CN109438427A - A kind of triazole schiff bases myricetin derivative, the preparation method and the usage of Sulfide-containing Hindered - Google Patents
A kind of triazole schiff bases myricetin derivative, the preparation method and the usage of Sulfide-containing Hindered Download PDFInfo
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- CN109438427A CN109438427A CN201811476187.7A CN201811476187A CN109438427A CN 109438427 A CN109438427 A CN 109438427A CN 201811476187 A CN201811476187 A CN 201811476187A CN 109438427 A CN109438427 A CN 109438427A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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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
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
- A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Abstract
The invention discloses triazole schiff bases myricetin derivative, the preparation method and the usages of a kind of Sulfide-containing Hindered, shown in general structure following [A]: where R is phenyl, substituted-phenyl, aromatic heterocyclic；N is that the number of carbon in carbochain is respectively 3,4,5.The present invention has preferable control efficiency to tobacco mosaic virus (TMV), citrus processing and hundred leaf spoting bacteria of rice.
Description
Technical field
The present invention relates to chemical technology field, the triazole schiff bases myricetin for relating in particular to a kind of Sulfide-containing Hindered is derivative
Object also relates to the preparation method of the triazole schiff bases myricetin derivative of the Sulfide-containing Hindered and the triazole Schiff of the Sulfide-containing Hindered
Application of the alkali myricetin derivative in terms of pressing down phytopathogen.
Background technique
Myricetin (3', 4', 5', 3,5,7- quercetagetin alcohol, Myricetin (Myr)), different name myricetin, poplar
Plum ketone is the polyhydroxy flavone compound separated from Chinese waxmyrtle bark, chemical formula C15H10O8, relative molecular weight
318.24, yellow needles or crystalline particulate, are dissolved in methanol, ethyl alcohol, acetone by 324-326 DEG C of fusing point, do not dissolve in chloroform, petroleum
Ether.It is present in Fagaceae (Fagaceae), pulse family (leguminosae), Primulaceae (primulaceae), Vitaceae
(vitaceae), in the plants such as composite family (compositae).Show that myricetin has antibacterial, anti-mistake according to modern pharmacology activity research
Quick, antiviral, hypoglycemic, anti-inflammatory, anti-oxidant, a variety of pharmacological activity of protection nerve etc. show resources advantage abundant and huge
Big potential utility value.
2007, (Naz, the S. such as Naz；Siddiqi,R.；Ahmad, S. Food Science, 2007,72 (9): M341-345.)
It is living to the In Vitro Bacteriostasis of 4 kinds of staphylococcus, Corynebacterium, streptococcus and bacillus subtilis Pseudomonas Pseudomonas to have studied myricetin
Property, the results showed that, myricetin has different degrees of bacteriostasis to above-mentioned 4 kinds of Pseudomonas.
2009, Liu is equal, and (Liu Hongbo, Shi Donghui, Chen Anliang, Ying Mengmeng, Zhang Liqin Waxberry leaf extract were common to 6 kinds
Your inhibitory activity of phytopathogen [J] Zhejiang Forestry College, 2009,26,95-99.) use growth rate method to myricetin
The bacteriostasis measurement of system is carried out, the experimental results showed that myricetin is to Rhizoctonia solani Kuhn, Sclerotinia sclerotiorum, tomato ash
6 kinds of pathogenic mattresses such as mildew bacterium, fusarium graminearum, Valsa mali, cotton-wilt fusarium have stronger inhibition to live
Property, EC50It is respectively: 0.32,0.33,1.09,0.69,0.34 and 2.09g/L, and to rice sheath blight disease mattress, Sclerotinia sclerotiorum
It is higher with the inhibitory activity of Valsa mali.
2014, (Rashed, the K. such as Rashed；A.；J.；Sokovic ', M. manufacturing crops
8 kinds of polyphenol compounds including myricetin are compared to 8 using micro-dilution method with product .2014,59,210-215.)
The test of the In Vitro Bacteriostatic of kind bacterium and 8 kinds of fungies.With bacillus cereus (B.cereus), yellow micrococcus luteus (M.flavus)
For three kinds of bacteriums of Escherichia coli (E.coli), the MIC of myricetin is respectively 2.50 ± 0.30,5.00 ± 0.60,15.00 ±
3.00 μ g/mL, MFC are respectively 5.00 ± 0.60,10.00 ± 0.00,20.00 ± 5.00 μ g/mL.In addition with aspergillus fumigatus
(A.fumigatus), for three kinds of fungies of green ochre Penicillium notatum (P.ochro-chloron) and trichoderma viride (T.viride),
Its MIC is respectively that 2.50 ± 0.03,10.00 ± 6.00,10.00 ± 3.00 μ g/mL, MFC are respectively 5.00 ± 0.60,25.00
±5.00,15.00±5.00μg/mL.Result of study shows that myricetin has the good biology for inhibiting bacterium and inhibiting fungi
Activity mainly has benefited from the C-4 carbonyl and C-3 of myricetin, 5,7 hydroxyls.
Myricetin is a kind of potential antivirotic of tool, 2004, (Shen Jianguo, Xie Liyan, Zhai Meizhi, the Jessica Lynch such as Shen
English, Xie Lianhui Waxberry leaf extract activity of resisting tobacco mosaic virus and its chemical component Primary Study [J] University Of Agriculture and Forestry In Fujian
Journal (natural science edition), 2004,33 (4): 441-443.) have studied inhibition work of the Waxberry leaf extract to tobacco mosaic virus (TMV)
Property, the results showed that, Waxberry leaf extract has preferable external passivation and antiviral dissemination to tobacco mosaic virus (TMV).
2012, (Yu, the M.S. such as Yu；Lee,J.；Lee,J.M.；Kim,Y.；Chin,Y.W.；Jee,J.G.；Keum,
Y.S.；Jeong, Y.J.. Bioorganic & Medicinal Chemistry Letters, 2012,22 (12): 4049-4054.) it is glimmering by carrying out
The double-stranded DNA of photoresonance energy transfer (FRET) untwists measuring method or the use of colorimetric is basic hydrolysis experiment method, has studied red bayberry
Element finds the inhibiting effect of external SARS virus, research: myricetin potentially inhibits SARS virus helicase protein, influences
The activity of ATP enzyme, but there is no unwinding activities, and myricetin do not show normal breast epithelial MCF10A cell
Cytotoxicity.Having further related to myricetin has good inhibiting effect to external SARS virus.
In conclusion myricetin has preferable bacteriostatic activity and antiviral activity in terms of medical research.Grinding before
It is less to the modification of myricetin to study carefully worker, mainly the bioactivity of myricetin itself is studied.([1] Zhong Xinmin contains
The synthesis of nitrogen class myricetin derivative and bioactivity research [D] Guizhou University 2017. [2] Xiao Wei, Ruan Xianghui, Li Qin, Zhang Ju
It puts down, Zhong Xinmin, Xie Yan, Wang Xiaobin, Huang Minguo, the synthesis of the amides myricetin derivative such as Xue Wei and bacteriostatic activity [J] high
Synthesis and the biology of equal schools' chemistry journal 2017,38,35-40. [3] Ruan Xianghui azole or chalcone myricetin derivative
Activity research [D] Guizhou University 2018) show myricetin derivative equally there is antibacterial and antiviral bioactivity.But also
There is not the myricetin that the triazole schiff bases active group of Sulfide-containing Hindered is introduced into myricetin the triazole schiff bases for synthesizing Sulfide-containing Hindered to spread out
Biology and the report for carrying out agricultural active test.
Summary of the invention
A kind of pair of tobacco mosaic virus (TMV) being there is provided it is an object of the invention to overcome disadvantages mentioned above, citrus processing and
Hundred leaf spoting bacteria of rice has the myricetin derivative of the Sulfide-containing Hindered triazole schiff bases of preferable control efficiency.
Another object of the present invention is to provide the preparation methods of the myricetin derivative of the Sulfide-containing Hindered triazole schiff bases.
A further object of the present invention is to provide the myricetin derivatives of the Sulfide-containing Hindered triazole schiff bases in Antiphytoviral
With the application in terms of suppression phytopathogen.
A kind of myricetin derivative of Sulfide-containing Hindered triazole schiff bases of the invention, general structure are as follows:
Wherein, R is phenyl, substituted-phenyl, aromatic heterocyclic；N is that the number of carbon in carbochain is respectively 3,4,5.
A kind of preparation method of the myricetin derivative of Sulfide-containing Hindered triazole schiff bases of the invention, synthetic route are as follows:
(1) using hydrazine hydrate, carbon disulfide as raw material, by being heated to reflux, solid recrystallization prepare diazanyl thio-hydrazide (in
Mesosome 1):
(2) using diazanyl thio-hydrazide (intermediate 1) and glacial acetic acid as raw material, by being heated to reflux, solid recrystallization preparation
4- amino -5- methyl -4H-1,2-4- triazole -3- sulfydryl (intermediate 2):
(3) with 4- amino -5- methyl -4H-1,2-4- triazole -3- sulfydryl (intermediate 2) and substitution aldehyde for raw material, with dense sulphur
Acid is catalyst, using ethyl alcohol as solvent, prepares 4 (substituted methylene) -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediates
3):
(4) using myricetrin and iodomethane as raw material, using potassium carbonate as catalyst, acidity, which is adjusted, prepares 3- hydroxyl -3 ', and 4 ',
5 ', 5,7- pentamethoxyl myricetin (intermediate 4):
(5) with 3- hydroxyl -3 ', two bromoalkanes of 4 ', 5 ', 5,7- pentamethoxyl myricetin (intermediate 4) and different chain length
It is catalyst with potassium carbonate for raw material, n,N-Dimethylformamide (DMF) is that solvent prepares bromo- 5, the 7- dimethoxy -2- of 3-
(3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (intermediate 5), as follows:
(6) with 3- bromo- 5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (intermediate 5) and
4 (substituted methylene) -5- methyl -4H-1,2,4- triazole -3- sulfydryls (intermediate 3) are raw material, are catalyst with potassium carbonate, N,
Dinethylformamide (DMF) is the myricetin derivative (target compound A) that solvent prepares Sulfide-containing Hindered triazole schiff bases, as follows
It is shown:
Application of the myricetin derivative of Sulfide-containing Hindered triazole schiff bases of the invention in terms of inhibiting tobacco mosaic virus (TMV).
The myricetin derivative of Sulfide-containing Hindered triazole schiff bases of the invention is inhibiting citrus processing and rice bacterial leaf spot
The application of germ.
Compared with prior art, the present invention having apparent beneficial effect, as can be known from the above technical solutions: the present invention is with water
It closes hydrazine, carbon disulfide, glacial acetic acid, aldehyde etc. replaced to generate triazole schiff bases for raw material, be raw material generation with myricetrin, iodomethane etc.
3- hydroxyl -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetins, 3- hydroxyl -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetins are a with carbon again
Number is respectively 3,4,5 dibromo alkane reaction, and the product and triazole schiff bases of generation act on obtaining Sulfide-containing Hindered triazole schiff bases
Myricetin derivative.Thioether triazole Schiff base groups with excellent activity are introduced into the structure of myricetin by the present invention, i.e. poplar
The long thioether triazole schiff bases structure of different carbon chain is connected on the position the 3- hydroxyl of syphilis.It is uncommon a series of Sulfide-containing Hindered triazoles have been synthesized
The red bayberry chlorins compound of husband's alkali passes through Antiphytoviral to synthesized Sulfide-containing Hindered triazole schiff bases myricetin derivative and suppression
Phytopathogen active testing, the compound of the present invention have preferable Antiphytoviral (tobacco mosaic virus (TMV)) activity and excellent suppression
Phytopathogen (hundred leaf spoting bacteria of citrus processing and rice) activity can be used for preparing Antiphytoviral pesticide and prepare agricultural
Fungicide.
Specific embodiment
Embodiment 1
3- (3- ((5- methyl -4- ((benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) propoxyl group) -5,7- two
Methoxyl group -2- (3,4,5- trimethoxyphenyl) -4H- benzopyran-4-one (target compound A1) preparation method, including with
Lower step:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Thermometer is being housed, in the three-necked flask of dropping funel and condenser (suitable for reading to be connected with tail gas delivery line) plus 20mL
85% hydrazine hydrate and 60mL water controls temperature at 50 DEG C or so.In dropwise addition 6mL CS in l h under electromagnetic agitation2, then will
Mixed liquor is filtered in 90 DEG C of reflux 1h, cooling crystallization, is recrystallized, is obtained colourless acicular crystal (intermediate 1), yield in water:
82%.
(2) preparation of 4- amino -5- methyl -4H-1,2-4- triazole -3- sulfydryl (intermediate 2):
It takes 3.18g (0.03mol) diazanyl thio-hydrazide (intermediate 1) in flask, 10mL glacial acetic acid reflux 4h is added, it is cold
To room temperature, be evaporated under reduced pressure out unreacted acetic acid, wash crude product recrystallizes to obtain white crystals (intermediate 2) with water, yield:
77%.
(3) preparation of 4- ((benzal) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan (intermediate 3):
1g 4- amino -5- methyl -4H-1,2-4- triazole -3- sulfydryl (intermediate 2) is added in round-bottomed flask
Benzaldehyde (9.22mmol) and the dense sulphur of 1mL are added to after being completely dissolved for (7.68mmol) and 30mL dehydrated alcohol, heating stirring
Acid, continuation heating reflux reaction to (intermediate 2) disappear, and stand cooling, filter, ethanol washing filter cake, and 4- (benzal is obtained after drying
Base amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan (intermediate 3), yield: 68%.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin (intermediate 4):
4.64g myricetrin (10mmol), 22.09g K are sequentially added in 250mL round-bottomed flask2CO3(16mmol) and
7.50mL iodomethane (120mmol) is slowly added dropwise after stirring 0.5~1h under room temperature in 120mL DMF, is stirred at room temperature 48h, TLC with
Track reacts (methanol: ethyl acetate=1:4, V/V).After stopping reaction, filtering precipitating, filter residue washs filter residue with methylene chloride, closes
And filtrate, it is diluted with 100mL water, use or methylene chloride extraction three times, merge organic layer, are concentrated under reduced pressure, then that concentrate is molten
In 30mL dehydrated alcohol, it is warming up to reflux, after solution clarification, flow back lower addition 16mL concentrated hydrochloric acid, then there is yellow solid
It is precipitated, the reaction was continued 2h, cooling, filtering obtains crude product 3- hydroxyl -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin (intermediates
4), yield: 54%.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
1.17g (3mmol) 3- hydroxyl -3 ', 4 ', 5 ', 5,7-, five methoxy are sequentially added in the single necked round bottom flask of 100mL
Base myricetin (intermediate 4), 1.66g K2CO3After (12mmol) and 30mL DMF, stirring at normal temperature 0.5-1h, 2.42g 1 is added,
3- dibromopropane (12mmol), the reaction was continued at this temperature 12h, TLC monitoring reaction (ethyl acetate).After reaction stops, instead
The water dispersion of liquid 50mL is answered, ethyl acetate extracts (3 × 25mL), and obtained ethyl acetate layer successively uses the HCl of 1mol/L, satisfies
And NaHCO3, after saturation NaCl aqueous solution washs 2 times respectively, combined ethyl acetate layer, anhydrous Na SO4It is dry, be removed under reduced pressure it is molten
Agent, reduced pressure chromatography separating-purifying (petroleum ether: ethyl acetate=2:1, V/V) obtain white solid (intermediate 5), yield:
79%.
(6) 3- (3- ((4- ((benzal) amino) -5- methyl -4H-1,2,4- triazole -3- base) sulfenyl) propoxyl group) -5,
7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- benzopyran-4-one (target compound A1) preparation:
4- ((benzal) amino) -5- methyl -4H-1,2,4- triazole -3- sulphur is added in the single necked round bottom flask of 100mL
Alcohol (intermediate 3), K2CO3And DMF, stirring at normal temperature 0.5-1h, after be slowly added to bromo- 5, the 7- dimethoxy -2- (3,4,5- tri- of 3-
Methoxyphenyl) -4H- chromene -4- ketone (intermediate 5) DMF solution, then raise temperature to 100 DEG C, stir 6- at this temperature
8h.TLC tracking reaction, when reaction terminates, stopping reaction being cooled to room temperature, pours the mixture into 200mL ice water, use dichloro
Methane extracts (3 × 40mL), merges organic layer, and with saturated common salt water washing (3 × 40mL), anhydrous sodium sulfate is dry, depressurizes and removes
Solvent is removed, crude product is obtained, target compound is obtained through column chromatography (ethyl acetate: methanol=15:1~10:1, V/V) purification, produces
Rate: 53%.
Embodiment 2
3- (3- ((5- methyl -4- ((4- methylbenzilidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) propoxyl group) -
5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A2) preparation method, including with
Lower step:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 5- methyl -4- ((4- methylbenzilidene) amino) -4H-1,2,4- triazole -3- mercaptan:
Such as 1 (3) step of embodiment, difference is using p-tolyl aldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin:
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((4- methylbenzilidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A2) preparation:
Such as 1 (6) step of embodiment, difference is with 5- methyl -4- ((4- methylbenzilidene) amino) -4H-1,2,4- tri-
Azoles -3- mercaptan is raw material, yield: 61%.
Embodiment 3
3- (3- ((5- methyl -4- ((3- methylbenzilidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) propoxyl group) -
5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A3) preparation method, including with
Lower step:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 5- methyl -4- ((3- methylbenzilidene) amino) -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment, difference is using tolyl aldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((3- methylbenzilidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A3) preparation:
Such as 1 (6) step of embodiment, difference is with 5- methyl -4- ((3- methylbenzilidene) amino) -4H-1,2,4- tri-
Azoles -3- mercaptan is raw material, yield: 69%.
Embodiment 4
3- (3- ((5- methyl -4- ((4- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A4) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 4- ((4- benzylidene) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment, difference is using P-methoxybenzal-dehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((4- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A4) preparation:
Such as 1 (6) step of embodiment, difference is with 4- ((4- benzylidene) amino) -5- methyl -4H-1,2,4-
Triazole -3- mercaptan is raw material, yield: 75%.
Embodiment 5
3- (3- ((5- methyl -4- ((2- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A5) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 4- ((2- benzylidene) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment, difference is using Benzaldehyde,2-methoxy as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((2- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A5) preparation:
Such as 1 (6) step of embodiment, difference is with 4- ((2- benzylidene) amino) -5- methyl -4H-1,2,4-
Triazole -3- mercaptan is raw material, yield: 66%.
Embodiment 6
3- (3- ((5- methyl -4- ((3,4- dimethyl benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A6) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 4- ((3,4- dimethyl benzylidene) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan:
Such as 1 (3) step of embodiment, difference is with 3,4- dimethylbenzaldehyde for raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((3,4- dimethyl benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl)
Propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A6) preparation:
Such as 1 (6) step of embodiment, difference is with 4- ((3,4- dimethyl benzylidene) amino) -5- methyl -4H-1,2,
4- triazole -3- mercaptan is raw material, yield: 51%.
Embodiment 7
3- (3- ((5- methyl -4- ((3,4- dimethoxybenzylidenegroup group) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A7) preparation method,
The following steps are included:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 4- ((3,4- dimethoxybenzylidenegroup group) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment, difference is using Veratraldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((3,4- dimethoxybenzylidenegroup group) amino) -4H-1,2,4- triazole -3- base) sulphur
Base) propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A7) system
It is standby:
Such as 1 (6) step of embodiment, difference is with 4- ((3,4- dimethyl benzylidene) amino) -5- methyl -4H-1,2,
4- triazole -3- mercaptan is raw material, yield: 64%.
Embodiment 8
3- (3- ((5- methyl -4- ((2,4- dimethoxybenzylidenegroup group) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A8) preparation method,
The following steps are included:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 4- ((2,4- dimethoxybenzylidenegroup group) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment, difference is with 2,4- dimethoxy benzaldehyde for raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((2,4- dimethoxybenzylidenegroup group) amino) -4H-1,2,4- triazole -3- base) sulphur
Base) propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A8) system
It is standby:
Such as 1 (6) step of embodiment, difference is with 4- ((2,4- dimethyl benzylidene) amino) -5- methyl -4H-1,2,
4- triazole -3- mercaptan is raw material, yield: 56%.
Embodiment 9
3- (3- ((5- methyl -4- ((4- tert-butyl benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A9) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 4- ((4- tert-butyl benzal) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment, difference is using p-t-Butylbenzaldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((4- tert-butyl benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A9) preparation:
Such as 1 (6) step of embodiment, difference is with 4- ((4- tert-butyl benzal) amino) -5- methyl -4H-1,2,4-
Triazole -3- mercaptan is raw material, yield: 44%.
Embodiment 10
3- (3- ((5- methyl -4- ((2- thienyl methene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A10) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 5- methyl -4- ((thiophene -2- methylene) amino) -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment, difference is using 2 thiophene carboxaldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (3- bromine propoxyl group) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment.
(6) 3- (3- ((5- methyl -4- ((2- thienyl methene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) third
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A10) preparation:
Such as 1 (6) step of embodiment, difference is with 5- methyl -4- ((2- thienyl methene) amino) -4H-1,2,4-
Triazole -3- mercaptan is raw material, yield: 40%.
Embodiment 11
3- (4- ((5- methyl -4- ((benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) butoxy) -5,7- two
Methoxyl group -2- (3,4,5- trimethoxyphenyl) -4H- benzopyran-4-one (target compound A11) preparation method, including it is following
Step:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 4- ((benzylidene) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 1 (5) step of embodiment, difference is using Isosorbide-5-Nitrae-dibromobutane as raw material.
(6) 3- (4- ((5- methyl -4- ((benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) butoxy) -5,
7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- benzopyran-4-one (target compound A11) preparation:
Such as 1 (6) step of embodiment, difference is with 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- front threes
Phenyl) -4H- chromene -4- ketone be raw material, yield: 52%.
Embodiment 12
3- (4- ((5- methyl -4- ((4- methylbenzilidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) butoxy) -
5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A12) preparation method, including with
Lower step:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 11 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 11 (2) step of embodiment.
(3) preparation of 5- methyl -4- ((4- methylbenzilidene) amino) -4H-1,2,4- triazole -3- mercaptan
Such as 11 (3) step of embodiment, difference is using p-tolyl aldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 11 (4) step of embodiment.
(5) 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 11 (5) step of embodiment.
(6) 3- (4- ((5- methyl -4- ((4- methylbenzilidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A12) preparation:
Such as 11 (6) step of embodiment, difference is with 5- methyl -4- ((4- methylbenzilidene) amino) -4H-1,2,4- tri-
Azoles -3- mercaptan is raw material, yield: 46%.
Embodiment 13
3- (4- ((5- methyl -4- ((3- methylbenzilidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) butoxy) -
5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A13) preparation method, including with
Lower step:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 11 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 11 (2) step of embodiment.
(3) preparation of 5- methyl -4- ((3- methylbenzilidene) amino) -4H-1,2,4- triazole -3- mercaptan
Such as 11 (3) step of embodiment, difference is using tolyl aldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 11 (4) step of embodiment.
(5) 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 11 (5) step of embodiment.
(6) 3- (4- ((5- methyl -4- ((3- methylbenzilidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A13) preparation:
Such as 11 (6) step of embodiment, difference is with 5- methyl -4- ((3- methylbenzilidene) amino) -4H-1,2,4- tri-
Azoles -3- mercaptan is raw material, yield: 43%.
Embodiment 14
3- (4- ((5- methyl -4- ((4- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A14) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 11 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 11 (2) step of embodiment.
(3) preparation of 4- ((4- benzylidene) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 11 (3) step of embodiment, difference is using P-methoxybenzal-dehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 11 (4) step of embodiment.
(5) 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 11 (5) step of embodiment.
(6) 3- (4- ((5- methyl -4- ((4- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A14) preparation:
Such as 11 (6) step of embodiment, difference is with 4- ((4- benzylidene) amino) -5- methyl -4H-1,2,4-
Triazole -3- mercaptan is raw material, yield: 65%.
Embodiment 15
3- (4- ((5- methyl -4- ((2- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A15) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 11 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 11 (2) step of embodiment.
(3) preparation of 4- ((2- benzylidene) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 11 (3) step of embodiment, difference is using Benzaldehyde,2-methoxy as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 11 (4) step of embodiment.
(5) 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 11 (5) step of embodiment.
(6) 3- (4- ((5- methyl -4- ((2- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A15) preparation:
Such as 11 (6) step of embodiment, difference is with 4- ((2- benzylidene) amino) -5- methyl -4H-1,2,4-
Triazole -3- mercaptan is raw material, yield: 58%.
Embodiment 16
3- (4- ((5- methyl -4- ((3,4- dimethyl benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A16) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 11 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 11 (2) step of embodiment.
(3) preparation of 4- ((3,4- dimethyl benzylidene) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 11 (3) step of embodiment, difference is with 3,4- dimethylbenzaldehyde for raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 11 (4) step of embodiment.
(5) 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 11 (5) step of embodiment.
(6) 3- (4- ((5- methyl -4- ((3,4- dimethyl benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl)
Butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A16) preparation:
Such as 11 (6) step of embodiment, difference is with 4- ((3,4- dimethyl benzylidene) amino) -5- methyl -4H-1,2,
4- triazole -3- mercaptan is raw material, yield: 42%.
Embodiment 17
3- (4- ((5- methyl -4- ((3,4- dimethoxybenzylidenegroup group) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A17) preparation method,
The following steps are included:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 11 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 11 (2) step of embodiment.
(3) preparation of 4- ((3,4- dimethoxybenzylidenegroup group) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 11 (3) step of embodiment, difference is using Veratraldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 11 (4) step of embodiment.
(5) 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 11 (5) step of embodiment.
(6) 3- (4- ((5- methyl -4- ((3,4- dimethoxybenzylidenegroup group) amino) -4H-1,2,4- triazole -3- base) sulphur
Base) butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A17) system
It is standby:
Such as 11 (6) step of embodiment, difference is with 4- ((3,4- dimethoxybenzylidenegroup group) amino) -5- methyl -4H-1,
2,4- triazole -3- mercaptan are raw material, yield: 61%.
Embodiment 18
3- (4- ((5- methyl -4- ((4- tert-butyl benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A18) preparation method, packet
Include following steps:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 11 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 11 (2) step of embodiment.
(3) preparation of 4- ((4- tert-butyl benzal) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 11 (3) step of embodiment, difference is using p-t-Butylbenzaldehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 11 (4) step of embodiment.
(5) 3- (4- bromine butoxy) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (in
Mesosome 5) preparation:
Such as 11 (5) step of embodiment.
(6) 3- (4- ((5- methyl -4- ((4- tert-butyl benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) fourth
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A18) preparation:
Such as 11 (6) step of embodiment, difference is with 4- ((4- tert-butyl benzal) amino) -5- methyl -4H-1,2,4-
Triazole -3- mercaptan is raw material, yield: 45%.
Embodiment 19
3- ((5- ((5- methyl -4- ((benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) amyl) oxygroup) -5,
7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A19) preparation method, including it is following
Step:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 1 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 1 (2) step of embodiment.
(3) preparation of 4- ((benzal) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 1 (3) step of embodiment.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (4) step of embodiment.
(5) 3- ((5- bromo amyl) oxygen) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4-
The preparation of ketone (intermediate 5):
Such as 1 (5) step of embodiment, difference is that pentamethylene bromide is raw material with 1.
(6) 3- ((5- ((5- methyl -4- ((benzal) amino) -4H-1,2,4- triazole -3- base) sulfenyl) amyl) oxygen
Base) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A19) preparation:
Such as 1 (6) step of embodiment, difference is with 3- ((5- bromo amyl) oxygen) -5,7- dimethoxy -2- (3,4,5-
Trimethoxyphenyl) -4H- chromene -4- ketone be raw material, yield: 51%.
Embodiment 20
3- ((5- ((5- methyl -4- ((4- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) amyl)
Oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A20) preparation method,
The following steps are included:
(1) preparation of diazanyl thio-hydrazide (intermediate 1):
Such as 19 (1) step of embodiment.
(2) preparation of 4- amino -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediate 2):
Such as 19 (2) step of embodiment.
(3) preparation of 4- ((4- benzylidene) amino) -5- methyl -4H-1,2,4- triazole -3- mercaptan
Such as 19 (3) step of embodiment, difference is using P-methoxybenzal-dehyde as raw material.
(4) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 19 (4) step of embodiment.
(5) 3- ((5- bromo amyl) oxygen) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4-
The preparation of ketone (intermediate 5):
Such as 19 (5) step of embodiment.
(6) 3- ((5- ((5- methyl -4- ((4- benzylidene) amino) -4H-1,2,4- triazole -3- base) sulfenyl) penta
Base) oxygroup) -5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (target compound A20) system
It is standby:
Such as 19 (6) step of embodiment, difference is with 4- ((4- benzylidene) amino) -5- methyl -4H-1,2,4-
Triazole -3- mercaptan is raw material, yield: 66%.
1 target compound physicochemical property of table
2 target compound hydrogen nuclear magnetic resonance modal data of table
3 target compound carbon-13 nmr spectra data of table
Test example 1
Activity of resisting tobacco mosaic virus test:
(1) test method
A. Virus purification
Quadratic method (Zhou, X.P. are avenged using week；Xu,Z.X.；Xu,J.；Li,D.B.J.South
Chin.Agric.Univ.1995,16,74-79.), inoculation 3 weeks or more are chosen, TMV systemic infection host Nicotiana
Tabacum.L plant upper blade, is homogenized in phosphate buffer, double gauze filtering, 8000g centrifugation, through 2 polyethylene glycol
Processing, then be centrifuged, precipitating phosphate buffer suspends to get the refining liquid body of TMV is arrived.Entire experiment carries out at 4 DEG C.With purple
The absorbance value of outer spectrophotometric determination 260nm wavelength calculates virus concentration according to formula.
Virus concentration (mg/mL)=(A260× extension rate)/E0.1% 1cm 260nm
Wherein E indicates extinction coefficient, i.e. when wavelength 260nm, concentration is the suspension of 0.1% (1mg/mL), is in light path
Absorbance value when 1cm.The E of TMV0.1% 1cm 260nmIt is 5.0.
B. the living body therapeutic effect that medicament infects TMV
Living body therapeutic effect of the medicament to infecting: the Nicotiana glutinosa of growing way consistent 5-6 leaf phase is selected to pinch, Xiang Quanye sprinkles evenly gold
Emery dips viral juice (6 × 10 with spread pen-3Mg/mL) full leaf virus inoculation is rinsed with clear water after natural drying.To blade
After dry, medicament is gently spread in Zuo Banye with writing brush, the solvent for the concentration that right half leaf spreads corresponding solvent compares, 6-7d postscript
Withered spot number is recorded, inhibiting rate is calculated according to the following formula.
C. the living body protective effect that medicament infects TMV
The living body protective effect that medicament infects TMV: it selects the Nicotiana glutinosa of growing way consistent 5~6 leaf phase to pinch, is existed with writing brush
Zuo Banye gently spreads medicament, and the solvent for the concentration that right half leaf spreads corresponding solvent compares.After for 24 hours, Xiang Quanye sprinkles evenly Buddha's warrior attendant
Sand dips viral juice (6 × 10 with spread pen-3Mg/mL) full leaf virus inoculation is rinsed with clear water, and withered spot number is recorded after 6~7d,
Inhibiting rate is calculated according to the following formula.
D. the living body protective effect that medicament infects TMV
Medicament is mixed into passivation 30min with isometric viral juice, the mixed liquor of medicament and virus, people are dipped with spread pen
Work frictional inoculation is supported below blade with smooth plank on the left half of blade of the blade sprinkled with diamond dust.Aqua sterilisa and virus
Right half leaf of juice combined inoculation.Every chemicals treatment sets 3 plants, and plant is then placed on moisturizing in illumination box by every plant of 5-6 piece leaf
Culture controls 23 ± 1 DEG C of temperature, the number for generating withered spot is observed and recorded after illumination 10000Lux, 6-7d.
Wherein, the average withered spot number for being not coated with application half leaf of agent and the half leaf withered spot number for spreading medicament all use each group to weigh three times
Multiple average.Calculate inhibiting rate.
(2) the biological activity test result of resisting tobacco mosaic virus
4 target compound of table is to the treatment of tobacco mosaic virus (TMV), protection and passivation activity
It is control with virazole raw medicine and commodity medicament Ningnanmycin using half leaf withered spot method, is 500 μ g/ for examination concentration
When mL, target compound A is tested1~A20To the therapeutic activity of tobacco mosaic virus (TMV) (TMV), protection activity and passivation activity
(being shown in Table 4).The test result shows: most of target compound has preferable therapeutic activity, protection activity and passivation to TMV
Activity.Wherein, target compound A6、A10、A11、A14Preferable therapeutic effect possessed to TMV, inhibiting rate is respectively 49.4,
52.4,50.8,50.2%, be more than virazole raw medicine (39.9%), close to Ningnanmycin (52.7%).Target compound A6、A11
Preferable protective effect is possessed to TMV, inhibiting rate is respectively 58.7,57.2,58.0%, is better than virazole raw medicine
(51.8%), close to Ningnanmycin (65.7%).Target compound A7、A9、A20To TMV passivation activity be respectively 88.6,77.5,
74.6%, wherein A7Inhibiting rate close to Ningnanmycin (90.4%).
Test example 2
Anti- vegetative bacteria active testing:
(1) test method
Using nephelometry, under 50 and 25 μ g/mL concentration, test target compound is to citrus processing and the white leaf of rice
The external inhibitory activity of blight bacterium, comparison medicament is Yekuzuo and Thiodiazole-copper in experiment.By citrus processing and the white leaf of rice
Blight bacterium is cultivated on NA solid medium, is subsequently placed in 28 DEG C of constant-temperature bacterial culture box and cultivates to growing single colonie.Choosing
Suitable central yellow single colonie is taken, puts it in NB fluid nutrient medium, training is vibrated in 28 DEG C, 180r/min constant-temperature table
It is spare to support logarithmic growth phase.50 and 25 μ g/mL concentration are configured by compound and comparison medicament, 1mL is taken to be added to equipped with 4mL
In the test tube of NB fluid nutrient medium, then measure the NB fluid nutrient medium that 40 μ L contain citrus processing and rice leaf spot bacteria
It is added in test tube, in 28 DEG C, 180r/min constant-temperature table shaken cultivation 48h.On spectrophotometer, measure at 595nm wavelength
The OD of the sterile NB fluid nutrient medium of dosing595Value, while measuring the bacterium solution OD of each concentration595Value.
Correct OD595Value=OD containing bacterium culture medium595Aseptic culture medium OD595
Inhibiting rate (%)=(control medium bacterium solution OD after correction595Correct pastille culture medium OD595It is compareed after)/correction
Value × 100%. culture medium bacterium solution OD
(2) the biological activity test result of anti-plant pathogen
5 target compound A of table1~A16Bacteriostatic activity (inhibiting rate %)a
aIt is average to repeat three times；bYekuzuo and Thiodiazole-copper (20% wettable powder) are used as positive control.
It is being 50,25 μ g/mL for examination concentration using commodity medicament Thiodiazole-copper and Yekuzuo as positive control using nephelometry
When, target compound is tested to the inhibitory activity (being shown in Table 5) of hundred leaf spoting bacteria of citrus processing and rice.As the result is shown:
All compounds have certain inhibitory activity to citrus processing and rice leaf spot bacteria.It, should to citrus processing
Series compound the inhibiting rate of 50 μ g/mL and 25 μ g/mL be more than comparison medicine Yekuzuo and Thiodiazole-copper (respectively 49.49,
36.82,47.94,36.12%).To rice leaf spot bacteria, inhibiting rate of the series compound in 50 μ g/mL and 25 μ g/mL
Better than comparison medicine Yekuzuo and Thiodiazole-copper, (respectively 32.54,27.65,24.12,19.13%), have preferable broad spectrum activity.
The above assay activity statistics indicate that the myricetin derivative containing quinoxaline to TMV and phytopathogen (citrus bacterial canker disease
Hundred leaf spoting bacteria of bacterium and rice) there is certain inhibiting effect, part of target compound is to plant virus and phytopathogen
Excellent inhibitory activity is shown, can be used as potential Antiphytoviral drug and antibacterial medicines, with good application prospect.
In conclusion being only presently preferred embodiments of the present invention, it is not intended to limit the present invention in any form, appoints
What is to the above embodiments according to the technical essence of the invention any simply to repair without departing from technical solution of the present invention content
Change, equivalent variations and modification, all of which are still within the scope of the technical scheme of the invention.
Claims (4)
1. a kind of myricetin derivative of Sulfide-containing Hindered triazole schiff bases, general structure are as follows:
,
Wherein, R is phenyl, substituted-phenyl, aromatic heterocyclic；N is that the number of carbon in carbochain is respectively 3,4,5.
2. a kind of preparation method of the myricetin derivative of Sulfide-containing Hindered triazole schiff bases, synthetic route are as follows:
(1) using hydrazine hydrate, carbon disulfide as raw material, by being heated to reflux, it is (intermediate that solid recrystallization prepares diazanyl thio-hydrazide
Body 1):
；
(2) using diazanyl thio-hydrazide (intermediate 1) and glacial acetic acid as raw material, by being heated to reflux, solid recrystallization preparation 4- ammonia
Base -5- methyl -4H- 1,2- 4- triazole -3- sulfydryl (intermediate 2):
；
(3) with 4- amino -5- methyl -4H- 1,2- 4- triazole -3- sulfydryl (intermediate 2) and substitution aldehyde are raw material, with dense sulphur
Acid is catalyst, using ethyl alcohol as solvent, prepares 4 (substituted methylene) -5- methyl -4H-1,2,4- triazole -3- sulfydryl (intermediates
3):
；
(4) using myricetrin and iodomethane as raw material, using potassium carbonate as catalyst, acidity, which is adjusted, prepares 3- hydroxyl -3 ', and 4 ', 5 ',
5,7- pentamethoxyl myricetin (intermediate 4):
；
(5) with 3- hydroxyl -3 ', two bromoalkanes of 4 ', 5 ', 5,7- pentamethoxyl myricetin (intermediate 4) and different chain length are original
Material is catalyst with potassium carbonate, n,N-Dimethylformamide (DMF) be solvent prepare bromo- 5, the 7- dimethoxy -2- of 3- (3,4,
5- trimethoxyphenyl) -4H- chromene -4- ketone (intermediate 5), as follows:
；
(6) with 3- bromo- 5,7- dimethoxy -2- (3,4,5- trimethoxyphenyl) -4H- chromene -4- ketone (intermediate 5) and 4
(substituted methylene) -5- methyl -4H-1,2,4- triazole -3- sulfydryls (intermediate 3) are raw material, are catalyst with potassium carbonate, N,
Dinethylformamide (DMF) is the myricetin derivative (target compound A) that solvent prepares Sulfide-containing Hindered triazole schiff bases, as follows
It is shown:
。
3. a kind of application of myricetin derivative of Sulfide-containing Hindered triazole schiff bases in terms of inhibiting tobacco mosaic virus (TMV).
4. a kind of myricetin derivative of Sulfide-containing Hindered triazole schiff bases is inhibiting citrus processing and rice leaf spot bacteria
Using.
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