CN119977959A - A green synthesis method of indole condensed tetracyclic skeleton and its weed control application - Google Patents

A green synthesis method of indole condensed tetracyclic skeleton and its weed control application Download PDF

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CN119977959A
CN119977959A CN202411392432.1A CN202411392432A CN119977959A CN 119977959 A CN119977959 A CN 119977959A CN 202411392432 A CN202411392432 A CN 202411392432A CN 119977959 A CN119977959 A CN 119977959A
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indole
formula
fused
methyl
synthesis method
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李帅帅
郭凤伟
马嘉昕
胡方芝
王静
丁占帅
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Qingdao Agricultural University
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Qingdao Agricultural University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P13/00—Herbicides; Algicides

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Agronomy & Crop Science (AREA)
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  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention discloses an indole fused and hetero four-ring skeleton, a synthesis method and application thereof. The invention provides an indole fused hetero four-ring framework structure. The invention provides a synthesis method of the indole fused tetracyclic compound, which comprises the following steps of uniformly mixing N-arylmethyl indole and o-alkoxy substituted benzaldehyde in a solvent, and reacting at 100-120 ℃ under an acidic condition to obtain the indole fused tetracyclic compound. The invention also provides application of the indole fused hetero-tetracyclic skeleton in preparation of herbicide. According to the method for green synthesis of the indole fused heterotetracyclic compound, the N-arylmethylindole and the o-alkoxy substituted benzaldehyde realize efficient construction of the indole fused heterotetracyclic skeleton through hydrogen migration cyclization reaction based on a shearing-stitching strategy.

Description

Green synthesis method and weeding application of indole fused and hetero four-ring framework
Technical Field
The invention relates to the technical field of pharmaceutical intermediates and chemical synthesis, in particular to an indole fused hetero four-ring structure, a synthesis method and application thereof.
Background
The indole fused heterotetracyclic structure is widely applied to a plurality of natural products and drug molecules, has important application values in medicine and pesticide, for example, the natural product (-) -goniomitine has the indole fused heterotetracyclic structure, and shows very good anti-inflammatory activity. However, the lack of efficient synthesis methods for constructing indole fused tetracyclic compounds seriously hampers the research on the biological activity of subsequent indole fused tetracyclic molecules. Therefore, the efficient construction of the indole fused and hetero four-ring has important significance for drug development.
For example, in 2014, the task group John P.Wolfe, mitsuch state university, U.S. has realized a transition metal palladium-catalyzed intramolecular olefin amine aromatization reaction, and has synthesized indoline-type fused heterotetracyclic molecules in one step with high efficiency (J.Org. chem. 2014, 79, 4212-4217).
The indole fused heterotetracyclic structure has remarkable biological activity, and the reported method can synthesize the indoline fused heterotetracyclic structure, but a high-efficiency synthesis method of the indole fused heterotetracyclic structure is not reported. Therefore, the development of a method for efficiently and directly synthesizing indole fused heterocyclic compounds has important significance for developing novel herbicides and medicaments, in particular medicaments for treating diseases such as tumors, pains, depression and the like.
Disclosure of Invention
Aiming at overcoming the defects of the prior art, the invention provides an indole fused hetero four-ring structure with bioactivity, and a synthesis method and application thereof. The indole fused heterotetracyclic skeleton provided by the invention provides a new model molecule for drug development. According to the synthesis method of the indole fused hetero-tetracyclic skeleton, provided by the invention, N-arylmethyl indole and o-alkoxy substituted benzaldehyde are subjected to hydrogen migration cyclization reaction based on a shearing-sewing strategy for the first time, the skeleton is efficiently synthesized in one step, the operation is simple, the efficiency is high, the practicability is high, and the constructed skeleton contains various functional groups, so that the later synthesis and the application of the skeleton are facilitated.
The technical scheme of the invention is realized as follows:
the structural formula of the indole fused heterotetracyclic skeleton is shown in formula 1:
In the formula 1, R 1 is any one of methoxy and benzene ring, R 2 is any one of methoxy, fluorine, chlorine, bromine and methyl, R 3 is any one of tert-butyl and methyl, R 4 is any one of substituted benzene, naphthalene ring and methyl, wherein R 1、R2、R3、R4 are the same or different and each independently represents a substituent.
The compounds of the present invention may exist in the form of one or more stereoisomers. The various isomers include tautomers, geometric isomers, enantiomers, diastereomers and the like. These isomers and mixtures of these isomers are all within the scope of the present invention.
Based on the same inventive concept, the invention also provides a synthesis method of the indole fused hetero four-ring skeleton, and a synthesis process route diagram of the invention is shown in figure 1, and the method comprises the following steps:
Uniformly mixing N-arylmethyl indole and o-alkoxy substituted benzaldehyde in a solvent, and reacting at 100-120 ℃ under an acidic condition to prepare an indole fused heterocyclic compound;
wherein, the structural formula of the N-arylmethyl indole is shown as formula 2:
in the formula 2, R 1 is any one of methoxy and benzene ring, R 2 is any one of methoxy, fluorine, chlorine, bromine and methyl;
Wherein, the structural formula of the o-alkoxy substituted benzaldehyde is shown in a formula 3:
In the formula 3, R 3 is any one of tert-butyl and methyl, and R 4 is any one of substituted benzene, naphthalene ring and methyl.
The reaction condition can be detected by thin layer chromatography, and purification is carried out after the reaction is finished, so that the purified product of the indole fused heterocyclic compound is obtained.
The reaction process specifically comprises the following steps:
Two molecules of N-arylmethyl indole carry out nucleophilic addition reaction on o-alkoxy substituted benzaldehyde under an acidic condition to generate triarylmethane intermediate 7a, then reverse-Pack alkylation reaction is carried out to generate intermediate I, 1, 5-negative hydrogen migration is carried out to generate intermediate II, cyclization is carried out to generate indolo-oxaseven-membered ring skeleton intermediate III, and nucleophilic substitution reaction in the molecule is carried out on intermediate III to generate indole fused heterocyclic four-ring compound. The synthetic principle route is specifically as follows:
preferably, the synthesis process as described above is carried out at 120 ℃.
According to the synthesis method, the molar ratio of the N-arylmethylindole to the o-alkoxy substituted benzaldehyde is (1-2): 1. Preferably, the molar ratio of the N-arylmethylindole to the o-alkoxy-substituted benzaldehyde is 1.2:1.
The above synthesis method, wherein the solvent is dichloroethane, toluene, dimethyl carbonate or ethyl acetate.
According to the synthesis method, the solvent is added in an amount of 10-25L per mol of N-arylmethylindole and o-alkoxy substituted benzaldehyde. Preferably, the solvent is used in an amount of 10L solvent per mole of N-arylmethylindole and o-alkoxy-substituted benzaldehyde.
In the synthesis method, the acid catalyst is added before the reaction, and the catalyst is Lewis acid. Preferably, the catalyst is any one of boron trifluoride diethyl etherate, p-toluenesulfonic acid, camphorsulfonic acid and copper triflate.
According to the synthesis method, the dosage of the acid catalyst is 20-100 mol%. Preferably, the catalyst is used in an amount of 30 mol%.
Based on the same inventive concept, the present invention also provides a pharmaceutical composition comprising an indole fused heterotetracyclic skeleton as described above, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, geometric isomers, enantiomers, diastereomers, or mixtures or prodrugs thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof. The carrier, diluent, excipient are not particularly limited in the present invention, and may be carriers, diluents, excipients well known to those skilled in the art as suitable for pharmaceutical compositions.
Based on the same inventive concept, the invention also provides application of the indole fused heterotetracyclic skeleton in preparation of herbicide.
The beneficial effects of the invention are as follows:
1. According to the invention, the indole fused heterotetracyclic skeleton is efficiently synthesized through multi-step continuous reaction under mild conditions, a convenient and concise synthesis method is provided for the indole fused heterotetracyclic skeleton, and the efficient construction of the indole fused heterotetracyclic skeleton is realized through the hydrogen migration cyclization reaction based on a shearing-stitching strategy for the first time.
2. The invention develops a method for efficiently synthesizing indole fused heterocyclic compounds containing a plurality of functional groups, provides a compound library of indole fused heterocyclic compounds, and provides a novel model molecule for drug development.
3. The invention provides experimental basis for the efficient construction of indole fused and hetero-tetracyclic skeletons with good biological activity, and has good practical significance and application value.
Drawings
FIG. 1 is a synthetic process scheme of the present invention.
Detailed Description
The following description of the embodiments of the present invention will clearly and fully describe the technical solutions of the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used in this specification includes any and all combinations of one or more of the associated listed items.
The experimental methods used in the following examples are conventional methods unless otherwise specified, reagents, materials, instruments and the like used in the following examples are commercially available, and the reaction vessel used in the following examples is a thick-walled pressure-resistant tube of 25 mL.
Example 1
1. The embodiment provides a synthetic method of an indole fused and hetero four-ring skeleton, which comprises the following steps:
Taking 0.13 mmolN-arylmethylindole in a reaction bottle, sequentially adding 0.10 mmol o-alkoxy substituted benzaldehyde and 0.03 mmol catalyst, and finally adding 1mL solvent. The reaction temperature of the system is controlled, stirring is continued, and the reaction is tracked by thin layer chromatography plate sample application until the raw materials are completely reacted. After the reaction is completed, separating and purifying by using a silica gel column, and rotary steaming the purified product to obtain a target product.
The reaction formula is as follows:
2. According to the method, 7 parallel test groups are established, and different acid catalysts and solvents are respectively adopted. The catalyst is boron trifluoride diethyl etherate (BF 3·OEt2), copper triflate Cu (OTf) 2, camphorsulfonic acid (CSA) and p-toluenesulfonic acid (p-TsOH .H2 O), and the solvent is Dichloroethane (DCE), toluene (Toluene), dimethyl carbonate and Ethyl Acetate (EA). The specific acid catalyst, solvent, reaction temperature and corresponding yields used in the test group are shown in table 1:
TABLE 1 corresponding yields under different acid catalysts and solvents
Note that N-arylmethylindole (0.13 mmol), solvent (1 mL), o-alkoxy-substituted benzaldehyde (0.1 mmol), acid catalyst amount (0.03. 0.03 mmol) were isolated as isolated yields. As a result of the above parallel analysis, the yield of the product was highest when boron trifluoride diethyl ether (BF 3·OEt2) was used as an acidic catalyst.
3. According to the method, the following 3 parallel test groups are set, and different reaction conditions, such as different reaction temperatures, are respectively adopted. The specific settings for the different test groups are shown in Table 2:
TABLE 2 reaction yield Table at different temperatures
Note that catalyst BF 3·OEt2 (0.03 mmol) and solvent (1 mL) were isolated.
As is clear from the analysis of the above parallel test results, the synthesis reaction of the present invention was carried out under the conditions of ethyl acetate (1 mL) as a solvent, N-arylmethylindole (0.13 mmol), o-alkoxy substituted benzaldehyde (0.1 mmol), boron trifluoride diethyl ether (BF 3·OEt2) (0.03 mmol) as a catalyst, and 120 ℃ to obtain the highest yield of the product.
In the following examples 2 to 11, a reaction was carried out in accordance with the procedure of example 1, 0.13 mmolN-arylmethylindole was taken in a reaction flask, 0.1. 0.1 mmol o-alkoxy-substituted benzaldehyde and 0.03. 0.03 mmol catalyst boron trifluoride diethyl ether (BF 3·OEt2) were added in this order, and finally 1 mL ethyl acetate was added. The reaction temperature of the system is controlled to be 120 ℃, stirring is continuously carried out, and the reaction is tracked by thin layer chromatography plate sample application until the raw materials are completely reacted. After the reaction is completed, separating and purifying by using a silica gel column, and rotary steaming the purified product to obtain a target product.
Example 2
Raw materials:
Product 2a, chemical formula C 35H35NO3
Structural formula:
Yield 95%
1H NMR(500 MHz, DMSO-d6) δ 8.33 (dd, J = 8.2, 4.4 Hz, 1H), 7.56 (q, J = 7.9, 6.0 Hz, 1H), 7.32 – 7.23 (m, 1H), 7.21 – 7.11 (m, 5H), 7.09 (dt, J = 8.9, 4.6 Hz, 1H), 6.97 (q, J = 6.5 Hz, 2H), 6.80 – 6.69 (m, 1H), 6.57 (d, J = 7.0 Hz, 1H), 6.43 (q, J = 7.6, 5.8 Hz, 1H), 6.32 (t, J = 5.9 Hz, 1H), 5.77 (d, J = 4.9 Hz, 1H), 5.58 (dd, J = 16.5, 7.0 Hz, 1H), 5.25 (dd, J = 16.4, 6.3 Hz, 1H), 4.11 (d, J = 4.6 Hz, 2H), 3.81 (dd, J = 12.3, 8.1 Hz, 6H), 1.53 – 1.34 (m, 9H).13C NMR(125 MHz, DMSO-d6) δ 160.0, 157.8, 153.5, 144.1, 137.5, 135.9, 135.5, 134.7, 129.2, 128.7, 128.6, 127.8, 127.0, 126.5, 124.2, 121.0, 119.6, 119.5, 119.2, 118.0, 109.8, 107.2, 103.5, 98.1, 56.1, 55.8 45.1, 36.9, 35.0, 30.4, 24.3.HRMS (ESI) m/z:[M+H]+calcd for C35H36NO3 +518.2690; found:518.2693.
Example 3
Raw materials:
The product 3a has the chemical formula C 41H39NO3
Structural formula:
Yield 80%
1H NMR(400 MHz, DMSO-d6) δ 8.32 (s, 1H), 7.57 – 7.50 (m, 3H), 7.40 (t, J = 7.9 Hz, 4H), 7.33 – 7.24 (m, 2H), 7.21 – 7.12 (m, 3H), 7.00 – 6.90 (m, 2H), 6.73 (d, J = 2.3 Hz, 1H), 6.56 (d, J = 2.3 Hz, 1H), 6.38 (t, J = 7.7 Hz, 1H), 6.27 (dd, J = 7.6, 1.6 Hz, 1H), 5.76 (s, 1H), 5.59 (d, J = 16.6 Hz, 1H), 5.28 (d, J = 16.4 Hz, 1H), 4.15 – 4.02 (m, 2H), 3.81 (d, J = 2.0 Hz, 6H), 1.41 (s, 9H).13C NMR(100 MHz, DMSO-d6) δ 159.7, 157.8, 153.5, 143.4, 140.4, 138.5, 137.4, 135.7, 135.5, 134.5, 129.3, 129.1, 128.6, 128.3, 127.7, 127.1, 127.0, 126.9, 124.2, 121.0, 119.6, 119.6, 119.1, 117.7, 109.8, 107.3, 103.5, 98.1, 56.2, 55.8, 45.1, 36.5, 35.0, 30.3, 30.2, 24.2.HRMS (ESI) m/z:[M+H]+calcd for C41H40NO3 +594.3003; found: 594.3007.
Example 4
Raw materials:
the product 4a has the chemical formula C 35H34FNO3
Structural formula:
Yield 86%
1H NMR(500 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.53 (dd, J = 8.7, 4.4 Hz, 1H), 7.15 (d, J = 6.6 Hz, 4H), 7.11 – 7.06 (m, 1H), 7.01 – 6.91 (m, 3H), 6.70 (d, J = 2.4 Hz, 1H), 6.55 (d, J = 2.4 Hz, 1H), 6.44 (t, J = 7.6 Hz, 1H), 6.32 – 6.18 (m, 1H), 5.74 (d, J = 4.7 Hz, 1H), 5.57 (d, J = 16.7 Hz, 1H), 5.26 (d, J = 16.4 Hz, 1H), 4.11 – 3.98 (m, 2H), 3.80 (d, J = 8.5 Hz, 6H), 1.42 (s, 9H).13C NMR(100 MHz, DMSO-d6) δ 159.7, 157.8, 157.5 (d, J = 230.0 Hz), 153.5, 144.0, 137.7 (d, J = 2.0 Hz), 134.3, 132.1, 129.0, 128.8, 128.7, 127.9, 127.1, 126.6, 124.3, 119.8, 117.6, 110.8 (d, J = 9.0 Hz), 108.8 (d, J = 26.0 Hz), 107.9 (d, J = 4.0 Hz), 104.9 (d, J = 23.0 Hz), 103.4, 98.1, 56.1, 55.8, 45.2, 37.0, 35.0, 30.3, 24.2.HRMS (ESI) m/z:[M+H] + calcd for C35H35FNO3 +536.2596; found:536.2590.
Example 5
Raw materials:
Product 5a, chemical formula C 35H34ClNO3
Structural formula:
Yield 71%
1H NMR(500 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.25 (d, J = 2.1 Hz, 1H), 7.17 (dt, J = 6.8, 1.1 Hz, 1H), 7.14 (t, J = 2.4 Hz, 3H), 7.13 – 7.07 (m, 2H), 6.96 (dd, J = 7.8, 1.7 Hz, 1H), 6.70 (d, J = 2.4 Hz, 1H), 6.56 (d, J = 2.4 Hz, 1H), 6.43 (t, J = 7.7 Hz, 1H), 6.23 (dd, J = 7.6, 1.6 Hz, 1H), 5.75 (s, 1H), 5.58 (d, J = 16.5 Hz, 1H), 5.26 (d, J = 16.4 Hz, 1H), 4.10 – 4.00 (m, 2H), 3.80 (d, J = 4.6 Hz, 6H), 1.42 (s, 9H).13C NMR(100 MHz, DMSO-d6) δ 159.7, 157.8, 153.4, 143.9, 137.8, 137.4, 134.2, 133.9, 129.5, 129.0, 128.8, 127.9, 127.1, 126.7, 124.4, 124.2, 120.8, 119.8, 118.4, 117.5, 111.4, 107.7, 103.4, 98.2, 56.1, 55.8, 45.1, 36.9, 35.0, 30.3, 24.0.HRMS (ESI) m/z:[M+H]+calcd for C35H35ClNO3 +552.2300; found: 552.2305.
Example 6
Raw materials:
Product 6a, chemical formula C 35H34BrNO3
Structural formula:
Yield 63%
1H NMR(400 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.50 (d, J = 8.7 Hz, 1H), 7.39 (d, J = 1.9 Hz, 1H), 7.24 (dd, J = 8.6, 2.0 Hz, 1H), 7.19 – 7.05 (m, 5H), 6.95 (dd, J = 7.8, 1.7 Hz, 1H), 6.69 (d, J = 2.3 Hz, 1H), 6.55 (d, J = 2.4 Hz, 1H), 6.42 (t, J = 7.7 Hz, 1H), 6.21 (dd, J = 7.6, 1.6 Hz, 1H), 5.75 (s, 1H), 5.57 (d, J = 16.5 Hz, 1H), 5.25 (d, J = 16.4 Hz, 1H), 4.04 (d, J = 3.1 Hz, 2H), 3.80 (d, J = 2.9 Hz, 6H), 1.42 (s, 9H).13C NMR(100 MHz, DMSO-d6) δ 159.7, 157.8, 153.4, 143.9, 137.8, 137.3, 134.2, 134.1, 130.2, 128.9, 128.8, 127.9, 127.8, 127.2, 126.7, 124.4, 123.3, 121.4, 119.8, 117.6, 112.2, 111.9, 107.7, 103.4, 98.2, 56.2, 55.8, 45.1, 36.9, 35.0, 30.3, 24.1.HRMS (ESI) m/z:[M+H]+calcd for C35H35BrNO3 +596.1795; found: 596.1796.
Example 7
Raw materials:
Product 7a, formula C 39H37NO3
Structural formula:
Yield 95%
1H NMR(500 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.80 – 7.72 (m, 1H), 7.71 – 7.62 (m, 2H), 7.61 – 7.53 (m, 2H), 7.43 – 7.35 (m, 2H), 7.30 – 7.21 (m, 2H), 7.18 – 7.12 (m, 1H), 6.98 – 6.93 (m, 1H), 6.90 (dd, J = 7.6, 1.9 Hz, 1H), 6.75 (d, J = 2.3 Hz, 1H), 6.55 (d, J = 2.4 Hz, 1H), 6.42 – 6.22 (m, 2H), 5.86 (s, 1H), 5.61 (d, J = 16.5 Hz, 1H), 5.36 (d, J = 16.4 Hz, 1H), 4.08 (d, J = 2.8 Hz, 2H), 3.80 (d, J = 12.8 Hz, 6H), 1.41 (s, 9H).13C NMR(100 MHz, DMSO-d6) δ 159.7, 157.9, 153.5, 141.5, 137.4, 135.6, 135.5, 134.7, 133.3, 132.0, 129.1, 128.6, 128.3, 128.1, 127.7, 126.8, 126.6, 126.4, 126.0, 124.2, 121.1, 119.6, 119.1, 117.6, 109.9, 107.4, 103.5, 98.1, 56.1, 55.8, 45.1, 37.1, 35.0, 30.3, 24.2.HRMS (ESI) m/z:[M+H]+calcd for C39H38NO3 +568.2846; found: 568.2850.
Example 8
Raw materials:
product 8a, chemical formula C 31H35NO3
Structural formula:
yield 55%
1H NMR(500 MHz, DMSO-d6) δ 8.35 (s, 1H), 7.48 (dd, J = 8.1, 1.0 Hz, 1H), 7.19 – 7.07 (m, 2H), 7.02 – 6.92 (m, 2H), 6.59 (s, 2H), 6.48 (t, J = 7.7 Hz, 1H), 6.38 (dd, J = 7.7, 1.7 Hz, 1H), 5.31 (s, 2H), 4.29 (s, 2H), 3.85 (s, 3H), 3.81 (s, 3H), 1.77 (s, 6H), 1.44 (s, 9H).13C NMR(100 MHz, DMSO-d6) δ 159.5, 158.9, 153.7, 142.0, 137.1, 134.4, 131.0, 129.8, 129.2, 126.7, 124.2, 122.2, 120.8, 119.9, 119.5, 118.5, 110.0, 105.3, 102.5, 99.7, 56.0, 55.6, 44.7, 36.0, 35.0, 30.4, 28.4, 25.9.HRMS (ESI) m/z:[M+H]+calcd for C31H36NO3 +470.2690; found: 470.2693.
Example 9
Raw materials:
Product 9a, chemical formula C 35H34BrNO3
Structural formula:
Yield 92%
1H NMR(400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.32 – 7.23 (m, 3H), 7.18– 7.12 (m, 1H), 7.07 – 7.00 (m, 2H), 7.00–6.91 (m, 2H), 6.71 (d, J = 2.3 Hz, 1H), 6.54 (d, J = 2.3 Hz, 1H), 6.39 (t, J = 7.6 Hz, 1H), 6.23 (dd, J = 7.6, 1.6 Hz, 1H), 5.65 (s, 1H), 5.56 (d, J = 16.6 Hz, 1H), 5.26 (d, J = 16.4 Hz, 1H), 4.08 – 3.97 (m, 2H), 3.79 (d, J = 8.5 Hz, 6H), 1.41 (s, 9H).13C NMR(100MHz, DMSO-d6) δ 159.8, 157.7, 153.4, 143.5, 137.4, 135.4, 135.0, 134.3, 131.5, 130.1, 129.0, 128.6, 126.9, 124.2, 121.1, 119.6, 119.5, 119.1, 117.3, 109.9, 107.5, 103.4, 98.1, 56.1, 55.8, 44.9, 36.4, 35.0, 30.3, 24.1.HRMS (ESI) m/z:[M+H]+calcd for C35H35BrNO3 +596.1795; found: 596.1794.
Example 10
Raw materials:
Product 10a, formula C 36H37NO3
Structural formula:
Yield is 75%
1H NMR(500 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.57 – 7.46 (m, 1H), 7.20 (d, J = 7.7 Hz, 2H), 7.14 – 7.04 (m, 3H), 6.98 (d, J = 8.0 Hz, 2H), 6.88 (dd, J = 10.6, 7.3 Hz, 2H), 6.68 (d, J = 3.0 Hz, 1H), 6.41 (d, J = 3.0 Hz, 1H), 6.32 (td, J = 7.6, 2.5 Hz, 1H), 5.96 (d, J = 7.6 Hz, 1H), 5.58 (d, J = 16.9 Hz, 1H), 5.38 (d, J = 16.7 Hz, 1H), 3.79 (d, J = 2.6 Hz, 3H), 3.72 – 3.61 (m, 2H), 3.24 (d, J = 2.9 Hz, 3H), 2.02 (s, 3H), 1.39 (s, 9H).13C NMR(100 MHz, DMSO-d6) δ 159.3, 158.8, 153.2, 148.6, 140.7, 136.9, 134.5, 131.2, 129.4, 129.0, 127.8, 127.4, 127.2, 125.3, 123.8, 123.4, 120.9, 119.7, 119.2, 118.7, 110.0, 107.2, 102.7, 100.4, 55.8, 55.6, 44.6, 42.9, 34.9, 30.3, 25.4, 24.3.HRMS (ESI) m/z:[M+H]+calcd for C36H38NO3 +532.2846; found: 532.2845.
Example 11
Raw materials:
the product 11a has the chemical formula C 36H37NO3
Structural formula:
Yield 88%
1H NMR(500 MHz, DMSO-d6) δ 8.29 (s, 1H), 7.17 – 7.10 (m, 4H), 7.09 – 7.05 (m, 1H), 7.04 (dd, J = 7.4, 1.8 Hz, 1H), 6.94 (dd, J = 7.8, 1.6 Hz, 1H), 6.87 – 6.78 (m, 2H), 6.76 (d, J = 2.3 Hz, 1H), 6.53 (d, J = 2.4 Hz, 1H), 6.40 (t, J = 7.7 Hz, 1H), 6.25 (dd, J = 7.5, 1.7 Hz, 1H), 5.96 (d, J = 16.4 Hz, 1H), 5.69 (s, 1H), 5.60 (d, J = 16.2 Hz, 1H), 4.13 – 3.97 (m, 2H), 3.79 (d, J = 15.3 Hz, 6H), 2.89 (s, 3H), 1.42 (s, 9H).13C NMR(100 MHz, DMSO-d6) δ 159.6, 157.5, 153.5, 144.1, 137.4, 136.1, 135.2, 134.9, 129.2, 129.1, 128.7, 127.8, 126.7, 126.5, 124.2, 124.0, 121.3, 119.6, 119.5, 117.4, 117.1, 107.3, 103.4, 98.1, 56.1, 55.8, 47.9, 36.7, 35.0, 30.3, 24.2, 20.3.HRMS (ESI) m/z:[M+H]+calcd for C36H38NO3 +532.2846; found: 532.2844.
Weeding test results the compounds of the invention have the inhibition rate to barnyard grass stem and root respectively
Note that: "+++" "indicates a concentration of 50mg/L the lower inhibition rate ranges from 90% to 100%;" +++ "indicates a concentration of 50mg/L the lower inhibition rate ranges from 70% to 90%; lower inhibition ratio range 70% -90%.
The inhibition rate of most of the compounds in the invention to barnyard grass roots and stems is more than 70% at the concentration of 50mg/L, and the compounds in the invention have better effect of inhibiting the growth of rhizomes, thus having good application prospect in weeding.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.

Claims (8)

1. The indole fused heterotetracyclic skeleton is characterized in that the structural formula is shown in formula 1:
In the formula 1, R 1 is any one of methoxy and benzene ring, R 2 is any one of methoxy, fluorine, chlorine, bromine and methyl, R 3 is any one of tert-butyl and methyl, R 4 is any one of substituted benzene, naphthalene ring and methyl, wherein R 1、R2、R3、R4 are the same or different and each independently represents a substituent.
2. The method for synthesizing the indole fused tetracyclic active skeleton according to claim 1, comprising the following steps:
Uniformly mixing N-arylmethyl indole and o-alkoxy substituted benzaldehyde in a solvent, and reacting at 100-120 ℃ under the catalysis of Lewis acid to prepare an indole fused heterocyclic compound;
wherein, the structural formula of the N-arylmethyl indole is shown as formula 2:
in the formula 2, R 1 is any one of methoxy and benzene ring, R 2 is any one of methoxy, fluorine, chlorine, bromine and methyl;
Wherein, the structural formula of the o-alkoxy substituted benzaldehyde is shown in a formula 3:
In the formula 3, R 3 is any one of tert-butyl and methyl, and R 4 is any one of substituted benzene, naphthalene ring and methyl.
3. The synthesis method according to claim 2, wherein the molar ratio of the N-arylmethylindole to the o-alkoxy-substituted benzaldehyde is (1-2): 1.
4. The synthetic method according to claim 2, wherein the solvent is dichloroethane, toluene, dimethyl carbonate, ethyl acetate.
5. The synthesis method according to claim 2, wherein the solvent is added in an amount of 10-25L per mol of N-arylmethylindole and o-alkoxy-substituted benzaldehyde.
6. The method of synthesis according to claim 2, wherein the lewis acid catalyst is any of boron trifluoride diethyl ether, p-toluene sulfonic acid, camphorsulfonic acid, copper triflate.
7. The synthesis method according to claim 2, wherein the catalyst is used in an amount of 20 to 100 mol%.
8. Use of an indole fused heterotetracyclic bioactive framework according to claim 1 for the preparation of a herbicide.
CN202411392432.1A 2024-10-08 2024-10-08 A green synthesis method of indole condensed tetracyclic skeleton and its weed control application Pending CN119977959A (en)

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