Authors:Sravanthi Chada, Devender Mandala and Paul Watts
A key reaction in one of the routes to efavirenz, an essential drug used in the treatment of acquired immunodeficiency syndrome (AIDS), is the ortho-lithiation reaction of N-Boc-4-chloroaniline. For the first time, we demonstrate that the reaction may be conducted using n-BuLi and show that the reaction may be performed in a flow reactor with a significantly higher yield (70%) compared to batch (28%) when using n-BuLi for the ortho-metalation reaction at a temperature of −45 °C. In addition, it was shown that tetramethylethylenediamine (TMEDA) did not need to be added to the flow reaction, which simplified the purification procedure.
Authors:Paul Watts, Giancarlo Pascali and Piero A. Salvadori
Positron emission tomography (PET) is a very powerful diagnostic technique routinely used in a variety of medical applications. This review article summarises the developments of using microreactor technology for the radiochemical synthesis of PETagents. The advantages of manufacturing these imaging drugs using microreactors are described, and a review of reactions conducted to date is outlined.
Herein, we illustrate how microreactor technology can be used as a tool for reaction screening and optimization, in addition to improving the reaction chemistry. We report the in-situ generation of azo compounds by reactive quenching of diazonium intermediates in microreactors. This involves an electrophilic aromatic substitution reaction, namely, an azo-coupling reaction performed in continuous-flow systems in the presence of a phase transfer catalyst with great emphasis on compounds that do not easily couple. Capitalizing on the benefits of a large surface area and the short molecular diffusion distances observed in microreactors, in-situ phase transfer catalyzed azo-coupling reaction of diphenylamine to p-nitroaniline was investigated. A rapid and easy optimization protocol was established which yielded a 99%, 22%, and 33% conversion of diphenylamine, carbazole, and triphenylamine, respectively, in approximately 2.4 min.
In this perspective article, the use of continuous flow synthesis to prepare advanced pharmaceutical intermediates in developing economies is highlighted. Case studies are presented to suggest that cost effective local manufacture of life saving drugs, may potentially be implemented to facilitate better access to drugs to the underprivileged.
Authors:Matthew Simmons, Charlotte Wiles, Vincent Rocher, M. Grazia Francesconi and Paul Watts
The preparation of magnetic iron oxide nanoparticles within microreactors is reported. The proportion of γ-Fe2O3 and Fe3O4 in the sample was determined, an important parameter for reproducibility in applications.
Authors:Andrew Watt, Deiniol Skillicorn, Jediah Clark, Rachel Evans, Paul Hewlett and Nick Perham
Heterosexual men and women differ in their sensitivity to cues indicating material status. This dissociation has been explained by appealing to sexual selection processes that encourage women to evaluate men on the basis of their material status but could perhaps be explained by sex differences in contextual attention, or, associative representations.
In Experiment 1, heterosexual women rated the attractiveness of an opposite sex model in 4 conditions; (1) attractive context, (2) attractive context with implied ownership, (3) unattractive context, and (4) unattractive context with ownership implied. A second experiment used a fictitious stockbroker learning task (with both men and women) in 2 biconditional discriminations to measure contextual attention (stage 1) and then to explore the structure of contextual representation (stage 2) using a transfer of occasion setting test.
In Experiment 1, females increased ratings in attractive contexts, both when context ownership was implied and when it was not. In the first stage of Experiment 2, men and women were equally sensitive to contextual cues. In stage 2, women’s learning was impaired when a stimulus previously used as a target was employed as a context (they showed transfer of occasions setting), men showed no such difference.
Sex differences in sensitivity to cues indicating material status may reflect how men and women tend to encode the relationships between background/context stimuli and target stimuli. Women automatically attend to the background and modulate the value of targets using a hierarchical form of representation, whilst men represent background-target associations configurally.