Photoactive materials enabled by and for emerging synthetic technologies

In recent years there has been a significant increase in the development and commercialisation of new synthetic tools and technologies, which offer significant advantages compared to traditional round-bottomed flask chemistry. This work explores the use of some of these emerging technologies with the goal of developing new photocatalytic processes, which would not otherwise be easily feasible with batch techniques. Specifically, we have used continuous flow chemistry, mechanochemistry, and 3D printing in four distinct research projects. This thesis is split into five chapters in total. Chapter 1 aims to act as a global introduction to the different synthetic technologies that were used and compare their utility and drawbacks against traditional batch synthetic methodologies. The remaining chapters 2-5 each represent a separate research project that utilises these new technologies. Each chapter contains its own introduction to the topic of research along with conclusions and proposed future work. Specifically, in Chapter 2, a rapid, high yielding, and work-up free synthesis of an unusual organic luminophore is developed. Its twisted, propeller-like geometry gives rise to much sought aggregation induced emission properties. Moreover, we were able to use this material as a reusable heterogeneous photosensitiser to produce singlet oxygen under continuous flow conditions. In Chapter 3, we report the unprecedented ring contraction of 1,2,6-thiadiazines to 1,2,5- thiadiazole 1-oxides. The transformation is fast, work-up free, offers quantitative yields, and is mediated by auto-photosensitised singlet oxygen. We exploited continuous flow processes to further improve the reaction scope and efficiency. Then, in Chapter 4 we describe the batch and mechanochemical syntheses of optically active dihydroxamic acids ligands, and their subsequent use for the synthesis of metalloorganic assemblies. Finally, Chapter 5 demonstrates how mechanochemical and 3D printing technologies were used to access a series of N-aryl amides from O-protected hydroxamic acids. The broad scope of this work aims to demonstrate the usefulness of alternative reactor designs in chemical synthesis and encourage their implementation by others

Mechanochemical Synthesis of N-Aryl Amides from O-Protected Hydroxamic Acids

Two robust and efficient mechanochemical protocols for the synthesis of an array of N-arylamides have been developed. This was achieved by a C-N cross-coupling between O-pivaloyl hydroxamic acids and aryl iodides or aryl boronic acids, in the presence of a stoichiometric amount of a copper mediator. The effectiveness of this method is highlighted by the high-yielding (up to 94%), scalable (up to 8 mmol), and rapid (20 minutes) synthesis of N-aryl amides (15 examples), using a variety of deactivated and sterically encumbered substrates, whilst employing mild conditions and in the absence of solvents. In addition, it was determined that whilst the O-pivaloyl hydroxamic acid precursors can be synthesised mechanochemically, iron contamination originating from the steel jars was found to occur which can hinder the efficacy of this process. Furthermore, 3D printing was used to produce custom milling jars that could successfully accommodate a scaled-up version of the two protocols

Ανάπτυξη συνθετικής μεθοδολογίας για τη σύνθεση Ν1-(β-D-γλυκοπυρανοζυλο)-Ν4-(2-αρυλο-1,3-διοξοϊσοινδολιν-5-υλο)κυτοσινών

Βασιζόμενοι σε προηγούμενες μελέτες, παρατηρείται ότι η ύπαρξη συμπυκνωμένου αρωματικού συστήματος που φέρει γέφυρα καρβονυλίου καθώς και αμιδική γέφυρα οδήγησε σε έναν από τους ισχυρότερους αναστολείς, για το καταλυτικό κέντρο, που έχει συντεθεί μέχρι σήμερα στο εργαστήριο μας την Ν1-(β-D-γλυκοπυρανοζυλο)-Ν4-(1,3-διοξοϊσοινδολιν-5-υλο)κυτοσίνη (ένωση 12). Επειδή άλλοι ισχυροί αναστολείς που έχουν συντεθεί στο εργαστήριό μας περιέχουν μια φαινυλομάδα στη θέση που βρίσκεται το άζωτο της ισοϊνδολινόνης, αποφασίσαμε να χρησιμοποιήσουμε την 12 ως ένωση οδηγό για τη σύνθεση 2-άρυλο- και 2-ετεροάρυλο- παραγώγων. Στην παρούσα εργασία έγιναν προσπάθειες σύνθεσης ενώσεων με τα παραπάνω χαρακτηριστικά. Χρησιμοποιήθηκαν αμίνες οι οποίες δεν ήταν εμπορικά διαθέσιμες, επομένως η σύνθεση επικεντρώθηκε στη σύνθεση των συγκεκριμένων αμινών. Ωστόσο, λόγω του ότι οι συγκεκριμένες αμίνες ήταν απενεργοποιημένες ως προς μια πυρηνόφιλη προσβολή (οι ομάδες –C=O, έλκουν ηλεκτρονιακή πυκνότητα) δεν κατέστη δυνατό το τελευταίο στάδιο της σύνθεσης. Επομένως αναζητήθηκαν νέες συνθετικοί οδοί οι οποίες και αναλύονται.Based on previous studies, it is noted that the existence of a condensed aromatic system carrying carbon bridge and amidic tower has led to one of the strongest inhibitors for the catalytic center, which has so far synthesized in our laboratory N1- (β-D-glucopyranosyl ) -N4- (1,3-dioxoisoindolin-5-yl) cytosine (compound 12). Because other potent inhibitors synthesized in our laboratory contain a phenyl group at the position of the isoindolinone isozyse, it has been decided to use 12 as a lead compound for the synthesis of 2-aryl- and 2-heteroaryl derivatives. In the present work efforts have been made to synthesize compounds having the above characteristics. Amines were used which were not commercially available, so the composition was focused on the synthesis of the particular amines. However, due to the fact that the specific amines were inactivated in relation to a nucleophilic attack (the -C = O groups, attract electron density), the last stage of synthesis was not possible. Therefore, new synthetic pathways have been sought and analyzed

Investigation of solid base catalysts for biodiesel production from fish oil

The authors would like to acknowledge Innovate UK for funding. Additionally, the authors would like to thank Dr Gavin Peters for the TGA and ICP-OES measurements. Finally, we would like to thank the Engineering and Physical Sciences Research Council, University of St Andrews, and CRITICAT Centre for Doctoral Training for financial support [Ph.D. studentship to M.D.V.T, S.G, and E. B; Grant code: EP/L016419/1].A series of composite CaO-Ca3Al2O6 mixed oxides were investigated as potential catalysts for biodiesel synthesis from waste fish oil. Different Ca/Al ratios, in the range of 1.5 to 6 were studied, alongside pure CaO. The catalysts were characterised by X-ray diffraction (XRD), scanning electron microscopy (SEM) and CO2-Temperature Program Desorption (TPD). The catalytic activity of the materials was studied for the transesterification reaction of cod liver oil with methanol at 65 °C, with 1:12 oil to methanol molar ratio and 10 wt% of catalyst. Over 97% conversion of the triglycerides to methyl esters was achieved for the 6Ca/Al catalyst after 2 h reaction time. This was similar to the performance of CaO. However, 6Ca/Al catalyst was reused successfully for seven consecutive tests, in contrast to CaO that was reused for only five tests, before it deactivated. Therefore, by incorporating the Ca3Al2O6, it was possible to enhance the stability of the catalytically active species and improve the lifetime of the catalyst. Post-test catalyst characterisation showed the formation of an intermediate phase (calcium diglyceroxide) that enhanced the catalyst’s performance and tolerance to air exposure and humidity. Finally, the catalyst deactivation, after seven cycles, took place due to the formation of Ca(OH)2 and CaCO3 species.PostprintPeer reviewe

The photochemical mediated ring contraction of 4H-1,2,6-thiadiazines to afford 1,2,5-thiadiazol-3(2H)-one 1-oxides

E.B. and C.G.T. are grateful to Heriot-Watt University and the EPSRC CRITICAT Centre for Doctoral Training (E.B. Ph.D. Studentship: EP/L016419/1, C.G.T Ph.D. Studentship: EP/LO14419/1) for funding and training. C.G.T. is grateful to the Heriot-Watt Annual Fund for financial support. P.A.K. and A.S.K. thank the University of Cyprus for the Internal Grant “Thiadiazine-Based Organic Photovoltaics”, and the Cyprus Research Promotion Foundation (Grant Nos. ΣΤΡΑΤΗΙΙ/0308/06, NEKYP/0308/02 ΥΓΕΙΑ/0506/19, and ΕΝΙΣΧ/0308/83). M.J.P. thanks the EPSRC for funding (Grant Nos. EP/T021675 and EP/V006746), and the Leverhulme Trust (Grant No. PG-2020-208). S.A.M. thanks the EPSRC for funding (Grant No. EP/T019867/1).1,2,6-Thiadiazines treated with visible light and 3O2 under ambient conditions are converted into difficult-to-access 1,2,5-thiadiazole 1-oxides (35 examples, yields of 39–100%). Experimental and theoretical studies reveal that 1,2,6-thiadiazines act as triplet photosensitizers that produce 1O2 and then undergo a chemoselective [3 + 2] cycloaddition to give an endoperoxide that ring contracts with selective carbon atom excision and complete atom economy. The reaction was optimized under both batch and continuous-flow conditions and is also efficient in green solvents.Publisher PDFPeer reviewe

8,8'-(Benzo[c][1,2,5]thiadiazole-4,7-diyl)bis(quinolin-4(1H)-one): A Twisted Photosensitizer with AIE Properties

A new benzothiadiazole (BTZ) luminogen is prepared via the Suzuki-Miyaura Pd-catalysed C-C cross-coupling of 8-iodoquinolin-4(1H)-one and a BTZ bispinacol boronic ester. The rapid reaction (5 min) affords the air-, thermo-, and photostable product in 97% yield as a yellow precipitate that can be isolated by filtration. The luminogen exhibits aggregated-induced emission (AIE) properties, which are attributed to its photoactive BTZ core and nonplanar geometry. It also behaves as a molecular heterogeneous photosensitizer for the production of singlet oxygen under continuous flow condition

Photochemical Ring Editing: Access to Privileged 1,2,5-Thiadiazole Scaffolds via Efficient Carbon Excision from Thiadiazines Under Ambient, Aerobic Conditions

Thiadiazoles are a privileged motif in medicinal chemistry, however selective mono-oxidation of the endocyclic sulfur, without over oxidation, is challenging. Herein, we report the quantitative conversion of 1,2,6-thiadiazines to 1,2,5-thiadiazole 1-oxides in the presence of visible light and molecular oxygen under ambient conditions. Experimental and computational studies reveal a probable mechanistic pathway for the cycloaddition-ring contraction cascade: under visible light irradiation in the presence of molecular oxygen, 1,2,6-thiadiazines act as triplet photosensitisers that produce singlet oxygen and subsequently undergo an unprecedented, chemoselective [3 + 2] cycloaddition reaction. The resulting endoperoxide undergoes a ring contraction, with selective carbon atom excision and complete atom economy. The reaction was optimised under both batch and continuous-flow conditions and proven to be efficient in wide range of solvents, including green solvents. Flow conditions enabled precise control over irradiance exposure, enabling exclusive access to photosensitive thiadiazole products. A comprehensive scope of 1,2,6-thiadiazines provided 35 examples of novel, difficult-to-access 1,2,5-thiadiazole 1-oxide structures

CCDC 2167996, 2167997, 2167999, 2168000, 2168147, 2168157, 2168187, 2168217–2168220, 2168224–2168226, 2168263–2168264, 2168266, 2168267, 2173994, and 2173995 : Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures