Synthesis of N-hydroxyurea derivatives of 1,3,5-substituted-1,2,4-triazoles.

December 26, 2023

• Title:

  Synthesis of N-hydroxyurea derivatives of 1,3,5-substituted-1,2,4-triazoles. Reagents and conditions: (i) hydroxylamine hydrochlo-ride, 1 N HCl, 30 °C, 24 h; (ii) 12, K2CO3, acetone, reflux, 3 h; (iii) sodium  cyanoborohydride, 4 N HCl, 30 °C, 4 h; (iv) potassium cyanate, glacial  acetic acid, MeOH, 30 °C, 4 h; (v) TFA/methylanisole, 0 °C–r.t., 24 h.

• Image Source:

  Discovery of potential anti-inflammatory drugs: Diaryl-1,2,4-triazoles bearing N-hydroxyurea moiety as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase

• Mark:

  Scheme 2

• Associated context:

  The strategy to synthesize N-hydroxyurea derivatives 15a–j is  shown in Scheme 2. Commercially available bromoacetalde-  hyde diethyl acetal 11 was converted directly to oxime which was treated with intermediates 6a–j to yield the requisite  oximes 13a–j in high overall yields. Reduction of the oximes to  the hydroxylamines 14a–j was carried out by treatment of  13a–j with a 3-fold excess of NaBH3CN in the presence of 4 N  HCl. The conversion of 14a–j to the aimed compounds  N-hydroxyureas 15a–j was performed via the addition of  KOCN/HOAc in methanol.