Patent Watch

July 21, 2014

Here are two better ways to synthesize enamino carbonyl compounds. In these two patents, N. Lui and J.-D. Heinrich describe alternative methods for preparing insecticidal compound 2. The inventors state that enamine carbonyl compounds usually are prepared from tetronic acid (the γ-lactone of 4-hydroxyacetoacetic acid) and an amine. The high cost of tetronic acid, however, is a disadvantage for commercial production, and alternative routes to enamine carbonyl compounds are needed.

The first patent discloses the preparation of 2, shown in Figure 1. Carboxamide 1 is treated with a Brønsted acid; the example in the patent uses KHSO4, but others are covered in the claims. The reaction is run in butyronitrile solvent, and the product is isolated in 77% yield. 1H NMR data are provided, but the product purity is not specifically reported.

First synthesis of compound 2

The preparation of 1, also described in the first patent, consists of a coupling reaction between amine 3 and ester 4, shown in Figure 1. The product is recrystallized from isopropyl alcohol. Again, 1H NMR data are given, but the yield and purity are not reported.

The second patent describes an alternative method for preparing 2 (Figure 2). This sequence begins with the reaction between a 100% excess of diisopropyl malonate (5) and chloroacetyl chloride (6) in the presence of t-BuOK to give ester 7. The reaction gives a 1:1 mixture of 7 and residual starting material 5. The inventors state that the mixture is suitable for use in the next step, but the example for the second step uses purified 7. The mixture of 5 and 7 can be separated by column chromatography, and 1H NMR data for 7 are provided.

Second synthesis of compound 2

The reaction of 7 with amine 3 in butyronitrile solvent proceeds in the presence of a Brønsted acid; again, KHSO4 is used in the example. Product 2 is isolated in 95% yield. (Bayer Cropscience AG [Monheim, Germany]. US Patents 8,680,285 and 8,680,286, March 25, 2014; Keith Turner)