Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• a method for the acetylation of isoamyl alcohol (9) catalyzed by Candida antarctica lipase B (Scheme 3) [26]. A biphasic system consisting of n-heptane and an aqueous buffer solution is used and efficiently mixed in a Corning AFRTM Low Flow reactor providing a fine dispersion of the reaction mixture

• and, thus, a large interface between the phases. Subsequently, the biphasic system is directly separated, employing a PTFE membrane separator, to afford a solution of isoamyl acetate in n-heptane, while the aqueous layer containing the lipase could be recycled. At 60 °C with a residence time of 8.6

• analyzed by GC, or, as demonstrated for the preparation of phenylethyl acetate, further diluted with ethyl acetate, and the biphasic system is separated in flow providing phenylethyl acetate in 82% isolated yield. Using this method, a variety of 2-phenylethyl-, cinnamyl-, geranyl-, n-hexyl-, and isoamyl

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

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• -substituted boronic acids [14][15]. An optimisation study showed that the presence of AgTFA (dehalogenation reagent) and NH4PF6 (Pd(II) stabilizing salt) in the reaction mixture was necessary. Additionally, the solvent was changed from a methanol/water mixture to a DCE/water biphasic system. It was also

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• quaternization proceeded regioselectively using the t-BuOH/HClO4 system [25]. Further, the salts 7 were treated with sodium hydroxide in the biphasic system water/chloroform giving aminides 8, which were extracted from the reaction mixtures by chloroform. The obtained aminides 8 are yellow solids and soluble in

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• obtained in a lower yield (52%) but high diastereoselectivity, similar to those previously reported [59][61]. The authors also explored the PKR in a catalytic version based on a biphasic system of ethylene glycol/toluene, which generally enhanced both yields and stereoselectivities, as well as simplifying

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• . [52] and by Mousavizadeh et al. [53] through the three-component reactions of indole and coumarin, but in all cases, ordinary aliphatic and aromatic aldehydes as the third partner, mediated by a catalyst or by a biphasic system as solvent, respectively, were used. The lack of structural diversity in

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• asymmetric alkylation of tert-butyl glycinate benzophenone Schiff base 3 with alkyl halides 4 in a toluene–50% KOH biphasic system (Scheme 1). The corresponding α-alkyl-α-amino acid derivatives 5 were obtained in excellent yields with very low enantioselectivities (up to 9%). This is the first example of

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• for N,N´-diacylation. To avoid this, the reaction was performed employing a diluted solution of the amine in a biphasic system (CHCl3/aqueous NaOH), low temperature (0 °C) and the use of anhydrides as acylating agents, if commercially available. The results are shown in Table 1. For R3 = H, products

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• biphasic system was kept under stirring and the organic layer was continuously collected into a flask. Removal of CH2Cl2 gave pure amino compound 2a in 94% yield. This system allowed to easily obtaining almost 1 g of pure 2a in about 4 hours (see Supporting Information File 1 for further details

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• -tetra(prop-2-yn-1-yl)-1,4,8,11-tetraazacyclotetradecane diperchlorate is reported. Keywords: azamacrocycles; biphasic system; cyclam; cyclen; N-alkylation; Findings The tetraazamacrocycles cyclam (1) and cyclen (2) have been the subject of considerable interest over many years [1][2][3][4][5][6][7

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• optimized biphasic system composed by EtOAc/EtOH/H2O, 9:2:10, v/v/v, shaken in a separatory funnel and kept until the phase separation. The separation was then conducted in isocratic ascending mode at room temperature, using the lower phase of the previously prepared mixture as stationary phase and the

• volume was determined as 320 mL. The butanol fraction was injected after dissolution in 20 mL of a mixture 1:1 of the selected biphasic system. 70 fractions of 50 mL were collected in the ascending mode. After switching to descending mode, 20 additional fractions of 50 mL were collected. Extrusion

• relative to control cells (considered as 100%). UPLC profile of the butanol fraction of the leaves of Jungia sellowii after shaking the flask with the selected biphasic system (details in the Experimental section). UP: upper phase (top chromatogram), LP: lower phase (bottom chromatogram). Detection at 242

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• phase require longer reaction times, provided by the CSTR, to compensate for low mass transfer rates in the biphasic system. The green metrics of the reaction have been assessed and compared to existing procedures and have shown the continuous process is improved over previous procedures. The organic

• products, and no decomposition of the N-chloromorpholine product. When the same reaction was carried out using a toluene–water biphasic system, the calorimeter trace was more complex with mass transfer effects making interpretation difficult (Supporting Information File 1). The calorimetric analysis shows

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• (Scheme 48). Ohsima and co-workers [182] have reported a rhodium-catalyzed [2 + 2 + 2] cyclotrimerization of triynes 283 in a water-organic biphasic system. The biphasic system provides dilute reaction conditions suitable for macrocyclization. Selective cross-annulation between hydrophobic diynes and

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• yield (76%) by using allyl bromide in biphasic system composed of CH2Cl2/50% NaOH and the additive TBAHS as the catalyst at room temperature. The obtained 10-(prop-2-en-1-yl)-10H-phenothiazine was subsequently conducted into an oxymercuration–demercuration reaction accordingly to the procedure proposed

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• also a few reports on AT reactions in water–organic solvent mixtures when reactive nucleophilic species were used (primary amine) and under biphasic conditions with a phase-transfer agent as shown in Scheme 10 [38]. In this study, water and CCl4 were used to produce the biphasic system. NaOH is the

• addition of a base immediately gives rise to the formation of pyrophosphate (31P NMR around −12 ppm alkyl pyrophosphate and −25 ppm tetraaryl pyrophosphate) and to phosphate in the presence of additional water (31P NMR dialkyl phosphate 0.4 ppm and diaryl phosphate −9.6 ppm). With the use of a biphasic

• system it is likely that the reaction takes place in the CCl4 phase because all the reagents, except the hydroxide anion, are soluble in CCl4. The hydroxide anion is actually transferred to the organic phase thanks to the phase-transfer agent. Different halogenating agents were used to produce in situ

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• difficulty of enzyme recovery. Recently, Wang et al. have shown that the activity and recyclability of the CalB enzyme can be enhanced by the use of a polymersome Pickering emulsion. As such, a biphasic system could be used by loading the enzyme in the aqueous phase and organic reagents in the polymersome [3

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• elimination of the sulfone substituent. Additionally, Ley et al. [19] recently prepared a range of α-hydroxy acids in flow starting from the corresponding amino acids, involving diazotization of the amine to the diazonium salt in a biphasic system. Inspired by Ley’s approach, which is significantly more atom

• ester (2) and sodium nitrite in a biphasic system of dichloromethane and an aqueous sodium acetate buffer. Dichloromethane was chosen as the organic phase to dissolve the water insoluble EDA, because of its low water uptake and low boiling point and its compatibility with potential follow-up reactions

• demonstrate the high reproducibility of the system. FLLEX module Having established a microreactor protocol for the continuous-flow synthesis of EDA, the next issue was to separate the product from the biphasic system in which it was collected. In order to increase safety and decrease the hold-up of EDA, the

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• of perfluorodecyldiphenylphosphine coordinate to palladium dichloride to form a catalytically active palladium complex that is useful for a fluorous/organic biphasic system. Cummins devised radical phosphination of bromobenzene or bromocyclohexane with white phosphorus by means of a trivalent

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• passing through the gas-flow reactor a flow stream of dichloromethane containing a red dye was allowed to degas in a lower pressure environment. A camera mounted over a flat tubing array captured images of the resulting biphasic system. The images were automatically filtered to locate the areas of

Impact of cyclodextrins on the behavior of amphiphilic ligands in aqueous organometallic catalysis

• Hervé Bricout,
• Estelle Léonard,
• Christophe Len,
• David Landy,
• Frédéric Hapiot and
• Eric Monflier

Beilstein J. Org. Chem. 2012, 8, 1479–1484, doi:10.3762/bjoc.8.167

• increase in the catalytic performances. Keywords: amphiphilic phosphanes; biphasic system; cyclodextrins; micelles; Introduction Facing the need of developing a greener chemistry, chemists have recently focused their investigations on clean transformation processes to convert organic molecules into

Translation of microwave methodology to continuous flow for the efficient synthesis of diaryl ethers via a base-mediated S_NAr reaction

• Charlotte Wiles and
• Paul Watts

Beilstein J. Org. Chem. 2011, 7, 1360–1371, doi:10.3762/bjoc.7.160

• disadvantageous for the stopped-flow microwave reactor. Herein, we employed an aqueous solution of K2CO3, which resulted in a biphasic microreaction system. In batch this approach would prove disadvantageous as it would result in a biphasic system in which poor mass transport between the organic and aqueous

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• acetamido acrylate by means of a chiral Rh catalyst based on a fluorous BINAPHOS ligand. In this case, the substrate and the product are dissolved in water while the liphophilic catalyst is maintained in a scCO2 phase, in a so-called inverted biphasic system [53][54]. A regime based on repetitive batch

• biphasic system produced a decrease in the conversion but the aldehyde selectivity was recovered and, more importantly, the l/b selectivity experienced a threefold increase. It has been considered that the main role of scCO2 is to reduce the residence time of the product aldehyde in the catalyst solution

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

A biphasic oxidation of alcohols to aldehydes and ketones using a simplified packed- bed microreactor

• Andrew Bogdan and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2009, 5, No. 17, doi:10.3762/bjoc.5.17

• , increasing the safety of large-scale oxidations. Furthermore, it was determined that the use of a packed-bed microreactor facilitates efficient mixing of a biphasic system without destroying the solid support, a common problem with stirred systems [4]. Results and Discussion Previously we reported that