Asymmetric hydroformylation (AHF)
of 2-vinyl-6-methoxynaphthalene
demonstrates important design characteristics of a vertical pipes-in-series
plug flow reactor (PFR). The regio- and enantioselectivity of the
AHF reaction provide a chemical probe of gas–liquid mixing
in a flow reactor for comparison with well-stirred batch reactors.
Results obtained with the flow reactor compare favorably to those
obtained in batch. Thus, AHF provides an efficient, in-flow enantioselective
synthesis of (S)-Naproxen.
A research scale continuous reactor system was designed and developed for high pressure asymmetric hydroformylation (AHF) reactions with an 8 h reaction time. The continuous reactor achieved high k L a, low axial dispersion, and an 8 mL liquid holdup volume. The reactor consisted of 20 vertical bubble flow pipes-in-series, connected by small diameter tubing jumpers. This type of continuous reactor is proven to be scalable up to 360 L in our GMP pharmaceutical manufacturing plant for high pressure hydrogenation. The continuous reactor was used for the AHF of styrene and 2-vinyl-6methoxynaphthalene catalyzed by rhodium(bisdiazaphospholane) (BDP) complexes. The CSTRs-in-series numerical model fit the experimental data better than the plug flow with dispersion model. Samples were taken along the length of the continuous reactor and used for kinetic data modeling. Vapor liquid mass transfer rate constants were about 3 orders of magnitude higher than reaction rate constants.
Aim
Emotional stress reactivity may be a mediating factor in the association between trauma and psychosis. This review aimed to (i) identify, summarise and critically evaluate the link between emotional stress reactivity and psychotic experiences (ii) examine evidence for a 'dose–response' relationship between stress reactivity and psychosis in the wider psychosis phenotype (i.e., sub‐clinical symptoms).
Methods
Electronic database searches (PsychINFO, MEDLINE, EMBASE) were conducted for studies which investigated the link between stress reactivity and psychosis, psychotic symptoms, or a vulnerability to developing psychosis (wider phenotype). Cross‐sectional, experimental and experience sampling method study designs were eligible for inclusion.
Results
Fourty five eligible articles were identified (N participants = 8830). Narrative synthesis showed that increased emotional stress reactivity was associated with psychosis and subclinical psychotic experiences across all study designs, however, findings were inconsistent across studies. The preliminary meta‐analysis (k = 4, n = 383) showed increases in emotional stress reactivity was associated with higher negative affect in response to event‐related stress, in those with psychosis compared to controls (mean difference in beta coefficients = 0.05, 95% CI 0.02–0.08, p = .004). However, this difference was small with a considerable degree of heterogeneity (p = .001, I2 = 81%) so results should be interpreted with caution.
Conclusions
Overall, the evidence suggests that there is a link between emotional stress reactivity and psychosis in those with psychosis, those at high risk of developing psychosis and in relation to subclinical psychotic‐like experiences in the general population.
An optimized route to enantiopure tetra-carboxylic acid and tetra-carboxamide bis(diazaphospholane) ligands that obviates chromatographic purification is presented. This synthesis, which is demonstrated on 15 and 100 g scales, features a scalable classical resolution of tetra-carboxylic acid enantiomers with recycling of the resolving agent. When paired with a rhodium metal center, these bis(diazaphospholane) ligands are highly active and selective in asymmetric hydroformylation applications.
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