Practical Large-Scale Synthesis of 6‑Bromo-2-naphthylmethanesulfonamide Using Semmler–Wolff Reaction

A practical, scalable synthetic process for a sulfonamide was developed featuring a Semmler–Wolff aromatization as the key step. The optimized reaction conditions using HCl in HOAc give directly the desired naphthylamine in high yield as opposed to a naphthylacetamide commonly formed in the Semmler–Wolff reactions. One little known byproduct of anomalous rearrangement, ketoamine, was observed and a mechanism proposed to explain its formation. Employing the optimized process, 360 kg was prepared to support drug development

Table1_Reservoir characteristics and factors influencing shahejie marl in the shulu sag, bohai bay basin, eastern China.XLSX

Shahejie marl in the Shulu Sag is a crucial resource for unconventional hydrocarbon exploration in China. Although breakthroughs have been made in tight oil exploration in this area, the mechanisms underlying the formation of this marl reservoir and factors controlling its ‘sweet spots’ have not been thoroughly studied. To understand the pore structure characteristics and factors influencing the marl reservoir, we analyzed core samples from Wells ST1 and ST3. A series of experiments was conducted on the samples, such as X-ray diffraction, focused ion beam scanning electron microscopy, micro-CT, and total organic carbon test. Additionally, the physical properties of different marl rock fabrics were studied with auxiliary tests, such as mercury intrusion capillary pressure analyses, nuclear magnetic resonance, porosity and permeability tests, and thin-section observation. The results revealed that the marl reservoir is characterized by low porosity (1.61%) and low permeability (2.56mD). The porosity and permeability (1.61% and 3.26mD) of laminated marl were better than those (0.92% and 1.68mD) of massive marl. Clay minerals and quartz content in laminated (11.8 and 8.2%) was less than in massive marl (16.2 and 13.3%). The marl pores include intercrystalline pores, dissolution pores, and microfractures. Additionally, the laminated marl pores were primarily distributed along the dark lamina, with good connectivity. A few isolated and uniform holes were observed in the massive marl. Influenced by rock fabric and mineral composition, layered fractures were mainly developed in the laminated marl, while structural fractures were the main type of microfractures in the massive marl. The primary sedimentary mechanism was the main geological action underlying the differences in marl rock fabric; this mechanism affects the physical properties of the marl reservoir, which are key factors to be considered when searching for the marl reservoir ‘sweet spots’. Particular attention should be paid to these factors during tight oil exploration and development in similar sedimentary basins.</p

Additional file 1: of Genetic analyses in a cohort of 191 pulmonary arterial hypertension patients

Table S1. PAH panel genes. Table S2. Variants of unknown significance (VUS) detected in the panel genes. Table S3. CNVs in ENG and ACVRL1 by panelcn.MOPS and MLPA. Table S4. Genotype-phenotype correlation between biallelic EIF2AK4 mutations carriers and other PAH patients. Figure S1. Molecular genetic testing schedule. Figure S2. 4 HPAH families without an identified causative mutation. Figure S3. GC content in BMPR2, ENG and ACVRL1. (DOCX 1809 kb