Sustainable synthesis of antibacterial 3-aryl-2H-benzo[b,1,4]oxazin-2-ones via SNAr Csp2–Csp2 coupling DOI Creative Commons

Fatemeh Salehzadeh,

Maryam Esmkhani,

Milad Noori

et al.

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: Nov. 25, 2024

Introduction The increasing prevalence of antibiotic-resistant pathogens necessitates the urgent development new antibacterial agents. Concurrently, synthetic chemistry is moving towards more sustainable practices that minimize environmental impact. This study aims to synthesize 3-aryl-2 H -benzo[b][1,4]oxazin-2-one derivatives, including natural product cephalandole A, using a approach avoids metal catalysts. Methods We employed nucleophilic aromatic substitution (SNAr) under microwave-assisted conditions facilitate synthesis targeted compounds. metal-free carbon–carbon coupling reaction was optimized for efficiency, yielding good results with reduced times. synthesized derivatives were then subjected an in silico molecular docking predict their potential against key bacterial targets, focusing on binding affinity and interaction profiles. Results SNAr method provided yields 55% 82% significantly times ranging from 7 12 minutes, simplifying overall workup process. Among compounds, 3-( 1H -indol-3-yl)-6-methyl-2H-benzo[b][1,4]oxazin-2-one ( 6b ) emerged as promising candidate, demonstrating favorable interactions studies. Discussion integration methodologies screening offers novel effective strategy drug discovery. Our findings highlight compounds agents emphasize importance adopting eco-friendly approaches pharmaceutical chemistry. research contributes global effort combat antibiotic resistance by providing further biological evaluation.

Language: Английский

Isothiourea‐Catalysed Acylative Dynamic Kinetic Resolution of Tetra‐substituted Morpholinone and Benzoxazinone Lactols DOI Creative Commons
Haoxiang Zhu, Alejandro Manchado, Abdikani Omar Farah

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(37)

Published: May 7, 2024

The development of methods to allow the selective acylative dynamic kinetic resolution (DKR) tetra-substituted lactols is a recognised synthetic challenge. In this manuscript, highly enantioselective isothiourea-catalysed DKR morpholinone and benzoxazinone-derived reported. scope limitations methodology have been developed, with high enantioselectivity good excellent yields (up 89 %, 99 : 1 er) observed across broad range substrate derivatives incorporating substitution at N(4) C(2), di- spirocyclic C(5) C(6), as well benzannulation (>35 examples in total). process amenable scale-up on g laboratory scale. factors leading selectivity probed through computation, an N-C=O⋅⋅⋅isothiouronium interaction identified key producing ester products enantioenriched form.

Language: Английский

Citations

3
Rh(III)-Catalyzed C(sp3)–H Thiolation of 8-Methylquinolines Promoted by Benzoic Anhydride DOI

Cheng-Kai Yuan,

Yan-Nian Pan,

Yifei Wu

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(17), P. 11975 - 11982

Published: Aug. 20, 2024

Herein, we developed a ligand-promoted Rh(III)-catalyzed C(sp

Language: Английский

Citations

1
Recent Progress in the Synthesis of Benzoxazin-4-Ones, Applications in N-Directed Ortho-Functionalizations, and Biological Significance DOI Creative Commons
Ziad Moussa, Mani Ramanathan, Harbi Tomah Al‐Masri

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5710 - 5710

Published: Dec. 3, 2024

The development of efficient synthetic procedures to access fused N, O-heterocyclic skeletons has been a pivotal research topic in organic synthesis for several years. Owing the applications O-fused heterocycles synthesis, material sciences, and medicinal chemistry, significant efforts have dedicated design novel methods their construction. To this end, 1,3-benzoxazin-4-ones are privileged candidates molecules often found natural products, agrochemicals, materials science applications. In review, we aim summarize existing literature on from 2010 onwards. Moreover, also identified as an excellent native directing group ortho-functionalization via C-H activation, which is strenuous task requiring pre-functionalized substrates. latter part report, compiled interesting examples

Language: Английский

Citations

0
Photoinduced Regioselective Decarbonylative and Decarboxylative C–O Bond Functionalizations: Approach toward Chemoselective Scissions of Isatoic Anhydride and Unraveling the Enroutes through Control Experiments and DFT Studies DOI
Rahul Dev Mandal, Dwaipayan Das, Anindita Sarkar

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Distinctive, green, innovative, and well-organized photoinduced (metal- or photocatalyst-free) regioselective decarbonylative decarboxylative C–O bond functionalization protocols to access aryl 2-aminobenzoates 2-substituted benzoxazinone derivatives in excellent yields have been devised. These are achieved through the chemoselective scission of isatoic anhydride with ketones, diaryliodonium triflate, nitroalkene, phthalazinone, phenol derivatives, which, turn, served as representative "electrophilic nucleophilic" coupling partners. Control experiments DFT calculations reveal that electrophilic radical-bearing partners specifically follow decarbonylation pathway, while nucleophilic conjugates facilitate decarboxylation process. Thus, devised methods represent fragmentation anhydride, which occurs due electronic nature Again, C–O/O–C formation is also a novel outcome this methodology. We green method for synthesizing 2-aminobenzoate-subtituted paracetamol route. A fluorescence quenching study indicates phenyl 2-aminobenzoate detects Fe(II) ions, exhibiting no reactivity toward various other metal ions. Additionally, transition-metal-catalyzed C–H vinyl sulfone was performed at ease significant yields, appreciated strategy developed by us.

Language: Английский

Citations

0
Isothiourea‐Catalysed Acylative Dynamic Kinetic Resolution of Tetra‐substituted Morpholinone and Benzoxazinone Lactols DOI Creative Commons
Haoxiang Zhu, Alejandro Manchado, Abdikani Omar Farah

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(37)

Published: May 7, 2024

Abstract The development of methods to allow the selective acylative dynamic kinetic resolution (DKR) tetra‐substituted lactols is a recognised synthetic challenge. In this manuscript, highly enantioselective isothiourea‐catalysed DKR morpholinone and benzoxazinone‐derived reported. scope limitations methodology have been developed, with high enantioselectivity good excellent yields (up 89 %, 99 : 1 er) observed across broad range substrate derivatives incorporating substitution at N(4) C(2), di‐ spirocyclic C(5) C(6), as well benzannulation (>35 examples in total). process amenable scale‐up on g laboratory scale. factors leading selectivity probed through computation, an N−C=O⋅⋅⋅isothiouronium interaction identified key producing ester products enantioenriched form.

Language: Английский

Citations

0
Sustainable synthesis of antibacterial 3-aryl-2H-benzo[b,1,4]oxazin-2-ones via SNAr Csp2–Csp2 coupling DOI Creative Commons

Fatemeh Salehzadeh,

Maryam Esmkhani,

Milad Noori

et al.

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: Nov. 25, 2024

Introduction The increasing prevalence of antibiotic-resistant pathogens necessitates the urgent development new antibacterial agents. Concurrently, synthetic chemistry is moving towards more sustainable practices that minimize environmental impact. This study aims to synthesize 3-aryl-2 H -benzo[b][1,4]oxazin-2-one derivatives, including natural product cephalandole A, using a approach avoids metal catalysts. Methods We employed nucleophilic aromatic substitution (SNAr) under microwave-assisted conditions facilitate synthesis targeted compounds. metal-free carbon–carbon coupling reaction was optimized for efficiency, yielding good results with reduced times. synthesized derivatives were then subjected an in silico molecular docking predict their potential against key bacterial targets, focusing on binding affinity and interaction profiles. Results SNAr method provided yields 55% 82% significantly times ranging from 7 12 minutes, simplifying overall workup process. Among compounds, 3-( 1H -indol-3-yl)-6-methyl-2H-benzo[b][1,4]oxazin-2-one ( 6b ) emerged as promising candidate, demonstrating favorable interactions studies. Discussion integration methodologies screening offers novel effective strategy drug discovery. Our findings highlight compounds agents emphasize importance adopting eco-friendly approaches pharmaceutical chemistry. research contributes global effort combat antibiotic resistance by providing further biological evaluation.

Language: Английский

Citations

0