Patent Watch

May 31, 2013

Take some better routes to insecticidal compounds. P. Jeschke and 13 co-inventors developed methods for preparing a series of enaminocarbonyl compounds such as 3 that can be used for pest control. The reaction of tetronic acid 1 with chloropyridine derivative 2 in the presence of p-toluenesulfonic acid (TsOH) produces compound 3 in 52% yield after it is purified by column chromatography (ColC) (Figure 1).

Synthesis of enaminocarbonyl compounds and their precursors

Compound 3 can be chlorinated to form 4 or methylated to give 5 (Figure 1). Chlorinating 3 with N-chlorosuccinimide (NCS) in the presence of Et3N produces 4. The product is isolated in 63% yield after ColC purification. The bromo analogue is similarly obtained by using N-bromosuccinimide, also in 63% isolated yield. Compound 5 is prepared by treating 3 with t-BuLi and MeI; the purified product is isolated in 47% yield after ColC.

The preparation of starting material 1 is also shown in Figure 1. The reaction of dichloro compound 6 with 2,2-difluoroethylamine in the presence of Et3N gives 1 in 53% isolated yield. The purity is not reported. 1H NMR data are provided for products 1, 3, 4, and 5.

The inventors used different routes to prepare analogues of 3 in which the difluoroethyl group is replaced by 2-fluoroethyl, 3-fluoropropyl, 3,3-dichloroallyl, or 2-fluorovinyl. In one sequence, 9 is prepared from chloropyridine derivative 7 and gem-dichloroalkene 8 (Figure 2). The reaction is carried out by treating 7 with NaH, then heating the intermediate with 8. After workup, the product is isolated and purified by ColC to give 9 in 50% yield.

Synthesis of analogues of compound 3

The inventors used another route to synthesize analogue 12. 2-Fluoroethyl derivative 10 is treated with NaH, and the mixture is heated with dichloropyridine 11. The product is isolated in 50% yield after ColC purification. The patent’s claims also include analogues of 3 in which the chlorine atom on the pyridine nucleus is replaced by fluorine, bromine, or trifluoromethyl.

A nonpyridine compound, 13, is specifically covered in the claims. There are no specifics of the route used to prepare it, but 1H NMR data are provided.

Finally, the inventors describe the synthesis of substrate 10 from 2 and 2-fluoroethylamine hydrochloride in the presence of NaOAc and TsOH. After workup, the product is purified by recrystallization from EtOAc and cyclohexane; and 10 is recovered in 42% yield. This route is also used to prepare the difluoroethyl analogue of 10, but there are no details. Only the 1H NMR data are provided.

The patent includes tests results of the effectiveness of the compounds as insecticides. All of the inventors’ synthetic routes use commercially available reagents. (CropScience AG [Monheim, Germany]. US Patent 8,404,855, March 26, 2013; Keith Turner)

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