Pestic. Sci. 1986,17,441-448 Some fluorine-containing Pheromone Analogues" Geoffrey G. Briggs, George R. Cayley, Glenn W. Dawson, David C. Griffiths, Ewen D. M. Macaulay, John A. Pickett, Mary M. Pileb, Lester J. Wadhams and Christine M. Woodcock Rothamsted Experimental Station, Harpenden, Hertfordshire AL5 2JQ and 'Department of Entomology, London School of Hygiene and Tropical Medicine, Keppel Street, London WCl E 7HT (Manuscript received27November1985) Two analogues of the aphid alarm pheromone (E)-fi-farnesene, a trifluorofarnesene and a difluoro-1-norfamesene, were found to be highly active and were more readily detectable than the parent compound. For (2)-hexadec-11-end, a compo- nent of some lepidopteran sex attractant pheromones, replacement of the carbonyl oxygen with a difluoromethyl group to give a difluoroheptadecadiene resulted in loss of activity. A trifluoroacetoxyhexadecanolide was a more volatile analogue of the mosquito oviposition pheromone (-)-(5R,6S)-6-acetoxy-5-hexadecanolide and was highly active. 1. Introduction The use of pheromones and other behaviour-controlling chemicals against invertebrate pests of arable crops shows considerable promise for reducing the environmental impact of crop protection, and for circumventing problems of insecticide resistance. The advantages of behaviour-controlling chemicals are related to their high target specificity and to the fact that such materials are essentially non-toxic. However, there are several problems that need to be solved before widespread use of behaviour-controlling chemicals can be established. To solve the chemical and physical problems, two approaches have ,been adopted. One approach was to prepare synthetic pheromone precursors, or propheromones, which have appropriate physical properties for use in the field and which will release the active chemical under certain field conditions.* The other is to prepare analogues by isosteric replacement.* This is invaluable in the development of pesticides, but seemed unpromising here because phero- mones, being employed on the outside of the organism, are detected by extremely selective sensory systems. However, hydrogen can be replaced by fluorine without notable steric consequence^,^ and it seemed possible that fluoro analogues of pheromones might retain biological acitivity . Recently, some investigations into fluoro analogues of pheromones yielded active molecules. For example, fluorine substituted into the aliphatic chain of lepidopteran sex pheromone components gave two compounds that elicited electroantennograph responses similar to those produced by synthetic pher~mone.~ Substitution of a trifluoromethyl group for a methyl group in the acetate group of another lepidopteran sex pheromone produced a compound with antipheromone, or inhibitory, activity in a laboratory bi~assay.~ An account is given here of attempts to prepare active fluorine-containing pheromone analogues with improved chemical or physical properties. Three types of pheromone were chosen for investigation: the aphid alarm pheromone (E)-fl-farnesene (Ia);"9 a typical aldehydic component of lepidopteran sex pheromones (2)-hexadec-11-enal (IIa);" and the mosquito oviposition pheromone (-)-(5R, 6S)-6-acetoxy-5-hexadecanolide (ma) ,11 see Figure 1. "Presented at the symposium Fluorine-conraining pesticides on 21 October 1985 in London, organised by the Pesticides Group, Society of Chemical Industry. 441