(E) -acrylic acid derivative containing xanthine-8-group and preparation method and application thereof
阅读说明：本技术 一种含黄嘌呤-8-基的(e)-丙烯酸衍生物及其制备方法和应用 ((E) -acrylic acid derivative containing xanthine-8-group and preparation method and application thereof ) 是由 王宝雷 张舒昀 刘航 于 2021-09-13 设计创作，主要内容包括：本发明涉及一种含黄嘌呤-8-基的(E)-丙烯酸衍生物及其制备方法和应用。在1,3,7-三取代-8-甲基黄嘌呤原料基础上,通过系列反应所得含黄嘌呤-8-基的(E)-丙烯酸衍生物如通式I所示。通式I化合物具有良好的杀虫活性,特别是对东方粘虫、小菜蛾十分有效,可作为杀虫组合物的活性组分,用于制备农用杀虫剂,用于防治农业虫害。(The invention relates to a (E) -acrylic acid derivative containing xanthine-8-group and a preparation method and application thereof. The (E) -acrylic acid derivative containing the xanthine-8-group, which is obtained by a series of reactions on the basis of 1,3, 7-trisubstituted-8-methylxanthine raw material, is shown as a general formula I. The compound of the general formula I has good insecticidal activity, is particularly effective to oriental armyworm and diamondback moth, can be used as an active component of an insecticidal composition, is used for preparing agricultural insecticides, and is used for preventing and controlling agricultural insect pests.)
1. A xanthine-8-group containing (E) -acrylic acid derivative, characterized by having a structural formula shown in general formula I:
in the formula:
x is O, S or N;
R1～R3is C1-C6Alkyl or halo C1-C6An alkyl group;
when X is O or S, no R4；R5Is C1-C6Alkyl, halo C1-C6Alkyl, aryl or aryl substituted C1-C3Alkyl, wherein the hydrogen on the aryl ring may also be further substituted by: halogen, C1-C6Alkyl, halo C1-C6Alkyl, cyano, nitro, phenyl, C1-C6Alkoxy, halo C1-C6Alkoxy radical, C1-C6Alkylthio, halo C1-C6Alkylthio radical, C2-C6Alkenyl, halo C2-C6Alkenyl radical, C3-C6Alkynyl, halo C3-C6Alkynyl, C2-C6Alkenyloxy, halogeno C2-C6Alkenyloxy radical, C3-C6Alkynyloxy, halo C3-C6Alkynyloxy, phenoxy, pyridyloxy, methylenedioxy (-OCH)2O-)；
When X is N, R4Is H or C1-C6An alkyl group; r5Is C1-C6Alkyl, halo C1-C6Alkyl, aryl or aryl substituted C1-C3Alkyl, wherein the hydrogen on the aryl ring may also be further substituted by: halogen, C1-C6Alkyl, halo C1-C6Alkyl, cyano, nitro, phenyl, C1-C6Alkoxy, halo C1-C6Alkoxy radical, C1-C6Alkylthio, halo C1-C6Alkylthio, phenoxy, pyridyloxy.
2. The xanthine-8-group containing (E) -acrylic acid derivatives according to claim 1, wherein in the definition of the derivatives, the terms used, both alone and in compound words, are generally defined as follows:
the halogen is fluorine, chlorine, bromine or iodine;
the alkyl is a straight chain, branched chain alkyl or cycloalkyl, wherein the cycloalkyl comprises a cyclic chain form or an alkyl form with a cyclic chain, in particular a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl or cyclohexyl group;
the aryl is phenyl or aromatic heterocyclic radical, in particular to furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl or triazinyl radical;
said alkenyl is a straight-chain or branched chain having 2 to 6 carbon atoms and may have a double bond at any position, in particular vinyl, propenyl, allyl, 2-methylprop-2-en-1-yl, but-3-en-1-yl, 2-methylbut-2-en-1-yl, 3-methylbut-2-en-1-yl, pent-3-en-1-yl, pent-4-en-1-yl, 2-methylpent-2-en-1-yl, 3-methylpent-2-en-1-yl, hex-2-en-1-yl, hex-3-en-1-yl, hex-4-en-1-yl or hex-5-en-1-yl groups;
said alkynyl is a straight or branched chain having 3 to 6 carbon atoms and may have a triple bond at any position, in particular a propynyl, propargyl, but-2-yn-1-yl, but-3-yn-1-yl, pent-2-yn-1-yl, pent-3-yn-1-yl, pent-4-yn-1-yl, 4-methylpent-2-yn-1-yl, hex-3-yn-1-yl, hex-4-yn-1-yl or hex-5-yn-1-yl group;
the carbon skeleton of the alkoxy is the same as that of the alkyl defined in the definition, and the alkoxy refers to a group with an oxygen atom at the end of the alkyl under the precondition, and specifically is a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, n-hexoxy, cyclopropoxy, cyclopropylmethoxy, cyclobutoxy, cyclobutylmethoxy, cyclopentyloxy, cyclopentylmethoxy or cyclohexoxy group;
the carbon skeleton of the alkylthio group is the same as that of the alkyl group defined by the alkylthio group, and the alkylthio group refers to a group of which the tail end of the alkyl group is connected with a sulfur atom, and specifically refers to a methylthio group, an ethylthio group, a n-propylthio group, an isopropylthio group, a n-butylthio group, an isobutylthio group, a n-pentylthio group, an isopentylthio group, a n-hexylthio group, a cyclopropylthio group, a cyclopropylmethylthio group, a cyclobutylthio group, a cyclopentylthio group, a cyclopentylmethylthio group or a cyclohexylthio group;
the carbon skeleton of the alkenyloxy group is the same as that of the alkenyl group defined in the specification, and the alkenyl group is defined as described above, and the alkenyloxy group refers to a group in which an oxygen atom is bonded to the end of the alkenyl group in the specification;
the carbon skeleton of the alkynyloxy is the same as that of the alkynyl defined in the specification, and the alkynyl is defined as described above, and the alkynyloxy refers to a group with an oxygen atom at the tail end of the alkynyl under the condition that the alkynyl is defined as above;
the halogenated alkyl group is a straight-chain alkyl group, a branched-chain alkyl group or a cyclic alkyl group, and hydrogen atoms on the alkyl groups can be partially or completely substituted by halogen atoms; "haloalkoxy", "haloalkylthio", "haloalkenyl", "haloalkynyl", "haloalkenyloxy" and "haloalkynyloxy" are as defined under the term "haloalkyl";
so-called may be further substituted, the number of substituents thereof may be one or more; the hydrogen on the aromatic ring is further substituted by methylenedioxy (-OCH)2O-) substitution means that two adjacent hydrogens on the aromatic ring are simultaneously substituted with methylenedioxy to form a ring.
3. The (E) -acrylic acid derivative containing a xanthine-8-yl group according to claim 2, wherein:
x is O or N;
R1～R3is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclopropylmethyl, 2-fluoroethyl, 2, 2-difluoroethyl, 2,2, 2-trifluoroethyl, 3-fluoropropyl, 3, 3-difluoropropyl or 3,3, 3-trifluoropropyl;
when X is O, no R4，R5Is methyl, ethylA group selected from the group consisting of a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, an isohexyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclopropylmethyl group, a haloethyl group, a halo-n-propyl group, a halo-isopropyl group, a halo-n-butyl group, a halo-isobutyl group, a halo-sec-butyl group, a halo-tert-butyl group, a halo-n-pentyl group, a halo-isopentyl group, a halo-n-hexyl group, a halo-isohexyl group, a halo-cyclopropyl group, a halo-cyclobutyl group, a halo-cyclopentyl group, a halo-cyclohexyl group, a halo-cyclopropylmethyl group, an aryl group, an arylmethyl group, a 1-arylethyl group, a 2-arylethyl group, a 1-arylpropyl group, a 2-arylpropyl group and a 3-arylpropyl group, the halogenation is that hydrogen atoms on the carbon skeleton are replaced by single or multiple halogen atoms, wherein the halogen is defined as the same as the above;
said aryl group is phenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl, the hydrogen of the aryl ring may be further substituted by: halogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, trifluoromethyl, 2,2, 2-trifluoroethyl, heptafluoroisopropyl, cyano, nitro, phenyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethoxy, 2,2, 2-trifluoroethoxy, methylthio, ethylthio, trifluoromethylthio, trifluoroethylthio, vinyl, propenyl, allyl, propargyl, allyloxy, 3-dichloroallyloxy, propargyloxy, phenoxy, pyridyloxy or methylenedioxy (-OCH)2O-), wherein halogen is as defined above; the above may be further substituted, and the number of substituents thereof may be one or more; the hydrogen on the aromatic ring is further substituted by methylenedioxy (-OCH)2O-) substitution means that two adjacent hydrogens on the benzene ring are simultaneously substituted with methylenedioxy to form a ring;
when X is N, R4Is H, methyl, ethyl, n-propyl, isopropyl,N-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, R5Is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, halomethyl, haloethyl, halo-n-propyl, haloisopropyl, halo-n-butyl, halo-isobutyl, halo-sec-butyl, halo-tert-butyl, halo-n-pentyl, halo-isopentyl, halo-n-hexyl, halo-isohexyl, halo-cyclopropyl, halo-cyclobutyl, halo-cyclopentyl, halo-cyclohexyl, halo-cyclopropylmethyl, aryl, arylmethyl, 1-arylethyl, 2-arylethyl, 1-arylpropyl, 2-arylpropyl or 3-arylpropyl, the halogenation is that hydrogen atoms on the carbon skeleton are replaced by single or multiple halogen atoms, wherein the halogen is defined as the same as the above;
said aryl group is phenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl, the hydrogen of the aryl ring may be further substituted by: halogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, trifluoromethyl, 2,2, 2-trifluoroethyl, heptafluoroisopropyl, cyano, nitro, phenyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethoxy, 2,2, 2-trifluoroethoxy, methylthio, ethylthio, trifluoromethylthio, trifluoroethylthio, phenoxy or pyridyloxy, wherein halogen is as defined above; the above may be further substituted, and the number of substituents may be one or more.
4. The (E) -acrylic acid derivative containing a xanthine-8-yl group according to claim 3, wherein:
x is O or N;
R1～R3is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl or isohexyl;
when X is O, no R4，R5Is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropylmethyl, halomethyl, haloethyl, halo-n-propyl, haloisopropyl, halo-n-butyl, haloisobutyl, halo-sec-butyl, halo-tert-butyl, halo-n-pentyl, halo-isopentyl, halo-n-hexyl, halo-isohexyl, aryl, arylmethyl or 1-arylethyl, said halo being where a hydrogen atom on the carbon skeleton is substituted by a single or multiple halogen atoms, wherein halogen is as defined above;
the aryl is phenyl, thienyl, thiazolyl or pyridyl, and the hydrogen on the aryl ring can be further substituted by the following groups: halogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, trifluoromethyl, 2,2, 2-trifluoroethyl, heptafluoroisopropyl, nitro, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethoxy, 2,2, 2-trifluoroethoxy, vinyl, propenyl, allyl, allyloxy, 3-dichloroallyloxy, phenoxy or methylenedioxy (-OCH)2O-), wherein halogen is as defined above; the above may be further substituted, and the number of substituents thereof may be one or more; the hydrogen on the aromatic ring is further substituted by methylenedioxy (-OCH)2O-) substitution means that two adjacent hydrogens on the benzene ring are simultaneously substituted with methylenedioxy to form a ring;
when X is N, R4Is H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl or isohexyl, R5Is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropylmethyl, aryl orAn arylmethyl group; the aryl group is phenyl, the ring hydrogen of which may be further substituted by: halogen, trifluoromethyl, 2,2, 2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, n-propoxy or isopropoxy, wherein halogen is as defined above; the above may be further substituted, and the number of substituents may be one or more.
5. The (E) -acrylic acid derivative containing a xanthine-8-yl group according to claim 4, wherein:
x is O or N;
R1～R3is methyl;
when X is O, no R4，R5Is methyl, isopropyl, n-butyl, cyclopropylmethyl, 2,2, 2-trifluoroethyl, 2-fluorophenyl, 3-fluorophenyl, 2, 6-difluorophenyl, 2, 6-dichlorophenyl, 2, 6-dichloro-4-nitrophenyl, 2-isopropyl-5-methylphenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, 4-allyl-2-methoxyphenyl, (5-chloropyridin-2-yl) methyl, (5-chlorothien-2-yl) methyl, (2-chlorothiazol-5-yl) methyl, 4-phenoxy, 3, 4-methylenedioxyphenyl, 1- (5- (trifluoromethyl) pyridin-2-yl) ethyl or 4- (3, 3-dichloroallyl) oxy;
when X is N, R4Is H or methyl, R5Is methyl, isopropyl, cyclopropylmethyl, 4-chlorophenyl, 4-methoxyphenyl, 2, 6-difluorobenzyl, 4- (trifluoromethyl) benzyl.
6. The process for producing (E) -acrylic acid derivatives containing a xanthine-8-yl group as claimed in claim 1, which comprises:
a compound of formula E is reacted with 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI), 4-Dimethylaminopyridine (DMAP) and the corresponding alcohol or phenol or amine in dichloromethane at room temperatureReacting for 6-12 hours to obtain a compound shown in the general formula I; the molar ratio of the compound of formula E to EDCI, DMAP and the corresponding alcohol or phenol or amine is 1: 1.5: 0.05: 1; in the formula R1、R2、R3、R4、R5Having the same definitions as given in claim 1 above.
7. The process for preparing (E) -acrylic acid derivatives containing a xanthine-8-yl group according to claim 6, wherein the intermediate compound of formula E is prepared by:
(1) reacting the compound of the formula C with methoxy formyl methylene triphenylphosphine in dichloromethane at room temperature for 4 hours to obtain a compound of a formula D, wherein the molar ratio of the compound of the formula C to the methoxy formyl methylene triphenylphosphine is 1: 1;
(2) reacting a compound of a formula D with sodium hydroxide in a mixed solvent of tetrahydrofuran and water at room temperature for 4 hours to obtain a compound of a formula E, wherein the molar ratio of the compound of the formula D to the sodium hydroxide is 1: 1; in the formula R1、R2、R3Having the same definitions as given in claim 1 above.
8. The process for preparing (E) -acrylic acid derivatives containing a xanthine-8-yl group according to claim 7, wherein the intermediate compound of formula C is prepared by:
reacting the compound of formula A with N-bromosuccinimide (NBS) and Azobisisobutyronitrile (AIBN) in carbon tetrachloride at 70-85 ℃ for 12 hours to obtain a compound of formula B, and reacting the compound of formula B with 4-methylmorpholine-4-oxide and a molecular sieve in acetonitrile at room temperature for 4 hours to obtain a compound of formula C, wherein the compound of formula A is shown in the specificationThe molar ratio of the compound of the formula A, NBS and AIBN is 1: 1.2: 0.05; the molar ratio of the compound shown in the formula B to the 4-methylmorpholine-4-oxide is 1: 1.5; in the formula R1、R2、R3Having the same definitions as given in claim 1 above.
9. Use of a xanthine-8-yl-containing (E) -acrylic acid derivative as claimed in any of claims 1 to 5 for preparing agricultural insecticides.
10. Use of a xanthine-8-yl containing (E) -acrylic acid derivative according to claim 9 for the preparation of agricultural insecticides, which are insecticides against oriental armyworm and diamondback moth; the application for preparing the agricultural insecticide also comprises that the derivative is used as an active component of an insecticidal composition for preparing the agricultural insecticide; the insecticidal composition also comprises a carrier which is acceptable in agriculture, forestry and hygiene.
Technical Field
The invention belongs to the field of agricultural pesticides, and particularly relates to a (E) -acrylic acid derivative containing xanthine-8-yl and a preparation method and application thereof.
Background
The prevention and control of pests are of great significance to the smooth development of various industries such as agriculture, forestry, pasture, sideline, fishing, public health and the like. Aiming at the problems of ecological environment pollution, drug resistance of pests and the like of the traditional pesticide, researchers are required to continuously develop innovation, so that new pesticide varieties with high efficiency, low toxicity, safety and different action modes are developed to meet new requirements.
Xanthine is a nitrogen-containing heterocycle known under the chemical name 3, 7-dihydro-1H-purine-2, 6-dione. Xanthine compounds are widely found in nature as a class of natural products, and various forms of xanthine alkaloids are contained in tea, coffee, cocoa, chocolate, and the like, for example, caffeine (1,3, 7-trimethyl-3, 7-dihydro-1H-purine-2, 6-dione), theophylline (1, 3-dimethyl-3, 7-dihydro-1H-purine-2, 6-dione), theobromine (3, 7-dimethyl-3, 7-dihydro-1H-purine-2, 6-dione), and the like. The compounds are closely related to the dietary life of people, and have low toxicity to human bodies. In addition, their medicinal value for the treatment of diseases is also well known, and various natural and synthetic xanthines and derivatives thereof are useful for the treatment of respiratory diseases, neurodegenerative diseases, renal diseases, hypertension and cardiovascular diseases. Although there are few reports on the research of the pesticide field, the research mainly aims at the research of natural methylxanthine alkaloids such as caffeine, for example: at lower concentrations, caffeine is able to kill beetle larvae (Pest man. sci.2018,74,511); recently, sulfur-containing derivatives of caffeine have been reported to have control effects on tomato diseases infected with root-knot nematodes (WO 2020075107A 1,2020). The development of new pesticides based on the xanthine skeleton structure has a certain potential.
Disclosure of Invention
The invention aims to provide a novel-structure (E) -acrylic acid derivative containing xanthine-8-yl, a preparation method and application thereof, and the derivative has good insecticidal activity and can be applied to the comprehensive control of various insect pests.
In order to research and develop a new compound with excellent insecticidal activity, according to the active fragment splicing principle, the 8 th site of a xanthine structure skeleton is modified, an acrylic group is introduced, and structural derivation is carried out, so that a series of (E) -acrylic acid derivatives containing xanthine-8-yl are synthesized, and the research shows that the derivatives have good insecticidal activity on diamondback moths and oriental armyworms.
The invention introduces the structure of the acrylic acid derivative into the xanthine structure skeleton to synthesize the (E) -acrylic acid derivative containing xanthine-8-group for the first time, and the derivative has the characteristics of trans-acrylate or trans-acrylamide and xanthine skeleton structures and has higher insecticidal activity.
The invention provides a (E) -acrylic acid derivative containing xanthine-8-group, which has a structural formula shown as a general formula I:
in the formula:
x is O, S or N;
R1～R3is C1-C6Alkyl or halo C1-C6An alkyl group;
when X is O or S, no R4；R5Is C1-C6Alkyl, halo C1-C6Alkyl, aryl or aryl substituted C1-C3Alkyl, wherein the hydrogen on the aryl ring may also be further substituted by: halogen, C1-C6Alkyl, halo C1-C6Alkyl, cyano, nitro, phenyl, C1-C6Alkoxy, halo C1-C6Alkoxy radical, C1-C6Alkylthio, halo C1-C6Alkylthio radical, C2-C6Alkenyl, halo C2-C6Alkenyl radical, C3-C6Alkynyl, halo C3-C6Alkynyl, C2-C6Alkenyloxy, halogeno C2-C6Alkenyloxy radical, C3-C6Alkynyloxy, halo C3-C6Alkynyloxy, phenoxy, pyridyloxy, methylenedioxy (-OCH)2O-)；
When the X is an integer of N, the compound is,R4is H or C1-C6An alkyl group; r5Is C1-C6Alkyl, halo C1-C6Alkyl, aryl or aryl substituted C1-C3Alkyl, wherein the hydrogen on the aryl ring may also be further substituted by: halogen, C1-C6Alkyl, halo C1-C6Alkyl, cyano, nitro, phenyl, C1-C6Alkoxy, halo C1-C6Alkoxy radical, C1-C6Alkylthio, halo C1-C6Alkylthio, phenoxy, pyridyloxy;
in the definition of the above derivatives, the terms used, whether used alone or in compound words, are generally defined as follows:
halogen is fluorine, chlorine, bromine or iodine;
alkyl is straight, branched or cyclic alkyl, wherein cyclic alkyl includes cyclic chain forms or alkyl forms with cyclic chains, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, and the like;
aryl is phenyl or an aromatic heterocyclic group such as a furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl group and the like;
alkenyl is a straight-chain or branched chain having 2 to 6 carbon atoms and may have a double bond in any position, e.g. vinyl, propenyl, allyl, 2-methylprop-2-en-1-yl, but-3-en-1-yl, 2-methylbut-2-en-1-yl, 3-methylbut-2-en-1-yl, pent-3-en-1-yl, pent-4-en-1-yl, 2-methylpent-2-en-1-yl, 3-methylpent-2-en-1-yl, hex-2-en-1-yl, hex-3-en-1-yl, hex-4-en-1-yl or hex-5-en-1-yl, and the like;
alkynyl is a straight-chain or branched chain having 3 to 6 carbon atoms and may have a triple bond in any position, for example a propynyl, propargyl, but-2-yn-1-yl, but-3-yn-1-yl, pent-2-yn-1-yl, pent-3-yn-1-yl, pent-4-yn-1-yl, 4-methylpent-2-yn-1-yl, hex-3-yn-1-yl, hex-4-yn-1-yl or hex-5-yn-1-yl group or the like;
the carbon skeleton of the alkoxy group is the same as that of the alkyl group as defined above, and the alkoxy group in this case means a group in which an oxygen atom is bonded to the terminal of the alkyl group, such as a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a n-pentoxy group, an isopentoxy group, a n-hexoxy group, a cyclopropoxy group, a cyclopropylmethoxy group, a cyclobutoxy group, a cyclobutylmethoxy group, a cyclopentyloxy group, a cyclopentylmethoxy group, or a cyclohexyloxy group;
the carbon skeleton of the alkylthio group is the same as that of the alkyl group as defined above, and the alkylthio group in this case means a group having a sulfur atom at the terminal of the alkyl group, such as a methylthio group, an ethylthio group, a n-propylthio group, an isopropylthio group, a n-butylthio group, an isobutylthio group, a n-pentylthio group, an isopentylthio group, a n-hexylthio group, a cyclopropylthio group, a cyclopropylmethylthio group, a cyclobutylthio group, a cyclopentylthio group, a cyclopentylmethylthio group or a cyclohexylthio group;
the carbon skeleton of the alkenyloxy group is the same as that of the alkenyl group defined above, and the alkenyl group is defined as above, provided that the alkenyloxy group means a group having an oxygen atom attached to the terminal of the alkenyl group, such as vinyloxy group, allyloxy group, etc.;
the carbon skeleton of the alkynyloxy group is the same as that of the alkynyl group as defined above, and the alkynyl group is defined as described above, under which the alkynyloxy group means a group having an oxygen atom attached to the terminal of the alkynyl group, such as propargyloxy and the like;
haloalkyl is a straight-chain alkyl, branched-chain alkyl or cycloalkyl group, the hydrogen atoms on these alkyl groups may be partially or fully substituted by halogen atoms; "haloalkoxy", "haloalkylthio", "haloalkenyl", "haloalkynyl", "haloalkenyloxy" and "haloalkynyloxy" are as defined under the term "haloalkyl";
so-called may be further substituted, the number of substituents thereof may beTo be one or more; the hydrogen on the aromatic ring is further substituted by methylenedioxy (-OCH)2O-) substitution means that two adjacent hydrogens on the aromatic ring are simultaneously substituted with methylenedioxy to form a ring.
The compounds of the general formula I according to the invention can be prepared by a process in which the substituents R are1、R2、R3、R4、R5As hereinbefore defined unless otherwise indicated:
step 1, reacting a compound of a formula A with N-bromosuccinimide (NBS) and Azobisisobutyronitrile (AIBN) in carbon tetrachloride at 70-85 ℃ for 12 hours to obtain a compound of a formula B; the molar ratio of the compound of the formula A, NBS and AIBN is 1: 1.2: 0.05.
Step 2, reacting the compound of the formula B with 4-methylmorpholine-4-oxide and a molecular sieve in acetonitrile at room temperature for 4 hours to obtain a compound of a formula C; the molar ratio of the compound of the formula B to 4-methylmorpholine-4-oxide is 1: 1.5.
Step 3, reacting the compound of the formula C with methoxy formyl methylene triphenylphosphine in dichloromethane at room temperature for 4 hours to obtain a compound of a formula D; the molar ratio of the compound of the formula C to the methoxy formyl methylene triphenylphosphine is 1: 1.
Step 4, reacting the compound of the formula D with sodium hydroxide in a mixed solvent of tetrahydrofuran and water at room temperature for 4 hours to obtain a compound of a formula E; the molar ratio of the compound of the formula D to the sodium hydroxide is 1: 1.
Step 5, reacting the compound of the formula E with 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI), 4-Dimethylaminopyridine (DMAP) and the corresponding alcohol or phenol or amine in dichloromethane at room temperature for 6-12 hours to obtain the compound of the general formula I; the molar ratio of the compound of formula E to EDCI, DMAP and the corresponding alcohol or phenol or amine is 1: 1.5: 0.05: 1.
The invention also provides the application of the compound in the general formula I in pest control, namely the application of the (E) -acrylic acid derivative containing the xanthine-8-group in preparing agricultural pesticides. In particular to the application of the (E) -acrylic acid derivative containing the xanthine-8-group in preparing the insecticide for killing oriental armyworm and diamondback moth.
The invention has the advantages and beneficial effects that:
the invention provides a novel-structure (E) -acrylic acid derivative (a compound shown in a general formula I) containing xanthine-8-yl, which has high insecticidal activity, has good control effect on pests such as oriental armyworm and diamondback moth and the like, can be used as an active component of an insecticidal composition, is used for preparing agricultural insecticides, and can be applied to the control of pests.
Detailed Description
The present invention will be further described with reference to the following examples, which are intended to better understand the contents of the present invention and to embody the essential features of the present invention, and therefore, the examples should not be construed as limiting the scope of the present invention. It is also specifically noted herein that the particular experimental procedures and equipment referred to in the examples are, unless otherwise specified, conducted in accordance with conventional procedures or conditions as recommended by the manufacturer's instructions and that the reagents referred to are commercially available without further specification.
Example 1
A method for preparing a compound I-1(2, 6-difluorophenyl- (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylate).
The reaction route is shown as the following formula:
the preparation method comprises the following steps:
step 1: preparation of 8- (bromomethyl) -1,3, 7-trimethyl-3, 7-dihydro-1H-purine-2, 6-dione (Compound of formula B-1)
1,3,7, 8-tetramethyl-3, 7-dihydro-1H-purine-2, 6-dione (A-1, 4.16g), NBS (3.90g) and AIBN (0.16g) are added into a 250mL three-necked flask, a condenser tube and an air suction head are connected on the three-necked flask, air in the three-necked flask is replaced by argon gas in a pumping way for 3 times, then carbon tetrachloride of 50mL is added into the flask, the reaction is carried out for 12 hours at the temperature of 70-85 ℃, after the temperature is cooled to the room temperature, a sodium sulfite solution is added into the three-necked flask, the mixture is shaken and filtered, the solid is washed by water, and the solid is dried to obtain 8- (bromomethyl) -1,3, 7-trimethyl-3, 7-dihydro-1H-purine-2, 6-dione (the compound of the formula B-1).
Step 2: preparation of 1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purine-8-carbaldehyde (compound of formula C-1)
8- (bromomethyl) -1,3, 7-trimethyl-3, 7-dihydro-1H-purine-2, 6-dione (B-1, 5g) prepared in step 1, 4-methylmorpholine-4-oxide (2.54g) and molecular sieve (3g) were sequentially charged into a 250mL two-necked flask, and the air in the two-necked flask was replaced with argon gas by suction 3 times, followed by addition of 100mL acetonitrile and reaction at room temperature for 4 hours. Then, the system was filtered, the residue was washed with dichloromethane, the filtrate was concentrated under reduced pressure to remove the solvent to obtain a crude product, which was purified by column chromatography (dichloromethane/methanol, v/v ═ 50:1) to obtain 1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purine-8-carbaldehyde (compound of formula C-1).
And step 3: preparation of methyl (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2-3, 6, 7-tetrahydro-1H-purin-8-yl) acrylate (compound of formula D-1)
A50 mL two-necked flask was charged with 1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purine-8-carbaldehyde prepared in step 2 (C-1, 1.02g) and methoxycarbonylmethylenetriphenylphosphine (2.03g), and the air in the two-necked flask was replaced with argon by 3 times, followed by addition of dichloromethane (20mL) and reaction at room temperature for 4 hours. The solvent in the reaction system is evaporated, ethanol is added into the system, the mixture is stirred for 1 hour at room temperature, and then the mixture is filtered. Washing the solid with ethanol, and drying the solid to obtain (E) -methyl 3- (1,3, 7-trimethyl-2, 6-dioxo-2-3, 6, 7-tetrahydro-1H-purin-8-yl) acrylate (compound of formula D-1).
And 4, step 4: preparation of (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylic acid (compound of formula E-1)
A50 mL two-necked flask was charged with methyl (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2-3, 6, 7-tetrahydro-1H-purin-8-yl) acrylate (D-1, 2.03g) prepared in step 3, sodium hydroxide (0.6g), water (5mL) and tetrahydrofuran (5mL), and reacted at room temperature for 4 hours. Removing tetrahydrofuran in the reaction system by evaporation, dropwise adding diluted hydrochloric acid with the concentration of 1mol/L into the reaction system, adjusting the pH to be 1, separating out solids, and filtering to obtain the compound (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylic acid (the compound of the formula E-1).
And 5: preparation of 2, 6-difluorophenyl- (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylate (Compound I-1).
The compound prepared in step 4, preparation of (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylic acid (E-1, 0.14g), 2, 6-difluorophenol (0.078g), EDCI (0.115g), DMAP (0.006g) and 2mL of dichloromethane were charged into a 50mL round-bottomed flask, and the reaction was stirred at room temperature for 10 hours (TLC trace). After the reaction is finished, 10mL of water is added into the reaction system, dichloromethane is used for extraction for 3 times, organic phases are combined, the organic phases are dried by anhydrous sodium sulfate and filtered, the filtrate is concentrated to obtain a crude product, and the crude product is purified by column chromatography (dichloromethane/methanol, v/v is 30:1) to obtain a compound I-1, namely a white solid, wherein the yield is 71%.
Example 2
A method for preparing (5-chloropyridin-2-yl) methyl (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylate (compound I-2).
Compound E-1(0.14g), (5-chloropyridin-2-yl) methanol (0.085g) prepared in example 1, EDCI (0.115g), DMAP (0.006g) and 2mL dichloromethane were added to a 25mL round-bottomed flask and the reaction was stirred at room temperature for 10 hours (follow-up by TLC). After the reaction is finished, 10mL of water is added into the reaction system, dichloromethane is used for extraction for 3 times, organic phases are combined, the organic phases are dried by anhydrous sodium sulfate, filtration is carried out, a filtrate is concentrated to obtain a crude product, and the crude product is purified by column chromatography (dichloromethane/methanol, v/v is 30:1) to obtain a compound I-2, namely a white solid, wherein the yield is 67%.
Example 3
A process for producing 2-isopropyl-5-methylphenyl (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylate (Compound I-5).
Compound E-1(0.14g) prepared in example 1, 2-isopropyl-5-methylphenol (0.09g), EDCI (0.115g), DMAP (0.006g) and 2mL of dichloromethane were charged into a 25mL round-bottomed flask, and the reaction was stirred at room temperature for 10 hours (TLC follow-up). After the reaction is finished, 10mL of water is added into the reaction system, dichloromethane is used for extraction for 3 times, organic phases are combined, the organic phases are dried by anhydrous sodium sulfate, filtration is carried out, a filtrate is concentrated to obtain a crude product, and the crude product is purified by column chromatography (dichloromethane/methanol, v/v is 30:1) to obtain a compound I-5, namely a white solid, wherein the yield is 66%.
Example 4
(E) A method for producing (compound I-14) butyl (3-1, 3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylate.
Compound E-1 prepared in example 1(0.14g), n-butanol (0.054mL), EDCI (0.115g), DMAP (0.006g), and 2mL dichloromethane were added to a 25mL round-bottomed flask, and the reaction was stirred at room temperature for 10 hours (TLC follow-up). After the reaction is finished, 10mL of water is added into the reaction system, dichloromethane is used for extraction for 3 times, organic phases are combined, the organic phases are dried by anhydrous sodium sulfate, filtration is carried out, a filtrate is concentrated to obtain a crude product, and the crude product is purified by column chromatography (dichloromethane/methanol, v/v is 30:1) to obtain a compound I-14, namely a white solid, wherein the yield is 71%.
Example 5
A method for producing 2,2, 2-trifluoroethyl- (E) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylate (Compound I-16).
Compound E-1(0.14g) prepared in example 1,2, 2, 2-trifluoroethanolic alcohol (0.035mL), EDCI (0.115g), DMAP (0.006g) and 2mL of dichloromethane were added to a 25mL round-bottomed flask and the reaction was stirred at room temperature for 10 hours (TLC follow-up). After the reaction is finished, 10mL of water is added into the reaction system, dichloromethane is used for extraction for 3 times, organic phases are combined, the organic phases are dried by anhydrous sodium sulfate, filtration is carried out, a filtrate is concentrated to obtain a crude product, and the crude product is purified by column chromatography (dichloromethane/methanol, v/v is 30:1) to obtain a compound I-16, namely a white solid, wherein the yield is 77%.
Example 6
(E) A process for producing (E) -N-cyclopropylmethyl-3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylamide (compound I-24).
Compound E-1 prepared in example 1(0.14g), cyclopropylmethylamine (0.041mL), EDCI (0.115g), DMAP (0.006g) and 2mL dichloromethane were added to a 25mL round-bottomed flask and the reaction was stirred at room temperature for 10 hours (follow-up by TLC). After the reaction is finished, 10mL of water is added into the reaction system, dichloromethane is used for extraction for 3 times, organic phases are combined, the organic phases are dried by anhydrous sodium sulfate, filtration is carried out, a filtrate is concentrated to obtain a crude product, and the crude product is purified by column chromatography (dichloromethane/methanol, v/v is 30:1) to obtain a compound I-24, namely a white solid, wherein the yield is 65%.
Example 7
(E) A method for producing (E) -N- (4- (trifluoromethyl) benzyl) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylamide (compound I-26).
Compound E-1(0.14g), (4- (trifluoromethyl) phenyl) methylamine (0.041mL), EDCI (0.115g), DMAP (0.006g) and 2mL dichloromethane prepared in example 1 were added to a 25mL round-bottom flask and the reaction was stirred at room temperature for 10 hours (follow-up by TLC). After the reaction is finished, 10mL of water is added into the reaction system, dichloromethane is used for extraction for 3 times, organic phases are combined, the organic phases are dried by anhydrous sodium sulfate, filtration is carried out, a filtrate is concentrated to obtain a crude product, and the crude product is purified by column chromatography (dichloromethane/methanol, v/v is 30:1) to obtain a compound I-26, namely a white solid, wherein the yield is 80%.
Example 8
(E) A method for producing (E) -N- (4-methoxyphenyl) -3- (1,3, 7-trimethyl-2, 6-dioxo-2, 3,6, 7-tetrahydro-1H-purin-8-yl) acrylamide (compound I-28).
Compound E-1(0.14g) prepared in example 1, 4-methoxyaniline (0.065g), EDCI (0.115g), DMAP (0.006g) and 2mL of dichloromethane were added to a 25mL round-bottom flask, and the reaction was stirred at room temperature for 10 hours (follow-up by TLC). After the reaction is finished, 10mL of water is added into the reaction system, the mixture is filtered, and the solid is fully washed by water to obtain a compound I-28, namely a yellow solid with the yield of 80%.
Table 1 below lists the structure and physical properties of some of the compounds of formula I. The nuclear magnetic resonance hydrogen spectrum and carbon spectrum data of part of the compound shown in the general formula I are listed in the table 2.
TABLE 1 Structure and physical Properties of some of the Compounds of formula I
TABLE 2 NMR hydrogen and carbon spectra data for some of the compounds of formula I
Examples of biological Activity testing of Compounds of formula I
Example 9
Determination of insecticidal Activity
Determination of biological Activity against Oriental armyworm (Mythimna separata Walker): the oriental armyworm insecticidal activity test method adopts a leaf soaking method, a test compound is prepared into a solution with a corresponding test concentration by using acetone, then corn leaves (5 multiplied by 1cm) in a seedling stage are soaked, residual liquid is thrown off after 3-5 s, the corn leaves are dried and placed into a 7cm culture dish, 10-head 4-year-old test larvae are inoculated, three groups of samples are made for each sample, and the room temperature is maintained at 25 +/-1 ℃. The blank control was fed larvae by dipping corn leaves with acetone solution only. And acquiring test results after 72h, taking the touch and the touch as the death standard of the larvae, and evaluating the lethality of the test compound to the armyworm larvae by 0-100%, wherein 0% represents no insecticidal effect, and 100% represents complete killing.
Determination of the biological Activity of Plutella xylostella (Plutella xylostella Linnaeus): a leaf soaking method is adopted for testing insecticidal activity of the plutella xylostella, a test compound is dissolved by 1mL of DMF, then the solution with corresponding test concentration is prepared by diluting with distilled water, then cabbage leaves (5 multiplied by 1cm) are soaked, after 3-5 s, residual liquid is thrown off, the dried cabbage leaves are placed into a test tube with the length of 10cm, 10 heads of 2-year-old plutella xylostella larvae are inoculated, three groups of samples are made for each sample, and the room temperature is maintained at 25 +/-1 ℃. Blank control cabbage leaves were impregnated with DMF diluted solution only to feed larvae. And acquiring test results after 72h, taking the touch and the touch as the death standard of the larvae, and evaluating the lethality of the test compound to the armyworm larvae by 0-100%, wherein 0% represents no insecticidal effect, and 100% represents complete killing.
TABLE 3 insecticidal Activity of some Compounds of general formula I against Oriental armyworm and Plutella xylostella
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