.7,27.2,21.6.HRMS(ESI)calcd for C33H27N5O5S(M+H)+606.1811,found 606.1806.
(S, E) -N' - (4-cyanophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-10)
Yellow solid 0.41g, yield 83%, melting point: 157 ℃ and 159 ℃.1H NMR(400MHz,DMSO-d6)δ11.64,11.40(s, 1H),10.31,10.18(s,1H),8.31-6.75(m,19H),6.10,5.48(s,1H),4.14,3.92(dd,J=15.2,5.2Hz, 1H),2.75,2.47(d,J=15.2Hz,1H),2.40,2.38(s,3H).13C NMR(100MHz,DMSO-d6)δ168.2,164.1,145.8,145.0,144.9,142.2,140.0,139.6,139.0,138.9,136.5,135.7,135.1,133.5,133.1, 132.8,131.9,130.7,129.5,129.3,128.1,128.0,127.9,127.7,127.5,125.1,124.5,121.8,121.5, 119.22,119.17,117.5,116.7,115.3,112.42,112.36,112.1,110.3,109.8,59.9,27.6,27.4,21.6. HRMS(ESI)calcd for C34H27N5O3S(M+H)+586.1913,found 586.1914.
(S, E) -N' - (4-tert-butylbenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-11)
Yellow solid 0.43g, yield 83%, melting point: 150 ℃ and 152 ℃.1H NMR(400MHz,DMSO-d6)δ11.28,11.07(s, 1H),10.28,10.15(s,1H),8.15,7.86(s,1H),7.81-6.77(m,18H),6.02,5.40(d,J=2.8Hz,1H), 4.12,3.87(dd,J=15.6,5.6Hz,1H),2.67(d,J=13.6Hz,1H),2.40(s,2H),2.38(s,1H),1.35(s, 6H),1.25(s,3H).13C NMR(100MHz,DMSO-d6)δ167.9,163.6,153.3,147.7,144.9,144.8,143.9, 140.0,139.6,136.5,135.7,135.2,132.8,131.9,131.9,131.7,130.7,129.5,129.3,128.2,128.1, 127.8,127.6,127.5,127.3,127.2,126.4,126.0,125.2,124.6,121.8,121.5,119.2,119.1,117.5, 116.6,115.3,112.1,110.4,109.9,59.9,35.1,35.0,31.5,27.7,27.2,21.6.HRMS(ESI)calcd for C37H36N4O3S(M+H)+617.2586,found 617.2578.
(S, E) -N' - (4-dimethylaminobenzenemethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-12)
Dark yellow solid 0.35g, yield 68%, melting point: 146 ℃ and 148 ℃.1H NMR(400MHz,DMSO-d6)δ11.01,10.83 (s,1H),10.27,10.15(s,1H),8.06-6.61(m,19H),6.02,5.40(s,1H), 4.19,3.88(d,J=11.2Hz,1H),3.01,2.91(s,6H),2.68(d,J=15.2Hz,1H),2.39,2.37(s,3H).13C NMR(100MHz,DMSO-d6)δ167.4,163.2,152.0,144.9,144.8,144.7,140.1,139.7,136.5,136.4, 135.8,135.2,132.8,132.0,130.7,129.5,129.3,128.8,128.6,128.2,128.1,127.9,127.6,127.5, 125.3,124.7,122.0,121.73,121.69,121.5,119.2,119.1,117.6,117.5,116.7,115.3,112.5,112.1, 110.5,110.1,60.0,59.8,40.3,27.8,27.1,21.6.HRMS(ESI)calcd for C35H33N5O3S(M+H)+ 604.2382,found 604.2382.
(S, E) -N '- (1, 1' -biphenyl-4-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-13)
Yellow solid 0.42g, yield 78%, melting point: 153-155 ℃.1H NMR(400MHz,DMSO-d6)δ11.42,11.20(s, 1H),10.31,10.19(s,1H),8.25,7.96(s,1H),7.94-6.78(m,23H),6.15-6.04,5.50-5.37(m,1H), 4.19,3.92(dd,J=15.6,5.6Hz,1H),2.74,2.46(d,J=14.0Hz,1H),2.40,2.38(s,3H).13C NMR (100MHz,DMSO-d6)δ167.4,163.3,146.8,144.5,144.4,143.1,141.6,141.5,139.5,139.4,139.2, 139.1,136.0,135.9,135.2,134.7,133.2,133.0,132.3,131.5,130.2,129.1,129.0,128.8,128.7, 127.92,127.85,127.7,127.6,127.5,127.3,127.3,127.1,127.0,126.9,126.7,126.6,124.7,121.0, 118.71,118.66,117.1,117.0,116.2,114.7,111.6,109.9,109.4,59.4,27.1,26.8,21.1.HRMS(ESI) calcd for C39H32N4O3S(M+H)+637.2273,found 637.2267.
(S, E) -N' - (3-Chlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-14)
Pale yellow solid 0.39g, yield 79%, melting point: 247 ℃ and 249 ℃.1H NMR(400MHz,DMSO-d6)δ11.53,11.30 (s,1H),10.31,10.18(s,1H),8.20,7.91(s,1H),7.89-6.78(m,18H),6.08,5.46(s,1H),4.07, 3.91(dd,J=15.2,5.2Hz,1H),2.74(d,J=15.2Hz,0.6H),2.45(d,J=17.6Hz,0.4H),2.39,2.37(s, 3H).13C NMR(100MHz,DMSO-d6)δ167.7,163.5,145.5,144.5,144.3,142.0,139.4,139.1, 136.3,136.2,136.0,135.9,135.1,134.7,133.9,133.6,132.3,131.5,131.0,130.6,130.2,130.2, 129.7,129.6,129.0,128.8,128.7,127.7,127.6,127.4,127.3,127.0,126.3,126.2,125.7,125.5, 124.7,124.1,121.3,121.0,118.71,118.67,117.04,116.98,116.2,115.2,111.6,109.8,109.5,59.6, 59.3,27.1,26.7,21.1.HRMS(ESI)calcd for C33H27ClN4O3S(M+H)+595.1570,found 595.1563.
(S, E) -N' - (2-Chlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-15)
Yellow solid 0.46g, yield 92%, melting point: 132 ℃ and 134 ℃.1H NMR(400MHz,DMSO-d6)δ11.63,11.33(s,1H),10.31,10.17(s,1H),8.62,8.31(s,1H),8.25-6.76(m,18H),6.08,5.46(s,1H),4.14(d,J= 11.8Hz,0.6H),3.93(d,J=13.2Hz,0.4H),2.74(d,J=15.2Hz,0.6H),2.44(s,0.4H),2.39(s, 3H).13C NMR(100MHz,DMSO-d6)δ168.0,163.9,145.0,144.8,143.8,140.3,140.0,139.6, 136.5,136.5,135.7,135,1,133.6,132.8,132.0,131.9,131.8,131.7,130.7,130.6,130.3,129.5, 129.3,128.5,128.2,128.1,127.94,127.87,127.8,127.6,127.5,127.4,127.2,125.2,124.5,121.8, 121.6,119.2,117.6,116.7,115.4,112.1,110.5,109.9,59.9,27.5,27.4,21.6.HRMS(ESI)calcd for C33H27ClN4O3S(M+H)+595.1570,found 595.1568.
(S, E) -N' - (2, 4-dichlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-16)
Yellow solid 0.39g, yield 74%, melting point: 140 ℃ and 142 ℃.1H NMR(400MHz,DMSO-d6)δ11.65,11.36 (s,1H),10.29,10.16(s,1H),8.57,8.24(s,1H),8.22-6.77(m,17H),6.07,5.45(s,1H),4.16- 4.05,3.96-3.85(m,1H),2.73,2.42(d,J=15.2Hz,1H), 2.39,2.37(s,3H).13C NMR(100MHz,DMSO-d6)δ168.0,164.0,145.0,144.9,142.8,140.0,139.6, 139.4,136.5,136.4,135.7,135.6,135.6,135.1,134.2,132.8,131.8,130.9,130.8,130.7,130.1, 129.8,129.5,129.3,128.8,128.6,128.4,128.3,128.2,128.1,127.9,127.7,127.60,127.5,125.1, 124.5,121.8,121.6,119.2,117.70,117.65,116.7,115.4,112.1,110.5,109.8,60.0,59.8,27.4,21.6. HRMS(ESI)calcd for C33H26Cl2N4O3S(M+H)+629.1181,found 629.1175.
(S, E) -N' - (3, 4-dichlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-17)
Yellow solid 0.48g, yield 75%, melting point: 144 ℃ and 146 ℃.1H NMR(400MHz,DMSO-d6)δ11.59,11.33(s,1H),10.30,10.17(s,1H),8.18,8.04(s,1H),7.91-6.77(m,17H),6.06,5.45(d,J=2.8Hz,1H), 4.06,3.89(dd,J=15.6,5.6Hz,1H),2.72,2.44(d,J=14.0Hz,1H),2.39,2.37(s,3H).13C NMR (100MHz,DMSO-d6)δ167.7,163.5,144.5,144.4,141.0,139.4,139.1,136.0,135.9,135.1,134.9, 134.8,134.7,132.3,132.2,131.9,131.6,13113,130.9,130.2,130.2,129.0,128.8,128.7,128.6, 128.4,127.6,127.5,127.4,127.2,127.0,126.8,126.5,124.6,124.1,121.3,121.0,118.7,117.0,116.9,116.2,115.2,111.6,109.8,109.4,59.5,59.3,27.1,26.8,21.1.HRMS(ESI)calcd for C33H26Cl2N4O3S(M+H)+629.1181,found 629.1178.
(S, E) -N' - (3, 4-dimethoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-18)
Yellow solid 0.46g, yield 87%, melting point: 146 ℃ and 148 ℃.1H NMR(400MHz,DMSO-d6)δ11.19,11.04(s, 1H),10.27,10.13(s,1H),8.09,7.81(s,1H),7.80-6.76(m,17H),6.01-5.95,5.41-5.37(m,1H), 4.06(dd,J=15.2,5.6Hz,1H),3.87(s,2H),3.85(s,2H),3.76(s,1H),3.71(s,1H),2.61,2.41(dd, J=15.6,2.4Hz,1H),2.39(s,3H).13C NMR(100MHz,DMSO-d6)δ167.9,163.4,151.2,151.1,149.6,149.4,147.9,145.0,144.8,143.8,139.9,139.7,136.5,136.4,135.6,135.2,132.7,132.0, 130.7,130.6,129.6,129.3,129.2,128.2,128.1,127.9,127.8,127.6,127.5,127.4,127.1,125.2, 124.6,122.5,121.7,121.5,121.3,119.2,119.1,117.5,117.2,116.7,116.1,112.3,112.14,112.10, 111.7,110.3,110.2,109.2,108.2,60.2,59.5,56.1,56.0,55.8,55.7,27.7,27.0,21.5.HRMS(ESI) calcd for C35H32N4O5S(M+H)+621.2171,found 621.2165.
(S, E) -N' - (benzo [ d ]][1,3]Dioxymethylene-5-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-19)
Yellow solid 0.44g, yield 87%, melting point: 143 ℃ and 145 ℃.1H NMR(400MHz,DMSO-d6)δ11.23,11.00(s, 1H),10.26,10.14(s,1H),8.10-6.76(m,18H),6.16,6.03(d,J=2.8Hz,1H),6.03-5.99,5.41- 5.37(m,1H),4.10,3.86(dd,J=15.6,5.6Hz,1H),2.68,2.41(dd,J=15.6,2.4Hz,1H),2.39,2.37 (s,3H).13C NMR(100MHz,DMSO-d6)δ167.8,163.6,149.6,149.5,148.7,148.4,147.6,144.9, 144.8,143.7,140.0,139.6,136.5,136.4,135.7,135.2,132.7,131.9,130.7,130.6,129.5,129.3, 129.2,129.0,128.8,128.2,128.1,127.9,127.8,127.6,127.5,125.2,124.6,123.8,123.6,121.8,121.5,119.2,119.1,117.6,117.5,116.7,115.3,112.1,110.4,110.0,109.1,108.8,105.5,105.5, 102.1,102.0,60.0,59.8,27.7,27.2,21.6.HRMS(ESI)calcd for C34H28N4O5S(M+H)+605.1858, found 605.1852.
(S, E) -N' - (2, 3-dihydrobenzo [ b ]][1,4]Dioxin-6-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-20)
Yellow solid 0.35g, yield 85%, melting point: 148 ℃ and 150 ℃.1H NMR(400MHz,DMSO-d6)δ11.23,11.02(s, 1H),10.28,10.16(s,1H),8.07-6.77(m,18H),6.01,5.40(s,1H),4.34(s,3H),4.18(s,1H),4.09, 3.87(dd,J=15.6,5.6Hz,1H),2.69,2.41(d,J=14.0Hz,1H),2.40,2.37(s,3H).13C NMR(100 MHz,DMSO-d6)δ172.5,168.3,152.2,150.5,150.4,149.7,149.6,149.0,148.7,148.3,144.8, 144.4,141.2,141.1,140.4,139.9,137.5,136.7,135.5,134.3,134.0,132.9,132.82,132.78,132.6, 132.5,132.3,132.2,130.0,129.3,126.5,126.2,125.9,125.8,123.9,123.8,123.0,122.6,122.3, 122.2,121.4,120.4,120.2,120.0,116.8,115.1,114.7,69.6,69.5,69.3,69.2,64.7,64.6,32.4,31.9, 26.3.HRMS(ESI)calcd for C35H30N4O5S(M+H)+619.2015,found 619.2018.
(S, E) -N' - (3, 5-di-tert-butyl-4-hydroxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-21)
Yellow solid 0.50g, yield 86%, melting point: 160 ℃ and 162 ℃.1H NMR(400MHz,DMSO-d6)δ11.09,11.04(s, 1H),10.32,10.16(s,1H),8.10,7.82(s,1H),7.78,7.74(d,J=8.4Hz,2H),7.59-6.79(m,15H), 5.94(s,1H),5.42(s,1H),4.08-3.99,3.93-3.85(m,1H),2.53,2.42(s,1H),2.40,2.38(s,3H), 1.47,1.36(s,18H).13C NMR(100MHz,DMSO-d6)δ167.9,163.3,156.6,156.5,149.3,144.9, 144.8,144.5,139.9,139.8,139.7,139.6,136.5,136.4,135.2,135.1,132.8,131.9,130.7,130.7, 129.6,129.3,128.2,128.0,127.9,127.7,127.6,127.4,126.1,125.7,125.2,124.6,124.3,124.0, 121.7,121.5,119.2,117.5,117.1,116.6,116.0,112.2,112.1,110.3,110.0,60.2,59.4,35.1,34.9, 30.6,26.5,21.6,21.5.HRMS(ESI)calcd for C41H44N4O4S(M+H)+689.3161,found 689.3163.
(S, E) -N' - (2, 2-dimethylpropenyl) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-22)
Yellow solid 0.41g, yield 89%, melting point: 137-139 ℃.1H NMR(400MHz,DMSO-d6)δ10.92,10.65(s, 1H),10.26,10.14(s,1H),7.76-6.83(m,15H),5.84,5.33(s,1H),4.04,3.86(dd,J=15.6,4.4Hz, 1H),2.54,2.41(s,1H),2.38(s,3H),1.20,0.92(s,9H).13C NMR(100MHz,DMSO-d6)δ167.6, 163.3,159.1,154.8,144.8,140.0,139.6,136.4,135.5,135.3,132.8,131.9,130.6,129.4,129.2, 128,1,128.0,127,8,127.5,127.4,125.2,124.6,121.6,121.4,119.1,119.0,117.6,117.6,116.6, 115.2,112.1,110.5,109.9,59.8,34.9,27.6,27.4,26.7,21.5.HRMS(ESI)calcd for C31H32N4O3S (M+H)+541.2273,found 541.2274.
(S, E) -N' - (4-bromo-2, 6-difluorobenzylidene) -5-phenyl-3-p-phenylTosyl-1, 2, 3, 6-tetrahydroazepinesAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-23)
Yellow solid 0.27g, yield 47%, melting point: 199 ℃ and 201 ℃.1H NMR(400MHz,DMSO-d6)δ11.55,11.34(s, 1H),10.30,10.16(s,1H),8.33,7.96(s,1H),7.80-6.80(m,16H),6.01-5.86,5.47-5.40(m,1H), 4.11(dd,J=15.6.,5.6Hz,1H),2.57(dd,J=15.2,1.6Hz,1H),2.40,2.38(s,3H).13C NMR(101 MHz,DMSO)δ167.6,163.3,160.2(d,J=256Hz),160.1(d,J=256Hz),144.5,144.4,137.32, 136.0,134.9,134.6,132.8,132.3,130.2,129.0,128.8,127.63,127.60,127.4,127.3,127.1,126.9, 124.6,124.0,122.7(t,J=13.0Hz),121.3,121.0,118.8,116.5,116.3,116.1,114.6,111.6,111.0(t, J=13.6Hz),109.9,109.2,59.41,59.2,26.9,26.2,21.1.HRMS(ESI)calcd for C33H25BrF2N4O3S (M+H)+675.0877,found 675.0871.
(S, E) -5-phenyl-N' - (pyridine-3-methylene) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-24)
Yellow solid 0.35g, yield 73%, melting point: 152 ℃ and 154 ℃.1H NMR(400MHz,DMSO-d6)δ11.56,11.31(s, 1H),10.29,10.17(s,1H),9.05-6.73(m,19H),6.09,5.46(s,1H),4.15,3.91(dd,J=15.6,4.0Hz,1H),2.73(d,J=15.2Hz,0.6H),2.45(d,J=16.4Hz,0.4H),2.39,2.37(s,3H).13C NMR(100 MHz,DMSO-d6)δ168.1,164.0,151.2,149.1,149.0,145.1,145.0,144.8,141.3,140.0,139.6, 136.5,136.4,135.7,135.2,134.0,133.8,132.7,132.0,130.7,130.5,130.4,129.5,129.3,128.2, 128.1,127.9,127.8,127.6,127.5,125.2,124.7,124.6,124.3,121.8,121.5,119.2,119.1,117.6,117.5,116.7,115.5,112.1,110.3,110.0,60.0,59.9,27.6,27.3,21.6.HRMS(ESI)calcd for C32H27N5O3S(M+H)+562.1913,found 562.1911.
(S, E) -5-phenyl-N' - (thiophene-2-methylene) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-25)
Dark brown solid 0.38g, yield 79%, melting point: 222 ℃ and 224 ℃.1H NMR(400MHz,DMSO-d6)δ11.32,11.15 (s,1H),10.32,10.17(s,1H),8.42,8.08(s,1H),7.83-6.74(m,17H),6.00-5.79,5.46-5.35(m,1H),4.11(dd,J=15.4,5.5Hz,0.6H),3.89(dd,J=15.7,5.4Hz,0.4H),2.64(d,J=14.8Hz,1H), 2.40,2.37(s,3H).13C NMR(100MHz,DMSO-d6)δ167.6,163.6,145.0,144.9,143.0,140.0, 139.6,139.5,139.2,138.8,136.5,136.4,135.5,135.1,132.8,131.9,131.4,131.1,130.7,129.6, 129.5,129.3,129.1,128.7,128.2,128.1,128.0,127.9,127.7,127.6,127.4,125.2,124.6,121.8, 121.5,119.2,117.6,116.6,115.3,112.1,110.3,109.9,59.9,59.7,27.6,27.1,21.6.HRMS(ESI) calcd for C31H26N4O3S2(M+H)+567.1524,found 567.1526.
(S, E) -N' - (pyrrole-2-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-26)
Pale yellow solid 0.33g, yield 72%, melting point: 154 ℃ and 156 ℃.1H NMR(400MHz,DMSO-d6)δ11.64,11.31 (s,1H),10.98,10.72(s,1H),10.24,10.14(s,1H),8.02,7.71(s,1H),7.81,7.77(d,J=8.0Hz,2H),,7.58-6.74(m,13H),6.51,6.38(s,1H),6.22,5.38(s,1H),6.07(s,1H),,4.34,3.87(dd,J=15.6, 5.6Hz,1H),2.66(d,J=15.2Hz,1H),2.39,2.37(s,3H).13C NMR(100MHz,DMSO-d6)δ167.4, 163.0,144.9,144.7,141.1,140.2,139.7,136.7,136.5,136.4,136.1,135.2,132.8,131.9,130.7, 130.6,129.5,129.2,128.3,128.1,128.0,127.8,127.6,127.5,127.2,125.5,124.7,122.9,122.7, 121.7,121.4,119.2,119.0,117.6,117.4,116.8,114.6,113.7,113.4,112.0,110.6,110.2,109.8, 109.6,59.9,27.7,27.5,21.6.HRMS(ESI)calcd for C31H27N5O3S(M+H)+550.1913,found 550.1908.
(S, E) -N' -octenyl-5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-formyl hydrazine (VI-27)
Pale yellow foamy solid 0.53g, yield 54%, melting point: 87-88 ℃.1H NMR(400MHz,DMSO-d6)δ10.85,10.66 (s,1H),10.26,10.14(s,1H),7.78-6.84(m,15H),5.84,5.31(d,J=2.8Hz,1H),4.00,3.81(dd,J =15.6,5.6Hz,1H),2.57,2.33(dd,J=15.2,2.0Hz,1H),2.37(s,3H),2.02,1.58(tq,J=14.8,7.2 Hz,2H),,1.47-1.11(m,10H),0.94-0.77(m,3H).13C NMR(100MHz,DMSO-d6)δ166.9, 162.6,151.7,147.9,144.4,144.3,139.6,139.2,136.0,135.9,135.1,134.7,132.3,131.4,130.2, 130.1,129.0,128.7,127.6,127.5,127.4,127.3,127.0,126.9,124.8,124.1,121.2,120.9,118.6, 118.5,117.0,116.9,116.2,114.6,111.6,109.9,109.3,59.1,54.7,31.7,31.6,31.3,31.1,28.7,28.6, 28.5,28.4,26.3,25.8,22.2,22.1,22.0,21.0,14.0,13.9.HRMS(ESI)calcd for C34H38N4O3S (M+H)+583.2736,found 583.2743.
Example 2: the activity against tobacco mosaic virus was determined by the following procedure:
1. virus purification and concentration determination:
virus purification and concentration determinations were performed in accordance with the tobamovirus SOP specifications compiled by the institute of elements institute of south-opening university. Centrifuging the virus crude extract with polyethylene glycol for 2 times, measuring concentration, and refrigerating at 4 deg.C for use.
2. Compound solution preparation:
weighing, adding DMF to dissolve to obtain 1 × 10 solution5Diluting the mother liquor with mu g/mL by using an aqueous solution containing 1 per mill of Tween 80 to the required concentration; the ningnanmycin preparation is directly diluted by adding water.
3. In vitro effect:
the Shanxi tobacco leaves with the proper age are inoculated by rubbing and washed by running water, and the virus concentration is 10 mug/mL. Cutting off after drying, cutting along the vein of the leaf, soaking the left and right half leaves in 1 ‰ of expectorant water and medicinal preparation respectively, taking out after 30min, performing moisture-keeping culture at suitable illumination temperature, repeating for 1 time and 3 times for each 3 leaves. And recording the number of the disease spots after 3d, and calculating the prevention effect.
4. The protection effect of the living body is as follows:
selecting 3-5 leaf-period Saxisi tobacco with uniform growth, spraying the whole plant, repeating for 3 times, and setting 1 ‰ Tween 80 aqueous solution as control. After 24h, the leaf surfaces are scattered with carborundum (500 meshes), the virus liquid is dipped by a writing brush, the whole leaf surfaces are lightly wiped for 2 times along the branch vein direction, the lower parts of the leaf surfaces are supported by palms, the virus concentration is 10 mu g/mL, and the inoculated leaf surfaces are washed by running water. And recording the number of the disease spots after 3d, and calculating the prevention effect.
5. Therapeutic action in vivo:
selecting 3-5 leaf-stage Saxismoke with uniform growth vigor, inoculating virus with whole leaf of writing brush at a virus concentration of 10 μ g/mL, and washing with running water after inoculation. After the leaves are harvested, the whole plant is sprayed with the pesticide, the treatment is repeated for 3 times, and a 1 per mill tween 80 aqueous solution is set for comparison. And recording the number of the disease spots after 3d, and calculating the prevention effect.
6. The living body passivation effect is as follows:
selecting 3-5 leaf-period Saxismoke with uniform growth, mixing the preparation with virus juice of the same volume, inactivating for 30min, performing friction inoculation with virus concentration of 20 μ g/mL, washing with running water after inoculation, repeating for 3 times, and setting Tween 80 water solution of 1 ‰ as reference. The number of lesions after 3d was counted and the result was calculated.
Inhibition (%) < percent [ (control number of scorched spots-number of treated scorched spots)/control number of scorched spots ]. times.100%
TABLE 1 TetrahydroazepineAnd [4, 5-b ]]Test result of anti-TMV activity of indole acylhydrazone derivatives
As can be seen from the activity data in Table 1, most of the tetrahydroazepinesAnd [4, 5-b ]]The indoxyl hydrazone derivatives show good Tobacco Mosaic Virus (TMV) living activity resistance, the tobacco mosaic virus living activity of most compounds is obviously superior to that of commercial varieties of ribavirin, and even the antiviral activity of part of compounds is similar to that of ningnanmycin.
Example 3: the bactericidal activity was determined by the following procedure:
taking tomato early blight as an example, other bacteria can be replaced.
In vitro test method: inoculating the tomato early blight bacteria to PDA culture medium, culturing for 7 days, preparing bacterial dish with diameter of 4cm at colony edge with puncher, inoculating to PDA culture medium containing 50ug/ml and no medicine, culturing for 4 days, measuring colony diameter, and comparing with control to calculate the inhibition percentage of the medicine.
TABLE 2 TetrahydroazepineAnd [4, 5-b ]]Result of bactericidal activity test of indole acylhydrazone derivatives
As can be seen from the bactericidal activity data in Table 2, most of the tetrahydroazepinesAnd [4, 5-b ]]The derivative of the indole acylhydrazone derivative shows broad-spectrum bactericidal activity on 14 fungi including cucumber fusarium wilt, peanut brown spot, apple ring spot, tomato early blight, wheat scab, potato late blight, rape sclerotium, cucumber gray mold, rice sheath blight, phytophthora capsici, rice bakanae, wheat sheath blight, corn microspore and watermelon anthracnose.
Example 4: the insecticidal activity is measured by the following procedure:
activity test of bollworm
The experimental method of the cotton bollworm comprises the following steps: the feed mixing method is a method in which 3mL of the solution is transferred from the prepared solution and added to about 27g of the freshly prepared feed to obtain a desired concentration of ten times the dilution. The preparation is uniformly mixed and poured into a clean 24-hole plate, then is inoculated into 24-head three-year-old cotton bollworms after being cooled, and the inspection result is observed after 3 to 4 days.
Activity test method of armyworm
The experimental method of the armyworm comprises the following steps: leaf soaking method. After the required concentration is prepared, soaking leaves with the diameter of about 5-6cm into the liquid medicine for 5-6 seconds, taking out, putting on absorbent paper for airing, putting in a designated culture dish, inoculating 10-head 3-year larvae, putting in an insect-raising room at 27 +/-1 ℃ for observing for 3-4 days, and then checking the result.
Activity test method of corn borer
The experimental method of the corn borer comprises the following steps: the leaf soaking method comprises soaking leaf with diameter of 5-6cm in the medicinal liquid for 5-6 s after the required concentration is set, taking out, air drying on absorbent paper, placing in a designated culture dish, inoculating 10-head 3-year larva, placing in insect-raising room at 27 + -1 deg.C, observing for 3-4 days, and inspecting the result.
Method for testing activity of mosquito larvae
Experimental method of mosquito larvae: culex pipiens light subspecies, normal population raised indoors. Weighing about 5mg of test compound into a penicillin drug bottle, adding 5mL of acetone (or a suitable solvent), and shaking to dissolve to obtain 1000ppm of mother liquor. 0.5mL of mother liquor is transferred and added into a 100mL beaker filled with 89.9mL of water, 10 heads of young mosquito larvae of 4 years old are selected and poured into the beaker together with 10mL of feeding liquid, and the concentration of the liquid medicine is 5 ppm. The sample is placed in a standard processing chamber, and the result is checked for 24 h. An aqueous solution containing 0.5mL of the experimental solvent was used as a blank.
Method for testing activity of diamondback moth larvae
The leaf dipping method proposed by the International Resistance Action Committee (IRAC) was adopted. 2mg of the drug sample was weighed on an analytical balance into a 10mL beaker, dissolved in 50uL of dimethylformamide (analytical grade), and added with 10mL of water to prepare 200ppm of the drug solution. Dipping the cabbage leaves with straight-head ophthalmological forceps for 2-3 seconds, and throwing off residual liquid. 1 tablet at a time, 3 tablets per sample. And the samples are sequentially placed on the processing paper according to the sample marking sequence. After the liquid medicine is dried, the liquid medicine is put into a straight pipe with the length of 10cm and provided with a mark, 2-year-old plutella xylostella larvae are inoculated, and the pipe orifice is covered by gauze. The experimental treatments were placed in a standard treatment chamber and the results checked after 96 h. Each compound was repeated 3 times. The control was prepared by adding the emulsifier and solvent to distilled water and stirring the mixture uniformly.
Tetranychus cinnabarinus adult mite activity test method
When the dwarf beans for experiments grow to two true leaves, plants with regular growth vigor, 4-5 square centimeters of leaf area and about 10 centimeters of plant height are selected for inoculation of insects, and the quantity of each plant of insects is controlled to be about 60-100. And after the inoculation of the insects for 24 hours, carrying out medicament treatment. The medicament treatment adopts a plant dipping method, and the dipping time is 5 seconds. After the plants are taken out of the liquid medicine, the plants are shaken slightly to throw off the redundant liquid medicine, then the plants are moved into a water culture tank and placed at room temperature. The results were examined under binoculars 24 hours after treatment. (average value of three parallel experiments)
TABLE 3 TetrahydroazepinesAnd [4, 5-b ]]Insecticidal activity test result of indole acylhydrazone derivatives
As can be seen from the activity data in Table 3, all the compounds exhibited excellent insecticidal activity against diamond back moth, and some of the derivatives such as I-6z containing pyrrolyl group exhibited broad spectrum insecticidal activity.
Claims (12)
1. TetrahydroazepineAnd [4, 5-b ]]Indolylhydrazone derivatives, the tetrahydroazepineAnd [4, 5-b ]]The indole acylhydrazone derivative is a compound shown as a general formula:
wherein R is1Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthryl group, a substituted or unsubstituted phenanthryl group, a nitrogen-containing heterocyclic ring having 2 to 10 carbon atoms, an oxygen-containing heterocyclic ring having 2 to 10 carbon atoms, a sulfur-containing heterocyclic ring having 2 to 10 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy and C1-C6 hydrocarbylOne or more of alkoxy of C1-C6, alkylamino of C1-C6, dioxymethylene and dioxyethylene;
R2、R3respectively represent hydrogen, alkyl of C1-C10, alkenyl of C2-C10, alkynyl of C2-C10, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted anthryl, substituted or unsubstituted phenanthryl, nitrogen-containing heterocycle containing 2-10 carbon atoms, oxygen-containing heterocycle containing 2-10 carbon atoms, sulfur-containing heterocycle containing 2-10 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from one or more of hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene.
2. The tetrahydroazepine of claim 1And [4, 5-b ]]Indole acylhydrazone derivatives, R1Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthryl group, a substituted or unsubstituted phenanthryl group, a nitrogen-containing heterocyclic ring having 2 to 8 carbon atoms, an oxygen-containing heterocyclic ring having 2 to 8 carbon atoms, a sulfur-containing heterocyclic ring having 2 to 8 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from one or more of hydroxyl, F, Cl, Br, I, cyano, nitro, trifluoromethyl, trifluoromethoxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy and alkylamino of C1-C5;
R2、R3is independently selected from alkyl of C1-C8, alkenyl of C2-C8, alkynyl of C2-C8, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted anthryl, or substituted or unsubstituted anthrylSubstituted or unsubstituted phenanthryl, nitrogen-containing heterocycles having 2 to 8 carbon atoms, oxygen-containing heterocycles having 2 to 8 carbon atoms, sulfur-containing heterocycles having 2 to 8 carbon atoms; the substituent of the substituted phenyl, the substituted naphthyl, the substituted anthryl and the substituted phenanthryl is independently selected from one or more of hydroxyl, F, Cl, Br, I, cyano, nitro, trifluoromethyl, trifluoromethoxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy and alkylamino of C1-C5.
3. The tetrahydroazepine of claim 1 or 2And [4, 5-b ]]An indole acylhydrazone derivative, wherein the compound is one of the compounds represented by the following formulas:
(S, E) -N' - (4-Chlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-1);
(S, E) -N' - (4-Chlorobenzylidene) -5- (4-methoxyphenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-2);
(S, E) -N' - (4-Chlorobenzylidene) -5- (4-chlorophenyl) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-3);
(S, E) -N' -benzylidene-5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-4);
(S, E) -N' - (4-Nitrophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-5);
(S, E) -N' - (4-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-6);
(S, E) -N' - (3-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-7);
(S, E) -N' - (2-methoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-8);
(S, E) -N' - (3-nitrophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-9);
(S, E) -N' - (4-cyanophenylmethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-10);
(S, E) -N' - (4-tert-butylbenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-11);
(S, E) -N' - (4-dimethylaminobenzenemethylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-12);
(S, E) -N '- (1, 1' -biphenyl-4-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-13);
(S, E) -N' - (3-Chlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-14);
(S, E) -N' - (2-Chlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-15);
(S, E) -N' - (2, 4-dichlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-16);
(S, E) -N' - (3, 4-dichlorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-17);
(S, E) -N' - (3, 4-dimethoxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-18);
(S, E) -N' - (benzo [ d ]][1,3]Dioxymethylene-5-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-19);
(S, E) -N' - (2, 3-dihydrobenzo [ b ]][1,4]Dioxin-6-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-20);
(S, E) -N' - (3, 5-di-tert-butyl-4-hydroxybenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-21);
(S, E) -N' - (2, 2-dimethylpropenyl) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-22);
(S, E) -N' - (4-bromo-2, 6-difluorobenzylidene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-23);
(S, E) -5-phenyl-N' - (pyridine-3-methylene) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-24);
(S, E) -5-phenyl-N' - (thiophene-2-methylene) -3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-25);
(S, E) -N' - (pyrrole-2-methylene) -5-phenyl-3-p-toluenesulfonyl-1, 2, 3, 6-tetrahydroazepineAnd [4, 5-b ]]Indole-2-carboxylic acid hydrazide (VI-26);
4. A tetrahydroazepine as defined in any one of claims 1 to 3And [4, 5-b ]]A process for the preparation of an indolylhydrazone derivative which comprises: first, L-tryptophan in SOCl2The L-tryptophan methyl ester I is generated by esterification reaction with methanol under catalysis, the Ts protecting group on the L-tryptophan methyl ester is formed into II under the basic condition of triethylamine, and the II is respectively reacted with the Ts protecting group on the L-tryptophan methyl esterNucleophilic substitution to generate III, and dehydration condensation ring-closing rearrangement to generate III under the catalytic action of trifluoromethanesulfonic acidThe corresponding IV and IV are hydrazinolyzed to generate the corresponding hydrazide V, and the intermediate V is respectively condensed with aldehyde to obtain the tetrahydroazepine shown in the general formulaAnd [4, 5-b ]]Indolylhydrazone compounds
6. The use according to claim 5, wherein the plant virus to which the use is directed is one or more of tobacco mosaic virus, pepper virus, rice virus, tomato virus, sweet potato virus, potato virus and melon virus and maize dwarf mosaic virus.
8. The tetrahydroazepine of claim 5And [4, 5-b ]]Use of indolylhydrazone derivatives for controlling plantsThe use of the compound, tetrahydroazepineAnd [4, 5-b ]]Indole acylhydrazone derivatives as and other anti-plant viral agents: diazosulfide (BTH), Tiadinil (TDL), 4-methyl-1, 2, 3-thiadiazole-5-formic acid (TDLA), DL-beta-aminobutyric acid (BABA), ribavirin, ningnanmycin, phenanthroindolizidine alkaloid antofine, bitriazole compound XY-13 and XY-30, virus A, salicylic acid and amino-oligosaccharin are prepared into a compound anti-plant virus agent for use.
10. The use according to claim 9, wherein the use is against one or more of the pathogens causing cucumber wilt, peanut brown spot, apple ring rot, tomato early blight, wheat gibberella, rice bakanae, rape sclerotia, phytophthora capsici, wheat sharp rot, corn speck, watermelon anthrax, potato late blight, rice sharp rot, cucumber gray mold.
12. The use according to claim 11, wherein the pest targeted by the use is one or more of Tetranychus cinnabarinus, diamondback moth, mosquito larvae, armyworm, Heliothis armigera, and Cnaphalocrocis medinalis.
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