Directing groups quinoxaline

Attempts to directly iodinate quinoxaline failed, and the synthesis of 2,3-diphenyl-5,8-dibromoquinoxaline is somewhat more involved (Scheme 9) [61]. Starting from ort/zo-phenylenediamine, reaction with SOCI2 gives benzothia-diazole in high yield. Bromination in HBr furnishes 4,7-dibromobenzothiadi-azole, which can be alkynylated or directly reduced [62]. Reduction of the dibromide with sodium borohydride leaves the halide substituents unmolested but opens the ring to furnish l,4-dibromo-2,3-diaminobenzene. Reaction of this intermediate with a 1,2-dione furnishes a 2,3-disubstituted 5,8-dibromo-quinoxaline. Pd-catalyzed alkynylation finishes the sequence off and removal of the TMS groups yields the desired 5,8-diethynylquinoxaline monomers (Table 9, entries 13,14). 

Similar selectivity issues can be found in triflamide-directed reactions (Scheme 23.48) [153]. Using a modified fluorinating reagent 26, mono- and difluorinated products can be obtained. A more recent development focuses on addressing this selectivity issue with an auxihary-based approach [ 154]. Finally, quinoxaline-based directing groups are also able to promote mono-selective C-H bond fluorinations in combination with N-fluorobenzenesulfonimide as F+ source [151],... 

A novel Pd(OAc)2-NFSI-TFA system was developed recently by Xu and cowoilc-ers demonstrating highly selective, ortto-monofluorination. In this case Pd coordination was directed by a diverse range of aryl-Af-heterocyclic directing groups (Scheme 9.15), such as quinoxaline, pyrazole, benzo[rf]oxazole, and pyrazine derivatives. A Pd(ll/IV) catalytic cycle was proposed. 

The presence of an orf/to-directing group, such as Cl or OMe, on the benzene ring of benzodiazines (quinazolinones, quinoxalines, phthalazines) favours lithiation of that ring at the peri position to a ring nitrogen." ... 

Such direct cyclizations usually occur in basic media to afford quinoxaline A-oxides. For success, C2 in the ethyl group needs to be a carbonyl entity or to be suitably activated. The following examples illustrate this valuable route to such A-oxides (and thence to quinoxalines see Section 4.6.2.1). 

Because quinoxalines are often converted into their N-oxides in order to facilitate other reactions, subsequent removal of the oxide entity without untoward effects is quite important. The choice of a reagent for such deoxygenation is frequently governed by the type(s) of passenger group present direct comparisons of several methods have bee presented. " The following classified examples illustrate most of the possibilities available. 

Recently, copper salts alone have been reported to effect the direct annulation of terminal alkynes by AT-(o-iodophenyl)trifluoroacetamide (Eq. 17) [49] and the analogous formation of pyrrolo[2,3-b]quinoxalines [50] with loss of the trifluoroacetyl group. 

The physicochemical properties of the water-soluble vitamins are extensively utilized in chemical methods. A method for quantitative vitamin C (ascorbic acid, AA) measurement in food and physiological samples is based on a reaction of the keto groups in dehydroascorbic acid (DHA) with o-phenylenediamine (OPD) to give a fluorescent quinoxaline. This method involves the oxidation of AA to DHA, followed by the measurement of total AA in the sample. The reductive capabilities of AA can especially be utilized for direct electrochemical (amperometric or coulometric) measurement when coupled with HPLC separation. 

In a different approach, Minakata and coworkers [94] developed a practical and high yielding PIDA-induced oxidative [4 + 2] annulation of o-phenylene diamines 122 and electron-deficient alkynes 126 for direct access to quinoxalines 127 bearing two electron-withdrawing groups (Scheme 31). The formation of quinoxalines 127 was proposed to occur via an initial generation of enamine 128, which was likely to undergo PIDA-mediated oxidative annulation and rearomatization. 

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