CN102627600A - Multivalent nicotine compound, and preparation method and application of multivalent nicotine compound - Google Patents
Multivalent nicotine compound, and preparation method and application of multivalent nicotine compound Download PDFInfo
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- CN102627600A CN102627600A CN201210121014XA CN201210121014A CN102627600A CN 102627600 A CN102627600 A CN 102627600A CN 201210121014X A CN201210121014X A CN 201210121014XA CN 201210121014 A CN201210121014 A CN 201210121014A CN 102627600 A CN102627600 A CN 102627600A
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Abstract
The invention discloses a multivalent nicotine compound which belongs to the technical fields of organic synthesis and chemical pesticide synthesis. A general formula of the compound is (I) in which A and B are molecules of the nicotine compound or composition groups of the nicotine compound. The invention further discloses a preparation method of this kind of compound. The preparation method has a simple synthesis technology and high yield. The invention further discloses the application of this kind of compound in pesticide preparation. The pesticide has the advantages of high efficiency, low toxicity, and excellent environment compatibility.
Description
Technical field
The invention belongs to organic synthesis and chemical pesticide synthesis technical field, be specifically related to a kind of multiple-effect valency nicotine compound.
Background technology
The biological activity of utilizing cluster effect to improve parent compound in medical research, shown very big potentiality (Angew.Chem.Int.Ed.Engl.1998,37,2754-2794.).The cluster effect technology is applied in the research of novel pesticide initiative; Utilize this principle that some existing agricultural chemicals or potential pesticide activity molecule are screened; Development and find activity higher, with the better novel pesticide molecule of Environmental compatibility, will reach the effect of getting twice the result with half the effort.At present, because a lot of pesticide species action site is single, excessively use to cause target to develop immunity to drugs.Utilize cluster effect synthetic multiple acting site compound might delay the resistance problem that single action target causes.
Field of medicaments also provides foundation for the synthetic multiple acting site of design compound retards target resistance, is monomeric 1475 times of tacrine as being the monolithic design synthetic with the tacrine with bunch tacrine two duster compound of tiring to the inhibition activity of mouse brain E.C. 3.1.1.7.This will significantly reduce the consumption of tacrine, so delay the target enzyme produce resistance (J.Med.Chem.2002,45,2277-2282).With respect to the medical research field, cluster effect just just begins in the research of pesticide field.In recent years, reported organophosphorus that methylene radical with different chain length, end alkyl diethylamide connect as Linker and amino formate two duster compound of tiring in succession, and its biological activity had been estimated.Relative monomer molecule, two compounds of tiring show stronger evident characteristics and bonding force to the d.a. site of E.C. 3.1.1.7.Live body give birth to be surveyed and to be shown, part two tire compound to aphid and red spider kill effect be issued to more than 95% in the situation of 200mg/L (Bioorg.Med.Chem.Lett.2011,21,6404-6408.).
Summary of the invention
First purpose of the present invention provides a kind of multiple-effect valency nicotine compound.
Second purpose of the present invention provides the preparation method of above-mentioned multiple-effect valency nicotine compound.
The 3rd purpose of the present invention provides the application in the sterilant preparation of above-mentioned multiple-effect valency nicotine compound.
A kind of multiple-effect valency nicotine compound, the general formula of said compound is (I):
A——Linker——B
(I)
Wherein A, B, Linker have following meaning:
A and B are identical or different, are respectively a kind of in the following groups:
-5-O-2-F-pyridine ,-5-O-2-Cl-pyridine ,-5-O-2-Br-pyridine ,-5-O-2-I-pyridine ,-5-HNCH
2-2-Cl-thiazole ,-5-HNCH
2-2-Br-thiazole ,-5-HNCH
2-2-F-thiazole ,-2-HNCH
2-4-Cl-furans ,-2-HNCH
2-furans ,-3-HNCH
2-furans ,-4-HNCH
2-furans ,-5-HNCH
2-2-I-furans;
Linker is a kind of in the terminal dicarbapentaborane group of terminal diamide base and straight chain of alkyl, straight chain of straight chain, and wherein the straight chain chain length is 2-15 methylene radical.
The preparation method of above-mentioned a kind of multiple-effect valency nicotine compound comprises:
(1) A, B are identical, A=B then, and synthesis step is: the nicotine compound that will contain the A group is dissolved in organic solvent, adds the two halogenated compounds of Linker, is heated to backflow, and suction filtration concentrates, and obtains product through chromatography post or underpressure distillation; Wherein containing the nicotine compound of A group and the mol ratio of the two halogenated compounds of Linker is: 2: 1.05-1.2; Wherein involved reaction formula is (1):
(2) A, B difference, synthesis step is: the nicotine compound that the first step will contain the A group is dissolved in organic solvent, adds salt of wormwood; The two halogenated compounds that add Linker; Be heated to backflow, suction filtration concentrates; Obtain single halo midbody of A through chromatography post or underpressure distillation, the involved reaction formula of reaction process is (2); Wherein containing the nicotine compound of A group and the mol ratio of the two halogenated compounds of Linker is: 1: 2.5-3.5; Second step was dissolved in organic solvent with single halo midbody, added salt of wormwood, added the nicotine compound that contains the B group, was warming up to backflow, filtered, and concentrated filtrate gets product through chromatography post or underpressure distillation; Wherein single halo midbody with the mol ratio that contains the nicotine compound of B group is: 1: 1.2-1.5; The involved reaction formula of reaction process is (3):
Above-mentioned organic solvent is: N, methylene dichloride, acetonitrile, methyl alcohol or acetone.
The reaction times is respectively 8-12h in the synthesis step of above-mentioned (1) and (2), and temperature of reaction is respectively the 45-80 degree.
Above-mentioned a kind of multiple-effect valency nicotine compound in the sterilant of preparation aphid, red spider or beet armyworm as the application of activeconstituents.
Beneficial effect of the present invention is: this type of multiple-effect valency nicotine compound, novel structure; Compound method is simple, and raw material is easy to get; Crop pests such as aphid, red spider and beet armyworm there is tangible insecticidal activity, can be applicable to the integrated control of farm crop.
Embodiment
Multiple-effect valency nicotine structural general formula of the present invention is (I), the Given this economy of compound and biological activity, and in general structure (I), it is as shown in the table for preferential substituting group:
Table 1.1 is depicted as A, the B group is identical, and Linker is the chain that the terminal diamide of 2 methylene radical connections forms, the characteristic of the compound of being formed.
Table 1.1
Table 1.2 is that A, B group are identical, Linker is the terminal dicarbapentaborane chain that 4 methylene radical connect, the characteristic of the compound of being formed.
Table 1.2
Table 2.1 is that A, B are different, and Linker is 2 chains that methylene radical is connected to form, the characteristic of the compound of being formed.
Table 2.1
Table 2.2. is that A, B group are different, and Linker is 6 chains that methylene radical is connected to form, the characteristic of the compound of being formed.
Table 2.2
Table 2.3 is that A, B group are different, and Linker is the terminal dicarbapentaborane chain that 3 methylene radical are connected to form, the characteristic of the compound of being formed.
Table 2.3
2.4 be that A, B group are different, Linker is the terminal diamide chain that 5 methylene radical connect, the compound of being formed.
Table 2.4
Following embodiment is the preparation method of multiple-effect valency nicotine compound, the present invention is explained further details, but do not limit the present invention.Enumerate the embodiment of the invention below:
Embodiment 1
Compound N 21, the preparation of { 1,2-two (6-chloropyridine-3-oxygen) } ethane.
Compound method: get 2.59g (20mmol) 2-chloro-5-pyridone and be dissolved in the 30ml acetone, add 0.57g (24mmol) sodium hydride, glycol dibromide 2.06g (11mmol) is heated to backflow, reaction 8h, and suction filtration concentrates acetone soln, crosses post, gets pure article 0.99g.Productive rate 35% concrete physico-chemical property is following: fusing point: 88-90 ℃.
1HNMR(CDCl
3，300M)δ＝8.11(m，2H)，7.26(m，4H)，4.38(s，4H)。Anal.Calcd.for?C
12H
10Cl
2N
2O
2，C?50.55％，H?3.54％，N?9.82％.Found：C50.05％，H3.62％，N?9.90％。
Embodiment 2
Compound N 22, the preparation of { 1,2-two (6-chloropyridine-3-oxygen) } propane.
Compound method is as embodiment 1, and different is that alkane is 1, and the 3-dibromopropane obtains white crystal compound N 22, productive rate 32%, and the concrete physico-chemical property of compound is following: fusing point: 95-98 ℃.
1HNMR(CDCl
3，300M)δ＝8.07(m，2H)，7.22(m，4H)，4.19(m，4H)2.28(m，2H)。Anal.Calcd?for?C
13H
12Cl
2N
2O
2，C?52.19％，H?4.04％，N?9.36％.Found：C50.06％，H3.92％，N?9.40％。
Embodiment 3
Compound N 24, the preparation of { 1,2-two (6-chloropyridine-3-oxygen) } pentane.
Compound method is as embodiment 1, and different is that alkane is pentamethylene bromide, obtains white crystal compound compound N 24, productive rate 32%, and the concrete physico-chemical property of compound is following: fusing point: 98-100 ℃.
1HNMR(CDCl
3，300M)δ＝8.05(m，2H)，7.21(m，4H)，4.06(m，4H)2.00(m，4H)1.61(s，2H)。Anal.Calcd?for?C
15H
16C
l2N
2O
2，C?55.06％，H?4.93％，N?8.56％.Found：C?50.16％，H?4.99％，N?8.63％。
Embodiment 4
Compound Q 81,2-chloropyridine-5-oxygen-propyl group-N-nitro imino--1,3-imidazolidine.
The preparation of midbody 2-chloro-pyridine 5-oxygen propyl bromide.Compound method: get 1.13g (10mmol) 2-chloro-5-picoline and be dissolved in the 30ml acetone, add 1.66g (12mmol) salt of wormwood, 1,3-dibromopropane 5.64g (30mmol); Be heated to backflow, reaction 10h, suction filtration; Concentrate acetone soln, cross post, get pure article 2.05g.Productive rate 80% concrete physico-chemical property is following: fusing point: 58-60 ℃.
1HNMR(CDCl
3，300M)δ＝8.08(m，1H)，7.23(m，2H)，4.35(m，2H)，3.65(m，2H)，2.23(m，2H)。Anal.Calcd?for?C
8H
9BrClNO，C?38.35％，H?3.62％，N?5.59％.Found：C38.45％，H3.70％，N?5.68％。
Get 2.55g (10mmol) 2-chloro-pyridine 5-oxygen propyl bromide and be dissolved in the methyl alcohol, add salt of wormwood 1.66g (12mmol), N-nitro imino--1, the 3-imidazolidine is warming up to backflow, and reaction 12h filters, and concentrated filtrate is crossed post and is got product Q81,1.2g, yield 39%.Concrete physico-chemical property is following: fusing point: 112-114 ℃.
1HNMR(CDCl
3，300M)δ＝8.12(s，1H)，8.05(m，1H)，7.25(m，2H)4.21(m，2H)3.84(m，4H)，，3.80(m，2H)2.19(m，2H)。Anal.Calcd?for?C
11H
14ClN
5O
3，C?44.08％，H?4.71％，N23.37％.Found：C?44.12％，H?4.80％，N?23.25％。
Embodiment 5
Compound Q 82,2-chloropyridine-5-oxygen-butyl-N-nitro imino--1,3-imidazolidine.
Compound method is as embodiment 4, and different is that alkane is 1, and the 4-dibromobutane obtains white solid compound Q 82.Yield 28.56%.The concrete physico-chemical property of compound is following: fusing point: 132-133 ℃.
1HNMR(CDCl
3，300M)δ＝8.13(s，1H)，8.06(m，1H)，7.24(m，2H)4.22(m，2H)3.86(m，4H)，，3.77(m，2H)2.12(m，4H)。Anal.Calcd?for?C
12H
16ClN
5O
3，C?45.94％，H?5.14％，N22.32％.Found：C?46.05％，H?5.21％，N?22.40％。
Embodiment 6
Compound Q 84,2-chloropyridine-5-oxygen-hexyl-N-nitro imino--1,3-imidazolidine.
Compound method is as embodiment 4, and different is that alkane is 1, and the 6-dibromo-hexane obtains white solid compound Q 84.Yield 38.44%.The concrete physico-chemical property of compound is following: fusing point: 145-147 ℃.
1HNMR(CDCl
3，300M)δ＝8.16(s，1H)，8.07(m，1H)，7.22(m，2H)4.30(m，2H)3.89(m，4H)，，3.75(m，4H)2.10(m，4H)，1.52(m，2H)。Anal.Calcd.for?C
14H
20ClN
5O
3，C?49.20％，H5.90％，N20.49％.Found：C49.31％，H6.01％，N?20.55％。
The purposes of multiple-effect valency nicotine compound, it is characterized in that as preparation anti-eliminate aphis, crop pests pesticide active ingredients such as red spider and beet armyworm.
It below is insecticidal activity evaluation to aphid and red spider; Concrete experimental technique is following: black peach aphid, tetranychid blade medicine embrane method: multiple-effect valency nicotine compound is mixed with 1% mother liquor with organic solvent (DMF or DMSO) earlier; Be diluted to the aqueous solution that contains the 0.05%-triton x-100 again and measure soup (200mg/L); The band worm blade that picking is suitable then, dipping is 10 seconds in soup, dries.The band worm blade that will soak the medicine processing is put into the glass culture dish (5.5 centimetres of diameters) of band filter paper, and three repetitions of each medicament are sealed, added a cover with preservative film.In (25 ± 1) ℃ illumination box, keep checking mortality ratio after 48 hours.Provado is as the contrast medicament, and its concentration is (20mg/L).
Experimental result such as following table 3.1:
3.1 multiple-effect valency nicotine compound is to the insecticidal activity assay of black peach aphid, two-spotted spider mite
Can find out from table 3.1; Multiple-effect valency nicotine compound is under the 200mg/L condition, and part N series compound shows the ideal insecticidal activity to two-spotted spider mite, mortality ratio reached 90% and more than; To black peach aphid; N29 and Q83 have shown insecticidal activity preferably equally, and primary dcreening operation is the result show, this neonicotine insecticidal active compound can be used as the activeconstituents of preparation two-spotted spider mite and black peach aphid sterilant.
Claims (5)
1. multiple-effect valency nicotine compound is characterized in that the general formula of said compound is (I):
A——Linker——B
(I)
Wherein A, B, Linker have following meaning:
A and B are identical or different, are respectively a kind of in the following groups:
-5-O-2-F-pyridine ,-5-O-2-Cl-pyridine ,-5-O-2-Br-pyridine ,-5-O-2-I-pyridine ,-5-HNCH
2-2-Cl-thiazole ,-5-HNCH
2-2-Br-thiazole ,-5-HNCH
2-2-F-thiazole ,-2-HNCH
2-4-Cl-furans ,-2-HNCH
2-furans ,-3-HNCH
2-furans ,-4-HNCH
2-furans ,-5-HNCH
2-2-I-furans;
Linker is a kind of in the terminal dicarbapentaborane group of terminal diamide base and straight chain of alkyl, straight chain of straight chain, and wherein the straight chain chain length is 2-15 methylene radical.
2. the preparation method of the described a kind of multiple-effect valency nicotine compound of claim 1 is characterized in that, comprising:
(1) A, B are identical, A=B then, and synthesis step is: the nicotine compound that will contain the A group is dissolved in organic solvent, adds the two halogenated compounds of Linker, is heated to backflow, and suction filtration concentrates, and obtains product through chromatography post or underpressure distillation; Wherein containing the nicotine compound of A group and the mol ratio of the two halogenated compounds of Linker is: 2: 1.05-1.2; Wherein involved reaction formula is (1):
(2) A, B difference, synthesis step is: the nicotine compound that the first step will contain the A group is dissolved in organic solvent, adds salt of wormwood; The two halogenated compounds that add Linker; Be heated to backflow, suction filtration concentrates; Obtain single halo midbody of A through chromatography post or underpressure distillation, the involved reaction formula of reaction process is (2); Wherein containing the nicotine compound of A group and the mol ratio of the two halogenated compounds of Linker is: 1: 2.5-3.5; Second step was dissolved in organic solvent with single halo midbody, added salt of wormwood, added the nicotine compound that contains the B group, was warming up to backflow, filtered, and concentrated filtrate gets product through chromatography post or underpressure distillation; Wherein single halo midbody with the mol ratio that contains the nicotine compound of B group is: 1: 1.2-1.5; The involved reaction formula of reaction process is (3):
3. the preparation method of a kind of multiple-effect valency nicotine compound according to claim 2 is characterized in that described organic solvent is: N, methylene dichloride, acetonitrile, methyl alcohol or acetone.
4. the preparation method of a kind of multiple-effect valency nicotine compound according to claim 2 is characterized in that the reaction times in the synthesis step of above-mentioned (1) and (2) is respectively 8-12h, and temperature of reaction is respectively the 45-80 degree.
The described a kind of multiple-effect valency nicotine compound of claim 1 in the sterilant of preparation aphid, red spider or beet armyworm as the application of activeconstituents.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10144713B1 (en) * | 2017-07-24 | 2018-12-04 | University Of South Florida | Bis-cyclic guanidines as antibacterial agents |
| CN114534361A (en) * | 2021-12-31 | 2022-05-27 | 南阳理工学院 | Method for combined extraction of essential oil, nicotine and extract from waste and inferior tobacco leaves |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10144713B1 (en) * | 2017-07-24 | 2018-12-04 | University Of South Florida | Bis-cyclic guanidines as antibacterial agents |
| WO2019022873A1 (en) | 2017-07-24 | 2019-01-31 | University Of South Florida | Novel bis-cyclic guanidines as antibacterial agents |
| US11214550B2 (en) | 2017-07-24 | 2022-01-04 | University Of South Florida | Bis-cyclic guanidines as antibacterial agents |
| US11718585B2 (en) | 2017-07-24 | 2023-08-08 | University Of South Florida | Bis-cyclic guanidines as antibacterial agents |
| CN114534361A (en) * | 2021-12-31 | 2022-05-27 | 南阳理工学院 | Method for combined extraction of essential oil, nicotine and extract from waste and inferior tobacco leaves |
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