Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• biphasic mode using a mixture of solvents, such as ethylene glycol and toluene [8]. The drive to carry out reactions in environmentally benign media also led to studies being carried out in “green” (environmentally friendly) solvents, such as aqueous media, some supercritical fluids (SCFs), ionic liquids

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• violent exothermic reaction induced by decomposition of AIBN [50]. Furthermore, in the second step (intramolecular nucleophilic substitution of β-iodoalcohols to afford epoxides), efficient mixing technique is required for biphasic aqueous–organic systems. To resolve all the troublesome issues, flow

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

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• α-amino phosphonates 78 (Scheme 20) [89]. [Ir(ppy)2(bpy)](PF6) was found to be the most effective catalyst. Interestingly, a biphasic mixture of toluene and water turned out to be the optimal solvent. The often-observed byproducts, amides derived from over-oxidation of the iminium ions, were

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

• quantities. Ethyl diazoacetate was prepared in a biphasic mixture comprising an aqueous solution of glycine ethyl ester, sodium nitrite and dichloromethane. Optimization of the reaction was focused on decreasing the residence time with the smallest amount of sodium nitrite possible. With these boundary

• 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

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

• -pressure tubing array the hydrogen gas comes out of solution, forming bubbles; (b) the camera records images of the biphasic flow; (c) the images are processed to identify and count the red pixels; (d) graph showing the quantity of

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• ). To the reaction mixture were added thiophenol (1.0 mmol), 10% aq Na2CO3 (5 mL) and tetrabutylammonium bromide (TBAB, catalytic) and the reaction mixture was stirred at room temperature for another 4 h. Aqueous work up of the biphasic reaction mixture furnished phenyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D

• biphasic reaction conditions. The thioglycoside formation became very slow without the addition of TBAB and the same product was obtained in a poor yield over a much longer period of time. In contrast, rapid SN2-substitution of the bromide ion at the anomeric center in α-glycosyl bromide with a

Aqueous reductive amination using a dendritic metal catalyst in a dialysis bag

• Jorgen S. Willemsen,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 960–965, doi:10.3762/bjoc.9.110

• to incomplete conversions. Incompatible catalysts can be physically separated in various ways, e.g., by applying biphasic reaction conditions [10], membrane reactors [11] or sol–gels [12]. Another way to circumvent incompatibility problems is to achieve compartmentalization by attaching the actual

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• free-energy relationships with X in the nucleophiles were biphasic concave upwards with a break region between X = H and 4-Cl, giving unusual positive ρX and negative βX values with less basic anilines (X = 4-Cl and 3-Cl). A stepwise mechanism with rate-limiting bond breaking for more basic anilines

• substituent effects of X on the reaction rates are not compatible with a typical nucleophilic substitution reaction. The Hammett and Brönsted plots with X are biphasic concave upwards with a break region between X = H and 4-Cl (break point of σX ≈ 0.13), giving unusual positive ρX and negative βX values with

• and substrates, respectively, is described in Equation 2 and Equation 3. The two ρXY values are obtained because the Hammett plots with X are biphasic. Figure 2 shows the plots of ρX versus σY and ρY versus σX to determine the ρXY values, according to Equation 3. The signs of ρXY are positive with

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• chlorination of cyclohexane (72) with sulfuryl chloride under 15 W black-light irradiation (Scheme 23); however, the reaction was relatively inefficient and productivity was low (0.18 mmol/h) [75]. A biphasic photocyanation of pyrene (74, Scheme 24) was shown to be efficient in a polymer microchannel reactor

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

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• periodate in a biphasic mixture of carbon tetrachloride, acetonitrile, and phosphate buffer (pH 7) produced the carboxylic acid 29 without epimerization at C1. After removal of the TBDMS protecting group with HF in acetonitrile, the hydroxy acid 18 was lactonized in the presence of DCC and catalytic amounts

• followed by cleavage of the acetate moiety with methanolic KOH to give a mixture of the alcohols 28/28*. Oxidation of the primary alcohol function with ruthenium(III) chloride and sodium periodate in a biphasic mixture of carbon tetrachloride, acetonitrile and phosphate buffer (pH 7) afforded the

Synthesis of new pyrrole–pyridine-based ligands using an in situ Suzuki coupling method

• Matthias Böttger,
• Björn Wiegmann,
• Steffen Schaumburg,
• Peter G. Jones,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2012, 8, 1037–1047, doi:10.3762/bjoc.8.116

• dichloromethane (110 mL) and cooled to 0 °C. Aqueous hydrochloric acid (27.5 mL, 2 M) was added dropwise under vigorous stirring, upon which the biphasic mixture turned yellow. The organic phase was separated, and the aqueous phase was neutralized with sodium carbonate and then extracted three times with

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• chemical shift of the C(H)=N proton [34]. Attempted methods for the chlorination of aryl aldoximes to aryl hydroximoyl chloride include the use of N-chlorosuccinimide [35], chloramine-T [36], biphasic sodium hypochlorite [37][38], and tert-butyl hypochlorite [39]. These methods led to either no reaction or

Reduction of benzylic alcohols and α-hydroxycarbonyl compounds by hydriodic acid in a biphasic reaction medium

• Michael Dobmeier,
• Josef M. Herrmann,
• Dieter Lenoir and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 330–336, doi:10.3762/bjoc.8.36

• protocol for the reduction of alcohols to hydrocarbons by using hydriodic acid, first described by Kiliani more than 140 years ago, was improved to be more applicable to organic synthesis. Instead of a strongly acidic, aqueous solution, a biphasic toluene–water reaction medium was used, which allowed the

• typically proceeds in aqueous solution and requires an excess of HI or strong mineral acids such as phosphoric or sulfuric acid [33][34][35]. We describe a biphasic reaction medium consisting of toluene and aqueous hydriodic acid. The phase separation allows milder reaction conditions compared to the

• HI favors the elimination of water, while higher HI concentrations lead to substitution and reduction products. Conclusion Toluene and aqueous hydriodic acid are a suitable biphasic reaction mixture for the reduction of a range of benzylic alcohols. The two-phase system makes the Kiliani protocol

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

• Nan Sun,
• Bin Li,
• Jianping Shao,
• Weimin Mo,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2012, 8, 61–70, doi:10.3762/bjoc.8.6

• -phenyl dithiocarbamate was generated by mixing aniline and 2.0 equiv of CS2 (based on aniline) in water with 1.0 equiv of NaOH at room temperature. After the complete disappearance of the aniline, the mixture was cooled to 0 °C and a solution of TCT (0.5 equiv) in CH2Cl2 was added. Then the biphasic

Synthesis and oxidation of some azole-containing thioethers

• Andrei S. Potapov,
• Nina P. Chernova,
• Vladimir D. Ogorodnikov,
• Tatiana V. Petrenko and
• Andrei I. Khlebnikov

Beilstein J. Org. Chem. 2011, 7, 1526–1532, doi:10.3762/bjoc.7.179

• -ethanedithiol. The benzotriazole-containing thioether 5 was prepared following a similar strategy to that for product 3 by using 1-chloromethylbenzotriazole as electrophile (Scheme 1). The mixture of aqueous Na2S and NaOH solution with acetonitrile is biphasic, and we found that the addition of a phase-transfer

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

• to heat up and cool down the system can significantly increase the reaction time. In addition, compared to previously reported microwave methodologies, employing a microreactor enabled us to investigate the use of a biphasic reaction system, reducing the costs associated with the transformation

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

• to a limited number of fields, a significant development in this area can be envisaged for the near future due to the clear advantages of these systems over the conventional ones. Keywords: biphasic systems; continuous flow processes; enantioselective catalysis; immobilized catalysts; polymer

• potential of biphasic ILs–scCO2 systems. Indeed, this system was further implemented by the same authors to obtain a fully continuous process [20]. In this context, a simple approach to implement biphasic ILs–scCO2 systems into continuous flow processes is to absorb the ILs on a porous support material

• (supported IL phase: SILP) [48][49][50][51]. This methodology allows simultaneously exploiting the full advantages of a homogeneous biphasic ILs–scCO2 system together with those provided by catalysts immobilized onto an insoluble support. In this way, continuous flow catalytic transformations with scFs as a

Koch–Haaf reaction of adamantanols in an acid-tolerant hastelloy-made microreactor

• Takahide Fukuyama,
• Yu Mukai and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2011, 7, 1288–1293, doi:10.3762/bjoc.7.149

• this reactor system, a hastelloy-made microextraction unit (a flow-workup system) was attached (Figure 2 and Figure 3). The microextraction unit has three inlets and one outlet (channel size: 1 mm i.d. × 14 cm). The reaction mixture was mixed at T-shaped junctions with Et2O and water, and a biphasic

• (flow rate: 2.5 mL/min) and water (2 mL/min) were introduced to extract the carbonylation product and remove excess acids (Scheme 1). The biphasic mixture was collected in a flask and the ether layer was concentrated in vacuo. 1-Adamantanecarboxylic acid (2a) was obtained in 89% isolated yield after

Triple-channel microreactor for biphasic gas–liquid reactions: Photosensitized oxygenations

• Ram Awatar Maurya,
• Chan Pil Park and
• Dong-Pyo Kim

Beilstein J. Org. Chem. 2011, 7, 1158–1163, doi:10.3762/bjoc.7.134

• Korea, Fax: (+82)-42-823-6665 10.3762/bjoc.7.134 Abstract A triple-channel microreactor fabricated by means of a soft-lithography technique was devised for efficient biphasic gas–liquid reactions. The excellent performance of the microreactor was demonstrated by carrying out photosensitized

• -step synthesis [30][31], process safety [32][33][34], photo-reactions [35][36][37][38][39], gas-liquid reactions [40][41][42][43], etc. In a biphasic gas–liquid reaction, mass transfer from the gas phase to the liquid phase proceeds through the interfacial area. In traditional batch reactors, the

• -volume ratio. Therefore, vigorous stirring, ultrasonic agitation, high pressure or supercritical conditions are typically applied to enhance mass transfer in batch reactors for gas–liquid biphasic reactions. Recently, we reported a dual-channel microreactor that dramatically improved the reaction rate of

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

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• ) lipophilicity allowing biphasic partitioning between butanol/water or purification by reversed-phase extraction, (ii) ability to be reduced to an aminooctyl chain for use in squarate conjugation chemistry, and (iii) capacity to be conjugated with fluorescent terminal alkynes using the Cu(I)-catalyzed azide

Synthesis of cationic dibenzosemibullvalene-based phase-transfer catalysts by di-π-methane rearrangements of pyrrolinium-annelated dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 119–126, doi:10.3762/bjoc.7.17

• . Calcd for C26H32ClNO4 (458.0): C, 68.18; H, 7.04; N, 3.06. Found: C, 68.22; H, 7.14; N, 3.06. Phase-transfer catalyzed (PTC) alkylation reactions a) Analysis with gas chromatography: A biphasic mixture of the quaternary ammonium catalyst 3d or TBAC (0.05 mmol), phenylacetonitrile (5, 506 mg, 4.32 mmol

• c) 3d as the catalyst. NMR-spectroscopically monitored PTC reactions: A biphasic mixture of the quaternary ammonium catalyst (0.03 mmol), the substrate (0.10 mmol), benzylchloride (1.25–1.50 equiv) and 2,7-dimethylnaphthalene (as internal standard, 0.025 mmol) in toluene (5 ml) and aqueous KOH