Extrusion - back to the future: using an established technique to reform automated chemical synthesis

YesHerein, the benefits which extrusion can provide for the automated continuous synthesis of organic compounds are highlighted. Extrusion is a well-established technique that has a vital role in the manufacturing processes of polymers, pharmaceuticals and food products. Furthermore, this technique has recently been applied to the solvent-free continuous synthesis of co-crystals and coordination compounds including metal-organic frameworks (MOFs). To date, a vast amount of research has already been conducted into reactive extrusion (REX), particularly in the polymer industry, which in many cases has involved organic transformations, however, it has not received significant recognition for this. This review highlights these transformations and discusses how this previous research can be applied to the future of organic compound manufacture.EPSRC (EP/L019655/1

The Saint of Llanbadrig: A Contested Dedication

Tomos Roberts (†) reviewed the later versions of this article more than once; 1 his advice related to Anglesey and Anglesey sources was invaluable. Graham Jones read and commented on earlier versions of the article, and his comments related to my doctoral research provided an indispensable, ongoing introduction to the study of saints ’ dedications. My initial research related to saints ’ dedications was presented at the “Geography and Saints Cults ” conference a

Continuous multi-step synthesis by extrusion - telescoping solvent-free reactions for greater efficiency

YesChemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous multi-component reaction (MCR), by twin screw extrusion (TSE), in the complete absence of solvent.EPSRC (EP/L019655/1)

Translating solid state organic synthesis from a mixer mill to a continuous twin screw extruder

YesA study on the translation of a solid-state synthetic reaction from a mechanochemical mixer-mill to a continuous twin-screw extruder is discussed herein. The study highlights some considerations to be made and parameters to be tested in the context of a model fluorination reaction, which is the first organic fluorination to be attempted using extrusion. Upon optimization, which features the first use of grinding auxiliary solids to enable effective synthetic extrusion, the difluorination reaction was successfully translated to the extruder, leading to a 100-fold improvement in Space Time Yield (STY); 29 kg m−3 day−1 in a mixer mill to 3395 kg m−3 day−1 in a twin screw extruder.D. L. B is grateful to the EPSRC for a First Grant (D. L. B. EP/P002951/1), CRD for a studentship award to J. L. H., Queen’s University Belfast for a Visiting Research Fellowship and the School of Chemistry at Cardiff University for generous support. S. L. J. is grateful to EPSRC for support (EP/L019655/1)

Gender and Patient Satisfaction with Primary Care: Tuning in to Women in Quality Measurement

This study analyzes the relationship between patient gender and satisfaction with primary care visits, using 1999 survey data on 1691 women and 760 men making primary care visits at multiple sites affiliated with a large academic health system designated as a National Center of Excellence in Women's Health (COE). The main findings are that in multivariate analyses controlling for patient and visit characteristics, different aspects of the content of primary care visits are important to women and men. Women's overall satisfaction with visits is more dependent than men's on informational content, continuity of care, and multidisciplinarity. Men's overall satisfaction is more dependent on the personal interest shown in them by providers. No differences in satisfaction are found between those seen in sites affiliated with the COE and other primary care sites within the health system that are not core sites of the COE. We conclude that quality improvement and research in women's primary care could benefit from gender analysis of patient satisfaction data and from more gender-sensitive patient satisfaction measures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63266/1/15246090050118189.pd

Greener dye synthesis: continuous, solvent-free synthesis of commodity perylene diimides by twin-screw extrusion

YesA continuous, scalable, and solvent‐free method for the synthesis of various naphthalic imides and perylene diimides (PDIs) using twin‐screw extrusion (TSE) is reported. Using TSE, naphthalic imides were obtained quantitatively without the need for excess amine reactant or product purification. With good functional‐group tolerance, alkyl and benzyl amine derived PDIs (incl. commercial dyes) were obtained in 50–99 % yield. Use of K2CO3, enabled synthesis of more difficult aniline‐derived PDIs. Furthermore, an automated continuous TSE process for Pigments Black 31 and 32 is demonstrated, with a throughput rate of about 1500 g day−1, corresponding to a space time yield of about 30×103 kg m−3 day−1, which is 1–2 orders of magnitude greater than for solvent‐based batch methods. These methods provide substantial waste reductions and improved efficiency compared to conventional solvent‐based methods.Engineering and Physical Sciences Research Council. Grant Numbers: EP/L019655/1, IAA1718-04-111

Making 2‐D Materials Mechanochemically by Twin‐Screw Extrusion:Continuous Exfoliation of Graphite to Multi‐Layered Graphene

Mechanochemistry has developed rapidly in recent years for efficient chemicals and materials synthesis. Twin screw extrusion (TSE) is a particularly promising technique in this regard because of its continuous and scalable nature. A key aspect of TSE is that it provides high shear and mixing. Because of the high shear, it potentially also offers a way to delaminate 2‐D materials. Indeed, the synthesis of 2‐D materials in a scalable and continuous manor remains a challenge in their industrialization. Here, as a proof‐of‐principle, the automated, continuous mechanochemical exfoliation of graphite to give multi‐layer graphene (MLG, ≈6 layers) by TSE is demonstrated. To achieve this, a solid‐and‐liquid‐assisted extrusion (SLAE) process is developed in which organic additives such as pyrene are rendered liquid due to the high temperatures used, to assist with the exfoliation, and simultaneously solid sodium chloride is used as a grinding aid. This gave MLG in high yield (25 wt%) with a short residence time (8 min) and notably with negligible evidence for structural deterioration (defects or oxidation)

Noria and its derivatives as hosts for chemically and thermally robust Type II porous liquids

Porous Liquids (PLs) are a new class of material that possess both fluidity and permanent porosity. As such they can act as enhanced, selective solvents and may ultimately find applications which are not possible for porous solids, such as continuous flow separation processes. Type II PLs consist of empty molecular hosts dissolved in size-excluded solvents and to date have mainly been based on hosts that have limited chemical and thermal stability. Here we identify Noria, a rigid cyclic oligomer as a new host for the synthesis of more robust Type II PLs. Although the structure of Noria is well-documented, we find that literature has overlooked the true composition of bulk Noria samples. We find that bulk samples typically consist of Noria (ca. 40%), a Noria isomer, specifically a resorcinarene trimer, “R3” (ca. 30%) and other unidentified oligomers (ca. 30%). Noria has been characterised crystallographically as a diethyl ether solvate and its 1H NMR spectrum fully assigned for the first time. The previously postulated but unreported R3 has also been characterised crystallographically as a dimethyl sulfoxide solvate, which confirms its alternative connectivity to Noria. Noria and R3 have low solubility which precludes their use in Type II PLs, however, the partially ethylated derivative Noria-OEt dissolves in the size-excluded solvent 15-crown-5 to give a new Type II PL. This PL exhibits enhanced uptake of methane (CH4) gas supporting the presence of empty pores in the liquid. Detailed molecular dynamics simulations support the existence of pores in the liquid and show that occupation of the pores by CH4 is favoured. Overall, this work revises the general accepted composition of bulk Noria samples and shows that Noria derivatives are appropriate for the synthesis of more robust Type II PLs

Mechanochemical synthesis of mononuclear gold(I) halide complexes of diphosphine ligands with tuneable luminescent properties

A mechanochemical method is reported for the synthesis of Au(diphos)X complexes of diphosphine (diphos = XantPhos and N-XantPhos) ligands and halide ions (X = Cl and I). The Au(XantPhos)X (1: X = Cl; 2: X = I) and Au(N-XantPhos)Cl (3) complexes exhibited either yellowish green (1) or bluish green (2) emission, whereas 3 was seemingly non-emissive in the solid state at room temperature. Blue- (2B) and bluish green (2G) luminescent concomitant solvates of 2 were obtained by recrystallization. Luminescent colour changes from blue (2B) or bluish green (2G) to yellow were observed when these forms were subjected to mechanical stimulus, while the original emission colour can be recovered in the presence of solvent vapours. Moreover, the luminescence of 2B can be reversibly altered between blue and yellow by heating/cooling-cycles. These results demonstrate the power of mechanochemistry in the rapid (4 min reaction time), efficient (up to 98% yield) and greener synthesis of luminescent and stimuli-responsive gold(I) complexes