The addition of a second metal has demonstrated various improvements such as stabilizing Au active species by preventing reduction of Au (I) or Au (III), [3][4][5][6][7] increasing electron density of active species, and thereby promoting chemisorption of HCl which inhibits reduction of the gold, [8][9][10][11] promoting a higher dispersion of the gold, [12,13] and decreasing the formation of nanoparticles by agglomeration. [14] However, the addition of another metal can also incur drawbacks such as lower selectivity, which can lead to coke deposition and rapid deactivation of the catalyst, [13] short lifetime of the catalyst, [3,15] or the requirement of high loadings of the second metal to achieve comparable results to the gold monometallic. [5,13,16] In addition to these issues, a secondary metal may also lead to complications with precious metal recovery from spent catalysts. [17,18] Therefore non-metallic promoters are an interesting alternative for enhancing the activity and stability of gold catalysts for acetylene hydrochlorination. Zhang et al. investigated the modification of gold catalysts with nitrogen, phosphorous, and oxygen containing ligands. The authors concluded that coordination with these heteroatoms stabilized cationic gold species due to increased electron density around the active species. This also promoted a higher surface concentration of HCl compared with acetylene which facilities the hydrochlorination The formation of highly active and stable acetylene hydrochlorination catalysts is of great industrial importance. The successful replacement of the highly toxic mercuric chloride catalyst with gold has led to a flurry of research in this area. One key aspect, which led to the commercialization of the gold catalyst is the use of thiosulphate as a stabilizing ligand. This study investigates the use of a range of sulfur containing compounds as promoters for production of highly active Au/C catalysts. Promotion is observed across a range of metal sulfates, non-metal sulfates, and sulfuric acid treatments. This observed enhancement can be optimized by careful consideration of either pre-or post-treatments, concentration of dopants used, and modification of washing steps. Pre-treatment of the carbon support with sulfuric acid (0.76 m) resulted in the most active Au/C in this series with an acetylene conversion of ≈70% at 200 °C.

New small ring derivatives can provide valuable motifs in new chemical space for drug design. 3-Aryl-3-sulfanyl azetidines are synthesized directly from azetidine-3-ols in excellent yield by a mild Fe-catalyzed thiol alkylation. A broad range of thiols and azetidinols bearing electron donating aromatics are successful, proceeding via an azetidine carbocation. The N-Cbz group is a requirement for good reactivity, and enables the NH-azetidine to be revealed. Further reactions of the azetidine sulfides demonstrate their potential for incorporation in drug discovery programs. New chemical motifs with appropriate physicochemical properties offer valuable opportunities in drug design. 1,2 As a result, there has been significant recent attention on the synthesis of new modules that may be readily incorporated in medicinal chemistry, as fragments, building blocks or isosteres. 3 Small heterocyclic rings are attractive in this context due to low molecular weight and defined exit vectors. 4,5 Small rings readily access new chemical and IP space, particularly when combined with medicinally relevant substituents, which is partly due to their limited synthetic accessibility preventing their investigation. Sulfur functional groups are prevalent in pharmaceuticals and agrochemicals, 6 with thioethers being important in their own right and as intermediates to access sulfoxide, sulfone and sulfoximine moieties. There are examples of azetidine thioethers in biologically active compounds in the literature with the majority 3-monosubstituted, including compounds having RBP4-lowering activity and antibacterial activity (Figure 1A). 7,8 3,3-Disubstituted azetidine sulfides, without additional C2 or C4 1 2a 5 a Isolated yields quoted. Alternative 3-aryl-azetidin-3-ol substrates (3-8) were prepared by the addition of Grignard reagents to commercially available N-Cbz azetidine-3-one (Scheme 2). 16 Preinstalled benzyl-and TIPS-protected phenols were tolerated under the reaction conditions producing 9 and 10 in excellent yield. Increasing the steric demands of the azetidinol with ortho-substituted aromatics gave azetidine 11 in 92% yield. Benzodioxole and trimethoxybenzene azetidinols reacted similarly well giving products 12 to 14 in good yield using benzylic, aryl or alkyl thiols respectively as nucleophiles. Importantly, indole containing sulfanylazetidine 15 was formed in 97% yield. As such, a range of 3-sulfanyl azetidines can be readily prepared with appealing functionalities of interest to medicinal chemists, varying both the thiol and preinstalled aryl group. 3-Phenylazetidin-3-ol returned starting material, even increasing the temperature to 80 °C, indicating the need for electron-rich aromatics to stabilize the postulated azetidine carbocation intermediate. The reaction could be extended to the 5 and 6-membered N-heterocycles giving piperidine 16 and pyrrolidine 17 in 95% and 93% yield respectively using benzylmercaptan. 6 Scheme 2. Scope of azetidinols. a a Isolated yields quoted. The derivatization of various 3-sulfanyl azetidi...

gem‐Diarylheterocycles display a wide range of biological activity. Here we present a systematic study into the formation of 4‐ to 6‐membered O‐ and N‐heterocycles and cyclobutanes bearing the diaryl motif through a catalytic Friedel–Crafts reaction from the corresponding benzylic alcohols. 3,3‐Diaryltetrahydrofurans, 4,4‐diaryltetrahydropyrans, 3,3‐diarylpyrrolidines, 4,4‐diaryl‐piperidines, as well as diarylcyclobutanes are examined, with results for 3,3‐diaryloxetanes and 3,3‐diarylazetidines presented for comparison. Three catalytic systems are investigated for each substrate [Ca(II), Li(I) and Fe(III)], across preinstalled aromatic groups of differing electronic character. In most cases examined, the diaryl product is obtained directly from the alcohol with good yields using the most appropriate catalyst system. In the absence of a nucleophile, the olefins from the 5‐ and 6‐membered substrates by elimination of water are obtained under the same reaction conditions.

Heterogeneous catalysis is immensely important, providing access to materials essential for the well-being of society and improved catalysts are continuously required. New catalysts are frequently tested under different conditions making it difficult to determine the best catalyst.Here we describe a general approach to identify the best catalyst using a data set based on all reactions under kinetic control to calculate a set of key performance indicators (KPIs). These KPIs are normalised to take into account the variation in reaction conditions. Plots of the normalised KPIs are then used to demonstrate the best catalyst using two case studies: (i) acetylene hydrochlorination, a reaction of current interest for vinyl chloride manufacture and (ii) the selective oxidation of methane to methanol using O2 in water; a reaction that has attracted very recent attention in the academic literature.

The commercialization of gold for acetylene hydrochlorination represents a major scientific landmark. The development of second-generation gold catalysts continues with a focus on derivatives and drop-in replacements with higher activity and stability. Here, we show the influence that the support surface oxygen has on the activity of carbon supported gold catalysts. Variation in the surface oxygen content of carbon is achieved through careful modification of the Hummers chemical oxidation method prior to the deposition of gold. All oxidized carbon-based catalysts resulted in a marked increase in activity at 200 °C when compared to the standard nontreated carbon, with an optimum oxygen content of ca. 18 at % being observed. Increasing oxygen and relative concentration of C–O functionality yields catalysts with light-off temperatures 30–50 °C below the standard catalyst. This understanding opens a promising avenue to produce high activity acetylene hydrochlorination catalysts that can operate at lower temperatures.