CN102391261A

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Info

Publication number: CN102391261A
Application number: CN2011103129260A
Authority: CN
Inventors: 徐德锋; 吕龙; 李绍顺; 唐庆红; 付群梅
Original assignee: Shanghai Institute of Organic Chemistry of CAS; Shanghai Jiao Tong University
Current assignee: Shanghai Institute of Organic Chemistry of CAS; Shanghai Jiao Tong University
Priority date: 2011-10-14
Filing date: 2011-10-14
Publication date: 2012-03-28

Abstract

本发明涉及一种N-取代噁二嗪类化合物及其制备方法和应用，该化合物的化学结构通式(I)如下：

化学结构通式(I)中Ar为苯环、萘环、吡啶或嘧啶环系。该化合物通过以下两个步骤制得：(1)以2-(苄基)-7-氯茚并[1，2-e][1，3，4]]噁二嗪-2，4a(3H，5H)-二羧酸-4a-甲基酯和氢气为原料，在溶剂a中以Pd/C为催化剂a，进行加氢反应，反应完毕后得到中间体B；(2)以(氯羰基)(芳基)氨基甲酸甲酯为中间体C，与步骤(1)得到的中间体B，在溶剂b中，在催化剂b的作用下，进行缩合反应，得到产物N取代噁二嗪类化合物。与现有技术相比，本发明化合物对粘虫的杀虫活性达到80％～100％。The present invention relates to a kind of N-substituted oxadiazine compound and its preparation method and application, the general chemical structure formula (I) of this compound is as follows:

Ar in the general chemical structure formula (I) is a benzene ring, a naphthalene ring, a pyridine or a pyrimidine ring system. The compound was prepared by the following two steps: (1) 2-(benzyl)-7-chloroindeno[1,2-e][1,3,4]]oxadiazine-2,4a(3H , 5H)-dicarboxylic acid-4a-methyl ester and hydrogen are raw materials, and in solvent a, Pd/C is used as catalyst a to carry out hydrogenation reaction, and intermediate B is obtained after the reaction is completed; (2) with (chlorocarbonyl ) (aryl) methyl carbamate is intermediate C, and intermediate B obtained in step (1), in solvent b, under the effect of catalyst b, carries out condensation reaction to obtain the product N-substituted oxadiazine compound . Compared with the prior art, the insecticidal activity of the compound against the armyworm reaches 80%-100%.

Description

Translated fromChinese

一种N-取代噁二嗪类化合物及其制备方法和应用A kind of N-substituted oxadiazine compound and its preparation method and application

技术领域technical field

本发明涉及一种杀虫剂，尤其是涉及一种具有杀虫活性的N-取代噁二嗪类化合物，其制备方法和应用。The invention relates to an insecticide, in particular to an N-substituted oxadiazine compound with insecticidal activity, its preparation method and application.

背景技术Background technique

噁二嗪类(oxadiazine)杀虫剂茚虫威(indoxacarb)是美国杜邦(Dupont)公司1992年开发的钠通道抑制广谱杀虫剂(W09211249)，基于一种新的杀虫作用机制，即阻断神经细胞的钠离子通道，减少和常用杀虫剂(如除虫菊酯、有机磷以及氨基甲酸酯类杀虫剂)发生交互抗性的可能。茚虫威本身是一种前体杀虫剂，通过在昆虫体内代谢去除酰胺氮原子上的甲氧羰基(-COOCH₃)后转化为活性化合物，在广谱范围内具有很高的杀虫活性而且融合了环境相容性好、对哺乳动物毒性低和对鸟类、鱼类以及益虫安全的优点，作为替代有机磷杀虫剂的理想品种之一。The oxadiazine (oxadiazine) insecticide indoxacarb (indoxacarb) is a sodium channel inhibitory broad-spectrum insecticide (W09211249) developed by Dupont (Dupont) in the United States in 1992. It is based on a new mechanism of insecticidal action, namely Blocking the sodium ion channels of nerve cells reduces the possibility of cross-resistance to commonly used insecticides (such as pyrethrins, organophosphates, and carbamate insecticides). Indoxacarb itself is a precursor insecticide, which is converted into an active compound after removing the methoxycarbonyl group (-COOCH₃ ) on the amide nitrogen atom through metabolism in the insect body, and has high insecticidal activity in a broad-spectrum range Moreover, it combines the advantages of good environmental compatibility, low toxicity to mammals and safety to birds, fish and beneficial insects, and is one of the ideal varieties to replace organophosphate insecticides.

茚虫威的先导化合物为苯甲酰脲类杀虫剂RH3421，Philips-Duphar公司在苯甲酰脲类杀虫剂1的基础上运用生物等排理论将1变为2，后来开发出环状结构3。在结构3中A，Z可为多种基团，并且可以同其他原子组成五元或六元环，为了便于合成环状结构3优化为4(PH60-42)，可能由于残留的原因，不能满足登记的要求，没有最终工业化。The lead compound of indoxacarb is the benzoylurea insecticide RH3421. Philips-Duphar used the bioisosteric theory to change 1 into 2 on the basis of the benzoylurea insecticide 1, and later developed a cyclic Structure 3. In structure 3, A and Z can be a variety of groups, and can form a five-membered or six-membered ring with other atoms. In order to facilitate the synthesis of ring structure 3, it is optimized to 4 (PH60-42), which may not be possible due to residual reasons. Meet the requirements for registration, without final industrialization.

Ricard Jacobson博士(罗门哈斯公司)于1980年开始针对化合物4，通过结构优化发现化合物5(RH3421)，RH3421不仅对鳞翅目、鞘翅目害虫有很好活性，在较低剂量下具有良好防治效果。作用机理新颖，是钠离子通道抑制剂，与苯甲酰脲类杀虫剂的机理完全不同。Dr. Ricard Jacobson (Rohm and Haas) began to target compound 4 in 1980, and found compound 5 (RH3421) through structural optimization. RH3421 not only has good activity against Lepidoptera and Coleoptera pests, but also has good activity at lower doses. Control effect. The mechanism of action is novel, and it is a sodium ion channel inhibitor, which is completely different from that of benzoylurea insecticides.

由于RH3421具有特异性作用机理，杜邦公司Thomas Stevenson等人开始对RH3421类化合物进行结构优化，在RH3421和化合物6的基础上，将1位上的N原子和3位上的C原子交换，得到化合物7，合成了一些化合物，离体生测结果表明较好的活性。Due to the specific mechanism of action of RH3421, DuPont Thomas Stevenson and others began to optimize the structure of RH3421 compounds. On the basis of RH3421 and compound 6, the N atom at the 1 position and the C atom at the 3 position were exchanged to obtain the compound 7. Some compounds were synthesized, and the results of in vitro bioassay showed good activity.

化合物6的衍生结构8和9，可能是由于氢键的原因，杜邦公司的ThomasStevenson等就设想将化合物物9中的吡唑4位的一个取代基如R2和3位苯环邻位合环即变为结构为10和11的化合物。Derivative structures 8 and 9 of compound 6 may be due to hydrogen bonds. ThomasStevenson of DuPont Co., Ltd., etc. conceived that a substituent at the 4-position of pyrazole in compound 9 such as R2 and the 3-position benzene ring ortho-position ring closure is into compounds of structures 10 and 11.

通过离体生测发现化合物11的活性优于12b，同时还对吡唑开环化合物12b进行研究，并发现B1为CH₂的活性要好于B1为CH₂CH₂的化合物，但合成的化合物的在活性谱以及残留活性方面均不令人满意，需要改进。通过结构活性分析他们发现环的大小直接影响到生物活性，并将化合物12a和12b进行了组合优化为13。通过研究发现化合物14在一定计量下对鳞翅目害虫具有很好的防治效果，但残留时间过长。Through in vitro bioassays, it was found that the activity of compound 11 was better than that of 12b. At the same time, the pyrazole ring-opening compound 12b was also studied, and it was found that the activity of B1 as_CH2 was better than that of the compound with_B1 as_CH2CH2 . However, the synthesized compound It is unsatisfactory in terms of activity spectrum and residual activity, and needs to be improved. Through structure-activity analysis, they found that the size of the ring directly affects the biological activity, and optimized the combination of compounds 12a and 12b into 13. Through research, it is found that compound 14 has a good control effect on lepidopteran pests at a certain dosage, but the residual time is too long.

对大量的实验结果数据进行分析，经过进一步优化研究，发现15适宜的残留活性和较好的生态性能，但对哺乳动物具有相对较高的活性。经过进一步的研究发现了茚虫威的结构，尽管茚虫威本身活性较弱但可以被害虫快速代谢为活性很高的茚虫威的合成研制再次表明合成化学是一门取之不尽的技术。After analyzing a large number of experimental results and data, after further optimization research, it is found that 15 has suitable residual activity and good ecological performance, but it has relatively high activity on mammals. After further research, the structure of indoxacarb was discovered. Although the activity of indoxacarb itself is weak, the synthesis and development of indoxacarb with high activity can be quickly metabolized by pests, which once again shows that synthetic chemistry is an inexhaustible technology. .

发明内容Contents of the invention

本发明的目的就是为了克服上述现有技术存在的缺陷而提供一种N-取代噁二嗪类化合物及其制备方法和应用。The purpose of the present invention is to provide an N-substituted oxadiazine compound and its preparation method and application in order to overcome the above-mentioned defects in the prior art.

本发明的目的可以通过以下技术方案来实现：一种N-取代噁二嗪类化合物，其特征在于，该化合物的化学结构通式(I)如下：The object of the present invention can be achieved through the following technical solutions: a kind of N-substituted oxadiazine compound, it is characterized in that, the general chemical structure formula (I) of this compound is as follows:

化学结构通式(I)中Ar为苯环、萘环、吡啶或嘧啶环系。Ar in the general chemical structure formula (I) is a benzene ring, a naphthalene ring, a pyridine or a pyrimidine ring system.

所述的化合物包括：Said compounds include:

(1)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(吡啶)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-001表示)，(1) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(pyridine)amino]formyl]indeno[1,2-e][1,3,4- ]Oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-001),

(2)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-002表示)，(2) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (naphthalene)amino]formyl]indeno[1,2-e][1,3,4- ]Oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-002),

(3)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(4-甲基吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-003表示)，(3) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(4-methylpyridine)]amino]formyl]indeno[1,2-e ][1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by code SIOC-Y-003),

(4)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(6-甲基吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-004表示)，(4) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(6-methylpyridine)]amino]formyl]indeno[1,2-e ][1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-004),

(5)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(5-溴吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-005表示)，(5) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(5-bromopyridine)]amino]formyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by code SIOC-Y-005),

(6)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(5-碘吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-006表示)，(6) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(5-iodopyridine)]amino]formyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by code SIOC-Y-006),

(8)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[4-(2-氯吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-008表示)，(8) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[4-(2-chloropyridine)]amino]formyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-008),

(9)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[3-(2-氯吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-009表示)，(9) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[3-(2-chloropyridine)]amino]formyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-009),

(10)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-甲氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-010表示)，(10) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-methoxynaphthalene)amino]formyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-010),

(11)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-乙氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-011表示)，(11) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-ethoxynaphthalene)amino]formyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-011),

(12)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-正丙氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-012表示)，(12) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-n-propoxynaphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-012),

(13)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-正戊氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-013表示)，(13) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-n-pentyloxynaphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-013),

(14)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-正己氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-014表示)，(14) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-n-hexyloxynaphthalene)amino]formyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-014),

(15)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-异丙氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-015表示)，(15) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-isopropoxynaphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-015),

(16)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-正丁氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-016表示)，(16) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-n-butoxynaphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-016),

(17)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(4，6-二甲氧基嘧啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-017表示)，(17) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(4,6-dimethoxypyrimidine)]amino]formyl]indeno[1 , 2-e][1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-017),

(18)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-特丁酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-018表示)，(18) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-tert-butyrate naphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-018),

(19)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-差劲基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-019表示)，(19) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-poor naphthalene)amino]formyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-019),

(20)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-丁酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-020表示)，(20) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-butyrate naphthalene)amino]formyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-020),

(21)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-乙酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-021表示)，(21) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-acetate naphthalene)amino]formyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-021),

(22)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-丙酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-022表示)，(22) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-propionate naphthalene)amino]formyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-022),

(23)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-甲氧甲醚萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-023表示)，(23) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-methoxymethyl ether naphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-023),

(24)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-苯甲酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-024表示)，(24) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-benzoate naphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-024),

(25)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-吡喃甲酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-025表示)，(25) (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-pyranoate naphthalene)amino]formyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by code SIOC-Y-025),

(26)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-甲氧甲酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-026表示)，(26) (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl (2-methoxyformyl naphthalene)amino]formyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by code SIOC-Y-026),

(27)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基2-(4-氯-6-甲氧基嘧啶)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-027表示)，(27) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl 2-(4-chloro-6-methoxypyrimidine)amino]formyl]indeno[1, 2-e][1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-027),

(28)(S)-7-氯-3，5-二氢-2-[[甲氧基羰基2-(4，6-二甲氧基嘧啶)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(用代号SIOC-Y-028表示)，(28) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl 2-(4,6-dimethoxypyrimidine)amino]formyl]indeno[1,2 -e][1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (represented by the code SIOC-Y-028),

(29)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-029表示)，(29) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-methoxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]Oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-029),

(30)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-乙氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-030表示)，(30) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-ethoxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]Oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-030),

(31)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-正丙氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-031表示)，(31) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-n-propoxyphenyl)carbamoyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-031),

(32)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-异氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-032表示)，(32) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-isooxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]Oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-032),

(33)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-正丁氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-033表示)，(33) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-n-butoxyphenyl)carbamoyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-033),

(34)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-正戊氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-034表示)，(34) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-n-pentyloxyphenyl)carbamoyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-034),

(35)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-正己氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-035表示)，(35) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-n-hexyloxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]Oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-035),

(36)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-三氟甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-036表示)，(36) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-trifluoromethoxyphenyl)carbamoyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by code SIOC-Y-036),

(37)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-三氟乙氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-037表示)，(37) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-trifluoroethoxyphenyl)carbamoyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-037),

(38)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-三氟甲基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-038表示)，(38) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-trifluoromethylphenyl)carbamoyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a-carboxylate methyl ester (represented by the code SIOC-Y-038),

(39)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(2-三氟甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-039表示)，(39) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(2-trifluoromethoxyphenyl)carbamoyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-039),

(40)(S)-7-氯-3，5一二氢-2-[甲氧基羰基2-[(3-三氟甲氧基苯基)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-040表示)，(40) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl 2-[(3-trifluoromethoxyphenyl)amino]formyl]indeno[1,2 -e][1,3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by code SIOC-Y-040),

(41)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(2-溴-4-三氟氧基苯基)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-041表示)，(41) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(2-bromo-4-trifluorooxyphenyl)amino]formyl]indeno[1,2 -e][1,3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-041),

(42)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-硝基苯基)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-042表示)，(42) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-nitrophenyl)amino]formyl]indeno[1,2-e][1, 3,4-]Oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-042),

(43)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-乙酰氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-043表示)，(43) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-acetoxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]Oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-043),

(44)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-044表示)，(44) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-methoxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]Oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-044),

(45)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-乙酰基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-045表示)，(45) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-acetylphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester (represented by the code SIOC-Y-045),

(46)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-甲酰氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-046表示)，(46) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-formyloxyphenyl)carbamoyl]indeno[1,2-e][1 , 3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-046),

(47)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-三氟甲硫基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-047表示)，(47) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-trifluoromethylthiophenyl)carbamoyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by code SIOC-Y-047),

(48)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(2，4-二甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-048表示)，(48) (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(2,4-dimethoxyphenyl)carbamoyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-048),

(49)(S)-(+)-7-氯-3，5-二氢-2-[甲氧基羰基(2，4-二硝基苯基)氨基羰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羟酸甲酯(用代号SIOC-Y-049表示)，(49) (S)-(+)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(2,4-dinitrophenyl)aminocarbonyl]indeno[1,2- e][1,3,4-]oxadiazine-4a(3H)-hydroxy acid methyl ester (represented by the code SIOC-Y-049),

(50)(S)-7-氯-3，5-二氢-2-[甲氧基羰基(2-三氟甲氧基-5-氯-苯基)氨基羰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羟酸甲酯(用代号SIOC-Y-050表示)，(50) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(2-trifluoromethoxy-5-chloro-phenyl)aminocarbonyl]indeno[1,2 -e][1,3,4-]oxadiazine-4a(3H)-hydroxy acid methyl ester (represented by the code SIOC-Y-050),

(51)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4一乙氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯(用代号SIOC-Y-051表示)，(51) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-ethoxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]Oxadiazine-4a-carboxylic acid methyl ester (represented by the code SIOC-Y-051),

(52)(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4一甲基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a羧酸甲酯的合成(用代号SIOC-Y-052表示)。(52) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-methylphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-] Synthesis of oxadiazine-4a carboxylate methyl ester (represented by the code SIOC-Y-052).

本发明化化合物结构和熔点如下：Compound structure of the present invention and fusing point are as follows:

一种N-取代噁二嗪类化合物的制备方法，其特征在于，该方法包括以下步骤：A preparation method of N-substituted oxadiazines, characterized in that the method comprises the following steps:

(1)以2-(苄基)-7-氯茚并[1，2-e][1，3，4]]噁二嗪-2，4a(3H，5H)-二羧酸-4a-甲基酯和氢气为原料，在溶剂a中以Pd/C为催化剂a，进行加氢反应，反应温度为20℃～120℃，反应压力为1-15个大气压，反应完毕后得到中间体B；(1) With 2-(benzyl)-7-chloroindeno[1,2-e][1,3,4]]oxadiazine-2,4a(3H,5H)-dicarboxylic acid-4a- Methyl ester and hydrogen are used as raw materials, and Pd/C is used as catalyst a in solvent a to carry out hydrogenation reaction. The reaction temperature is 20 ° C ~ 120 ° C, and the reaction pressure is 1-15 atmospheres. After the reaction is completed, intermediate B is obtained ;

(2)以(氯羰基)(芳基)氨基甲酸甲酯为中间体C，与步骤(1)得到的中间体B，在溶剂b中，在催化剂b的作用下，进行缩合反应，反应温度为0℃～100℃得到产物N取代噁二嗪类化合物。(2) With (chlorocarbonyl) (aryl) methyl carbamate as intermediate C, with intermediate B obtained in step (1), in solvent b, under the effect of catalyst b, carry out condensation reaction, reaction temperature The temperature is 0°C～100°C to obtain the product N-substituted oxadiazine compounds.

步骤(1)所述的溶剂a为乙酸甲酯、乙酸乙酯、甲醇、乙醇、乙腈、二氯甲烷、二氯乙烷、三氯甲烷、甲苯中的一种或两种以上的混合剂。The solvent a described in step (1) is one or a mixture of two or more of methyl acetate, ethyl acetate, methanol, ethanol, acetonitrile, methylene chloride, ethylene dichloride, chloroform, and toluene.

步骤(1)所述的反应温度为45℃～85℃，反应压力为4-6个大气压。The reaction temperature in the step (1) is 45° C. to 85° C., and the reaction pressure is 4-6 atmospheres.

步骤(2)所述的溶剂b为乙酸甲酯、乙酯乙酸乙酯、甲醇、乙醇、乙腈、二氯甲烷、二氯乙烷、三氯甲烷、甲苯中的一种或两种以上的混合剂。The solvent b described in step (2) is one or more mixtures of methyl acetate, ethyl acetate, methyl alcohol, ethanol, acetonitrile, methylene dichloride, ethylene dichloride, chloroform, toluene agent.

步骤(2)所述的催化剂b为N，N-二异丙基乙胺、三乙胺、吡啶或哌啶。The catalyst b described in step (2) is N,N-diisopropylethylamine, triethylamine, pyridine or piperidine.

步骤(2)所述的反应温度为20℃～60℃。The reaction temperature described in step (2) is 20°C to 60°C.

步骤(2)所得N取代噁二嗪类化合物采用重结晶方法进行分离纯化，或采用柱色谱分离的方法进行分离纯化，所述的重结晶方法采用的溶剂为甲醇、乙醇、异丙醇、乙酸甲酯、乙酸乙酯、乙腈、二氯甲烷、二氯乙烷、三氯甲烷、甲苯、石油醚中的一种或两种以上的混合剂。The N-substituted oxadiazine compound obtained in step (2) is separated and purified by recrystallization, or by column chromatography. The solvent used in the recrystallization method is methanol, ethanol, isopropanol, acetic acid One or a mixture of two or more of methyl ester, ethyl acetate, acetonitrile, dichloromethane, dichloroethane, chloroform, toluene, petroleum ether.

一种N-取代噁二嗪类化合物的应用，该化合物用于制备杀虫剂，对粘虫的杀虫活性达到80％～100％。The application of an N-substituted oxadiazine compound is used to prepare insecticides, and the insecticidal activity against armyworms reaches 80% to 100%.

与现有技术相比，本发明不断对结构(I)进行结构优化和改造，最终研究出一些新的具有高杀虫活性的N取代噁二嗪类化合物Y001-Y052。Compared with the prior art, the present invention continuously optimizes and transforms the structure (I), and finally develops some new N-substituted oxadiazine compounds Y001-Y052 with high insecticidal activity.

本发明涉及有N取代噁二嗪类化合物SIOC-Y-(001-052)对水稻褐飞虱、粘虫(小菜蛾)、红蜘蛛、苜蓿蚜等4个虫靶标的室内生物活性测试表明：化合物SIOC-Y-(001-052)在普筛浓度500mg/L时，其中化合物SIOC-Y-006、014、038、041-043、046、047、049、051对粘虫显示出100％的杀虫活性，036、037、039对粘虫显示出80％的杀虫活性，但对其他3种虫靶标室内杀虫活性较差或无杀虫作用。其余化合物对4种虫靶标室内杀虫活性均较差或无。The present invention relates to the indoor biological activity test of SIOC-Y-(001-052), an N-substituted oxadiazine compound, on four insect targets such as rice brown planthopper, armyworm (Plutella xylostella), spider mite, and alfalfa aphid. It shows that compound SIOC -Y-(001-052) at the general screening concentration of 500mg/L, wherein compounds SIOC-Y-006, 014, 038, 041-043, 046, 047, 049, 051 showed 100% insecticidal to armyworm Activity, 036, 037, 039 showed 80% insecticidal activity against armyworm, but poor or no insecticidal activity against the other three insect target indoor insecticides. The remaining compounds had poor or no indoor insecticidal activity against the four insect targets.

活性化合物降低浓度进一步筛选，结果表明SIOC-Y-047对粘虫仍表现出较好的杀虫活性，在浓度20mg/L时杀虫活性仍为100％。其余化合物降低浓度活性明显降低，在浓度20mg/L下室内对粘虫杀虫活性较差或无杀虫作用。结果表明化合物SIOC-Y-047对粘虫和斜纹夜蛾的活性略差与茚虫威，但EC₅₀属于同一数量级水平。The active compound was further screened at lower concentrations, and the results showed that SIOC-Y-047 still exhibited good insecticidal activity against armyworms, and the insecticidal activity was still 100% at a concentration of 20 mg/L. The activity of other compounds decreased significantly when the concentration was lowered, and the insecticidal activity against armyworm was poor or had no insecticidal effect indoors at a concentration of 20 mg/L. The results showed that the activity of compound SIOC-Y-047 against armyworm and Spodoptera litura was slightly worse than that of indoxacarb, but the EC₅₀ belonged to the same order of magnitude.

具体实施方式Detailed ways

下面结合具体实施例对本发明进行详细说明：本实施例在以本发明技术方案为前提下进行实施，给出了详细的实施方式和具体的操作过程，但本发明的保护范围不限于下述的实施例。The present invention is described in detail below in conjunction with specific embodiment: present embodiment implements under the premise of technical scheme of the present invention, has provided detailed embodiment and specific operation process, but protection scope of the present invention is not limited to following Example.

本实施例采用2-(苄基)-7-氯茚并[1，2-e][1，3，4]]噁二嗪-2，4a(3H，5H)-二羧酸-4a-甲基酯(A)为原料在Pd/C催化下进行加氢反应，加氢还原产物7-氯-2，3，4a，5-四氢茚并[1，2-e][1，3，4]]噁二嗪-4a-甲酸甲酯(B)再与(氯羰基)(芳基)氨基甲酸甲酯中间体(C)进行缩合反应等反应步骤制备N取代噁二嗪类化合物，反应式中Bn表示苄基，Ar表示芳基。This example uses 2-(benzyl)-7-chloroindeno[1,2-e][1,3,4]]oxadiazine-2,4a(3H,5H)-dicarboxylic acid-4a- Methyl ester (A) is used as a raw material for hydrogenation reaction under the catalysis of Pd/C, and the hydrogenation reduction product 7-chloro-2,3,4a,5-tetrahydroindeno[1,2-e][1,3 , 4]] methyl oxadiazine-4a-formate (B) and (chlorocarbonyl) (aryl) methyl carbamate intermediate (C) carry out condensation reaction and other reaction steps to prepare N-substituted oxadiazine compounds, In the reaction formula, Bn represents benzyl, and Ar represents aryl.

以下为本发明实施例的详细描述。The following is a detailed description of the embodiments of the present invention.

7-氯-2，3，4a，5-四氢茚并[1，2-e][1，3，4]]噁二嗪-4a-甲酸甲酯(B)的制备Preparation of 7-chloro-2,3,4a,5-tetrahydroindeno[1,2-e][1,3,4]]oxadiazine-4a-carboxylic acid methyl ester (B)

在50ml带导气管的三口反应瓶中，加入乙酸甲酯(20ml)，2-(苄基)-7-氯茚并[1，2-e][1，3，4]噁二嗪-2，4a(3H，5H)-二羧酸4a-甲基酯(200mg)，10％Pd/C(30mg)，氢气保护下反应30分钟；加入制得的酰氯(C)，加入N，N-二异丙基乙胺(200mg)，同时撤掉氢气保护，改换氮气保护，反应12-18小时；撤掉氮气保护，水洗，用二氯甲烷萃取，无水硫酸镁干燥，浓缩，并进行后处理得N取代噁二嗪类化合物。In a 50ml three-necked reaction flask with an airway tube, add methyl acetate (20ml), 2-(benzyl)-7-chloroindeno[1,2-e][1,3,4]oxadiazine-2 , 4a(3H, 5H)-dicarboxylic acid 4a-methyl ester (200mg), 10% Pd/C (30mg), reacted under hydrogen protection for 30 minutes; added the prepared acid chloride (C), added N,N- Diisopropylethylamine (200mg), remove the hydrogen protection at the same time, replace the nitrogen protection, and react for 12-18 hours; remove the nitrogen protection, wash with water, extract with dichloromethane, dry over anhydrous magnesium sulfate, concentrate, and carry out Treat N-substituted oxadiazine compounds.

本发明结构通式(I)化合物的制备方法包括以下两个反应进行，反应式如下：The preparation method of the compound of general structural formula (I) of the present invention comprises following two reactions and carries out, and reaction formula is as follows:

实施例1Example 1

(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(吡啶)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(SIOC-Y-001)的制备(S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(pyridine)amino]formyl]indeno[1,2-e][1,3,4-]oxadi Preparation of Ozine-4a(3H)-Carboxylic Acid Methyl Ester (SIOC-Y-001)

在50ml反应瓶中加入乙酸甲酯(20ml)，10％Pd/C(50mg)和2-(苄基)-7-氯茚并[1，2-e][1，3，4]噁二嗪-2，4a(3H，5H)-二羧酸4a-甲基酯(A)(200mg，0.5mmol)，氢气保护下反应30分钟；加入(氯羰基)(2-吡啶)氨基甲酸甲酯(130mg，0.6mmol)的乙酸甲酯溶液(10ml)，加入N，N-二异丙基乙胺(200mg，1.5mmol)同时撤掉氢气保护，改换氮气保护，反应12-18小时；撤掉氮气保护，水洗，用二氯甲烷萃取，无水硫酸镁干燥，浓缩，经硅胶柱层析分离，得淡黄色固体161.1mg，产率69.5％，熔点：150-152℃。Add methyl acetate (20ml), 10% Pd/C (50mg) and 2-(benzyl)-7-chloroindeno[1,2-e][1,3,4]oxadioxane in a 50ml reaction flask Oxyzine-2,4a(3H,5H)-dicarboxylic acid 4a-methyl ester (A) (200mg, 0.5mmol), react under hydrogen protection for 30 minutes; add (chlorocarbonyl)(2-pyridine)carbamate methyl ester (130mg, 0.6mmol) in methyl acetate solution (10ml), add N,N-diisopropylethylamine (200mg, 1.5mmol) and remove the hydrogen protection at the same time, replace the nitrogen protection, react for 12-18 hours; remove Protected under nitrogen, washed with water, extracted with dichloromethane, dried over anhydrous magnesium sulfate, concentrated, and separated by silica gel column chromatography to obtain 161.1 mg of a light yellow solid with a yield of 69.5% and a melting point of 150-152°C.

同理得SIOC-Y-002至SIOC-Y-052化合物。Similarly, SIOC-Y-002 to SIOC-Y-052 compounds can be obtained.

实施例2.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(SIOC-Y-002)的制备。Example 2. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (naphthalene)amino]formyl]indeno[1,2-e][1,3,4 -] Preparation of oxadiazine-4a(3H)-methyl carboxylate (SIOC-Y-002).

熔点：81-83℃。Melting point: 81-83°C.

¹H NMR(300MHz，CDCl₃)δ：8.14(d，J＝7.5Hz，1H)，7.96-7.83(m，2H)，7.66-7.44(m，4H)，7.36-7.25(m，3H)，5.70(d，J＝9.0Hz，1H)，5.26(d，J＝9.6Hz，1H)，3.76-3.64(m，6H)，3.48(d，J＝16.5Hz，1H)，3.27(d，J＝16.8Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.14 (d, J=7.5Hz, 1H), 7.96-7.83 (m, 2H), 7.66-7.44 (m, 4H), 7.36-7.25 (m, 3H), 5.70(d, J=9.0Hz, 1H), 5.26(d, J=9.6Hz, 1H), 3.76-3.64(m, 6H), 3.48(d, J=16.5Hz, 1H), 3.27(d, J = 16.8Hz, 1H).

3.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(4-甲基吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯(SIOC-Y-003)3. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(4-methylpyridine)]amino]formyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a(3H)-methyl carboxylate (SIOC-Y-003)

熔点：169-171℃。Melting point: 169-171°C.

¹H NMR(300MHz，CDCl₃)δ：8.17(d，J＝4.8Hz，1H)，7.43(s，1H)，7.38(d，J＝8.7Hz，1H)，7.30-7.22(m，2H)，6.89(d，J＝5.1Hz，1H)，5.82(d，J＝9.9Hz，1H)，5.24(d，J＝9.6Hz，1H)，3.74(s，3H)，3.70(s，3H)，3.45(d，J＝16.5Hz，1H)，3.22(d，J＝16.2Hz，1H)，2.36(s，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.17(d, J=4.8Hz, 1H), 7.43(s, 1H), 7.38(d, J=8.7Hz, 1H), 7.30-7.22(m, 2H) , 6.89(d, J=5.1Hz, 1H), 5.82(d, J=9.9Hz, 1H), 5.24(d, J=9.6Hz, 1H), 3.74(s, 3H), 3.70(s, 3H) , 3.45(d, J=16.5Hz, 1H), 3.22(d, J=16.2Hz, 1H), 2.36(s, 3H).

4.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(6-甲基吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯4. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(6-methylpyridine)]amino]formyl]indeno[1,2-e] [1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：84-86℃。Melting point: 84-86°C.

¹H NMR(300MHz，CDCl₃)δ：7.59(t，J＝7.8Hz，1H)，7.42(d，J＝8.4Hz，1H)，7.35(d，J＝8.4Hz，1H)，7.31-7.21(m，2H)，6.90(d，J＝7.5Hz，1H)，5.82(d，J＝10.2Hz，1H)，5.24(d，J＝10.2Hz，1H)，3.77(s，3H)，3.71(s，3H)，3.45(d，J＝16.5Hz，1H)，3.23(d，J＝16.2Hz，1H)，2.39(s，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.59(t, J=7.8Hz, 1H), 7.42(d, J=8.4Hz, 1H), 7.35(d, J=8.4Hz, 1H), 7.31-7.21 (m, 2H), 6.90(d, J=7.5Hz, 1H), 5.82(d, J=10.2Hz, 1H), 5.24(d, J=10.2Hz, 1H), 3.77(s, 3H), 3.71 (s, 3H), 3.45 (d, J = 16.5Hz, 1H), 3.23 (d, J = 16.2Hz, 1H), 2.39 (s, 3H).

5.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(5-溴吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯5. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(5-bromopyridine)]amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：127-129℃。Melting point: 127-129°C.

¹H NMR(300MHz，CDCl₃)δ：8.33(s，1H)，7.83(dd，J＝8.7，2.7Hz，1H)，7.63(d，J＝8.7Hz，1H)，7.37(d，J＝8.7Hz，1H)，7.32-7.22(m，2H)，5.84(d，J＝10.2Hz，1H)，5.26(d，J＝10.2Hz，1H)，3.78(s，3H)，3.72(s，3H)，3.47(d，J＝16.2Hz，1H)，3.25(d，J＝16.2Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.33(s, 1H), 7.83(dd, J=8.7, 2.7Hz, 1H), 7.63(d, J=8.7Hz, 1H), 7.37(d, J= 8.7Hz, 1H), 7.32-7.22(m, 2H), 5.84(d, J=10.2Hz, 1H), 5.26(d, J=10.2Hz, 1H), 3.78(s, 3H), 3.72(s, 3H), 3.47(d, J=16.2Hz, 1H), 3.25(d, J=16.2Hz, 1H).

6.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(5-碘吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯6. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(5-iodopyridine)]amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：154-156℃。Melting point: 154-156°C.

¹H NMR(300MHz，CDCl₃)δ：8.47(s，1H)，7.99(dd，J＝8.4，1.8Hz，1H)，7.54(d，J＝9.0Hz，1H)，7.36(d，J＝8.7Hz，1H)，7.31-7.22(m，2H)，5.83(d，J＝9.6Hz，1H)，5.25(d，J＝10.2Hz，1H)，3.77(s，3H)，3.72(s，3H)，3.46(d，J＝16.2Hz，1H)，3.25(d，J＝16.2Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.47(s, 1H), 7.99(dd, J=8.4, 1.8Hz, 1H), 7.54(d, J=9.0Hz, 1H), 7.36(d, J= 8.7Hz, 1H), 7.31-7.22(m, 2H), 5.83(d, J=9.6Hz, 1H), 5.25(d, J=10.2Hz, 1H), 3.77(s, 3H), 3.72(s, 3H), 3.46(d, J=16.2Hz, 1H), 3.25(d, J=16.2Hz, 1H).

8.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[4-(2-氯吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯8. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[4-(2-chloropyridine)]amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：63-66℃。Melting point: 63-66°C.

¹H NMR(300MHz，CDCl₃)δ：8.38(s，1H)，7.67(dd，J＝11.4，2.1Hz，1H)，7.50(d，J＝8.1Hz，1H)，7.40-7.28(m，3H)，5.72(d，J＝9.3Hz，1H)，5.21(d，J＝9.9Hz，1H)，3.75(s，3H)，3.69(s，3H)，3.49(d，J＝16.2Hz，1H)，3.26(d，J＝16.5Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.38(s, 1H), 7.67(dd, J=11.4, 2.1Hz, 1H), 7.50(d, J=8.1Hz, 1H), 7.40-7.28(m, 3H), 5.72(d, J=9.3Hz, 1H), 5.21(d, J=9.9Hz, 1H), 3.75(s, 3H), 3.69(s, 3H), 3.49(d, J=16.2Hz, 1H), 3.26 (d, J = 16.5 Hz, 1H).

9.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[3-(2-氯吡啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯9. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl[3-(2-chloropyridine)]amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：91-93℃。Melting point: 91-93°C.

¹H NMR(300MHz，CDCl₃)δ：8.33(dd，J＝4.5，1.8Hz，1H)，7.67(dd，J＝7.8，1.5Hz，1H)，7.49(d，J＝8.4Hz，1H)，7.37-7.27(m，3H)，5.64(d，J＝9.6Hz，1H)，5.23(d，J＝9.3Hz，1H)，3.77(s，3H)，3.71(s，3H)，3.46(d，J＝16.8Hz，1H)，3.23(d，J＝16.5Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.33 (dd, J=4.5, 1.8Hz, 1H), 7.67 (dd, J=7.8, 1.5Hz, 1H), 7.49 (d, J=8.4Hz, 1H) , 7.37-7.27(m, 3H), 5.64(d, J=9.6Hz, 1H), 5.23(d, J=9.3Hz, 1H), 3.77(s, 3H), 3.71(s, 3H), 3.46( d, J=16.8 Hz, 1H), 3.23 (d, J=16.5 Hz, 1H).

10.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-甲氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯10. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-methoxynaphthalene)amino]formyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：105-107℃。Melting point: 105-107°C.

¹H NMR(300MHz，CDCl₃)δ：7.98-7.74(m，3H)，7.60-7.24(m，6H)，5.63(d，J＝9.3Hz，1H)，5.30(d，J＝9.3Hz，1H)，3.76-3.67(m，9H)，3.43(d，J＝10.2Hz，1H)，3.28(d，J＝9.0Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.98-7.74(m, 3H), 7.60-7.24(m, 6H), 5.63(d, J=9.3Hz, 1H), 5.30(d, J=9.3Hz, 1H), 3.76-3.67(m, 9H), 3.43(d, J=10.2Hz, 1H), 3.28(d, J=9.0Hz, 1H).

11.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-乙氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯11. (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-ethoxynaphthalene)amino]formyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：75-77℃。Melting point: 75-77°C.

¹H NMR(300MHz，CDCl₃)δ：7.94-7.74(m，3H)，7.59-7.23(m，6H)，5.78-5.64(m，1H)，5.33-5.15(m，1H)，4.26-4.10(m，2H)，3.76-3.63(m，6H)，3.55-3.37(m，1H)，3.33-3.14(m，1H)，1.43-1.28(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.94-7.74 (m, 3H), 7.59-7.23 (m, 6H), 5.78-5.64 (m, 1H), 5.33-5.15 (m, 1H), 4.26-4.10 (m, 2H), 3.76-3.63 (m, 6H), 3.55-3.37 (m, 1H), 3.33-3.14 (m, 1H), 1.43-1.28 (m, 3H).

12.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-正丙氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯12. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-n-propoxynaphthalene)amino]formyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：77-79℃Melting point: 77-79°C

¹H NMR(300MHz，CDCl₃)δ：7.98-7.72(m，3H)，7.58-7.23(m，6H)，5.78-5.64(m，1H)，5.33-5.16(m，1H)，4.15-3.99(m，2H)，3.77-3.64(m，6H)，3.53-3.38(m，1H)，3.31-3.17(m，1H)，1.88-1.62(m，2H)，1.12-0.92(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.98-7.72 (m, 3H), 7.58-7.23 (m, 6H), 5.78-5.64 (m, 1H), 5.33-5.16 (m, 1H), 4.15-3.99 (m, 2H), 3.77-3.64(m, 6H), 3.53-3.38(m, 1H), 3.31-3.17(m, 1H), 1.88-1.62(m, 2H), 1.12-0.92(m, 3H) .

13.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-正戊氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯13. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-n-pentyloxynaphthalene)amino]formyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：55-57℃Melting point: 55-57°C

¹H NMR(300MHz，CDCl₃)δ：7.96-7.74(m，3H)，7.59-7.24(m，6H)，5.78-5.64(m，1H)，5.31-5.16(m，1H)，4.19-4.02(m，2H)，3.77-3.64(m，6H)，3.53-3.39(m，1H)，3.31-3.18(m，1H)，1.90-1.62(m，2H)，1.53-1.17(m，4H)，0.99-0.78(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.96-7.74 (m, 3H), 7.59-7.24 (m, 6H), 5.78-5.64 (m, 1H), 5.31-5.16 (m, 1H), 4.19-4.02 (m, 2H), 3.77-3.64(m, 6H), 3.53-3.39(m, 1H), 3.31-3.18(m, 1H), 1.90-1.62(m, 2H), 1.53-1.17(m, 4H) , 0.99-0.78 (m, 3H).

14.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-正己氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯14. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-n-hexyloxynaphthalene)amino]formyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：62-64℃Melting point: 62-64°C

¹H NMR(300MHz，CDCl₃)δ：7.92-7.73(m，3H)，7.57-7.20(m，6H)，5.77-5.62(m，1H)，5.30-5.15(m，1H)，4.18-4.03(m，2H)，3.76-3.63(m，6H)，3.52-3.39(m，1H)，3.32-3.18(m，1H)，1.85-1.62(m，2H)，1.51-1.12(m，6H)，0.94-0.78(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.92-7.73 (m, 3H), 7.57-7.20 (m, 6H), 5.77-5.62 (m, 1H), 5.30-5.15 (m, 1H), 4.18-4.03 (m, 2H), 3.76-3.63(m, 6H), 3.52-3.39(m, 1H), 3.32-3.18(m, 1H), 1.85-1.62(m, 2H), 1.51-1.12(m, 6H) , 0.94-0.78 (m, 3H).

15.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-异丙氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯15. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-isopropoxynaphthalene)amino]formyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：72-74℃Melting point: 72-74°C

¹H NMR(300MHz，CDCl₃)δ：7.95-7.71(m，3H)，7.63-7.21(m，6H)，5.80-5.66(m，1H)，5.33-5.16(m，1H)，4.79-4.59(m，1H)，3.74-3.63(m，6H)，3.50-3.37(m，1H)，3.29-3.16(m，1H)，1.38-1.23(m，6H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.95-7.71 (m, 3H), 7.63-7.21 (m, 6H), 5.80-5.66 (m, 1H), 5.33-5.16 (m, 1H), 4.79-4.59 (m, 1H), 3.74-3.63 (m, 6H), 3.50-3.37 (m, 1H), 3.29-3.16 (m, 1H), 1.38-1.23 (m, 6H).

16(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-正丁氧基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯16(S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl(2-n-butoxynaphthalene)amino]formyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：79-81℃。Melting point: 79-81°C.

¹H NMR(300MHz，CDCl₃)δ：7.96-7.74(m，3H)，7.59-7.23(m，6H)，5.78-5.64(m，1H)，5.33-5.14(m，1H)，4.20-4.05(m，2H)，3.77-3.64(m，6H)，3.55-3.37(m，1H)，3.34-3.15(m，1H)，1.86-1.55(m，4H)，1.05-0.88(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.96-7.74 (m, 3H), 7.59-7.23 (m, 6H), 5.78-5.64 (m, 1H), 5.33-5.14 (m, 1H), 4.20-4.05 (m, 2H), 3.77-3.64(m, 6H), 3.55-3.37(m, 1H), 3.34-3.15(m, 1H), 1.86-1.55(m, 4H), 1.05-0.88(m, 3H) .

17.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基[2-(4，6-二甲氧基嘧啶)]氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯17. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl[2-(4,6-dimethoxypyrimidine)]amino]formyl]indeno[1, 2-e][1,3,4-]oxadiazine-4a(3H)-carboxylate methyl ester

¹H NMR(300MHz，CDCl₃)δ：7.36(d，J＝9.0Hz，1H)，7.30-7.22(m，2H)，6.81(s，1H)，5.85(d，J＝9.9Hz，1H)，3.76(s，3H)，3.71(s，3H)，3.45(d，J＝16.5Hz，1H)，3.22(d，J＝15.9Hz，1H)，2.43(s，6H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.36(d, J=9.0Hz, 1H), 7.30-7.22(m, 2H), 6.81(s, 1H), 5.85(d, J=9.9Hz, 1H) , 3.76(s, 3H), 3.71(s, 3H), 3.45(d, J=16.5Hz, 1H), 3.22(d, J=15.9Hz, 1H), 2.43(s, 6H).

18.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-特丁酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯18. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-tert-butyrate naphthalene)amino]formyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：103-104℃Melting point: 103-104°C

¹H NMR(300MHz，CDCl₃)δ：7.94-7.72(m，3H)，7.56-7.25(m，6H)，5.72-5.60(m，1H)，5.33-5.14(m，1H)，3.77-3.59(m，6H)，3.54-3.37(m，1H)，3.34-3.17(m，1H)，1.26-1.10(m，9H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.94-7.72 (m, 3H), 7.56-7.25 (m, 6H), 5.72-5.60 (m, 1H), 5.33-5.14 (m, 1H), 3.77-3.59 (m, 6H), 3.54-3.37 (m, 1H), 3.34-3.17 (m, 1H), 1.26-1.10 (m, 9H).

19.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-差劲基萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯19. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-poor naphthalene)amino]formyl]indeno[1,2-e][1,3 ,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：107-109℃Melting point: 107-109°C

¹H NMR(300MHz，CDCl₃)δ：8.18(s，1H)，8.00(t，J＝8.1Hz，2H)，7.74(d，J＝8.1Hz，1H)7.66-7.47(m，5H)，6.52(brs，1H)，5.71(d，J＝9.6Hz，1H)，5.08(d，J＝9.9Hz，1H)，3.77(s，3H)，3.74(s，3H)，3.52(d，J＝15.9Hz，1H)，3.33(d，J＝15.6Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.18(s, 1H), 8.00(t, J=8.1Hz, 2H), 7.74(d, J=8.1Hz, 1H), 7.66-7.47(m, 5H), 6.52(brs, 1H), 5.71(d, J=9.6Hz, 1H), 5.08(d, J=9.9Hz, 1H), 3.77(s, 3H), 3.74(s, 3H), 3.52(d, J = 15.9Hz, 1H), 3.33 (d, J = 15.6Hz, 1H).

20.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-丁酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯20. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-butyrate naphthalene)amino]formyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：85-87℃Melting point: 85-87°C

¹H NMR(300MHz，CDCl₃)δ：8.07-7.80(m，4H)，7.63-7.45(m，2H)，7.35-7.15(m，3H)，5.75-5.60(m，1H)，5.27-5.13(m，1H)，3.73-3.67(m，6H)，3.48-3.37(m，1H)，3.27-3.17(m，1H)，2.62-2.44(m，2H)，1.84-1.57(m，4H)，0.91-0.83(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.07-7.80 (m, 4H), 7.63-7.45 (m, 2H), 7.35-7.15 (m, 3H), 5.75-5.60 (m, 1H), 5.27-5.13 (m, 1H), 3.73-3.67(m, 6H), 3.48-3.37(m, 1H), 3.27-3.17(m, 1H), 2.62-2.44(m, 2H), 1.84-1.57(m, 4H) , 0.91-0.83 (m, 3H).

21.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-乙酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯21. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-acetate naphthalene)amino]formyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：93-95℃Melting point: 93-95°C

¹H NMR(300MHz，CDCl₃)δ：8.08-7.80(m，4H)，7.68-7.44(m，3H)，7.40-7.16(m，2H)，5.74-5.62(m，1H)，5.29-5.16(m，1H)，3.74-3.61(m，6H)，3.42-3.33(m，1H)，3.27-3.15(m，1H)，2.33-2.16(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.08-7.80 (m, 4H), 7.68-7.44 (m, 3H), 7.40-7.16 (m, 2H), 5.74-5.62 (m, 1H), 5.29-5.16 (m, 1H), 3.74-3.61 (m, 6H), 3.42-3.33 (m, 1H), 3.27-3.15 (m, 1H), 2.33-2.16 (m, 3H).

22.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-丙酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯22. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-propionate naphthalene)amino]formyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：87-89℃Melting point: 87-89°C

¹H NMR(300MHz，CDCl₃)δ：8.07-7.79(m，4H)，7.65-7.45(m，2H)，7.36-7.14(m，3H)，5.75-5.58(m，1H)，5.28-5.12(m，1H)，3.75-3.57(m，6H)，3.49-3.35(m，1H)，3.29-3.14(m，1H)，2.68-2.46(m，2H)，1.31-1.18(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.07-7.79 (m, 4H), 7.65-7.45 (m, 2H), 7.36-7.14 (m, 3H), 5.75-5.58 (m, 1H), 5.28-5.12 (m, 1H), 3.75-3.57(m, 6H), 3.49-3.35(m, 1H), 3.29-3.14(m, 1H), 2.68-2.46(m, 2H), 1.31-1.18(m, 3H) .

23.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-甲氧甲醚萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯23. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-methoxymethyl ether naphthalene)amino]formyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：71-73℃Melting point: 71-73°C

¹H NMR(300MHz，CDCl₃)δ：8.01-7.74(m，3H)，7.63-7.33(m，4H)，7.32-7.22(m，2H)，5.75-5.60(m，1H)，5.35-6.15(m，3H)，3.80-3.63(m，6H)，3.54-3.38(m，4H)，3.30-3.18(m，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.01-7.74 (m, 3H), 7.63-7.33 (m, 4H), 7.32-7.22 (m, 2H), 5.75-5.60 (m, 1H), 5.35-6.15 (m, 3H), 3.80-3.63 (m, 6H), 3.54-3.38 (m, 4H), 3.30-3.18 (m, 1H).

24.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-苯甲酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯24. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-benzoate naphthalene)amino]formyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：109-111℃Melting point: 109-111°C

¹H NMR(300MHz，CDCl₃)δ：8.33-7.85(m，6H)，7.69-6.81(m，8H)，5.78-5.57(m，1H)，5.23-5.08(m，3H)，3.73-3.49(m，6H)，3.47-2.81(m，2H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.33-7.85 (m, 6H), 7.69-6.81 (m, 8H), 5.78-5.57 (m, 1H), 5.23-5.08 (m, 3H), 3.73-3.49 (m, 6H), 3.47-2.81 (m, 2H).

25.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-吡喃甲酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯25. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-pyranoate naphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：80-82℃Melting point: 80-82°C

¹H NMR(300MHz，CDCl₃)δ：8.11-7.85(m，4H)，7.75-7.37(m，6H)，7.31-7.16(m，2H)，5.78-5.61(m，1H)，5.26-5.16(m，1H)，3.75-3.57(m，6H)，3.54-3.03(m，2H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.11-7.85 (m, 4H), 7.75-7.37 (m, 6H), 7.31-7.16 (m, 2H), 5.78-5.61 (m, 1H), 5.26-5.16 (m, 1H), 3.75-3.57 (m, 6H), 3.54-3.03 (m, 2H).

26.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基(2-甲氧甲酸酯萘)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯26. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl(2-methoxyformyl naphthalene)amino]formyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：97-99℃Melting point: 97-99°C

¹H NMR(300MHz，CDCl₃)δ：8.10-7.80(m，4H)，7.66-7.47(m，3H)，7.45-7.30(m，2H)，5.75-5.64(m，1H)，5.26-5.18(m，1H)，3.79-3.64(m，6H)，3.53-3.40(m，1H)，3.37-3.24(m，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.10-7.80 (m, 4H), 7.66-7.47 (m, 3H), 7.45-7.30 (m, 2H), 5.75-5.64 (m, 1H), 5.26-5.18 (m, 1H), 3.79-3.64 (m, 6H), 3.53-3.40 (m, 1H), 3.37-3.24 (m, 1H).

27.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基2-(4-氯-6-甲氧基嘧啶)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯27. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl 2-(4-chloro-6-methoxypyrimidine)amino]formyl]indeno[1,2 -e][1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：61-63℃Melting point: 61-63°C

¹H NMR(300MHz，CDCl₃)δ：7.42-7.24(m，3H)，6.49(s，1H)，5.83(d，J＝9.9Hz，1H)，3.91(s，3H)，3.81(s，3H)，3.71(s，3H)，3.47(d，J＝16.2Hz，1H)，3.23(d，J＝16.2Hz，1H).¹ H NMR (300MHz, CDCl₃ ) δ: 7.42-7.24 (m, 3H), 6.49 (s, 1H), 5.83 (d, J=9.9Hz, 1H), 3.91 (s, 3H), 3.81 (s, 3H), 3.71(s, 3H), 3.47(d, J=16.2Hz, 1H), 3.23(d, J=16.2Hz, 1H).

28.(S)-7-氯-3，5-二氢-2-[[甲氧基羰基2-(4，6-二甲氧基嘧啶)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羧酸甲酯28. (S)-7-Chloro-3,5-dihydro-2-[[methoxycarbonyl 2-(4,6-dimethoxypyrimidine)amino]formyl]indeno[1,2- e][1,3,4-]oxadiazine-4a(3H)-methyl carboxylate

熔点：58-60℃Melting point: 58-60°C

¹H NMR(300MHz，CDCl₃)δ：7.40-7.22(m，3H)，5.83(d，J＝10.2Hz，1H)，5.77(s，1H)，5.22(d，J＝9.9Hz，1H)，3.85(s，6H)，3.80(s，3H)，3.69(s，3H)，3.46(d，J＝16.5Hz，1H)，3.21(d，J＝16.2Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.40-7.22(m, 3H), 5.83(d, J=10.2Hz, 1H), 5.77(s, 1H), 5.22(d, J=9.9Hz, 1H) , 3.85(s, 6H), 3.80(s, 3H), 3.69(s, 3H), 3.46(d, J=16.5Hz, 1H), 3.21(d, J=16.2Hz, 1H).

29.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯29. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-methoxyphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester

熔点：87-88℃Melting point: 87-88°C

¹H NMR(300MHz，CDCl₃)δ：8.41-8.23(m，3H)，8.09(d，J＝9.6Hz，1H)，7.66-7.39(m，5H)，7.37-7.28(m，2H)，5.68(t，J＝11.1Hz，1H)，5.24(t，J＝11.4Hz，1H)，3.99(s，3H)，3.70(s，6H)，3.47(d，J＝16.5Hz，1H)，3.25(d，J＝16.5Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.41-8.23 (m, 3H), 8.09 (d, J=9.6Hz, 1H), 7.66-7.39 (m, 5H), 7.37-7.28 (m, 2H), 5.68(t, J=11.1Hz, 1H), 5.24(t, J=11.4Hz, 1H), 3.99(s, 3H), 3.70(s, 6H), 3.47(d, J=16.5Hz, 1H), 3.25 (d, J=16.5Hz, 1H).

30.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-乙氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯30. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-ethoxyphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester

熔点：75-77℃Melting point: 75-77°C

¹H NMR(300MHz，CDCl₃)δ：8.39-8.27(m，1H)，8.08(d，J＝7.8Hz，1H)，7.64-7.27(m，6H)，6.82-6.71(m，1H)，5.68(t，J＝10.5Hz，1H)，5.24(t，J＝10.5Hz，1H)，4.27-4.13(m，2H)，3.72-3.64(s，6H)，3.47-3.36(m，1H)，3.32-3.18(m，1H)，1.58-1.46(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.39-8.27 (m, 1H), 8.08 (d, J=7.8Hz, 1H), 7.64-7.27 (m, 6H), 6.82-6.71 (m, 1H), 5.68(t, J=10.5Hz, 1H), 5.24(t, J=10.5Hz, 1H), 4.27-4.13(m, 2H), 3.72-3.64(s, 6H), 3.47-3.36(m, 1H) , 3.32-3.18 (m, 1H), 1.58-1.46 (m, 3H).

31.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-正丙氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯31. (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-n-propoxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：57-59℃Melting point: 57-59°C

¹H NMR(300MHz，CDCl₃)δ：8.40-8.27(m，1H)，8.07(d，J＝8.1Hz，1H)，7.63-7.21(m，6H)，6.82-6.71(m，1H)，5.67(t，J＝12.3Hz，1H)，5.23(t，J＝9.9Hz，1H)，4.16-4.00(m，2H)，3.73-3.63(m，6H)，3.36-3.26(m，1H)，3.18-3.07(m，1H)，1.18-0.96(m，5H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.40-8.27 (m, 1H), 8.07 (d, J=8.1Hz, 1H), 7.63-7.21 (m, 6H), 6.82-6.71 (m, 1H), 5.67(t, J=12.3Hz, 1H), 5.23(t, J=9.9Hz, 1H), 4.16-4.00(m, 2H), 3.73-3.63(m, 6H), 3.36-3.26(m, 1H) , 3.18-3.07 (m, 1H), 1.18-0.96 (m, 5H).

32.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-异氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯32. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-isooxyphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester

熔点：74-76℃Melting point: 74-76°C

¹H NMR(300MHz，CDCl₃)δ：8.41-8.27(m，1H)，8.09(d，J＝7.8Hz，1H)，7.65-7.41(m，4H)，7.38-7.30(m，2H)，6.80(d，J＝7.8Hz，1H)，5.72(t，J＝10.2Hz，1H)，5.27(t，J＝10.2Hz，1H)，4.83-4.68(m，1H)，3.75-3.67(s，6H)，3.49(d，J＝16.2Hz，1H)，3.28(d，J＝16.2Hz，1H)，1.46(s，6H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.41-8.27 (m, 1H), 8.09 (d, J=7.8Hz, 1H), 7.65-7.41 (m, 4H), 7.38-7.30 (m, 2H), 6.80(d, J=7.8Hz, 1H), 5.72(t, J=10.2Hz, 1H), 5.27(t, J=10.2Hz, 1H), 4.83-4.68(m, 1H), 3.75-3.67(s , 6H), 3.49 (d, J = 16.2Hz, 1H), 3.28 (d, J = 16.2Hz, 1H), 1.46 (s, 6H).

33.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-正丁氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯33. (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-n-butoxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：67-69℃Melting point: 67-69°C

¹H NMR(300MHz，CDCl₃)δ：8.42-8.27(m，1H)，8.09(d，J＝8.7Hz，1H)，7.65-7.26(m，6H)，6.83-6.73(m，1H)，5.69(t，J＝10.2Hz，1H)，5.25(t，J＝10.2Hz，1H)，4.22-4.08(m，2H)，3.75-3.67(s，6H)，3.49(d，J＝16.2Hz，1H)，3.27(d，J＝16.2Hz，1H)，2.00-1.84(m，2H)，1.70-1.53(m，2H)，1.09-0.98(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.42-8.27 (m, 1H), 8.09 (d, J=8.7Hz, 1H), 7.65-7.26 (m, 6H), 6.83-6.73 (m, 1H), 5.69(t, J=10.2Hz, 1H), 5.25(t, J=10.2Hz, 1H), 4.22-4.08(m, 2H), 3.75-3.67(s, 6H), 3.49(d, J=16.2Hz , 1H), 3.27 (d, J=16.2Hz, 1H), 2.00-1.84 (m, 2H), 1.70-1.53 (m, 2H), 1.09-0.98 (m, 3H).

34.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-正戊氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯34. (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-n-pentyloxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：95-97℃Melting point: 95-97°C

¹H NMR(300MHz，CDCl₃)δ：8.40-8.28(m，1H)，8.09(d，J＝7.5Hz，1H)，7.66-7.29(m，6H)，6.84-6.73(m，1H)，5.70(t，J＝9.0Hz，1H)，5.25(t，J＝9.0Hz，1H)，4.14(t，J＝6.0Hz，2H)，3.71(s，6H)，3.49(d，J＝16.2Hz，1H)，3.27(d，J＝16.2Hz，1H)，1.99-1.87(m，2H)，1.62-1.36(m，4H)，0.98(t，J＝6.9Hz，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.40-8.28 (m, 1H), 8.09 (d, J=7.5Hz, 1H), 7.66-7.29 (m, 6H), 6.84-6.73 (m, 1H), 5.70(t, J=9.0Hz, 1H), 5.25(t, J=9.0Hz, 1H), 4.14(t, J=6.0Hz, 2H), 3.71(s, 6H), 3.49(d, J=16.2 Hz, 1H), 3.27(d, J=16.2Hz, 1H), 1.99-1.87(m, 2H), 1.62-1.36(m, 4H), 0.98(t, J=6.9Hz, 3H).

35.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-正己氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯35. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-n-hexyloxyphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester

熔点：91-93℃Melting point: 91-93°C

¹H NMR(300MHz，CDCl₃)δ：8.42-8.28(m，1H)，8.09(d，J＝9.0Hz，1H)，7.64-7.26(m，6H)，6.85-6.73(m，1H)，5.69(t，J＝11.4Hz，1H)，5.26(t，J＝11.4Hz，1H)，4.22-4.09(m，2H)，3.75-3.67(s，6H)，3.49(d，J＝16.5Hz，1H)，3.27(d，J＝16.5Hz，1H)，2.01-1.86(m，2H)，1.66-1.49(m，2H)，1.47-1.34(m，4H)，0.99-0.81(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.42-8.28 (m, 1H), 8.09 (d, J=9.0Hz, 1H), 7.64-7.26 (m, 6H), 6.85-6.73 (m, 1H), 5.69(t, J=11.4Hz, 1H), 5.26(t, J=11.4Hz, 1H), 4.22-4.09(m, 2H), 3.75-3.67(s, 6H), 3.49(d, J=16.5Hz , 1H), 3.27(d, J=16.5Hz, 1H), 2.01-1.86(m, 2H), 1.66-1.49(m, 2H), 1.47-1.34(m, 4H), 0.99-0.81(m, 3H ).

36.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-三氟甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯36. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-trifluoromethoxyphenyl)carbamoyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a-carboxylate methyl ester

¹H NMR(300MHz，CDCl₃)δ：8.27-8.14(m，2H)，7.71-7.28(m，7H)，5.69(d，J＝9.6Hz，1H)，5.26(d，J＝9.6Hz，1H)3.73(s，6H)，3.50(d，J＝16.5Hz，1H)，3.28(d，J＝16.5Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.27-8.14 (m, 2H), 7.71-7.28 (m, 7H), 5.69 (d, J=9.6Hz, 1H), 5.26 (d, J=9.6Hz, 1H) 3.73(s, 6H), 3.50(d, J=16.5Hz, 1H), 3.28(d, J=16.5Hz, 1H).

37.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-三氟乙氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯37. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-trifluoroethoxyphenyl)carbamoyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：65-67℃Melting point: 65-67°C

¹H NMR(300MHz，CDCl₃)δ：8.41-8.26(m，1H)，8.14(d，J＝8.1Hz，1H)，7.71-7.25(m，6H)，6.79(d，J＝8.1Hz，1H)，5.80-5.64(m，1H)，5.36-5.18(m，1H)，5.54(q，J＝7.8Hz，2H)，5.51(d，J＝16.2Hz，1H)，5.29(d，J＝16.2Hz，1H)，3.73(s，6H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.41-8.26 (m, 1H), 8.14 (d, J=8.1Hz, 1H), 7.71-7.25 (m, 6H), 6.79 (d, J=8.1Hz, 1H), 5.80-5.64(m, 1H), 5.36-5.18(m, 1H), 5.54(q, J=7.8Hz, 2H), 5.51(d, J=16.2Hz, 1H), 5.29(d, J =16.2Hz, 1H), 3.73(s, 6H).

38.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-三氟甲基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯38. (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-trifluoromethylphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：96-98℃Melting point: 96-98°C

¹H NMR(300MHz，CDCl₃)δ：8.33-8.20(m，2H)，7.90(d，J＝7.8Hz，1H)，7.76-7.63(m，2H)，7.58(d，J＝7.8Hz，1H)，7.38-7.29(m，3H)，5.71(d，J＝8.4Hz，1H)，5.28(d，J＝8.4Hz，1H)，3.74(s，6H)，3.50(d，J＝16.8Hz，1H)，3.28(d，J＝16.8Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.33-8.20 (m, 2H), 7.90 (d, J=7.8Hz, 1H), 7.76-7.63 (m, 2H), 7.58 (d, J=7.8Hz, 1H), 7.38-7.29(m, 3H), 5.71(d, J=8.4Hz, 1H), 5.28(d, J=8.4Hz, 1H), 3.74(s, 6H), 3.50(d, J=16.8 Hz, 1H), 3.28 (d, J = 16.8 Hz, 1H).

39.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(2-三氟甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯39. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(2-trifluoromethoxyphenyl)carbamoyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a-carboxylate methyl ester

¹H NMR(300MHz，CDCl₃)δ：8.22(d，J＝9.0Hz，1H)，7.97-7.81(m，2H)，7.73(s，1H)，7.62-7.26(m，5H)，5.71(d，J＝9.0Hz，1H)，5.27(d，J＝9.0Hz，1H)，3.75(s，6H)，3.50(d，J＝16.5Hz，1H)，3.27(d，J＝16.5Hz，1H).¹ H NMR (300MHz, CDCl₃ ) δ: 8.22 (d, J=9.0Hz, 1H), 7.97-7.81 (m, 2H), 7.73 (s, 1H), 7.62-7.26 (m, 5H), 5.71 ( d, J=9.0Hz, 1H), 5.27(d, J=9.0Hz, 1H), 3.75(s, 6H), 3.50(d, J=16.5Hz, 1H), 3.27(d, J=16.5Hz, 1H).

熔点：91-93℃Melting point: 91-93°C

40.(S)-7-氯-3，5一二氢-2-[甲氧基羰基2-[(3-三氟甲氧基苯基)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯40. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl 2-[(3-trifluoromethoxyphenyl)amino]formyl]indeno[1,2- e][1,3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：91-93℃Melting point: 91-93°C

¹H NMR(300MHz，CDCl₃)δ：8.13(s，1H)，8.02-7.86(m，2H)，7.67(d，J＝7.5Hz，1H)，7.56(d，J＝7.5Hz，1H)，7.53-7.30(m，5H)，5.83-5.60(m，1H)，5.40-5.15(m，5H)，3.71(s，6H)，3.52(d，J＝16.2Hz，1H)，3.39-3.20(m，1H).¹ H NMR (300MHz, CDCl₃ ) δ: 8.13(s, 1H), 8.02-7.86(m, 2H), 7.67(d, J=7.5Hz, 1H), 7.56(d, J=7.5Hz, 1H) , 7.53-7.30(m, 5H), 5.83-5.60(m, 1H), 5.40-5.15(m, 5H), 3.71(s, 6H), 3.52(d, J=16.2Hz, 1H), 3.39-3.20 (m, 1H).

41.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(2-溴-4-三氟氧基苯基)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯41. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(2-bromo-4-trifluorooxyphenyl)amino]formyl]indeno[1,2- e][1,3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：55-57℃Melting point: 55-57°C

¹H NMR(300MHz，CDCl₃)δ：7.64-7.49(m，2H)，7.43-7.29(m，3H)，7.20(d，J＝7.8Hz，1H)，5.66(d，J＝9.0Hz，1H)，5.24(d，J＝9.9Hz，1H)，3.76(s，3H)，3.73(s，3H)，3.49(d，J＝16.8Hz，1H)，3.26(d，J＝16.5Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.64-7.49 (m, 2H), 7.43-7.29 (m, 3H), 7.20 (d, J=7.8Hz, 1H), 5.66 (d, J=9.0Hz, 1H), 5.24(d, J=9.9Hz, 1H), 3.76(s, 3H), 3.73(s, 3H), 3.49(d, J=16.8Hz, 1H), 3.26(d, J=16.5Hz, 1H).

42.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-硝基苯基)氨基]甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯42. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-nitrophenyl)amino]formyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester

熔点：69-71℃Melting point: 69-71°C

¹H NMR(300MHz，CDCl₃)δ：8.25(d，J＝7.8Hz，2H)，7.53-7.45(m，3H)，7.38-7.31(m，2H)，5.77(d，J＝10.2Hz，1H)，5.25(d，J＝9.6Hz，1H)，3.78(s，3H)，3.74(s，3H)，3.52(d，J＝15.9Hz，1H)，3.28(d，J＝16.5Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.25(d, J=7.8Hz, 2H), 7.53-7.45(m, 3H), 7.38-7.31(m, 2H), 5.77(d, J=10.2Hz, 1H), 5.25(d, J=9.6Hz, 1H), 3.78(s, 3H), 3.74(s, 3H), 3.52(d, J=15.9Hz, 1H), 3.28(d, J=16.5Hz, 1H).

43.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-乙酰氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯43. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-acetoxyphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester

熔点：49-51℃Melting point: 49-51°C

¹H NMR(300MHz，CDCl₃)δ：8.10-7.98(m，2H)，7.46(d，J＝8.4Hz，1H)，7.40-7.24(m，4H)，5.70(d，J＝9.6Hz，1H)，5.21(d，J＝9.9Hz，1H)，4.40-4.26(m，2H)，3.79-3.60(m，6H)，3.45(d，J＝15.9Hz，1H)，3.21(d，J＝16.2Hz，1H)，1.41-1.27(m，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.10-7.98 (m, 2H), 7.46 (d, J=8.4Hz, 1H), 7.40-7.24 (m, 4H), 5.70 (d, J=9.6Hz, 1H), 5.21(d, J=9.9Hz, 1H), 4.40-4.26(m, 2H), 3.79-3.60(m, 6H), 3.45(d, J=15.9Hz, 1H), 3.21(d, J =16.2Hz, 1H), 1.41-1.27(m, 3H).

44.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯44. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-methoxyphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester

熔点：49-51℃Melting point: 49-51°C

¹H NMR(300MHz，CDCl₃)δ：7.98(d，J＝8.4Hz，2H)，7.50(d，J＝8.1Hz，1H)，7.42(d，J＝8.7Hz，2H)，7.33(d，J＝8.1Hz，2H)，5.75(d，J＝10.2Hz，1H)，5.24(d，J＝9.9Hz，1H)，3.76(s，3H)，3.73(s，3H)，3.50(d，J＝16.2Hz，1H)，3.27(d，J＝16.2Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.98(d, J=8.4Hz, 2H), 7.50(d, J=8.1Hz, 1H), 7.42(d, J=8.7Hz, 2H), 7.33(d , J=8.1Hz, 2H), 5.75(d, J=10.2Hz, 1H), 5.24(d, J=9.9Hz, 1H), 3.76(s, 3H), 3.73(s, 3H), 3.50(d , J=16.2Hz, 1H), 3.27(d, J=16.2Hz, 1H).

45.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-乙酰基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯45. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-acetylphenyl)carbamoyl]indeno[1,2-e][1,3, 4-]oxadiazine-4a-carboxylate methyl ester

熔点：64-66℃Melting point: 64-66°C

¹H NMR(300MHz，CDCl₃)δ：8.03(d，J＝8.7Hz，2H)，7.48(d，J＝8.1Hz，1H)，7.43-7.28(m，4H)，5.73(d，J＝9.9Hz，1H)，5.22(d，J＝9.9Hz，1H)，3.90(s，3H)，3.75(s，3H)，3.70(s，3H)，3.58(d，J＝16.8Hz，1H)，3.25(d，J＝16.8Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.03(d, J=8.7Hz, 2H), 7.48(d, J=8.1Hz, 1H), 7.43-7.28(m, 4H), 5.73(d, J= 9.9Hz, 1H), 5.22(d, J=9.9Hz, 1H), 3.90(s, 3H), 3.75(s, 3H), 3.70(s, 3H), 3.58(d, J=16.8Hz, 1H) , 3.25 (d, J=16.8Hz, 1H).

46.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-甲酰氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯46. (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl(4-formyloxyphenyl)carbamoyl]indeno[1,2-e][1, 3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：69-71℃Melting point: 69-71°C

47.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4-三氟甲硫基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯47. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-trifluoromethylthiophenyl)carbamoyl]indeno[1,2-e][1 ,3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：36-38℃Melting point: 36-38°C

¹H NMR(300MHz，CDCl₃)δ：7.65(d，J＝8.4Hz，2H)，7.48(d，J＝8.4Hz，1H)，7.42-7.29(m，4H)，5.74(d，J＝9.6Hz，1H)，5.22(d，J＝9.6Hz，1H)，3.74(s，3H)，3.71(s，3H)，3.49(d，J＝16.5Hz，1H)，3.26(d，J＝16.5Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.65 (d, J = 8.4Hz, 2H), 7.48 (d, J = 8.4Hz, 1H), 7.42-7.29 (m, 4H), 5.74 (d, J = 9.6Hz, 1H), 5.22(d, J=9.6Hz, 1H), 3.74(s, 3H), 3.71(s, 3H), 3.49(d, J=16.5Hz, 1H), 3.26(d, J= 16.5Hz, 1H).

48.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(2，4-二甲氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯48. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(2,4-dimethoxyphenyl)carbamoyl]indeno[1,2-e][ 1,3,4-]oxadiazine-4a-carboxylate methyl ester

熔点：78-80℃Melting point: 78-80°C

¹H NMR(300MHz，CDCl₃)δ：7.50(d，J＝8.1Hz，1H)，7.34-7.25(m，2H)，6.92-6.76(m，3H)，5.68(d，J＝9.6Hz，1H)，5.21(d，J＝9.6Hz，1H)，3.78(s，3H)，3.73(s，3H)，3.71(s，6H)，3.47(d，J＝16.5Hz，1H)，3.25(d，J＝16.5Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.50(d, J=8.1Hz, 1H), 7.34-7.25(m, 2H), 6.92-6.76(m, 3H), 5.68(d, J=9.6Hz, 1H), 5.21(d, J=9.6Hz, 1H), 3.78(s, 3H), 3.73(s, 3H), 3.71(s, 6H), 3.47(d, J=16.5Hz, 1H), 3.25( d, J=16.5Hz, 1H).

49.(S)-(+)-7-氯-3，5-二氢-2-[甲氧基羰基(2，4-二硝基苯基)氨基羰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羟酸甲酯49. (S)-(+)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(2,4-dinitrophenyl)aminocarbonyl]indeno[1,2-e ][1,3,4-]oxadiazine-4a(3H)-hydroxy acid methyl ester

熔点：77-79℃Melting point: 77-79°C

¹H NMR(300MHz，CDCl₃)δ：8.47(d，J＝8.1Hz，1H)，7.61(d，J＝8.4Hz，1H)，7.44(d，J＝8.17Hz，1H)，7.39-7.30(m，3H)，5.66(d，J＝9.6Hz，1H)，5.25(d，J＝9.6Hz，1H)，3.78(s，3H)，3.74(s，3H)，3.49(d，J＝16.5Hz，1H)，3.26(d，J＝17.1Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 8.47 (d, J=8.1Hz, 1H), 7.61 (d, J=8.4Hz, 1H), 7.44 (d, J=8.17Hz, 1H), 7.39-7.30 (m, 3H), 5.66(d, J=9.6Hz, 1H), 5.25(d, J=9.6Hz, 1H), 3.78(s, 3H), 3.74(s, 3H), 3.49(d, J= 16.5Hz, 1H), 3.26 (d, J = 17.1Hz, 1H).

50.(S)-7-氯-3，5-二氢-2-[甲氧基羰基(2-三氟甲氧基-5-氯-苯基)氨基羰基]茚并[1，2-e][1，3，4-]噁二嗪-4a(3H)-羟酸甲酯50. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(2-trifluoromethoxy-5-chloro-phenyl)aminocarbonyl]indeno[1,2- e][1,3,4-]oxadiazine-4a(3H)-hydroxy acid methyl ester

熔点：46-48℃Melting point: 46-48°C

¹H NMR(300MHz，CDCl₃)δ：7.50(d，J＝8.7Hz，1H)，7.44(d，J＝2.1Hz，1H)，7.41-7.31(m，3H)，7.30-7-26(m，1H)，5.69(d，J＝9.6Hz，1H)，5.24(d，J＝9.3Hz，1H)，3.74(s，63H)，3.51(d，J＝16.8Hz，1H)，3.29(d，J＝16.8Hz，1H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.50(d, J=8.7Hz, 1H), 7.44(d, J=2.1Hz, 1H), 7.41-7.31(m, 3H), 7.30-7-26( m, 1H), 5.69(d, J=9.6Hz, 1H), 5.24(d, J=9.3Hz, 1H), 3.74(s, 63H), 3.51(d, J=16.8Hz, 1H), 3.29( d, J=16.8Hz, 1H).

熔点：47-49℃。Melting point: 47-49°C.

51.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4一乙氧基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a-羧酸甲酯51. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-ethoxyphenyl)carbamoyl]indeno[1,2-e][1,3 , 4-]oxadiazine-4a-carboxylate methyl ester

¹H NMR(300MHz，CDCl₃)δ：7.56(d，J＝8.4Hz，1H)，7.35-7.24(m，4H)，6.89(s，1H)，6.86(s，1H)，5.69(d，J＝9.6Hz，1H)，5.19(d，J＝10.2Hz，1H)，4.04-3.97(m，2H)，3.71(s，6H)，3.48(d，J＝16.2Hz，1H)，3.26(d，J＝16.5Hz，1H)，1.41-1.37(m，3H)¹ H NMR (300MHz, CDCl₃ ) δ: 7.56(d, J=8.4Hz, 1H), 7.35-7.24(m, 4H), 6.89(s, 1H), 6.86(s, 1H), 5.69(d, J=9.6Hz, 1H), 5.19(d, J=10.2Hz, 1H), 4.04-3.97(m, 2H), 3.71(s, 6H), 3.48(d, J=16.2Hz, 1H), 3.26( d, J=16.5Hz, 1H), 1.41-1.37(m, 3H)

熔点：137-139℃。Melting point: 137-139°C.

52.(S)-7-氯-3，5一二氢-2-[甲氧基羰基(4一甲基苯基)氨基甲酰基]茚并[1，2-e][1，3，4-]噁二嗪-4a羧酸甲酯的合成52. (S)-7-Chloro-3,5-dihydro-2-[methoxycarbonyl(4-methylphenyl)carbamoyl]indeno[1,2-e][1,3, Synthesis of 4-]oxadiazine-4a carboxylate methyl ester

熔点：151-153℃Melting point: 151-153°C

¹H NMR(300MHz，CDCl₃)δ：7.56(d，J＝8.1Hz，1H)，7.35(d，J＝8.1Hz，1H)，7.32(s，1H)，7.28-7.17(m，4H)，5.71(d，J＝9.9Hz，1H)，5.22(d，J＝9.9Hz，1H)，3.72(s，3H)，3.72(s，3H)，3.50(d，J＝16.8Hz，1H)，3.27(d，J＝16.5Hz，1H)，2.35(s，3H)。¹ H NMR (300MHz, CDCl₃ ) δ: 7.56(d, J=8.1Hz, 1H), 7.35(d, J=8.1Hz, 1H), 7.32(s, 1H), 7.28-7.17(m, 4H) , 5.71(d, J=9.9Hz, 1H), 5.22(d, J=9.9Hz, 1H), 3.72(s, 3H), 3.72(s, 3H), 3.50(d, J=16.8Hz, 1H) , 3.27(d, J=16.5Hz, 1H), 2.35(s, 3H).

杀虫剂室内生物活性测定Determination of Indoor Bioactivity of Insecticides

1材料与方法1 Materials and methods

1.1试验药剂1.1 Test drug

SIOC-Y-(001-052)原药；SIOC-Y-(001-052) original drug;

98％敌敌畏原油(张家港市新宇化工厂)、95％哒螨灵原药(安徽金泰农药化工有限公司)、95％丁硫克百威原药(浙江禾田化工有限公司)。86.5％茚虫威原药(浙江禾田化工有限公司)98% dichlorvos crude oil (Zhangjiagang Xinyu Chemical Factory), 95% pyridaben technical (Anhui Jintai Pesticide Chemical Co., Ltd.), 95% carbosulfan technical (Zhejiang Hetian Chemical Co., Ltd.). 86.5% Indoxacarb Technical (Zhejiang Hetian Chemical Co., Ltd.)

1.2试验靶标1.2 Test target

稻褐飞虱(Nilaparvata legen)、粘虫(Mythima separata)、小菜蛾(Plutellaxylostella)、红蜘蛛(Tetranychus cinnabarnus)、苜蓿蚜(Aphis medicagini)。以上虫种为室内常年累代饲养或从田间采集室内饲养多代虫种。Rice brown planthopper (Nilaparvata legen), armyworm (Mythima separata), diamondback moth (Plutellaxylostella), red spider mite (Tetranychus cinnabarnus), alfalfa aphid (Aphis medicagini). The above insect species were raised indoors for many generations or collected from the field for multi-generation indoor breeding.

1.3仪器设备1.3 Instruments and equipment

电子分析天平、培养皿、移液枪、Potter喷雾塔、毛笔等。Electronic analytical balances, Petri dishes, pipettes, Potter spray towers, brushes, etc.

1.4药剂处理1.4 Chemical treatment

用分析天平(0.0001g)称取一定质量的原药，加含有0.1％吐温-80的溶剂(DMF)，配制成1％制剂。称取一定质量的制剂，加蒸馏水(点滴法稀释用丙酮)稀释配制成测定所需浓度的药液。A certain mass of the original drug was weighed with an analytical balance (0.0001 g), and a solvent (DMF) containing 0.1% Tween-80 was added to prepare a 1% preparation. Weigh a certain amount of preparation, add distilled water (acetone for spot method dilution) to dilute and prepare the medicinal solution of the required concentration.

根据创制农药生物活性评价SOP(杀虫剂卷)，普筛浓度选择500mg/L。According to the creation of pesticide biological activity evaluation SOP (pesticide roll), the general screening concentration is selected as 500mg/L.

1.5试验方法1.5 Test method

1.5.1水稻褐飞虱筛选——培养皿苗虫定量喷雾法1.5.1 Screening of rice brown planthoppers—quantitative spray method of petri dish seedlings

将水稻苗用白石英沙固定于培养皿内，接用CO₂麻醉3龄中期若虫，置于POTTER喷雾塔下喷雾。喷雾后用透明塑料杯罩住，标记后放于观察室内。72h后检查结果。以敌敌畏和空白CK为对照。The rice seedlings were fixed in a petri dish with white quartz sand, and the mid-3rd instar nymphs were anesthetized with CO₂ , and sprayed under the POTTER spray tower. After spraying, cover it with a transparent plastic cup, mark it and put it in the observation room. Check the results after 72 hours. Dichlorvos and blank CK were used as controls.

1.5.2粘虫筛选——浸苗饲喂法1.5.2 Screening of armyworms - seedling soaking and feeding method

将玉米叶在药液中充分浸润后自然阴干，放入培养皿中，接3龄中期幼虫，加盖标记后置于观察室内。72h后检查结果。以敌敌畏和空白CK为对照。The corn leaves were fully soaked in the liquid medicine, dried naturally in the shade, put into a petri dish, received 3rd instar mid-stage larvae, covered and marked and placed in an observation room. Check the results after 72 hours. Dichlorvos and blank CK were used as controls.

1.5.3小菜蛾筛选——浸渍法1.5.3 Plutella xylostella screening - dipping method

将甘蓝片剪下，打孔成圆片，然后浸于药液中20s，放于Φ9cm塑料培养皿内(5片/皿)，接小菜蛾2龄幼虫15头/皿，放一张滤纸，加盖。置于26℃室内培养，72h后检查结果。试验重复4次。以尖头镊子轻触虫体，无反应视为死虫。以敌敌畏和空白CK为对照。Cut off the cabbage slices, punch holes into discs, then soak in the liquid medicine for 20 seconds, put them in a Φ9cm plastic petri dish (5 pieces/dish), pick up 15 2nd instar larvae of Plutella xylostella xylostella, put a piece of filter paper, cover . Incubate in a room at 26°C, and check the results after 72 hours. The experiment was repeated 4 times. Lightly touch the worm body with pointed tweezers, and if there is no response, it is regarded as a dead worm. Dichlorvos and blank CK were used as controls.

1.5.4朱砂叶螨筛选——浸渍法1.5.4 Screening of Tetranychus cinnabarinus - dipping method

将蚕豆叶片打成叶碟，背面朝上放在小块棉花上，置于塑料培养皿内，加少量水，接朱砂叶螨成螨。待成螨于叶片上稳定后，将叶片在药液中充分浸润5s后迅速用吸水纸吸去叶片表面水滴，重新置于棉花上，风干。72h后检查结果。以哒螨灵和空白CK为对照。Beat broad bean leaves into leaf discs, put the back side up on a small piece of cotton, put them in a plastic petri dish, add a small amount of water, and pick up Tetranychus cinnabarinus to become mites. After the adult mites stabilized on the leaves, the leaves were fully soaked in the liquid medicine for 5 seconds, and then the water droplets on the surface of the leaves were quickly absorbed with absorbent paper, and then placed on cotton again, and air-dried. Check the results after 72 hours. Pyridaben and blank CK were used as controls.

1.5.5苜蓿蚜筛选——浸渍法1.5.5 Screening of alfalfa aphids - dipping method

将蚕豆叶片剪去两端，背面朝上放在小块棉花上，置于塑料培养皿内，加少量水，接苜蓿蚜成蚜以产若蚜。24h后去除成蚜，继续培养2d后将叶片在药液中充分浸润5s后，重新置于棉花上，自然凉干。24h后检查结果。以丁硫克百威和空白CK为对照。Cut off both ends of broad bean leaves, put the back side up on a small piece of cotton, put it in a plastic petri dish, add a small amount of water, and pick up alfalfa aphids to produce nymphs. After 24 hours, the adult aphids were removed, and after continuing to cultivate for 2 days, the leaves were fully soaked in the medicinal solution for 5 seconds, then placed on cotton again, and dried naturally. Check the results after 24 hours. Carbosulfan and blank CK were used as controls.

1.6试验统计和进筛标准1.6 Test statistics and screening criteria

统计各个处理的死虫数和活虫数，计算死亡率(Abbott’s公式)。The number of dead insects and live insects in each treatment was counted, and the mortality rate was calculated (Abbott's formula).

2结果与分析2 Results and Analysis

化合物SIOC-Y-(001-052)对水稻褐飞虱、粘虫(小菜蛾)、红蜘蛛、苜蓿蚜等4个虫靶标的室内生物活性筛选结果表明：化合物SIOC-Y-(001-040)在普筛浓度500mg/L时，SIOC-Y-006、014、038、039、041、042、043、046、047、049对粘虫显示出100％的杀虫活性，036对粘虫显示出80％的杀虫活性。进一步筛选时，0047对粘虫仍表现出较好的杀虫活性，在浓度100mg/L和20mg/L时杀虫活性仍为100％。因此，建议SIOC-Y-006、014、036、038、039、041、042、043、046、047、049进行下一步筛选验证；其它化合物对水稻褐飞虱、粘虫、朱砂叶螨、苜蓿蚜等4个虫靶标均无明显活性。(筛选试验结果见附表1)The results of indoor biological activity screening of compound SIOC-Y-(001-052) against four insect targets including rice brown planthopper, armyworm (Plutella xylostella), spider mite, and alfalfa aphid showed that compound SIOC-Y-(001-040) was When the general screening concentration was 500mg/L, SIOC-Y-006, 014, 038, 039, 041, 042, 043, 046, 047, 049 showed 100% insecticidal activity against armyworm, and 036 showed 80% insecticidal activity against armyworm. % insecticidal activity. In further screening, 0047 still showed good insecticidal activity against armyworm, and the insecticidal activity was still 100% at the concentration of 100mg/L and 20mg/L. Therefore, it is recommended that SIOC-Y-006, 014, 036, 038, 039, 041, 042, 043, 046, 047, 049 be screened and verified in the next step; None of the 4 worm targets had significant activity. (See attached table 1 for screening test results)

附表1：化合物杀虫活性筛选结果(死亡率，％)Attached Table 1: Compound insecticidal activity screening results (mortality rate, %)

Claims

1. a N-substituted dioxazine compound is characterized in that, the chemical structure of general formula of this compound (I) as follows:

Ar is phenyl ring, naphthalene nucleus, pyridine or pyrimidine ring system in the chemical structure of general formula (I).

2. a kind of N-substituted dioxazine compound according to claim 1 is characterized in that described compound comprises:

(1) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (pyridine) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(2) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(3) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl [2-(4-picoline)] amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(4) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl [2-(6-picoline)] amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(5) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl [2-(5-bromopyridine)] amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(6) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl [2-(5-iodine pyridine)] amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(8) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl [4-(2-chloropyridine)] amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(9) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl [3-(2-chloropyridine)] amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(10) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-methoxynaphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(11) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-oxyethyl group naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(12) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-positive propoxy naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(13) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-n-pentyloxy naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(14) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (the positive hexyloxy naphthalene of 2-) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(15) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-isopropoxy naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(16) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-n-butoxy naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(17) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl [2-(4, the 6-dimethoxypyridin)] amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(18) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (the special butyric ester naphthalene of 2-) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(19) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (the disappointing basic naphthalene of 2-) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(20) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-butyric ester naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(21) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-acetic ester naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(22) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-propionic ester naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(23) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-methoxy methyl ether naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(24) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-benzoic ether naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(25) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-pyrans manthanoate naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(26) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl (2-methoxy manthanoate naphthalene) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(27) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl 2-(4-chloro-6-methoxy pyrimidine) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(28) (S)-7-chloro-3,5-dihydro-2-[[methoxycarbonyl 2-(4, the 6-dimethoxypyridin) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-carboxylate methyl ester,

(29) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-p-methoxy-phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(30) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-ethoxyl phenenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(31) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-positive propoxy phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(32) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (the different oxygen base of 4-phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(33) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-n-butoxy phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(34) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-n-pentyloxy phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(35) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (the positive hexyloxy phenyl of 4-) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(36) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-Trifluoromethoxyphen-l) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(37) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-trifluoro ethoxy phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(38) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-trifluoromethyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(39) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (2-Trifluoromethoxyphen-l) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(40) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl 2-[(3-Trifluoromethoxyphen-l) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(41) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (2-bromo-4-trifluoro oxygen base phenyl) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(42) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-nitrophenyl) amino] formyl radical] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(43) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-acetoxyl group phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(44) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-p-methoxy-phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(45) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-acetylphenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(46) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-methanoyl phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(47) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4-trifluoromethylthio phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(48) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (2, the 4-Dimethoxyphenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(49) (S)-(+)-7-chloro-3,5-dihydro-2-[methoxycarbonyl (2, the 4-dinitrophenyl) aminocarboxyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-hydroxy acid methyl esters,

(50) (S)-7-chloro-3,5-dihydro-2-[methoxycarbonyl (2-trifluoromethoxy-5-chloro-phenyl) aminocarboxyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a (3H)-hydroxy acid methyl esters,

(51) (S)-7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4 one ethoxyl phenenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a-carboxylate methyl ester,

(52) (S)-and 7-chloro-3,5 one dihydros-2-[methoxycarbonyl (4 monomethyl phenyl) formamyl] indeno [1,2-e] [1,3,4-] oxadiazine-4a carboxylate methyl ester synthetic.

3. the preparation method of a claim 1 or 2 described a kind of N-substituted dioxazine compounds is characterized in that this method may further comprise the steps:

(1) with 2-(benzyl)-7-chlorine indeno [1,2-e] [1,3; 4]] oxadiazine-2, and 4a (3H, 5H)-dicarboxylicacid-4a-methyl ester and hydrogen are raw material; In solvent a, be catalyzer a with Pd/C, carry out hydrogenation reaction, temperature of reaction is 20 ℃～120 ℃; Reaction pressure is a 1-15 normal atmosphere, obtains intermediate B after reaction finishes;

(2) be midbody C with (chloroformyl) (aryl) Urethylane, with the intermediate B that step (1) obtains, in solvent b, under the effect of catalyzer b, carry out condensation reaction, temperature of reaction is 0 ℃～100 ℃ and obtains product N substituted dioxazine compound.

4. the preparation method of a kind of N-substituted dioxazine compound according to claim 3; It is characterized in that the described solvent a of step (1) is one or more the mixture in methyl acetate, ETHYLE ACETATE, methyl alcohol, ethanol, acetonitrile, methylene dichloride, ethylene dichloride, trichloromethane, the toluene.

5. the preparation method of a kind of N-substituted dioxazine compound according to claim 3 is characterized in that, the described temperature of reaction of step (1) is 45 ℃～85 ℃, and reaction pressure is a 4-6 normal atmosphere.

6. the preparation method of a kind of N-substituted dioxazine compound according to claim 3; It is characterized in that the described solvent b of step (2) is one or more the mixture in methyl acetate, ethyl ester ETHYLE ACETATE, methyl alcohol, ethanol, acetonitrile, methylene dichloride, ethylene dichloride, trichloromethane, the toluene.

7. the preparation method of a kind of N-substituted dioxazine compound according to claim 3 is characterized in that, the described catalyzer b of step (2) is N, N-diisopropylethylamine, triethylamine, pyridine or piperidines.

8. the preparation method of a kind of N-substituted dioxazine compound according to claim 3 is characterized in that, the described temperature of reaction of step (2) is 20 ℃～60 ℃.

9. the preparation method of a kind of N-substituted dioxazine compound according to claim 3; It is characterized in that; Step (2) gained N substituted dioxazine compound adopts recrystallization method to carry out separation and purification; Or adopting the isolating method of column chromatography to carry out separation and purification, the solvent that described recrystallization method adopts is one or more the mixture in methyl alcohol, ethanol, Virahol, methyl acetate, ETHYLE ACETATE, acetonitrile, methylene dichloride, ethylene dichloride, trichloromethane, toluene, the sherwood oil.

10. the application of a claim 1 or 2 described a kind of N-substituted dioxazine compounds is characterized in that this compound is used to prepare sterilant, and the insecticidal activity of mythimna separata is reached 80%～100%.