On June 27, the Pesticide Control Institute of the Ministry of Agriculture and Rural Affairs announced the 7th batch of pesticide products to be approved for registration in 2024, of which 98% of the profluluramid TC of Nantong Taihe Chemical Co., Ltd. is planned to be listed for the first time in China, and the products are only exported to Cambodia.
Cyproflanilide is a m-diamide insecticide created by Nantong Taihe on the basis of biamide insecticides, which has the characteristics of high efficiency, low toxicity, wide insecticidal spectrum, good permeability, fast onset and long duration of effect, and can effectively control lepidopteran pests such as Spodoptera exigua, diamondback moth, Spodoptera litura, and Dimorphic borer. Coleopteran pests such as longhorn beetle and leaf beetle; as well as thrips, etc. The market promotion is benchmarked against the listed bromide bromide with the same m-diamide structure, and cycloproflulumide was granted a patent in China in 2019, and has applied for patents in the United States, Japan, Brazil, Germany and other countries, with promising market prospects.
01 Product Introduction
英文名称：cyproflanilide
Chinese name: cycloprofluluram
Other names: Cyprofluflubentamidide, Baishijia ®
Chemical Name: N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]-3-[cyclopropylmethyl-(4-fluorobenzoyl)amino]-2-fluorobenzamide
分子式：C28H17BrF12N2O2
Relative molecular weight: 721.332
CAS accession number: 2375110-88-4
Structural formula:
理化性质：原药为黄色固体；熔点:141.6-143.7；密度:1.6±0.1 g/cm3 ; 沸点:516.9±50.0 °C at760mmHg；折射率:1.544；闪光点:266.4±30.1 °C
02 Mechanism of action
Ciproflulunade is an allosteric modulator of γ-aminobutyric acid (GABA)-gated chloride channels, which blocks activated γ-aminobutyric acid chloride channels through allosteric blockade, causing over-excitement and spasms of pests and ultimately leading to death.
Although cycloprofluluramid has a diamide structure, it is not a traditional fish nitine receptor modulator, and its IRAC classification with bromfenfendiamide is classified as group 30, and the hottest isoxazoline insecticides (isoxazolefenamide, fluoxazlamide, oxluluramidid) are grouped.
Ciproflulunan has excellent gastric toxicity, contact killing and systemic activities.
03 Applications
Applied crops: rice, corn, cotton, soybeans, fruit trees, vegetables and other crops.
Target pests: for Lepidopteran borer, rice leaf roller, Spodoptera exigua, diamondback moth, fall armyworm, apple leaf-curling moth; Coleoptera jumping beetle, longhorn beetle; The control effect of thrips is excellent.
Developable dosage forms: 10% cycloflulumidam DC, 20% cycloflulumidam SC, 5% cycloflulumidam EC, 30% cycloflulumidam WP
04 Synthetic route
In the patent CN109497062A and CN116178198A, Tahoe reported the synthetic route of the compound cycloflulumid (route 1). Through the structural comparison of bromflufenamide and cyclofluluramide, the synthesis route of bromfenfendiamide can be referred to in the synthesis.
Route 1 (Tahoe route): using methyl 2-fluoro-3-aminobenzoate (the synthesis can refer to the Chinese patent CN111320548A, which is also an important pharmaceutical intermediate, and the price is expensive) as the starting material, 3-(N-(cyclopropylmethyl)-4-fluorobenzoylamido)-2-fluorobenzoyl chloride and bromodecafluoroaniline are condensed to obtain cyprofluluranid. The purity of cycloproflulum can reach more than 98.5%, and the total yield can reach more than 74% (based on methyl 2-fluoro-3-aminobenzoate). The synthetic route is as follows:
The other is the condensation reaction of 3-(N-(cyclopropylmethyl)-4-fluorobenzoyl)-2-fluorobenzoyl chloride and decafluoroaniline to obtain 3-(N-(cyclopropylmethyl)-4-fluorobenzamido)-2-fluoro-N-(4-(perfluoropropyl-2-yl)-2-(trifluoromethyl)phenyl)benzamide), and then 3-(N-(cyclopropylmethyl)-4-fluorobenzamido)-2-fluoro-N-(4-(perfluoropropyl-2-yl)-2-(trifluoromethyl)phenyl) Benzoamide undergoes bromination reaction to give cyproflulunamine. The purity of cycloproflulumide can reach more than 99.2%, and the total yield can reach more than 75% (based on methyl 2-fluoro-3-aminobenzoate). The synthetic route is as follows:
In the route, the raw materials 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline (i.e., decafluoroaniline) and 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline (i.e., bromodecafluoroaniline) can be prepared by reference to the method disclosed in the patent EP2319830A1.
Route 2: Referring to the synthesis route of bromfenfluorobenzamide, 2-fluoro-3-nitrobenzoic acid (which can be prepared from o-fluoronitrobenzene) is used as the starting material, and nucleophilic substitution reaction with dichlorothionite is used to generate 2-fluoro-3-nitrobenzoyl chloride, and then reacts with 2-bromo-4-(perfluoropropyl-2-yl)-2-(trifluoromethyl)aniline (bromodecafluoroaniline), with the participation of cyclopropyl formaldehyde and p-fluorobenzoyl chloride (also known as 4-fluorobenzoyl chloride, which is also an intermediate in the synthesis of fungicide flumaline). The target product cycloflulumidam was generated in 5 steps, and the synthesis route was as follows:
Route 3: On the basis of route 2, 2-fluoro-3-nitrobenzoyl chloride selects a condensation reaction with 4-(perfluoropropane-2-yl)-2-(trifluoromethyl) aniline (decafluoroaniline), and the target compound cyclosulflumidam is generated through 3 steps such as bromination. The synthetic route is as follows:
05 Prospects
Although cycloprofluluramid also has a biamide structure, it is not a fish nitine receptor modulator like bromoflubenzenebiamide, and its chemical structure is novel, the mechanism of action is unique, and there is no cross-resistance with the current traditional bisamide insecticides, which is an excellent tool for the management of bisamide resistance. Compared with the existing lepidopteran pest agents, cycloflululbam has a wider insecticidal spectrum and higher activity, showing good activity at very low doses, and the insecticidal speed is fast, the permeability is good, the duration of effect is long, and it is safe for environmental and non-target organisms. According to the promotion experience of brometrolphenylbisamide, its resistance also rises quickly, and attention should also be paid to compound and rotation drugs during promotion.
From the perspective of synthetic routes, there is still room for optimization and discussion in the details of the existing synthetic routes, and the cost is expected to be further reduced. In summary, ciproflulunan is in line with the development potential of becoming a terminal product.