Patent Watch

March 18, 2013

Find a safer way to make an herbicide precursor. 5-Substituted-8-alkoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-amines are used to prepare herbicides such as penoxsulam (1). Established methods for making these compounds involve handling hazardous reagents such as NH2NH2 and ClCN. Inventors C. Bott, C. T. Hamilton, and G. A. Roth disclose a process that avoids the use of hazardous materials.

The route for preparing 5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-amine (2), a precursor to 1, begins with the reaction of pyrimidine 3 with isothiocyanatocarboxylate ester 4 to give thiocarbamate 5, recovered in 67% yield. Intermediate 5 is treated with NH2OH·HCl in the presence of a base to form hydroxyimino compound 6 that can be isolated in 59% yield after recrystallization.

Heating 6 cyclizes it to give triazolo[1,5-c]pyrimidin-2-amine 7. This product can also be obtained from 5 without isolating 6: A mixture of 5 and NH2OH·HCl is suspended in t-BuOH, and 7 is precipitated by adding NaHCO3. The product is recovered in 83% yield.

In the final step, treating 7 with NaOMe forms 2, isolated in 88% yield. The purity of intermediates is not reported, but 1H and 13C NMR and mass spectrometric data are provided.

Compound 2 can also be made from an analogue of 3 that contains a methoxy group in place of chloro. The analogue of 5, recovered in 89% yield, is treated with NH2OH·HCl to form 2 quantitatively. (Dow Agrosciences [Indianapolis]. US Patent 8,338,596, Dec. 25, 2012; Keith Turner)

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