CN116693430A - 一种2-酰胺基叔丁基磺酰胺类化合物及其制备方法和应用 - Google Patents
一种2-酰胺基叔丁基磺酰胺类化合物及其制备方法和应用 Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title abstract description 11
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- 235000009566 rice Nutrition 0.000 claims abstract description 20
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- ZQEIXNIJLIKNTD-UHFFFAOYSA-N methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alaninate Chemical compound COCC(=O)N(C(C)C(=O)OC)C1=C(C)C=CC=C1C ZQEIXNIJLIKNTD-UHFFFAOYSA-N 0.000 description 2
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- CVINWVPRKDIGLL-UHFFFAOYSA-N 4-chloro-2-(trifluoromethyl)aniline Chemical group NC1=CC=C(Cl)C=C1C(F)(F)F CVINWVPRKDIGLL-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/46—Y being a hydrogen or a carbon atom
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
- A01N37/20—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof containing the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P3/00—Fungicides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Environmental Sciences (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Pest Control & Pesticides (AREA)
- General Health & Medical Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明涉及农用化学品技术领域,具体涉及一种2‑酰胺基叔丁基磺酰胺类化合物及其制备方法和应用。所述化合物具有如下通式:其中:R1基团为2,4,5‑三氯苯基、2,4,6‑三溴苯基或2‑三氟甲基‑4‑氯苯基;R2基团为烷基、苄基、苯基或杂环基团。本发明提供的2‑酰胺基叔丁基磺酰胺类化合物用于对油菜菌核病、番茄灰霉病、水稻纹枯病、水稻稻瘟病、禾谷镰刀病、辣椒疫霉病等真菌、卵菌引起的病害的防治;以及对柑橘溃疡病、水稻白叶枯病、白菜软腐病、瓜类果斑病、番茄溃疡病等细菌引起的病害的防治。
Description
技术领域
本发明涉及农用化学品技术领域,尤其涉及一种2-酰胺基叔丁基磺酰胺类化合物及其制备方法和应用。
背景技术
磺酰胺类化合物自发现以来一直受到广大科研工作者的关注,含有磺酰胺基团的化合物具有广泛的生物活性,在药物分子设计领域应用广泛,是一种十分重要的活性化合物类型。磺酰胺类化合物是人类发现的第一个对细菌有选择作用的药物,其可以被系统地应用于细菌感染而引起的各种问题。磺胺类化合物在医药和农药上具有广泛的生物活性,如:杀菌、除草、杀虫、抗癌、抗糖尿病等。近年来对磺酰胺类化合物的研究比较多,先后开发出了磺菌胺(Flusulfamide)、甲磺菌胺(Tolnifanide)等高效低毒的杀菌剂。在杀菌剂领域,磺酰胺类的产品并不多见,目前市场上应用比较广泛的仅有氰霜唑(Cyazofamid)。2-氧代环十二烷基磺酰胺对多种植物病原菌均有较好的抑制活性,以此为先导,对2-氧代环烷基磺酰胺类化合物进行了深入研究,并开发出了候选杀菌剂品种环己磺菌胺(Chesulfamide),用于防治番茄灰霉病(Botrytiscinerea)及黄瓜叶斑病(Corynesporacassiicola)。
在对新农药分子的设计过程中,引入活性片段需要桥基团的帮助。酰胺基团是化合物分子中最常见的桥基团,用于桥接其他活性片段,在新农药创制领域起着十分重要的作用,且酰胺类化合物大多具有高效、低毒、低残留、易降解等优点,这些独特的生物活性也符合创制绿色农药的条件。
因此,如何提供一种2-酰胺基叔丁基磺酰胺类化合物及其制备方法和应用是本领域技术人员亟待解决的技术问题。
发明内容
本发明的目的在于针对现有技术的不足提供一种2-酰胺基叔丁基磺酰胺类化合物及其制备方法和应用,用以解决现有杀菌剂中存在的杀菌剂效率低、毒性大、易残留、不易降解的技术问题。
为了实现上述发明目的,本发明提供以下技术方案:
本发明提供了一种2-酰胺基叔丁基磺酰胺类化合物,具有如下结构:
其中:R1基团为2,4,5-三氯苯基、2,4,6-三溴苯基或2-三氟甲基-4-氯苯基;R2基团为烷基、苄基、苯基或杂环基。
作为优选,所述R2基团为ClCH2-、Cl2CH-、Cl3C-、CH3-、CH3CH2-、CH3(CH2)2-、CH3(CH2)6-、C6H5-CH2-、4-F-C6H4-CH2-、4-F-C6H4-、3-F-C6H4-、2-F-C6H4-、4-Br-C6H4-、3-Br-C6H4-、2-Br-C6H4-、4-Cl-C6H4-、3-Cl-C6H4-、2-Cl-C6H4-、4-CF3-C6H4-、3-CF3-C6H4-、2-CF3-C6H4-、C6H5-、4-CH3-C6H4-、3-CH3-C6H4-、2-CH3-C6H4-、4-CF3O-C6H4-、2,6-Cl2-C6H3-、5-Cl-2-OCH3-C6H3-、3,5-CH3-C6H3-或
本发明还提供了一种2-酰胺基叔丁基磺酰胺类化合物的制备方法,包括如下步骤:
(1)将3,3-二甲基-2-氧代丁磺酸钾盐和草酰氯混合于溶剂中进行反应得到3,3-二甲基-2-氧代丁磺酰氯的溶液;所得3,3-二甲基-2-氧代丁磺酰氯的溶液与取代胺、三乙胺和二氯甲烷混合后进行胺化反应得到N-取代-3,3-二甲基-2-氧代丁磺酰胺;
(2)在通入氨气的条件下,将N-取代-3,3-二甲基-2-氧代丁磺酰胺、钛酸四异丙酯和硼氢化钠混合于溶剂中进行胺化反应,得到N-取代-3,3-二甲基-2-氨基丁磺酰胺;
(3)将取代酰氯、N-取代-3,3-二甲基-2-氨基丁磺酰胺和三乙胺混合于溶剂中进行酰胺化反应,得到2-酰胺基叔丁基磺酰胺类化合物。
作为优选,步骤(1)、步骤(2)和步骤(3)中,所述反应的温度独立的为20~40℃,反应的时间独立的为2~5h。
作为优选,步骤(1)中,所述溶剂为N,N-二甲基甲酰胺和二氯甲烷的混合溶液;所述3,3-二甲基-2-氧代丁磺酸钾盐、N,N-二甲基甲酰胺、二氯甲烷和草酰氯的用量比为0.05~0.20mol:2~7mL:70~300mL:0.05~0.20mol。
作为优选,步骤(1)中,所述3,3-二甲基-2-氧代丁磺酸钾盐、取代胺、三乙胺和二氯甲烷的用量比为0.05~0.15mol:0.03~0.10mol:0.03~0.10mol:60~180mL。
作为优选,步骤(2)中,所述溶剂为乙醇;所述N-取代-3,3-二甲基-2-氧代丁磺酰胺、钛酸四异丙酯、硼氢化钠和乙醇的用量比为0.01~0.08mol:0.01~0.08mol:0.03~0.30mol:10~250mL。
作为优选,步骤(3)中,所述溶剂为二氯甲烷,所述N-取代-3,3-二甲基-2-氨基丁磺酰胺、取代酰氯、三乙胺和二氯甲烷的用量比为1~5mmol:1.5~9mmol:1.5~9mmol:10~60mL。
本发明还提供了2-酰胺基叔丁基磺酰胺类化合物在农业杀菌剂中的应用,所述2-酰胺基叔丁基磺酰胺类化合物用于对植物病原真菌、卵菌和病原细菌中的一种或几种病原菌病害的防治;用于对油菜菌核病、番茄灰霉病、水稻纹枯病、水稻稻瘟病、禾谷镰刀病和辣椒疫霉病中的一种或几种真菌、卵菌引起的病害的防治;用于对柑橘溃疡病、水稻白叶枯病、白菜软腐病、瓜类果斑病和番茄溃疡病中的一种或几种细菌引起的病害的防治。
本发明的有益效果:
本发明制备的2-酰胺基叔丁基磺酰胺类化合物用于对植物病原真菌、卵菌和病原细菌中病原菌病害的防治;用于对油菜菌核病、番茄灰霉病、水稻纹枯病、水稻稻瘟病、禾谷镰刀病和辣椒疫霉病等真菌、卵菌引起的病害的防治;用于对柑橘溃疡病、水稻白叶枯病、白菜软腐病、瓜类果斑病和番茄溃疡病等细菌引起的病害的防治。
具体实施方式
本发明提供了一种2-酰胺基叔丁基磺酰胺类化合物,具有如下结构:
其中:R1基团为2,4,5-三氯苯基、2,4,6-三溴苯基或2-三氟甲基-4-氯苯基;R2基团为烷基、苄基、苯基或杂环基。
本发明中,所述R1基团优选为2,4,5-三氯苯基或2-三氟甲基-4-氯苯基,进一步优选为2,4,5-三氯苯基;R2基团优选为烷基、苯基或杂环基,进一步优选为烷基或苯基。
本发明中,所述R2基团为ClCH2-、Cl2CH-、Cl3C-、CH3-、CH3CH2-、CH3(CH2)2-、CH3(CH2)6-、C6H5-CH2-、4-F-C6H4-CH2-、4-F-C6H4-、3-F-C6H4-、2-F-C6H4-、4-Br-C6H4-、3-Br-C6H4-、2-Br-C6H4-、4-Cl-C6H4-、3-Cl-C6H4-、2-Cl-C6H4-、4-CF3-C6H4-、3-CF3-C6H4-、2-CF3-C6H4-、C6H5-、4-CH3-C6H4-、3-CH3-C6H4-、2-CH3-C6H4-、4-CF3O-C6H4-、2,6-Cl2-C6H3-、5-Cl-2-OCH3-C6H3-、3,5-CH3-C6H3-或优选为ClCH2-、Cl2CH-、Cl3C-、CH3-、CH3CH2-、CH3(CH2)2-、CH3(CH2)6-、C6H5-CH2-、4-F-C6H4-CH2-、4-F-C6H4-、3-F-C6H4-、2-F-C6H4-、4-Br-C6H4-、3-Br-C6H4-、2-Br-C6H4-、4-Cl-C6H4-、3-Cl-C6H4-、2-Cl-C6H4-、4-CF3-C6H4-、3-CF3-C6H4-、2-CF3-C6H4-、C6H5-、4-CH3-C6H4-、3-CH3-C6H4-、2-CH3-C6H4-、4-CF3O-C6H4-、2,6-Cl2-C6H3-、5-Cl-2-OCH3-C6H3-、或3,5-CH3-C6H3-,进一步优选为ClCH2-、Cl2CH-、Cl3C-、CH3-、CH3CH2-、CH3(CH2)2-、CH3(CH2)6-、C6H5-CH2-、4-F-C6H4-CH2-、4-F-C6H4-、3-F-C6H4-、2-F-C6H4-、4-Br-C6H4-、3-Br-C6H4-、2-Br-C6H4-、4-Cl-C6H4-、3-Cl-C6H4-、2-Cl-C6H4-、4-CF3-C6H4-、3-CF3-C6H4-、2-CF3-C6H4-、C6H5-、4-CH3-C6H4-、3-CH3-C6H4-、2-CH3-C6H4-、4-CF3O-C6H4-、2,6-Cl2-C6H3-或5-Cl-2-OCH3-C6H3-。
本发明还提供了一种2-酰胺基叔丁基磺酰胺类化合物的制备方法,包括如下步骤:
(1)将3,3-二甲基-2-氧代丁磺酸钾盐和草酰氯混合于溶剂中进行反应得到3,3-二甲基-2-氧代丁磺酰氯的溶液;所得3,3-二甲基-2-氧代丁磺酰氯的溶液与取代胺、三乙胺和二氯甲烷混合后进行胺化反应得到N-取代-3,3-二甲基-2-氧代丁磺酰胺;
(2)在通入氨气的条件下,将N-取代-3,3-二甲基-2-氧代丁磺酰胺、钛酸四异丙酯和硼氢化钠混合于溶剂中进行胺化反应,得到N-取代-3,3-二甲基-2-氨基丁磺酰胺;
(3)将取代酰氯、N-取代-3,3-二甲基-2-氨基丁磺酰胺和三乙胺混合于溶剂中进行酰胺化反应,得到2-酰胺基叔丁基磺酰胺类化合物。
本发明中,步骤(1)、步骤(2)和步骤(3)中,所述反应的温度独立的为20~40℃,优选为22~38℃,进一步优选为25~35℃;反应的时间独立的为2~5h,优选为2.5~4.5h,进一步优选为3~4h。
本发明中,步骤(1)中,所述取代胺、三乙胺和二氯甲烷先用冰水浴进行降温处理,然后再加入3,3-二甲基-2-氧代丁磺酰氯的溶液进行反应。
本发明中,步骤(1)中,所述3,3-二甲基-2-氧代丁磺酰氯的溶液与取代胺、三乙胺和二氯甲烷混合的温度为0~5℃,优选为1~4℃,进一步优选为2~3℃。
本发明中,步骤(1)中,所述溶剂为N,N-二甲基甲酰胺和二氯甲烷的混合溶液;所述3,3-二甲基-2-氧代丁磺酸钾盐、N,N-二甲基甲酰胺、二氯甲烷和草酰氯的用量比为0.05~0.20mol:2~7mL:70~300mL:0.05~0.20mol,优选为0.08~0.18mol:3~6mL:100~250mL:0.08~0.18mol,进一步优选为0.10~0.15mol:4~5mL:150~200mL:0.10~0.15mol。
本发明中,步骤(1)中,所述3,3-二甲基-2-氧代丁磺酸钾盐、取代胺、三乙胺和二氯甲烷的用量比为0.05~0.15mol:0.03~0.10mol:0.03~0.10mol:60~180mL,优选为0.07~0.13mol:0.04~0.08mol:0.04~0.08mol:80~160mL,进一步优选为0.09~0.12mol:0.05~0.07mol:0.05~0.07mol:100~130mL。
本发明中,步骤(2)中,所述溶剂为乙醇;所述N-取代-3,3-二甲基-2-氧代丁磺酰胺、钛酸四异丙酯、硼氢化钠和乙醇的用量比为0.01~0.08mol:0.01~0.08mol:0.03~0.30mol:10~250mL,优选为0.03~0.07mol:0.03~0.07mol:0.05~0.25mol:50~200mL,进一步优选为0.04~0.06mol:0.04~0.06mol:0.10~0.20mol:100~150mL。
本发明中,步骤(3)中,所述溶剂为二氯甲烷,所述N-取代-3,3-二甲基-2-氨基丁磺酰胺、取代酰氯、三乙胺和二氯甲烷的用量比为1~5mmol:1.5~9mmol:1.5~9mmol:10~60mL,优选为2~4.5mmol:2~8mmol:2~8mmol:15~55mL,进一步优选为2.5~4mmol:2.5~7mmol:3~7mmol:25~50mL。
本发明中,所述2-酰胺基叔丁基磺酰胺类化合物的合成路线如下:
本发明中,所述3,3-二甲基-2-氧代丁磺酸钾盐可通过将3,3-二甲基-2-丁酮、三氧化硫·二氧六环加合物和无水碳酸钾混合于溶剂中进行磺化反应得到。
本发明中,所述磺化反应的温度为-5~5℃,优选为-4~4℃,进一步优选为-3~3℃,磺化反应的时间为1~4h,优选为1.5~3h,进一步优选为2~2.5h。
本发明中,所述3,3-二甲基-2-丁酮溶液、三氧化硫·二氧六环加合物和无水碳酸钾的摩尔比为0.5~1.5:0.5~1.8:0.25~1.8,优选为0.8~1.3:0.8~1.5:0.6~1.5,进一步优选为0.9~1.1:0.9~1.2:0.8~1.2。
本发明还提供了2-酰胺基叔丁基磺酰胺类化合物在农业杀菌剂中的应用,所述2-酰胺基叔丁基磺酰胺类化合物用于对植物病原真菌、卵菌和病原细菌中的一种或几种病原菌病害的防治;用于对油菜菌核病、番茄灰霉病、水稻纹枯病、水稻稻瘟病、禾谷镰刀病和辣椒疫霉病中的一种或几种真菌、卵菌引起的病害的防治;用于对柑橘溃疡病、水稻白叶枯病、白菜软腐病、瓜类果斑病和番茄溃疡病中的一种或几种细菌引起的病害的防治。
下面结合实施例对本发明提供的技术方案进行详细的说明,但是不能把它们理解为对本发明保护范围的限定。
实施例1
以化合物LCJ-1为例,具体制备工艺流程如下所示:
制备过程为:在通入氮气下,将150mL二氯甲烷、0.09mol的3,3-二甲基-2氧代-丁磺酸钾、3.6mLDMF,搅拌均匀,缓慢滴加0.10mol草酰氯,在25℃下搅拌反应3h;抽滤,滤液缓慢滴加到已用冰水浴降温的由0.06mol2,4,5-三氯苯胺、0.06mol三乙胺,以及120mL二氯甲烷组成的反应液中,滴加过程中反应温度控制在0℃。滴加完毕,自然升温,反应3h,此时反应液为橙色透明溶液,TLC监测[V(石油醚):V(乙酸乙酯)=4:1]反应进程,结果显示反应液中无原料时停止反应,进行后处理操作。将反应液先后用75mL3mol/L盐酸,50mL饱和碳酸氢钠,50mL蒸馏水洗涤三次。洗过的反应液用无水Na2SO4干燥3小时,抽滤,滤液用旋转蒸发仪蒸干得粗产物。用丙酮+石油醚重结晶得N-取代-3,3-二甲基-2-氧代丁磺酰胺;
将氨气通入120mL乙醇、0.03molN-取代-3,3-二甲基-2-氧代丁磺酰胺、0.03mol四异丙氧基钛的混合液中反应5h;少量多次加入0.08mol硼氢化钠反应5h,后处理后经甲醇重结晶得到N-取代-3,3-二甲基-2-氨基丁磺酰胺;
将4.5mmol氯乙酰氯逐滴加入30mL干燥好的二氯甲烷、3mmolN-取代-3,3-二甲基-2-氨基丁磺酰胺、4.5mmol干燥好的三乙胺混合液中反应3h,经后处理后经柱层析(V石油醚:V乙酸乙酯=10:1)分离得到化合物LCJ-1。
实施例2~30
上述取代酰氯的取代基分别由Cl2CH-、Cl3C-、CH3-、CH3CH2-、CH3(CH2)2-、CH3(CH2)6-、C6H5-CH2-、4-F-C6H4-CH2-、4-F-C6H4-、3-F-C6H4-、2-F-C6H4-、4-Br-C6H4-、3-Br-C6H4-、2-Br-C6H4-、4-Cl-C6H4-、3-Cl-C6H4-、2-Cl-C6H4-、4-CF3-C6H4-、3-CF3-C6H4-、2-CF3-C6H4-、C6H5-、4-CH3-C6H4-、3-CH3-C6H4-、2-CH3-C6H4-、4-CF3O-C6H4-、2,6-Cl2-C6H3-、5-Cl-2-OCH3-C6H3-、3,5-CH3-C6H3-、SC4H3-,分别得到实施例2~30的化合物LCJ-2~LCJ-30。
实施例31
当取代胺为2,4,5-三溴苯胺,取代酰氯的取代基为ClCH2-时,得到化合物LCJ-31。
实施例32~34
当取代胺为2-三氟甲基-4-氯苯胺,取代酰氯的取代基分别为ClCH2-、3-Br-C6H4-、SC4H3-时,分别得到实施例32~34的化合物LCJ-32~LCJ-34。
实施例1~34制备得到的化合物LCJ-1~LCJ-34的理化数据如下表1所示;实施例1~34制备得到的化合物LCJ-1~LCJ-34的1HNMR和13CNMR数据如表2所示;它们的HRMS数据如表3所示。
表1化合物LCJ-1~LCJ-34的理化数据
表2化合物LCJ-1~LCJ-34的1HNMR和13CNMR数据
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表3化合物LCJ-1~LCJ-34的HRMS数据
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对上述实施例1~34进行性能测试:
(一)、化合物LCJ-1~LCJ-34对多种植物病原菌的杀菌活性测定
采用菌丝生长速率法测定化合物对多种植物病原菌的杀菌活性,具体方法如下:
将样品化合物分别称重后用丙酮溶解,定容制备成浓度为5000μg/mL试验用试剂,放低温冷藏箱里面,供活性测定使用。无菌状态下,取0.33mL的浓度为5000μg/mL的药剂与33mL融化(60±5℃)的PDA培养基混合均匀,制成浓度为50μg/mL的含毒培养基33mL,然后均匀的将33mL的含毒培养基均匀的倒入3个直径为9cm的培养皿中,每皿11mL。采用化合物1(结构如下所示)、化合物2(结构如下所示)、啶酰菌胺、多菌灵、腐霉利、甲霜灵作为对照药剂,设置丙酮溶剂为空白对照,普筛浓度为50μg/mL,待皿中含毒培养基冷凝后,分别接入培养好的直径为0.5cm的病原菌菌块。置于26℃培养箱中培养。待其空白对照中的菌落充分生长后,以十字交叉法测量各处理的菌落直径,取其平均值。以校正后的空白对照和处理的菌落平均直径计算抑制率,采用菌丝生长速率法测定各化合物对核盘菌的抑制活性。经接种培养后,测量菌落直径,按计算式计算抑制率,并计算相应化合物的EC50值,每种化合物和对照药剂均设3次重复。经计算,化合物LCJ-1~LCJ-34对多种植物病原菌的杀菌活性如下表4所示。
表4化合物LCJ-1~LCJ-34对多种植物病原菌的杀菌活性
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注:“/”代表未进行此项试验
由表4可以看出,本系列化合物不仅能抑制番茄灰霉病菌、水稻稻瘟病菌、油菜菌核病菌、甜瓜枯萎病菌以及水稻纹枯病菌等植物病原真菌的生长,而且对卵菌(辣椒疫霉菌)的生长同样具有很好的控制效果,具有广谱性。但不同化合物对于同一植物病原菌表现出的活性效果差别较大,总体来说R2基团为烷基取代的化合物表现出的杀菌效果较好。化合物LCJ-1、LCJ-2、LCJ-6、LCJ-9、LCJ-21、LCJ-31、LCJ-34对三种灰霉菌均表现出较好的抑制效果,优于对照药剂啶酰菌胺、腐霉利和多菌灵;其中以化合物LCJ-1和LCJ-21表现最佳;目标化合物对水稻稻瘟病菌的抑制率高于80%的有5个,分别为化合物LCJ-1(80.36%)、LCJ-2(93.75%)、LCJ-3(87.38%)、LCJ-7(83.04%)、LCJ-31(94.64%),略低于对照药剂多菌灵;筛选出4个化合物对油菜菌核病菌的抑制率高于80%,其中化合物LCJ-34的活性最高(89.39%),优于商品化杀菌剂多菌灵(85.71%),略低于啶酰菌胺(98.57%)和腐霉利(100%)筛选出3个化合物对甜瓜枯萎病菌的抑制率高于80%,分别为LCJ-1(85.82%)、LCJ-2(81.56%)、LCJ-32(85.61%),优于商品化杀菌剂腐霉利(60.28%),低于啶酰菌胺(98.58%)和多菌灵(100%);化合物LCJ-3对水稻纹枯病菌的活性最高,抑制率为91.24%,优于商品化杀菌剂啶酰菌胺(90.78%),略低于腐霉利(98.62%)和多菌灵(100%);筛选出4个化合物对辣椒疫霉病菌的抑制率高于80%,分别为LCJ-1(84.83%)、LCJ-4(93.79%)、LCJ-5(82.07%)、LCJ-7(80.69%),略低于商品化杀菌剂甲霜灵(97.93%)。本试验证明了本系列化合物的广谱杀菌活性,且大多数化合物活性优于对照药剂化合物1与化合物2。
(二)、化合物LCJ-1~LCJ-34对多种植物病原菌的杀细菌活性测定
通过96孔细胞培养板法(比浊法)测定目标化合物对5种细菌的杀菌活性。首先要活化菌株。将在超低温(-80℃)环境下的保存在25%灭菌甘油中细菌,采用划线法在LB平板培养基进行活化,放置在黑暗环境中,温度控制在28℃下培养3d,等待产生单菌落,将其转入100mL的LB液体培养基中,密封后放入振荡摇床,控制温度在28℃,转速为180r/min条件下振荡培养48-72h(不同细菌培养时间不同),使活化的菌种进入稳定生长期,即可进行下一步试验。
取10mL进入稳定生长期的细菌菌液加入至100mL的LB液体培养基中,摇晃,使其混合均匀。使用多通道移液器,按照每孔196μL的细菌菌液量加入到96孔板里中。再向细胞培养板每孔中加入4μL浓度为5000μg/mL的目标化合物溶液,使药液与孔内已有的带菌LB液体培养基均匀混合,配制成目标化合物在每孔中的浓度为100μg/mL。以硫酸链霉素为对照药剂、DMSO作为溶剂对照、LB液体培养基为空白对照、只含有菌液的培养基为生长对照。每种化合物和对照均设3次重复。用封口膜封严,在28℃、180r/min环境中振荡培养2d,直至空白对照孔内的菌液进入稳定生长期,即可开始调查。用紫外分光光度计,通过检测细胞培养板每孔中溶液的吸光度来评价化合物的杀菌效果,检测利用下面的公式计算抑制率:
校正OD值=含菌培养基OD值-无菌培养基OD值
表5化合物LCJ-1~LCJ-34的杀细菌活性测定
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由表5可以看出,本系列化合物多种植物病原细菌均有一定的杀菌效果,但不同化合物对于同一植物病原菌的表现出的活性效果差别较大。化合物LCJ-5、LCJ-12、LCJ-21、LCJ-29、LCJ-30对柑橘溃疡病菌的抑制率分别为62.21%、63.41%、100%、100%、87.14%,均优于阳性对照链霉素(56.92%);化合物LCJ-32、LCJ-33对瓜类果斑病菌的活性与链霉素相当,抑制率均为100%;化合物LCJ-1、LCJ-4、LCJ-5对水稻白叶枯病菌的抑制率分别为72.28%、78.36%、84.47%,略低于商品化药剂链霉素(88.74%)。该系列化合物对白菜软腐病菌和番茄溃疡病菌的活性较差,抑制率最高分别为14.17%(LCJ-19)和30.26%(LCJ-12),远远低于阳性对照链霉素(抑制率分别为100%和83.22%)。
由以上实施例可知,本发明提供了一种2-酰胺基叔丁基磺酰胺类化合物及其制备方法和应用。本发明的2-酰胺基叔丁基磺酰胺类化合物用于对植物病原真菌、卵菌和病原细菌中的一种或几种病原菌病害的防治;用于对油菜菌核病、番茄灰霉病、水稻纹枯病、水稻稻瘟病、禾谷镰刀病和辣椒疫霉病中的一种或几种真菌、卵菌引起的病害的防治;用于对柑橘溃疡病、水稻白叶枯病、白菜软腐病、瓜类果斑病和番茄溃疡病中的一种或几种细菌引起的病害的防治。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (9)
1.一种2-酰胺基叔丁基磺酰胺类化合物,其特征在于,具有如下结构:
其中:R1基团为2,4,5-三氯苯基、2,4,6-三溴苯基或2-三氟甲基-4-氯苯基;R2基团为烷基、苄基、苯基或杂环基。
2.根据权利要求1所述的2-酰胺基叔丁基磺酰胺类化合物,其特征在于,所述R2基团为ClCH2-、Cl2CH-、Cl3C-、CH3-、CH3CH2-、CH3(CH2)2-、CH3(CH2)6-、C6H5-CH2-、4-F-C6H4-CH2-、4-F-C6H4-、3-F-C6H4-、2-F-C6H4-、4-Br-C6H4-、3-Br-C6H4-、2-Br-C6H4-、4-Cl-C6H4-、3-Cl-C6H4-、2-Cl-C6H4-、4-CF3-C6H4-、3-CF3-C6H4-、2-CF3-C6H4-、C6H5-、4-CH3-C6H4-、3-CH3-C6H4-、2-CH3-C6H4-、4-CF3O-C6H4-、2,6-Cl2-C6H3-、5-Cl-2-OCH3-C6H3-、3,5-CH3-C6H3-或
3.权利要求1或2所述的2-酰胺基叔丁基磺酰胺类化合物的制备方法,其特征在于,包括如下步骤:
(1)将3,3-二甲基-2-氧代丁磺酸钾盐和草酰氯混合于溶剂中进行反应得到3,3-二甲基-2-氧代丁磺酰氯的溶液;所得3,3-二甲基-2-氧代丁磺酰氯的溶液与取代胺、三乙胺和二氯甲烷混合后进行胺化反应得到N-取代-3,3-二甲基-2-氧代丁磺酰胺;
(2)在通入氨气的条件下,将N-取代-3,3-二甲基-2-氧代丁磺酰胺、钛酸四异丙酯和硼氢化钠混合于溶剂中进行胺化反应,得到N-取代-3,3-二甲基-2-氨基丁磺酰胺;
(3)将取代酰氯、N-取代-3,3-二甲基-2-氨基丁磺酰胺和三乙胺混合于溶剂中进行酰胺化反应,得到2-酰胺基叔丁基磺酰胺类化合物。
4.根据权利要求3所述的制备方法,其特征在于,步骤(1)、步骤(2)和步骤(3)中,所述反应的温度独立的为20~40℃,反应的时间独立的为2~5h。
5.根据权利要求4所述的制备方法,其特征在于,步骤(1)中,所述溶剂为N,N-二甲基甲酰胺和二氯甲烷的混合溶液;所述3,3-二甲基-2-氧代丁磺酸钾盐、N,N-二甲基甲酰胺、二氯甲烷和草酰氯的用量比为0.05~0.20mol:2~7mL:70~300mL:0.05~0.20mol。
6.根据权利要求5所述的制备方法,其特征在于,步骤(1)中,所述3,3-二甲基-2-氧代丁磺酸钾盐、取代胺、三乙胺和二氯甲烷的用量比为0.05~0.15mol:0.03~0.10mol:0.03~0.10mol:60~180mL。
7.根据权利要求3~6任意一项所述的制备方法,其特征在于,步骤(2)中,所述溶剂为乙醇;所述N-取代-3,3-二甲基-2-氧代丁磺酰胺、钛酸四异丙酯、硼氢化钠和乙醇的用量比为0.01~0.08mol:0.01~0.08mol:0.03~0.30mol:10~250mL。
8.根据权利要求7所述的制备方法,其特征在于,步骤(3)中,所述溶剂为二氯甲烷,所述N-取代-3,3-二甲基-2-氨基丁磺酰胺、取代酰氯、三乙胺和二氯甲烷的用量比为1~5mmol:1.5~9mmol:1.5~9mmol:10~60mL。
9.权利要求1或2所述的2-酰胺基叔丁基磺酰胺类化合物在农业杀菌剂中的应用,其特征在于,所述2-酰胺基叔丁基磺酰胺类化合物用于对植物病原真菌、卵菌和病原细菌中的一种或几种病原菌病害的防治;用于对油菜菌核病、番茄灰霉病、水稻纹枯病、水稻稻瘟病、禾谷镰刀病和辣椒疫霉病中的一种或几种真菌、卵菌引起的病害的防治;用于对柑橘溃疡病、水稻白叶枯病、白菜软腐病、瓜类果斑病和番茄溃疡病中的一种或几种细菌引起的病害的防治。
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