2-Unsubstituted Imidazole N-Oxides as Novel Precursors of Chiral 3-Alkoxyimidazol-2-ylidenes Derived from trans-1,2-Diaminocyclohexane and Other Chiral Amino Compounds

‘Desymmetrization’ of trans-1,2-diaminocyclohexane by treatment with α,ω-dihalogenated alkylation reagents leads to mono-NH2 derivatives (‘primary-tertiary diamines’). Upon reaction with formaldehyde, these products formed monomeric formaldimines. Subsequently, reactions of the formaldimines with α-hydroxyiminoketones led to the corresponding 2-unsubstituted imidazole N-oxide derivatives, which were used here as new substrates for the in situ generation of chiral imidazol-2-ylidenes. Upon O-selective benzylation, new chiral imidazolium salts were obtained, which were deprotonated by treatment with triethylamine in the presence of elemental sulfur. Under these conditions, the intermediate imidazol-2-ylidenes were trapped by elemental sulfur, yielding the corresponding chiral non-enolizable imidazole-2-thiones in good yields. Analogous reaction sequences, starting with imidazole N-oxides derived from enantiopure primary amines, amino alcohols, and amino acids, leading to the corresponding 3-alkoxyimidazole-2-thiones were also studied

Boundary condition and fuel composition effects on injection processes of high-pressure sprays at the microscopic level

Detailed imaging of n-dodecane and ethanol sprays injected in a constant-flow, high-pressure, high-temperature optically accessible chamber was per-formed. High-speed, diffused back-illuminated long-distance microscopy was used to resolve the spray structure in the near-nozzle field. The effect of injection and ambient pressures, as well as fuel temperature and composition have been studied through measurements of the spray penetration rates, hydraulic delays and spreading angles. Additional information such as transient flow velocities have been extracted from the measurements and compared to a control-volume spray model. The analysis demonstrated the influence of outlet flow on spray development with lower penetration velocities and wider spreading angles during the transients (start and end of injection) than during the quasi-steady period of the injection. The effect of fuel com-position on penetration was limited, while spreading angle measurements showed wider sprays for ethanol. In contrast, varying fuel temperature led to varying penetration velocities, while spreading angle remained constant during the quasi-steady period of the injection. Fuel temperature affected injector performance, with shorter delays as fuel temperature was increased. The comparisons between predicted and measured penetration rates showed differences suggesting that the transient behavior of the spreading angle of the sprays modified spray development significantly in the near-field. The reasonable agreement between predicted and measured flow velocity at and after the end of injection suggested that the complete mixing assumptions made by the model were valid in the near nozzle region during this period, when injected flow velocities are reduced.The authors wish to thank Chris Carlen from Sandia National Laboratories for designing and manufacturing specific ultra-fast LEDs, as well as Jose Enrique del Rey and Juan Pablo Viera from CMT-Motores Termicos for their support during the experiments. Support for the research carried out by Julien Manin at CMT-Motores Termicos was provided by the U.S. Department of Energy, Office of Vehicle Technologies. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed Martin Company for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.Manin, J.; Bardi, M.; Pickett, LM.; Payri Marín, R. (2016). Boundary condition and fuel composition effects on injection processes of high-pressure sprays at the microscopic level. International Journal of Multiphase Flow. 83:267-278. https://doi.org/10.1016/j.ijmultiphaseflow.2015.12.001S2672788

Frequency, course and correlates of alcohol use from adolescence to young adulthood in a Swiss community survey

BACKGROUND: Few studies have analyzed the frequency of alcohol use across time from adolescence to young adulthood and its outcome in young adulthood. A Swiss longitudinal multilevel assessment project using various measures of psychopathology and psychosocial variables allowed for the study of the frequency and correlates of alcohol use so that this developmental trajectory may be better understood. METHOD: Alcohol use was studied by a questionnaire in a cohort of N = 593 subjects who had been assessed at three times between adolescence and young adulthood within the Zurich Psychology and Psychopathology Study (ZAPPS). Other assessment included questionnaire data measuring emotional and behavioural problems, life events, coping style, self-related cognitions, perceived parenting style and school environment, and size and efficiency of the social network. RESULTS: The increase of alcohol use from early adolescence to young adulthood showed only a few sex-specific differences in terms of the amount of alcohol consumption and the motives to drink. In late adolescence and young adulthood, males had a higher amount of alcohol consumption and were more frequently looking for drunkenness and feeling high. Males also experienced more negative consequences of alcohol use. A subgroup of heavy or problem drinkers showed a large range of emotional and behavioural problems and further indicators of impaired psychosocial functioning both in late adolescence and young adulthood. CONCLUSION: This Swiss community survey documents that alcohol use is problematic in a sizeable proportion of youth and goes hand in hand with a large number of psychosocial problems

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Reactions of (1,3,3-Trichloro-2,2,4,4-tetramethylcyclobutyl)sulfenyl Chloride with Some S- and O-Nucleophiles

The sterically crowded 3,3-trichloro-2,2,4,4-tetramethylcyclobutanethione (2c) easily reacts with phosphorus pentachloride in CCl4 yielding the relatively stable (1,3,3-trichloro-2,2,4,4-tetramethylcyclobutyl)sulfenyl chloride (3c). The reactions of 3c with benzylsulfane (4) and thiocamphor (5) occur with elimination of HCl leading to the unsymmetrical disulfanes 6 and 9. In the case of the sulfenates 10 and 12, which are formed as intermediates in the reactions of 3c with propargyl and allyl alcohol, respectively, the subsequent [2,3]-sigmatropic rearrangement yields the corresponding sulfoxides 11 and 13

3-(Dimethylamino)-5,6,7,8,9,10-hexahydro- 12,13-dimethoxy-4H-spiro[benzo-1-thia-2,5-diazacyclododecene-4,1'-cyclobutan]-6-one 1,1-Dioxide Dichloromethane Solvate (1/1) at 173K

The 12-membered ring in the title compound, C20H29N3O5S.CH2Cl2, has conformational disorder with the two C atoms adjacent to the fused benzene ring each occupying two sites. The major conformer is present in 74.3(8)% of the molecules. The formal N2=C bond in the 12-membered ring and the adjacent C-N bond of the dimethylamino substituent have almost identical lengths, indicative of the electron donor character of the dimethylamino group. The amide group has the trans conformation and forms an intramolecular hydrogen bond with one of the sulfonyl O atoms. The solvent molecule forms C-H...O hydrogen bonds with the organic substrate. This novel heterocycle has been formed by a ring enlargement reaction of the corresponding nine-membered 1,2-benzothiazonin-3-one 1,1-dioxide and 2-(dimethylamino)-1-azaspiro[2.3]hex-1-ene

Preparation and Structure of Optically Active Imidazolium Tetrafluoroborates; in Search of New Chiral Liquids

Enantiomerically pure (R)-1-(1-phenylethyl)imidazoles 4a,b can be prepared conveniently from alpha-(hydroxyimino)ketones 1, (R)-1-phenylethylamine and formaldehyde, followed by deoxygenation with Raney-Ni. Similarly, the reaction with (R,R)-trans-cyclohexane-1,2-diamine yields enantiomerically pure (R,R)-trans-1,1'-cyclohexane-1,2-diyl)imidazoles 4c,d. Alkylation of these imidazole derivatives with alkylbromides leads to the corresponding 3-alkylimidazolium bromides 6 and 8, respectively, which on treatment with sodium tetrafluoroborate are transformed into the corresponding tetrafluoroborates 7 and 9. Whereas some of the imidazolium salts 7 show properties of chiral ionic liquids, the bis-imidazolium tetrafluoroborates 9 are high-melting crystalline materials

2,3,4,5,6,7-Hexahydro-9,10-dimethoxy-l,2-benzothiazonin-3-one 1,1-dioxide

The amide group in the nine-membered ring of the title compound, C13H17NO5S, has the trans conformation. The molecules are linked into infinite one-dimensional chains by bifurcated intermolecular N-H...O hydrogen bonds involving the amide O atom and one of the sulfonyl O atoms of the same neigh- bouring molecule. The compound was prepared by the Friedel-Crafts acylation of 1,2-dimethoxybenzene and glutaric acid anhydride, followed by reduction of the aryl ketone, esterification, chlorosulfonation, treatment with ammonia, saponification and cyclization of the corresponding 5-(2-sulfamoylphenyl)butanoic acid