A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• close to optimal as possible. Certain drawbacks to using a flow-approach must also however be acknowledged. Problems may arise due to quenching requirements, the necessity for solvent switching, concentration limitations, compensating for different encountered reaction kinetics over multiple steps when

• reactor is, in certain instances, indicated to give rise to superior reaction kinetics [79]. It is also easy to create staged temperature gradients to compensate for changes in reaction kinetics based upon concentration or complicating effects such as product derived auto-catalysis. The use of immobilised

• intensification. The implicit high pressure self-contained environment created by a pumped flow system allows for superior reaction kinetics often achieved by elevating the working temperature of the system. This capability also opens up the opportunity for the integration of volatile and gaseous reagents into

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• additive that decides on preferential 2’-O-silylation. The salt has been suggested to influence reaction kinetics in the way that the silylation reagent TBDMS chloride is changed to the nitrate, which subsequently is consumed faster by nucleophilic attack of the 2’-OH group onto the silica atom as compared

Particle size effect in the mechanically assisted synthesis of β-cyclodextrin mesitylene sulfonate

• Stéphane Menuel,
• Sébastien Saitzek,
• Eric Monflier and
• Frédéric Hapiot

Beilstein J. Org. Chem. 2020, 16, 2598–2606, doi:10.3762/bjoc.16.211

• (Supporting Information File 1, Table S3). Accordingly, it appeared that different models seemed appropriate to picture the reaction kinetics, meaning that the process probably results from various contributions, including nucleation, geometrical contraction, diffusion and reaction-order models. However, one

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• reactor design. The flow field (momentum transport), mass transport, and light field (radiative transport) need to be coupled to compute the reaction kinetics (Figure 1) [11]. Microstructured chips used in photochemistry have various channel geometries, such as straight line, serpentine, square serpentine

Mechanochemical green synthesis of hyper-crosslinked cyclodextrin polymers

• Alberto Rubin Pedrazzo,
• Fabrizio Caldera,
• Marco Zanetti,
• Silvia Lucia Appleton,
• Nilesh Kumar Dhakar and
• Francesco Trotta

Beilstein J. Org. Chem. 2020, 16, 1554–1563, doi:10.3762/bjoc.16.127

• nearly quantitative yields, with the release of carbon dioxide and formation of IMH. The reaction kinetics of alcohols with N,N'-carbonyldiimidazole were generally slower, so the presence of reactive IM moieties may be particularly interesting for an easy functionalization via reaction with nucleophilic

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• accessible to the reaction media and the excitation photons, preventing the photocatalyst from being wasted in the bulk material. The immobilisation will generally reduce the reaction kinetics of the homogeneous photocatalyst as it is no longer dispersed in solution, but this can be mitigated through flow

Suzuki–Miyaura cross coupling is not an informative reaction to demonstrate the performance of new solvents

• James Sherwood

Beilstein J. Org. Chem. 2020, 16, 1001–1005, doi:10.3762/bjoc.16.89

• the key fundamental principles of boron and palladium speciation and the role of the base in the Suzuki–Miyaura reaction. For researchers developing safer solvents, the Mizoroki–Heck reaction is a more suitable cross-coupling methodology to demonstrate solvent performance [28]. The reaction kinetics

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• explored this reaction to assess its scope and identify structural features in the amines which significantly affect success, monitored the reaction kinetics using a pseudo-first order kinetics model, and further adapted the reaction conditions to allow for product formation in as little as 5 min, with

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• solvents may substantially influence reaction kinetics and product formation [102]. Biricik et al. [98] reported the preparation of polydentate aminophosphine 111 through a condensation–elimination–aminolysis reaction (Scheme 21). Reactions performed in diethyl ether and toluene resulted in bisphosphine

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• % yield, respectively. Consequently, the reaction was strictly done at 0 °C and below. Therefore, the use of NaN3 in high equivalence (4 equiv) was to probably improve reaction kinetics at low temperatures. Karpf and Trussardi [9] reported the synthesis of azide 5 from mesyl shikimate 4 and NaN3 (1.1

Understanding the unexpected effect of frequency on the kinetics of a covalent reaction under ball-milling conditions

• Ana M. Belenguer,
• Adam A. L. Michalchuk,
• Giulio I. Lampronti and
• Jeremy K. M. Sanders

Beilstein J. Org. Chem. 2019, 15, 1226–1235, doi:10.3762/bjoc.15.120

• rather important phenomenon in the reaction kinetics under mechanochemical conditions [59]. Conclusion The kinetic profiles observed for neat and LAG processes described in this work are anomalous when compared to traditional solid-state processes. They are characterized by lengthy induction periods and

• local defects accumulate preferentially at or near the crystal surface. Since the total area increases exponentially when the crystal size is reduced by the crystal breaking process, this can further explain the exponential nature of the onset-time dependence on the milling frequency. Milling reaction

• kinetics is a relatively unexplored field, and we have explored only one reaction, but it seems likely that similar effects will operate for other reactions. Experimental The kinetic studies presented here were performed under ball-mill neat grinding (NG) and under ball mill liquid-assisted grinding (LAG

Insertion of [1.1.1]propellane into aromatic disulfides

• Robin M. Bär,
• Gregor Heinrich,
• Martin Nieger,
• Olaf Fuhr and
• Stefan Bräse

Beilstein J. Org. Chem. 2019, 15, 1172–1180, doi:10.3762/bjoc.15.114

• about reaction kinetics. We acknowledge the support by two projects of the German Research Foundation, namely BR 1750/34-1 (use of the electronic lab notebook and repository Chemotion to disclose the herein described research data) and BR1750/40-1, JU2909/5-1 (service for the deposit of physical samples

Unexpected polymorphism during a catalyzed mechanochemical Knoevenagel condensation

• Sebastian Haferkamp,
• Andrea Paul,
• Adam A. L. Michalchuk and
• Franziska Emmerling

Beilstein J. Org. Chem. 2019, 15, 1141–1148, doi:10.3762/bjoc.15.110

• ] in understanding reaction kinetics of these processes. Early insight into formation pathways was provided ex situ, in which the mechanical treatment was stopped, and powder removed for analysis [10][11]. More recently, further detail has been gained by monitoring mechanochemical transformations in

Synthesis of polydicyclopentadiene using the Cp₂TiCl₂/Et₂AlCl catalytic system and thin-layer oxidation of the polymer in air

• Zhargolma B. Bazarova,
• Ludmila S. Soroka,
• Alex A. Lyapkov,
• Мekhman S. Yusubov and
• Francis Verpoort

Beilstein J. Org. Chem. 2019, 15, 733–745, doi:10.3762/bjoc.15.69

• supplied into the sample, the process rate is limited by the diffusion, and the oxidation takes place in a diffusion mode. The reaction kinetics is consecutive and hence, it is characterized by a wide range of rate constants and can be described by the following equation: where the first element on the

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• reaction kinetics and their labeling intensities after metabolic incorporation. To determine the efficiencies by which the derivatives are metabolized to sialic acids, we synthesized and investigated the corresponding cyclopropane derivatives because cyclopropenes are not stable under the analysis

• norbornenes, have high DAinv reaction kinetics, but suffer from low incorporation efficiencies [21]. Cyclopropenes, that combine fast reaction kinetics and small size, turned out to be excellent reporters for application in MGE [22][23][24][25][26][27]. Three cyclopropene-derivatized mannosamine derivatives

• moiety is connected by a carbamate-linkage. All three cyclopropene derivatives easily undergo DAinv reactions. Kinetic studies revealed that the carbamate derivative ManNCyoc has the highest reaction rate, followed by ManNCp and finally ManNCyc with the slowest reaction kinetics. Performing MGE

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• sufficient to carry out the process effectively [86][87]. In the PBD–polyisoprene (PI) cross metathesis, Gr1 can be replaced by Gr–H1 but longer reaction times are needed [87]. A control over the reaction kinetics can be sometimes complicated because the overall composition of a polymer mixture does not

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• catalytically inactive tricyclic state. Conversely, the inhibitor binding greatly destabilized the ylide formation. Together, these observations have significant implications for the reaction kinetics of the ThDP-dependent enzymes, and, potentially, for the use of unnatural substrates in such reactions

Selective ring-opening metathesis polymerization (ROMP) of cyclobutenes. Unsymmetrical ladderphane containing polycyclobutene and polynorbornene strands

• Yuan-Zhen Ke,
• Shou-Ling Huang,
• Guoqiao Lai and
• Tien-Yau Luh

Beilstein J. Org. Chem. 2019, 15, 44–51, doi:10.3762/bjoc.15.4

• examined the first order reaction kinetics of ROMPs of 4 and of 5 in the presence of 10 mol per cent of Grubbs first generation catalyst (6) [36] in DCM at 10 °C [37]. The rate constants for the reactions of 4 and 5 were 1.3 × 10−3 and 5.1 × 10−4 s−1, respectively. On the other hand, when the reaction was

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• provide a tres for optimal conversion. This was achieved according to reaction kinetics and hydrophobicity of the amine, which affects its partition between phases. Herein, we report improvements to this process and the use of N-alkyl-N-chloramine in subsequent continuous-flow reactions (Figure 1). These

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• colorimetric indicator byproduct encouraged its use in a reaction kinetics investigation, where both electronic and steric properties of the amine reactant were shown to influence rearrangement rates. Having demonstrated its utility in studying this reaction using a high-throughput assay, it is proposed that 1

Investigating radical cation chain processes in the electrocatalytic Diels–Alder reaction

• Yasushi Imada,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 642–647, doi:10.3762/bjoc.14.51

• reaction kinetics. However, the observed induction period indicated that this was not the case and an intermediate(s) was involved in the rate determining step. This mechanism could be rationalized on the basis of a radical cation chain process since the concentrations of both starting trans-anethole (1

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• reactivity on small variations in milling frequency. In particular, in situ measurements revealed the establishment of two different regimes of reaction kinetics at different frequencies, providing tentative insight into processes of mechanical activation in organic mechanochemical synthesis. Keywords

• mechanochemical synthesis of a MOF from ZnO and imidazole in the presence of a small amount of N,N-dimethylformamide [41]. This study revealed reaction kinetics consistent with a 2nd order reaction rate law, rationalized through a “pseudo-fluid” reaction model in which the rate-determining factor is the frequency

• , they might be relevant for the observed variation of reaction kinetics with milling frequency, especially as a recent variable-temperature in situ PXRD study has demonstrated that mechanochemical reaction rates can be highly sensitive to temperature [52]. Conclusion In conclusion, we have utilized an

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• devoted to control division processes. Challenge 3: characterizing the evolutionary dynamics of pre-Darwinian protocells. Rather than focusing on the reaction kinetics and evolutionary dynamics of populations of naked nucleic acid molecules (the core idea underlying the ‘RNA world’ hypothesis), or even

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• , the absorption peak at 400 nm disappeared, implying full conversion of 4-NP to 4-AP. The reaction kinetics of the reduction of 4-NP is considered to be pseudo-first order [48] and can be expressed by the following equation: where rt is the consumption rate of 4-NP at time t, ct is the concentration

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• formation of the TCD template. 2.3 Reaction kinetics and its implications When considering a mixture containing only building blocks A and B in the minimal replicator model (Figure 2), the formation of template molecules T can initially only take place via the bimolecular reaction pathway. The bimolecular