Role of Organic Carbon in Heterogeneous Reaction of NO₂ with Soot

A large uncertainty among the reported uptake coefficients of NO₂ on soot highlights the importance of the composition of soot in this reaction. Soot samples with different fractions of organic carbon (OC) were prepared by combusting <i>n</i>-hexane under controlled conditions. The heterogeneous reaction of NO₂ on soot was investigated using a flow tube reactor at ambient pressure. The soot with the highest fuel/oxygen ratio showed the largest uptake coefficient (γ_initial) of NO₂ and yield of HONO (<i>y</i>_HONO). Compared to fresh soot samples, preheated samples exhibited a great decrease in uptake coefficient of NO₂ and HONO yield due to the removal of OC from soot. Ozonized soot also showed a lower reactivity toward NO₂ than fresh soot, which can be ascribed to the consumption of OC with a reduced state (OC_R). A linear dependence of the NO₂ uptake coefficient and yields of HONO and NO on the OC_R content of the soot was established, with γ_initial(NO₂) = (1.54 ± 1.39) × 10^–6 + (1.96 ± 0.35) × 10^–7 × OC_R, <i>y</i>_HONO = (11.6 ± 16.1) + (1.3 ± 0.40) × OC_R, and <i>y</i>_NO = (13.1 ± 1.9) – (0.2 ± 0.05) × OC_R, respectively

Small Stories and Language of Persuasion in WeChat Advertisements

Abstract for presentation at ALAA2016/ALS2016 joint day

Chemoselective Copper-Catalyzed Ullmann-Type Coupling of Oxazolidinones with Bromoiodoarenes

We describe the highly selective copper-catalyzed Ullmann-type coupling of bromoiodoarenes with oxazolidinones. 3,4,7,8-Tetramethyl-1,10-phenanthroline (Me₄Phen) was identified as an optimal ligand promoting the desired C–N bond formation, while minimizing the competitive bromo–iodo exchange pathway that leads to formation of iodo-substituted and bis-coupled side products. The developed method is highly selective with a >98:2 ratio of the bromo- vs iodo-substituted compounds obtained in the isolated products

Heterogeneous Photochemical Conversion of NO₂ to HONO on the Humic Acid Surface under Simulated Sunlight

The poor understanding of HONO sources in the daytime highlights the importance of the heterogeneous photochemical reaction of NO₂ with aerosol or soil surfaces. The conversion of NO₂ to HONO on humic acid (HA) under simulated sunlight was investigated using a flow tube reactor at ambient pressure. The uptake coefficient (γ) of NO₂ linearly increased with irradiation intensity and HA mass in the range of 0–2.0 μg/cm², while it decreased with the NO₂ concentration. The HONO yield was found to be independent of irradiation intensity, HA mass, and NO₂ concentration. The temperature (278–308 K) had little influence on both γ and HONO yield. Additionally, γ increased continuously with relative humidity (RH, 7–70%), and a maximum HONO yield was observed at 40% RH. The heterogeneous photochemical reaction of NO₂ with HA was explained by the Langmuir–Hinshelwood mechanism

Palladium-Catalyzed Site-Selective Amidation of Dichloroazines

A highly site-selective amidation reaction of substituted 2,4-dichloroazines is reported. Palladium acetate/1,1′-bis­(diphenylphosphino)­ferrocene (dppf) was identified as the optimal catalyst system, producing >99:1 C-2/C-4 selectivity for most examples. The generality of this transformation was demonstrated through a survey of a diverse amide/substituted 2,4-dichloroazine scope, leading to the preparation of the desired C-2 amidated products in good to excellent yields

Palladium-Catalyzed Site-Selective Amidation of Dichloroazines

A highly site-selective amidation reaction of substituted 2,4-dichloroazines is reported. Palladium acetate/1,1′-bis­(diphenylphosphino)­ferrocene (dppf) was identified as the optimal catalyst system, producing >99:1 C-2/C-4 selectivity for most examples. The generality of this transformation was demonstrated through a survey of a diverse amide/substituted 2,4-dichloroazine scope, leading to the preparation of the desired C-2 amidated products in good to excellent yields

An Efficient Through-Process for Chk1 Kinase Inhibitor GDC-0575

We report an efficient route to prepare Chk1 kinase inhibitor GDC-0575 from 5-bromo-4-chloro-3-nitro-7-azaindole featuring a sequence of nucleophilic aromatic substitution, hydrogenative nitro-reduction, and a robust, high-yielding end-game involving deprotection–crystallization steps. The developed route was demonstrated on 10 kg scale in 30% overall yield to provide the target API in >99.8 A % HPLC purity

Development of a Streamlined Manufacturing Process for the Highly Substituted Quinazoline Core Present in KRAS G12C Inhibitor <i>Divarasib</i>

A streamlined process for the synthesis of a highly functionalized quinazoline that enabled late-stage preparation of KRAS G12C inhibitor divarasib is presented herein. The highlights of the synthesis are a telescoped four-step preparation of the key 2-amino-4-bromo-3-fluorobenzonitrile intermediate, a critical aromatic chlorination using NCS and catalytic HCl, a cyclization to a quinazoline dione employing CO2 and DBU, and a DABCO−MsOH-catalyzed Halex reaction to form target quinazoline fluoride 2. In the chlorination step, we encountered an unusual halogen scrambling, resulting in critical 4,5-dichloro and 4,5-dibromo impurities that needed to be controlled down to low levels due to minimal purging power in downstream chemistry. The manufacturing process was demonstrated by the preparation of >500 kg of quinazoline 2 in 39% overall yield and 99.5 area % HPLC purity over nine chemical steps and five isolations

Magnesium Ethoxide Promoted Conversion of Nitriles to Amidines and Its Application in 5,6-Dihydroimidazobenzoxazepine Synthesis

Magnesium ethoxide has been shown to be a mild, safe, and scalable alternative to trimethylaluminum for the direct addition of amines to aryl nitriles to access cyclic amidines. A variety of electronically diverse oxa-, thia-, and diazepine products were successfully synthesized in moderate to high yields. Further elaboration of these compounds to 5,6-dihydroimidazobenzoxazepines, a privileged class of pharmacologically active heterocycles, highlights the utility of this method