Review
Chemistry, Organic
Merlin Kleoff, Paul Kiler, Philipp Heretsch
Summary: This review provides an overview of selected methods for synthesizing odorants utilizing continuous flow technology, categorizing them by main odor families. The importance and application of odorants in perfumery are briefly discussed.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Jacek J. Walkowiak, Casper van Duijnhoven, Pia Boeschen, Nadja A. Wolter, Joanna Michalska-Walkowiak, Martin Dulle, Andrij Pich
Summary: Raspberry-like poly(oligoethylene methacrylate-b-N-vinylcaprolactam)/polystyrene (POEGMA-b-PVCL/PS) patchy particles (PPs) and complex colloidal particle clusters (CCPCs) were successfully fabricated using a two-step or one-step cascade flow process. The internal structure and surface morphology of the particles were studied under different polymerization conditions. The use of a tubular flow reactor for photo-initiated reversible addition-fragmentation transfer precipitation polymerization (Photo-RPP) provided advantages over heat dissipation and homogeneous light distribution.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Article
Chemistry, Applied
Peter Sagmeister, Dainis Kaldre, Joerg Sedelmeier, Christian Moessner, Kurt Puntener, Dominique Kummli, Jason D. Williams, C. Oliver Kappe
Summary: Continuous flow processing is an effective method for the formation of 1,5-tetrazoles, achieving high yields with high concentration and short residence time. Two orthogonal PAT methods, NMR and FTIR, were utilized for real-time quantification of starting materials and products, facilitating successful technology transfer and process optimization.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Chemistry, Multidisciplinary
Peter Sagmeister, Rene Lebl, Ismael Castillo, Jakob Rehrl, Julia Kruisz, Martin Sipek, Martin Horn, Stephan Sacher, David Cantillo, Jason D. Williams, C. Oliver Kappe
Summary: The study integrates four complementary process analytical technology tools in the multistep synthesis of the active pharmaceutical ingredient mesalazine, and develops advanced data analysis models to quantify desired products, intermediates, and impurities in real time. The system's capabilities have been demonstrated through steady state and dynamic experiments, representing a significant advancement in data-driven continuous flow synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Bruno Cerra, Francesco Venturoni, Maria Souma, Giada Ceccarelli, Anna Maria Lozza, Daniela Passeri, Francesca De Franco, Ian R. Baxendale, Roberto Pellicciari, Antonio Macchiarulo, Antimo Gioiello
Summary: In this report, we describe our synthetic efforts in supporting the development of bile alcohol sulfate INT-767. We have successfully developed a large-scale preparation route and synthesized analogues. Through key reactions and the use of flow technology, we have overcome critical bottlenecks. The final synthetic route can be used to produce the desired amount of INT-767, and potential metabolites have been synthesized and evaluated.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Agricultural Engineering
Xue-Qi Wang, Zhe-Hui Zhang, Xiaohong Ren, Zeming Rong, Zhuohua Sun, Tong-Qi Yuan
Summary: Recent achievements in lignin depolymerization have provided various platform chemicals and the potential for upgrading to high-end products. This study proposes an environmentally friendly synthesis route for the production of an alternative to an important fragrance ingredient.
INDUSTRIAL CROPS AND PRODUCTS
(2022)
Review
Chemistry, Organic
Olivier R. P. David, Franco Doro
Summary: This article reviews major breakthroughs in the field of perfumery, including fragrance ingredients, technological advances in scent delivery, and consumer product innovations. The innovations are presented chronologically, covering a span of 150 years. The article provides a historical overview of the impact of scientific and technological advancements in fragrance chemistry on consumer goods, while honoring pioneering chemists.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Applied
Peter Sagmeister, Michael Prieschl, Dainis Kaldre, Chethana Gadiyar, Christian Moessner, Joerg Sedelmeier, Jason D. Williams, C. Oliver Kappe
Summary: We used continuous flow processing to synthesize a cannabinoid receptor type 2 agonist, RG7774, by performing the first two steps of a new route. The formation of alkyl azide and the subsequent [3 + 2] cycloaddition were successfully achieved using flow processing. Different flow reactor setups were examined, and the use of CSTRs improved the mass intensity and productivity of the reaction. The developed kinetic models were also utilized for the proposed scale-up setup of a combined PFR + CSTR cascade for pilot-scale production of the desired triazole product.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Chemistry, Multidisciplinary
Adam D. Clayton, Edward O. Pyzer-Knapp, Mark Purdie, Martin F. Jones, Alexandre Barthelme, John Pavey, Nikil Kapur, Thomas W. Chamberlain, A. John Blacker, Richard A. Bourne
Summary: The optimization of multistep chemical syntheses is crucial for rapid development of new pharmaceuticals. A continuous flow platform was developed to automate the optimization of telescoped reactions. By integrating Bayesian optimization techniques, an 81% overall yield was achieved in just 14 hours, and a favorable competing pathway for the desired product was identified.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Xabier Lopez de Pariza, Tim Erdmann, Pedro L. Arrechea, Leron Perez, Charles Dausse, Nathaniel H. Park, James L. Hedrick, Haritz Sardon
Summary: Conducting polymerizations under continuous-flow conditions has advantages over batch experimentation, especially in the synthesis of polyurethanes, allowing for rapid and precise control over material properties and improving process monitoring and control to minimize batch-to-batch variations.
CHEMISTRY OF MATERIALS
(2021)
Article
Chemistry, Organic
Rui Li, Kai Wei, Wen Chen, Liang Li, Hongbin Zhang
Summary: A new process for the construction of 3,4,5-substituted isothiazoles is reported in this paper, utilizing reaction cascades including Pummerer-like rearrangement, nucleophilic condensation, and sulfenamide cyclization under mild conditions. This process provides good to excellent yields of isothiazoles bearing fluorine and other functional groups from readily available starting materials.
Article
Chemistry, Applied
Jorge Garcia-Lacuna, Marcus Baumann
Summary: A new photochemical flow process is reported for the generation of benzyne precursors and their subsequent conversion into heterocyclic targets. This process allows for high yields, throughput, and easy isolation of multigram quantities of products. Furthermore, the functionalization of a pendent carboxyl group highlights the potential applications of these triazine entities. Evaluation: 8/10.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Engineering, Chemical
Wei He, Congcong Zhang, Wenyan Zhang, Yuchen Zhu, Zheng Fang, Lili Zhao, Kai Guo
Summary: The synthesis of 5-hydroxymethyl-2-furancarboxylic acid directly from fructose was achieved by integrating catalyst design and process intensification. Novel bifunctional catalysts and supported catalysts were developed for the dehydration and oxidation steps, respectively. The study also elucidated the effects of solvent adjustment, structural optimization, support composition, and computational modeling on the catalytic performance and mechanism.
CHEMICAL ENGINEERING SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Davide Moi, Maria Chiara Cabua, Viktoria Velichko, Andrea Cocco, Annalisa Chiappone, Rita Mocci, Stefania Porcu, Monica Piras, Stefano Bianco, Fabio Pesciaioli, Francesco Secci
Summary: A straightforward continuous-flow method for the synthesis of cyclopropyl carbaldehydes and ketones has been developed using 2-hydroxycyclobutanones and aryl thiols. Under mild conditions, multigram quantities of cyclopropyl adducts can be easily obtained with the aid of acid-catalysis and reusable Amberlyst-35 as a catalyst. The physical-chemical properties of the packed bed and the continuous-flow system were characterized in detail through various analyses.
Article
Polymer Science
Katia Bacha, Julien Estager, Sylvie Brassart-Pasco, Catherine Chemotti, Antony E. Fernandes, Jean-Pierre Mbakidi, Magali Deleu, Sandrine Bouquillon
Summary: New dendrimers were synthesized from PPI and PAMAM dendrimers using an efficient acid-base reaction with various phenolic acids, and the syntheses were optimized in both microwave and microfluidic reactors. These dendrimers, which are ionic and hydrophilic, exhibited excellent antioxidant properties and showed cytotoxic effects on fibroblast dermal cells.
Article
Chemistry, Organic
Michele Ruggeri, Amanda W. Dombrowski, Stevan W. Djuric, Ian R. Baxendale
JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Guido Gambacorta, David C. Apperley, Ian R. Baxendale
Article
Chemistry, Multidisciplinary
Christoph Suster, Ian R. Baxendale, Marko D. Mihovilovic, Christian Stanetty
FRONTIERS IN CHEMISTRY
(2020)
Article
Chemistry, Applied
Guido Gambacorta, Ian R. Baxendale
Summary: In this study, a continuous-flow preparation of 2-benzoxazolinone via the Hofmann rearrangement of salicylamide using trichloroisocyanuric acid as the chlorinating agent was implemented. The system was optimized to avoid solid accumulation and enable the production of large quantities of pure desired material. Additionally, a TCCA-based chlorination of 2-benzoxazolone to the corresponding 5-chloro derivative was carried out under batch conditions.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Biochemical Research Methods
Tunca Dogan, Ece Akhan Guzelcan, Marcus Baumann, Altay Koyas, Heval Atas, Ian Baxendale, Maria Martin, Rengul Cetin-Atalay
Summary: DRUIDom is a new method that identifies bio-interactions between drug candidate compounds and targets by utilizing the domain modularity of proteins, thereby overcoming problems associated with current approaches.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Chemistry, Organic
Ben M. J. Lancaster, Alexander J. Nicholls, Ian R. Baxendale
Summary: This communication describes an unprecedented substitution cascade, in which 4-methylpyridine acts as a carbon nucleophile in an unusual SNAr process to form a novel triarylmethane structure. The proposed mechanism is supported by single crystal X-ray analysis, highlighting the efficient synthesis of complex triarylmethane architectures with both substituted phenyl and pyridyl aromatics in a single step.
Article
Chemistry, Organic
Alexander J. Nicholls, Ian R. Baxendale
Summary: This short note describes the synthesis of an amorphous benzo[1,2,3]dithiazole chloride salt, commonly known as Herz salt, using the Herz reaction. The conversions of this species to various useful adducts in medicinal and materials chemistry have been well established, but isolation examples in the literature and characterization data are limited. For the first time, this study provides mass spectrometry data for this compound and proposes a new mechanism of its formation based on new experimental observations and data.
Article
Materials Science, Multidisciplinary
Te Hu, Ian R. Baxendale, Yuchang Su, Fangjiang Li, Shaomi Duan, Yaping Zhang, Honxin Fan
Summary: Combining XRD pattern analysis with DSC curves and thermodynamic equations can optimize the preparation conditions of nanomaterials and improve the speed of the preparation scheme.
APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING
(2022)
Article
Chemistry, Organic
James S. Sharley, Guido Gambacorta, Ana Maria Collado Perez, Estela Espinos Ferri, Amadeo Fernandez Miranda, Jorge Sanchez Quesada, Ian R. Baxendale
Summary: In this study, a process for the synthesis of cyclic allylic nitro compounds using greener solvent and lower cost, more robust catalyst was developed. The optimized conditions were able to selectively synthesize important fragrance intermediates such as alpha-dehydroherbac, demonstrating their scope and utility.
Article
Chemistry, Organic
James S. Sharley, Guido Gambacorta, Ana Maria Collado Perez, Estela Espinos Ferri, Amadeo Fernandez Miranda, Isabelle Fernandez Fernandez, Jorge Sanchez Quesada, Ian R. Baxendale
Summary: A new method for the oxidation of Hedione 1 to dehydrohedione 2 has been developed based on a one-pot alpha-chlorination-elimination sequence, which allows for easy scalability. The unprecedented spontaneous elimination of alpha-chloro in methanol enables the oxidation to be carried out as a one-pot protocol, eliminating the need for multiple steps/reactions. A continuous flow process utilizing sulfuryl chloride has also been demonstrated, providing a steady and safe evolution of SO2 gas during the reaction.
Article
Multidisciplinary Sciences
James S. Sharley, Guido Gambacorta, Ana Maria Collado Perez, Estela Espinos Ferri, Amadeo Fernandez Miranda, Jorge Sanchez Quesada, Ian R. Baxendale
Summary: This article presents a dataset of spectroscopic analysis performed on starting materials, intermediates, and products related to the synthesis of Hedione. The data was collected at Durham university between October 2020 and September 2021 for the development of a preparative method to Dehydrohedione. The proton, Carbon-13, and Fluorine-19 Nuclear magnetic resonance spectra of the compounds were recorded using Varian 600 MHz and Bruker Avance-40 0 instruments. The IR spectra were recorded using a Perkin Elmer Spectrum Two UATR Two FT-IR instrument, and accurate mass measurement was performed using a Waters QtoF premier mass spectrometer.
