Synthesis and Synthetic Application of Chloro- and Bromofuroxans

Abstract

Furoxans are potentially useful heteroaromatic units in pharmaceuticals and agrichemicals. However, the applications for furoxan-based compounds have been hampered due to the underdevelopment of their synthetic methods. Herein we report a new synthetic approach for the synthesis of chloro-and bromofuroxans. The starting materials were dichloro-and dibromofuroxans, and the substituents were directly introduced to the furoxan ring in a modular fashion. The synthesized monohalofuroxans served as substrates for the installation of a second substituent to prepare further functionalized furoxans.

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

“…Since then, these nitric oxide donors have shown important biological activities due to their unique electronic and coordination ability [ 37 – 38 ], such as antitumor [ 39 ] and antiparasitic [ 40 – 41 ]. Previously, furoxans were synthesized via dimerization of hydroximoyl chlorides in the presence of a base, such as trimethylamine in ether [ 42 ], or Na 2 CO 3 in DME [ 43 ]. Our results showed that when 5% water, 95% methanol was used as a solvent mixture, the dimerization of hydroximoyl chlorides happened fast at room temperature without the need of a base.…”

Recent progress in synthesis and application of furoxan

“…The other alkoxides yielded adducts in poor yields ( Scheme 10c ), which was ascribed to a side reaction in which a dissociated bromide attacks the carbon at the α-position of the oxygen atom of the introduced alkoxy group, leading to the dissociation of the furoxanyl oxide anion ( Scheme 10d ). 33 …”

“…The reaction of alkynyl lithium reagent with dichlorofuroxan provided 4-chloro-3-alkynylfuroxan 25, a rare class of chlorofuroxans ( Scheme 22a ). 33 In contrast to most of the S N Ar reactions (such as alkoxylation) of furoxans with two leaving groups, which generally undergo substitution reaction at the 4-position, this alkynylation reaction proceeded selectively at the 3-position. This selectivity was proposed to originate from the coordination of the metal atom of the nucleophile with the out-of-ring oxygen atom of the furoxan at the 2-position, which serves as a directing group.…”

Recent Advances in the Synthesis and Biomedical Applications of Heterocyclic NO-Donors

“…Recently, a novel reactivity pattern of furoxans based on their radical functionalization was established ( Scheme 27 ). It was found that alkyl radicals generated from carboxylic acids in mild conditions add to the C(3) carbon atom of the furoxan ring in corresponding bromo or arylsulfonyl derivatives 47 followed by elimination of functional moiety and formation of target products 48 [ 91 , 92 ]. This protocol enables wide opportunities for the design of pharmacologically oriented furoxan-based compounds.…”