Photochemical Preparation of 1,2-Dihydro‑3H‑indazol-3-ones in Aqueous Solvent at Room Temperature

o-Nitrosobenzaldehyde is a reactive intermediate useful in the synthesis of nitrogen heterocycles. Previous strategies for using o-nitrosobenzaldehyde involve its isolation via chromatography and/or formation under harsh conditions. Herein, this intermediate was photochemically generated in situ from o-nitrobenzyl alcohols in a mild, efficient manner for the construction of 1,2-dihydro-3 H-indazol-3-ones using an aqueous solvent at room temperature. This convenient reaction offers several advantages over reported methods. The commercially available photoreactor employed 3 × 18 W bulbs outputting broad emission above 365 nm

N–N Bond Formation between Primary Amines and Nitrosos: Direct Synthesis of 2‑Substituted Indazolones with Mechanistic Insights

A concise, one-step route to indazolones from primary alkyl amines and o-nitrobenzyl alcohols is reported. The key step in this readily scalable indazolone forming process involves base-mediated in situ o-nitrobenzyl alcohol → o-nitrosobenzaldehyde conversion. Although this functional group interconversion is known to be useful for 2 H-indazole synthesis, its reactivity was modulated for indazolone formation

Accessing Multiple Classes of 2H‑Indazoles: Mechanistic Implications for the Cadogan and Davis–Beirut Reactions

The Cadogan cyclization is a robust but harsh method for the synthesis of 2 H-indazoles, a valuable class of nitrogen heterocycles. Although nitrene generation by exhaustive deoxygenation is widely accepted as the operating mechanism in the reductive cyclization of nitroaromatics, non-nitrene pathways have only been theorized previously. Here, 2 H-indazole N-oxides were synthesized through an interrupted Cadogan/Davis-Beirut reaction and are presented as direct evidence of competent oxygenated intermediates; mechanistic implications for both reactions are discussed. Isolation and characterization of these N-oxides enabled a formal Cadogan cyclization at room temperature for 2 H-indazole synthesis

Davis–Beirut Reaction: A Photochemical Brønsted Acid Catalyzed Route to N‑Aryl 2H‑Indazoles

The Davis-Beirut reaction provides access to 2H-indazoles from aromatic nitro compounds. However, N-aryl targets have been traditionally challenging to access due to competitive alternate reaction pathways. Previously, the key nitroso imine intermediate was generated under alkaline conditions, but as reported here, the photochemistry of o-nitrobenzyl alcohols empowered Brønsted acid catalyzed conditions for accessing N-aryl targets. Anilines and alkyl amines give different outcomes under optimized conditions; the proposed mechanism was studied using quantum chemical calculations

Electrochemical Carbon Dioxide Capture and Concentration

Electrochemical carbon capture and concentration (eCCC) offers a promising alternative to thermochemical processes as it circumvents the limitations of temperature-driven capture and release. This review will begin by discussing the history of eCCC, describing early work in the field and the motivation for pursuing such a process. We will then transition towards discussing more recent approaches, with a heavier emphasis on methods that employ redox mediators to facilitate CO2 capture and release. These methods rely more on optimization through chemical design and include pH-mediated systems, electrochemically-mediated amine regeneration, and direct capture with redox-active molecules. For each approach, we provide a general overview of the system, discuss redox mediator chemistries that have been studied in literature, and highlight requirements for future generations of redox mediators. We also describe previous demonstrations of each method and current cell/system designs that have been used at the lab-scale. To conclude, we summarize achievements in the field, current challenges, and opportunities for improving these technologies. Overall, this review is a comprehensive survey of the eCCC field and evaluates the chemical, theoretical, and electrochemical engineering aspects of this approach. We hope this work can be used to assist the community in the development of modern economical eCCC technologies that can be utilized in large-scale CCS processes

N–N Bond Formation between Primary Amines and Nitrosos: Direct Synthesis of 2‑Substituted Indazolones with Mechanistic Insights

A concise, one-step route to indazolones from primary alkyl amines and <i>o</i>-nitrobenzyl alcohols is reported. The key step in this readily scalable indazolone forming process involves base-mediated <i>in situ o</i>-nitrobenzyl alcohol → <i>o</i>-nitrosobenzaldehyde conversion. Although this functional group interconversion is known to be useful for 2<i>H</i>-indazole synthesis, its reactivity was modulated for indazolone formation

Combination potentiator (‘co-potentiator’) therapy for CF caused by CFTR mutants, including N1303K, that are poorly responsive to single potentiators

BACKGROUND: Current modulator therapies for some cystic fibrosis-causing CFTR mutants, including N1303K, have limited efficacy. We provide evidence here to support combination potentiator (co-potentiator) therapy for mutant CFTRs that are poorly responsive to single potentiators. METHODS: Functional synergy screens done on N1303K and W1282X CFTR, in which small molecules were tested with VX-770, identified arylsulfonamide-pyrrolopyridine, phenoxy-benzimidazole and flavone co-potentiators. RESULTS: A previously identified arylsulfonamide-pyrrolopyridine co-potentiator (ASP-11) added with VX-770 increased N1303K-CFTR current 7-fold more than VX-770 alone. ASP-11 increased by ~65% of the current of G551D-CFTR compared to VX-770, was additive with VX-770 on F508del-CFTR, and activated wild-type CFTR in the absence of a cAMP agonist. ASP-11 efficacy with VX-770 was demonstrated in primary CF human airway cell cultures having N1303K, W1282X and G551D CFTR mutations. Structure-activity studies on 11 synthesized ASP-11 analogs produced compounds with EC50 down to 0.5 μM. CONCLUSIONS: These studies support combination potentiator therapy for CF caused by some CFTR mutations that are not effectively treated by single potentiators

Electrochemical Carbon Dioxide Capture and Concentration

Electrochemical carbon capture and concentration (eCCC) offers a promising alternative to thermochemical processes as it circumvents the limitations of temperature-driven capture and release. This review will discuss a wide range of eCCC approaches, starting with the first examples reported in the 1960s and 1970s, then transitioning into more recent approaches and future outlooks. For each approach, the achievements in the field, current challenges, and opportunities for improvement will be described. This review is a comprehensive survey of the eCCC field and evaluates the chemical, theoretical, and electrochemical engineering aspects of different methods to aid in the development of modern economical eCCC technologies that can be utilized in large-scale carbon capture and sequestration (CCS) processes