Green Hydrothermal Synthesis of Fluorescent 2,3‐Diarylquinoxalines and Large‐Scale Computational Comparison to Existing Alternatives

Abstract

Here, the hydrothermal synthesis (HTS) of 2,3‐diarylquinoxalines from 1,2‐diketones and o‐phenylendiamines (o‐PDAs) was achieved. The synthesis is simple, fast, and generates high yields, without requiring any organic solvents, strong acids or toxic catalysts. Reaction times down to <10 min without decrease in yield could be achieved through adding acetic acid as promoter, even for highly apolar biquinoxalines (yield >90 % in all cases). Moreover, it was shown that HTS has high compatibility: (i) hydrochlorides, a standard commercial form of amines, could be used directly as combined amine source and acidic catalyst, and (ii) Boc‐diprotected o‐PDA could be directly employed as substrate that underwent HT deprotection. A systematic large‐scale computational comparison of all reported syntheses of the presented quinoxalines from the same starting compounds showed that this method is more environmentally friendly and less toxic than all existing methods and revealed generic synthetic routes for improving reaction yields. Finally, the application of the synthesized compounds as fluorescent dyes for cell staining was explored.

Synthesis of 2,3-Diarylquinoxaline Carboxylic Acids in High-Temperature Water

“…In a first experiment, we reacted equimolar amounts of 4,4′-dimethoxybenzil ( 1 ) and 3,4-diaminobenzoic acid ( 2 ) in 5% HOAc under the previously reported conditions, i.e., T r = 230 °C, t r = 10 minutes. 12 As expected, analysis of the crude product by 1 H NMR showed that the target quinoxaline 3 was obtained as the major product. However, further signals suggested the presence of a second product in a lower amount than compound 3 .…”

“…The HTS of quinoxalines is compatible with a broad scope of starting materials bearing diverse functional groups. However, in our recent work, 12 we did not investigate substrates bearing carboxylic acids (CO 2 H) as ( i ) they might condense with the amino groups available in o -PDA analogues towards forming, e.g., benzimidazoles, or ( ii ) decarboxylation of the CO 2 H functions might occur in HTW. In the present work, we address the compatibility of the HTS of quinoxalines with carboxylic acid groups.…”

“…In our recently reported HTS of quinoxalines, we found that o -phenylendiamine dihydrochloride ( o -PDA·2HCl) reacts with benzil to produce 2,3-diphenylquinoxaline in solely water (i.e., without added HOAc) at T r = 230 °C. 12 Analogously to o -PDA·2HCl, the CO 2 H function in the 3,4-diaminobenzoic acid is a source of protons. We hypothesized that the inherent acidity of the 3,4-diaminobenzoic acid might also self-catalyze the reaction and influence the yields of compound 3 and 4 .…”

Hydrothermal polymerization of porous aromatic polyimide networks and machine learning-assisted computational morphology evolution interpretation

“…Aside PIs, HTP has recently been shown to be also amenable to the synthesis of polyamide networks, which in the reported example are, however, linked by linear amide functions (and hence no heterocyclic linkages), and based on both aromatic and also alicyclic moieties, 22 polyazomethines (also not featuring heterocyclic linkages but linear azomethine (aka secondary aldimine) linkages), 23 and polybenzimidazoles and benzoyl-imidazole polymers (aka BBB – benzimidazolebenzophenanthroline-type semiladder polymers). 24 HT cyclocondensations can also be used for generating small organic molecules, the technique is then rather termed hydrothermal synthesis (HTS), with examples comprising rylene bisimides, 25 benzimidazoles, 26 quinoxalines, 76 and the fused bisbenzoylimidazole perinone. 27 HTS/HTP relies on superheated liquid H 2 O as medium, generated through heating H 2 O above its boiling point in a closed vessel (typically an autoclave).…”

Geomimetic Hydrothermal Synthesis of Polyimide‐Based Covalent Organic Frameworks

“…Inspired by this geothermal process, hydrothermal reaction occurring under high temperature and pressure can offer a convenient access toward the synthesis of a range of crystalline materials, such as gemstones, zeolites, and carbonaceous materials [4] . In addition, the use of hydrothermal reactions is promising for the synthesis of organic materials because of its simplicity, environmental sustainability, and low cost [5–9] …”