Selective cross-dehydrogenative C–O coupling of N-hydroxy compounds with pyrazolones. Introduction of the diacetyliminoxyl radical into the practice of organic synthesis

Abstract

Oxidative C-O coupling of pyrazolones with N-hydroxy compounds of different classes (N-hydroxyphthalimide, N-hydroxybenzotriazole, oximes) was achieved; both one-electron oxidants (Fe(ClO 4 ) 3 , (NH 4 ) 2 Ce(NO 3 ) 6 ) and two-electron oxidants (PhI(OAc) 2 , Pb(OAc) 4 ) are applicable, and the yields reach 91%. Apparently, the coupling proceeds via the formation of N-oxyl radicals from N-hydroxy compounds. One of the N-oxyl intermediates, the diacetyliminoxyl radical, was found to be exclusively stable in solution in spite of being sterically unhindered; it was isolated from an oxidant and used as a new reagent for the synthesis and mechanism study. The products of C-O coupling of pyrazolones with N-hydroxyphthalimide can be easily transformed into aminooxy compounds, valuable substances for combinatorial chemistry.

Mild Nitration of Pyrazolin‐5‐ones by a Combination of Fe(NO3)3 and NaNO2: Discovery of a New Readily Available Class of Fungicides, 4‐Nitropyrazolin‐5‐ones

“…Then two sequences are possible: (1) Attack of NO 2 on pyrazolin‐5‐one 1 a – l with the formation of radical A followed by its oxidation by Fe 3+ or NO 2 or (2) abstraction of a hydrogen atom from the pyrazolin‐5‐one 1 a – l by NO 2 with the formation of radical B followed by its coupling with a second NO 2 . The addition of free radicals to the pyrazolin‐5‐ones via intermediates A or B is supported by the previously reported reactions between pyrazolin‐5‐ones and N ‐oxyl radicals . Both hydrogen‐atom abstraction and addition to double C=C bonds are typical reactions of NO 2 .…”

“…By employing this procedure, low‐to‐moderate yields of pyrazolin‐5‐ones containing a Ph substituent at positions N1 or C3 were obtained (products 2 j – l , 16–53 %). We proposed that the oxidation of these pyrazolin‐5‐ones by Fe 3+ occurred faster than the generation of NO 2 from the nitrite ion. To minimize the side oxidation of 1 j – l by Fe(NO 3 ) 3 , a series of experiments were conducted in which Fe(NO 3 ) 3 was allowed to react with NaNO 2 first, and only then the pyrazolin‐5‐ones 1 j – l were added to the reaction mixture (such a procedure is referred to below as the “inverse order of addition”).…”

“…Through this order of addition, Fe(NO 3 ) 3 was allowed to react with NaNO 2 before the addition of pyrazolin‐5‐one. In the case of the standard order of addition of reagents, Fe III can react simultaneously with NaNO 2 and pyrazolin‐5‐one, which is undesirable for pyrazolin‐5‐ones that readily undergo side‐oxidation reactions under the action of Fe III . The isolated yields of the target nitropyrazolin‐5‐ones 2 a and 2 k depending on the order of addition of reagents are shown in Scheme .…”

“…In the next stage of our study, the applicability of the proposed system for the nitration of various CH acids was investigated. The prerequisite for these experiments was that the deprotonated or tautomeric forms of the CH acids contained π‐conjugated systems that could be attacked by NO 2 similarly to the pyrazolin‐5‐one π system . Indeed, a series of nitro derivatives of the CH acids 4 a – e were synthesized by using the developed Fe(NO 3 ) 3 /NaNO 2 system (Table ).…”

“…In addition, the oxidative destruction of the pyrazolin‐5‐one ring is also known . Among the recent work devoted to the functionalization of pyrazolin‐5‐ones by the attack of electrophiles or radicals at the 4‐position of the heterocycle, only one involved the creation of the C−N bond, in which azodicarboxylates were used as the nitrogen electrophiles …”