Abstract
Quinoxaline derivatives demonstrate many distinguished chemical, biological, and physical properties and have a wide application in dyes, electroluminescent material, organic semiconductors, biological agents, etc. However, the synthesis of quinoxaline still suffers from several drawbacks, for instance, longer reaction time, unsatisfactory yields, and use of metal catalysts. Here, utilizing microdroplet-assisted reaction, we demonstrate the successive synthesis of several important quinoxaline derivatives. For case studies of 1H-indeno [1, 2-b] quinoxaline and 3,5-dimethyl-2-phenylquinoxaline, the present microdroplet approach can complete in milliseconds and the conversion rate reached 90% without adding any catalyst, which is considerably quicker and higher than conversional bulk-phase reactions. When combined with MS detection, high-throughput screening of the optimal reaction conditions can be achieved. Several impacts of droplet volume, reaction flow rate, distance from the MS inlet, spray voltage, and flow rate of the auxiliary gas can be screened on-site quickly for enhanced reaction speed and yields. More importantly, this platform is capable to be used for the scaled-up microdroplet synthesis of quinoxaline diversities. Considering the facile, economic, and environmentally friendly features of the microdroplet approach, we sincerely hope that the current strategy can effectively promote the academic research and industrial fabrications of functional quinoxaline substances for chemical, biological, and pharmaceutical application developments.
Highlights
As one of the most important nitrogen heterocycles, quinoxaline moiety is widely recognized to be the main nuclei for the synthesis of numerous biologically active compounds (Ajani, 2014)
For the preparation of secondary amides from ketoximes through the well-known Beckmann rearrangement, Liu et al have employed the microdroplet technique and reached a yield as high as 78.7–91.3% for benzoylaniline within several seconds, compared to a yield of typically 10.1–66.1% in several hours in the bulk phase (Zhang et al, 2019). Intrigued by these distinct features of the microdropletassisted reactions, here we report the use of a microdroplet reaction for the rapid and high-throughput screening of optimized conditions of the condensation reaction, which has been successfully utilized for the synthesis of substituted quinoxalines
In order to search for the optimized conditions for microdroplet quinoxaline synthesis, a model reaction of benzene-1, 2-diamine, and 1,2-indanedione was chosen (Figure 2A)
Summary
As one of the most important nitrogen heterocycles, quinoxaline moiety is widely recognized to be the main nuclei for the synthesis of numerous biologically active compounds (Ajani, 2014) Numerous quinoxaline derivatives, such as levomycin, actinoleutin, and echinomycin, show high biological activities and are used as therapeutic agents (Bailly et al, 1999; Seitz et al, 2002). Microdroplet Reaction for Screening Conditions substances such as organic dyes, electroluminescent materials, and organic semiconductors (Dailey et al, 2001; Sonawane and Rangnekar, 2002; Justin Thomas et al, 2005) Due to these distinguished chemical, biological, and physical features of quinoxalines, there has been tremendous interest in devising a simple and efficient method for the synthesis of such structures (Kamal et al, 2006). Numerous efforts have been paid on the synthesis of quinoxaline moieties
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
