gem-Difluorovinyl derivatives as insecticides and acaricides

• Published in: Chimia Vol. 58; no. 3; pp. 108 - 116
• Main Authors: Pitterna, T, Boger, M, Maienfisch, P
• Format: Journal Article
• Language: English
• Published: BASEL NEW SWISS CHEMICAL SOC 01.03.2004; Swiss Chemical Society
• Subjects: 6,6-difluorohex-5-enoic acid; Acaricide; Cga 304'111; Chemistry; Chemistry, Multidisciplinary; Gem-difluorovinyl; Insecticide; Physical Sciences; Science & Technology; acaricide; insecticide; REAGENTS; CGA 304'1111; 6,6-difluorohex-5-enoic acid gem-difluorovinyl
• ISSN: 0009-4293; 2673-2424
• DOI: 10.2533/000942904777678163

The insecticidal lead 1,1-difluorododec-1-ene was optimised. This compound has attractive insecticidal activity against tobacco budworm (Heliothis virescens), banded cucumber beetle (Diabrotica balteata), pea aphid (Aphis cracciovora), brown planthopper (Nilaparvata lugens), and green rice leafhopper (Nephotettix cincticeps). Among different pharmacophore analogues, only 1,1-dichlorododec-1-ene and 1,1-difluoro-2-iodododec-l-ene showed weak insecticidal activity, whereas similar compounds such as 1-chloro-1-fluorododec-1-ene, 1 -fluorododec-1 -ene, and 1,1 -difluoro-2-bromododec-1 -ene were inactive. Only bridge analogues with even-numbered carbon chains were active, for example 1,1-difluorodec-1-ene and 1,1-difluorotetradec-1-ene. Odd-numbered analogues such as 1,1-difluoronon-l-ene, 1,1-difluoroundec-l-ene, 1,1-difluorotridec-l-ene, and 1,1-difluoro-pentadec-1 -ene showed no activity. Modification of the tail group led to the analogues 12,12-difluorododec-1 1 -enoic acid and its methyl ester, 12,12-difluorododec-1 1-en-1-ol, 1, 1-difluoro-1 2-methoxydodec-1-ene, and 12,12-difluorododec-1 1-enylamine, all of which showed insecticidal activity. 12,12-difluorododec-1 1-enoic acid methyl ester, 12,12-difluorododec-1 1-enoic acid, and 12,12-difluorododec-1 1-en-1-ol were also active against spider mites (Tetranychus ssp). Thus, in a first optimisation cycle, broad activity against insect pests and mites was discovered. Two requirements, the gem-difluorovinyl pharmacophore and an even-numbered carbon chain, were found to be essential for activity. This latter requirement is in line with the proposed mode of action, which involves inhibition of the P-oxidation of fatty acids in insect mitochondria. In a second optimisation cycle, it was found that 6,6-difluorohex-5-enoic acid and its derivatives, such as acids, amides, and hydrazides, possess even superior properties as insecticides and acaricides. This led to the discovery of 6,6-difluorohex-5-enoic acid 2-[4-(4-trifluoromethylbenzyloxy)-phenoxy]-ethyl ester (CGA 304'111). This compound showed excellent performance in field trials against a wide range of pests, as well as a more favourable toxicological profile than earlier derivatives. For a largescale synthesis of CGA 304'111, five different synthetic routes for 6,6-difluorohex-5-enoic acid were developed. The best route involved radical addition of CBrCIF2 to pent-4-enoic acid. Removal of bromine by hydrogenation, elimination of chloride and hydrolysis of the ester concluded this most efficient sequence. Thus, a practical synthesis for CGA 304'111 was identified, which allowed the preparation of samples on a several 100 g scale.