Sandmeyer Chlorosulfonylation of (Hetero)Aromatic Amines Using DABSO as an SO 2 Surrogate

Sulfonyl chlorides not only play a crucial role in protecting group chemistry but also are important starting materials in the synthesis of sulfonamides, which are in-demand motifs in drug discovery chemistry. Despite their importance, the number of different synthetic approaches to sulfonyl chlorides is limited, and most of them rely on traditional oxidative chlorination chemistry from thiol precursors. In this report, we disclose a novel Sandmeyer-type sulfonyl chloride synthesis from feedstock anilines and DABSO, used as a stable SO2 surrogate, in the presence of HCl and a Cu catalyst. The method works on a wide range of anilines and allows for the isolation of the sulfonyl chloride after aqueous workup or its direct conversion into the sulfonamide by simple addition of an amine after the completion of the Sandmeyer reaction. The scalability of this method was demonstrated on a 20 g scale, and the corresponding heterocyclic sulfonyl chloride was isolated in 80% yield and excellent purity

Development of a Scalable Route for a Key Benzothiazole Building Block via a Pd-Catalyzed Migita Coupling with a Nonsmelly Thiol Surrogate

2-Methylbenzo[d]thiazole-6-carbonitrile was internally identified as an important building block and therefore, kg amounts of it needed to be urgently supplied. As the desired benzothiazole was only available in small quantities for a high price (∼1000 USD/g), a robust and scalable route needed to be rapidly developed. The key to success was the use of a 2-iodophenyl N-acetamide precursor to construct the 2-methylbenzo[d]thiazole core via a Pd-catalyzed Migita coupling followed by subsequent intramolecular condensation of the intermediate thiophenol onto the N-acetyl group. To avoid the use of malodorous thiols on scale, 2-ethylhexyl 3-mercaptopropionate was used as a nonsmelly, inexpensive thiol surrogate. The Migita coupling was extensively optimized and allowed the reaction to be performed in a dose-controlled manner with regard to the addition of the thiol surrogate at 40 °C, by using only 0.1 mol % Pd2dba3. The subsequent intramolecular cyclization step was promoted by the one-pot addition of DBU. After aqueous workup and crystallization, 2-methylbenzo[d]thiazole-6-carbonitrile was obtained in 81% yield and excellent purity (99.7% a/a) on a 2.0 kg scale

Synthesis of Sterically Hindered <i>N</i>‑Acylated Amino Acids from <i>N</i>‑Carboxyanhydrides

Sterically hindered <i>N</i>-acyl, <i>gem</i>-disubstituted amino acids are easily prepared via the addition of organometallic reagents to <i>N</i>-carboxy­anhydrides (NCA). The process tolerates a wide variety of functional groups and allows the synthesis of amide products not readily accessible by traditional acylation chemistry. The existence of an isocyanate intermediate was established by <i>in situ</i> IR spectroscopy

Scalable Synthesis of Trifluoromethylated Imidazo-Fused N‑Heterocycles Using TFAA and Trifluoroacetamide as CF₃‑Reagents

A scalable synthesis of trifluoromethylated imidazo-fused N-heterocyles from heterocyclic benzylamines using TFAA as trifluoromethylating reagent is presented. The reaction proceeds via intermediate benzylic <i>N</i>-trifluoroacetamides followed by dehydrative cyclization to the products. To further broaden the scope and practicality, a new method for the preparation of benzylic <i>N</i>-trifluoroacetamides via alkylation of trifluoroacetamide with benzyl (pseudo)­halides was developed. Both methods proceed under mild conditions, and their symbiosis provides access to a wide range of novel CF₃-heterocycles

Multiscale analysis of vegetation surface fluxes : from seconds to years

The variability in land surface heat (H), water vapor (LE), and CO2 (or net ecosystem exchange, NEE) fluxes was investigated at scales ranging from fractions of seconds to years using eddy-covariance flux measurements above a pine forest. Because these fluxes significantly vary at all these time scales and because large gaps in the record are unavoidable in such experiments, standard Fourier expansion methods for computing the spectral and cospectral statistical properties were not possible. Instead, orthonormal wavelet transformations are proposed and used. The are ideal at resolving process variability with respect to both scale and time and are able to isolate and remove the effects of missing data (or gaps) from spectral and cospectral calculations. Using the spectra, we demonstrated unique aspects in three appropriate ranges of time scales: turbulent time scales (fractions of seconds to minutes), meteorological time scales (hour to weeks), and seasonal to interannual time scales corresponding to climate and vegetation dynamics. We have shown that: (1) existing turbulence theories describe the short time scales well, (2) coupled physiological and transport models (e.g. CANVEG) reproduce the wavelet spectral characteristics of all three land surface fluxes for meteorological time scales, and (3) seasonal dynamics in vegetation physiology and structure inject strong correlations between land surface fluxes and forcing variables at monthly to seasonal time scales. The broad implications of this study center on the possibility of developing low-dimensional models of land surface water, energy, and carbon exchange. If the bulk of the flux variability is dominated by a narrow band or bands of modes, and these modes “resonate” with key state and forcing variables, then low-dimensional models may relate these forcing and state variables to NEE and LE

Inferring scalar sources and sinks within canopies using forward and inverse methods

It is becoming clear that the description of water exchange over vegetated surfaces can benefit from a simultaneous consideration of heat and C02 exchanges, as all these exchange processes are intertwined at the most fundamental level. Over the last two decades, several approaches have been developed to infer scalar sources and sinks within canopies without resorting to gradient-diffusion theory. This study investigates recent developments in multi-layer methods to compute distributions and strengths of scalar sources and sinks within the canopy volume. Two types of model formulations are considered: 1) forward methods which require vertical foliage distribution along with canopy radiative, physiological, biochemical, and drag properties and 2) inverse methods which require measured mean scalar concentration distribution within the canopy. These approaches are able to reproduce measured turbulent fluxes above the canopy without relying on empirical relationship between turbulent scalar fluxes and mean concentration gradients. However, both approaches share the need for accurate description of the second moments of the velocity statistics inside the canopy

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.The aim of this study was to inform vaccination prioritization by modelling the impact of vaccination on elective inpatient surgery. The study found that patients aged at least 70 years needing elective surgery should be prioritized alongside other high-risk groups during early vaccination programmes. Once vaccines are rolled out to younger populations, prioritizing surgical patients is advantageous

Search for high-mass resonances decaying to a jet and a Lorentz-boosted resonance in proton-proton collisions at $\sqrt{s}=13\text{ }\text{ }\mathrm{TeV}

Physics letters / B 832, 137263 (2022). doi:10.1016/j.physletb.2022.137263 Published by North-Holland Publ., Amsterda