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

• interfacial area between the gas and liquid phases is quite small and the ratio of the interfacial area to the volume further decreases with the volume of the reaction mixture. Thus, in scale-up batch reactors the rate of reaction is significantly decreased due to the considerably reduced interfacial-area-to

• (Table 2). To compare the productivity for scale-up synthesis, the space–time yield of the triple-channel microreactor and that of the round bottom flask was calculated at various times during the course of the reaction. The space–time yield data reveals that triple-channel microreactors are quite

Scaling up of continuous-flow, microwave-assisted, organic reactions by varying the size of Pd-functionalized catalytic monoliths

• Ping He,
• Stephen J. Haswell,
• Paul D. I. Fletcher,
• Stephen M. Kelly and
• Andrew Mansfield

Beilstein J. Org. Chem. 2011, 7, 1150–1157, doi:10.3762/bjoc.7.133

• to scale up the rate of product formation without a loss in the intrinsic reaction performance, by using a continuous-flow, microwave-assisted, Pd-supported silica-monolith reactor. The Pd-monolith-3.2 and Pd-monolith-6.4 (both with the same length of 3 cm) were used to perform the model reaction (1

• conversion. This methodology was also used to test Suzuki–Miyaura reactions with a variety of substrates, as shown in Table 3. It can be seen that this scale-up strategy also works very well, with the amount of product obtained with the Pd-monolith-6.4 being four times greater than that obtained with the Pd

• length monolith, the scale-up method as used here, offers the advantage that the pressure drop required to produce a certain flow rate decreases with increasing diameter. However, as microwave penetration is necessary to obtain reliable heating characteristics, there will come a point at which the

Evaluation of a commercial packed bed flow hydrogenator for reaction screening, optimization, and synthesis

• Marian C. Bryan,
• David Wernick,
• Christopher D. Hein,
• James V. Petersen,
• John W. Eschelbach and
• Elizabeth M. Doherty

Beilstein J. Org. Chem. 2011, 7, 1141–1149, doi:10.3762/bjoc.7.132

• H-Cube® and the effect of that dispersion on the reaction outcome [15]. As a result of that study, we generated a predictive correlation between non-steady state and continuous flow scale-up conditions for simple reductions. In this report, using the reduction of styrene to ethylbenzene over 10% Pd

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• reaction mixture in a sealed vessel to temperatures far above the boiling point of the solvent under atmospheric conditions. Since batch microwave chemistry is inherently difficult to scale up to production quantities [14][15][16], translating high-speed, high-temperature microwave chemistry to scalable

• toxic but also highly explosive, a scale-up of this batch protocol is clearly not possible. A key advantage of using microreactors compared to conventional batch reactors is the ability to process potentially hazardous compounds or reagents safely [1][2][3][4][5][6][7][8][9][29][30][31][32]. In a

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

• significantly lower yields. Another obvious drawback of the initially described route [65] when considering scale up, is the number of sequential steps in the synthesis (8 steps, 21% overall yield) (Scheme 43). Hence an improved synthesis was sought [66]. This revised route utilised a palladium-mediated

Studies on Pd/NiFe₂O₄ catalyzed ligand-free Suzuki reaction in aqueous phase: synthesis of biaryls, terphenyls and polyaryls

• Sanjay R. Borhade and
• Suresh B. Waghmode

Beilstein J. Org. Chem. 2011, 7, 310–319, doi:10.3762/bjoc.7.41

• solvents such as water to make the scale up procedure economical and viable for industrial applications [33][34][35][36][37]. This has led to the use of water soluble ligands, additives and reusable heterogeneous supported Pd catalysts [38][39]. However, the limited availability of water soluble aryl

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• ]. Industrial scale-up of these methods has already been applied on the 100 kg scale for arylpiperazines and different diarylamines [21]. In addition, Nolan et al. and Organ et al. have reported Pd-N-heterocyclic carbene (NHC)-catalysed Buchwald–Hartwig amination protocols that provide access to a range of

• dehalogenated by-product to 4% (Scheme 4). The beneficial effect of added water may be due to better dissolution of K3PO4. Scale-up to gram amounts was possible without any significant decrease in yield. The reaction failed with both copper-mediated Ullmann-type reactions and heterogeneous palladium catalysis

• (Scheme 13). The method benefits from controlled regiochemistry and is applicable to various aliphatic and aromatic amines 58. Although the reaction scope was limited to 1-bromo-2-iodobenzenes 59, scale-up to multigram quantities was possible [65]. A key intermediate 64 of imatinib 61, a standard anti

Development of dynamic kinetic resolution on large scale for (±)-1-phenylethylamine

• Lisa K. Thalén and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2010, 6, 823–829, doi:10.3762/bjoc.6.97

• screening.a Scale up of dynamic kinetic resolution.a Acknowledgements Financial support from the European FP7 network INTENANT (“Integrated synthesis and purification of single enantiomers”) is gratefully acknowledged. Christine Rösch (née Hoben) is gratefully acknowledged for her contribution to some of the

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• enough to allow scale-up. Thus, we elected to use the simplest carbohydrates, i.e., those which are easy to prepare and easy to handle, e.g., the peracetylated monosaccharide 1 [16]. Although other derivatives, such as the 2,3,4,6-tetra-O-acetyl-1-O-trichloroacetimidoyl mannose might give rise to better

• glycosylation yields, the scale-up of these reactions was shown to be difficult. As a spacer, we chose triethylene glycol. The reaction of 1 with 8-azido-3,6-dioxaoctyloctan-1-ol (prepared in several steps from triethylene glycol) [17] was found to be unsatisfactory since the by-products formed in the reaction

Synthesis of bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine oxide – a tailor-made photoinitiator for dental adhesives

• Norbert Moszner,
• Iris Lamparth,
• Jörg Angermann,
• Urs Karl Fischer,
• Frank Zeuner,
• Thorsten Bock,
• Robert Liska and
• Volker Rheinberger

Beilstein J. Org. Chem. 2010, 6, No. 26, doi:10.3762/bjoc.6.26

• phosphine. These were found to be 3:5, 4:1 or 8:1 by HPLC. Only temperatures higher than 60 °C ensure a fast and complete oxidation of the bisacylphosphine. Finally, different batches of WBAPO were investigated by LC-MS during the scale-up of the synthesis. The results show that a side-chain extended WBAPO

Acid- mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

• Katsunori Tanaka and
• Koichi Fukase

Beilstein J. Org. Chem. 2009, 5, No. 40, doi:10.3762/bjoc.5.40

• ; microfluidic reactions can offer a direct and practical route to the desired compounds without the usual scale-up problems associated with mixing efficiency and the temperature control. They can therefore be regarded as one of the new strategies for the practical synthesis, or in favorable cases, the

• reactive sialyl donors having C-5 cyclic imides (Table 1), especially N-phthalimide 1a, by virtue of the “fixed-dipole moment effects” (α-only, 92% on 50 mg scale) [41]. The scale-up in a batch process, however, significantly decreased the yield and selectivity. Thus, a 100 mg scale reaction of 1a gave

Continuous flow based catch and release protocol for the synthesis of α-ketoesters

• Alessandro Palmieri,
• Steven V. Ley,
• Anastasios Polyzos,
• Mark Ladlow and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2009, 5, No. 23, doi:10.3762/bjoc.5.23

• –20 mL/min, and can be configured for multistep or parallel operation. Exiting products can be collected as aliquots using an automated fraction collector for reaction optimisation or as a bulk sample for scale-up. In addition, product purification can be achieved as part of the overall flow process

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• alternatives to the traditional ‘round-bottomed flask’ concept, which is still typically widely used for most chemical reactions [1][2][3][4][5][6][7][8]. Many advantages have been attributed to the use of flow devices, such as improved heat and mass transfer as well as mixing, and also easier scale-up and

• conditions, reliable and consistent stereoselectivities as well as yields can be maintained; scale-up and rapid screening is also facilitated. While many notable examples of asymmetric synthesis using continuous flow technology have been reported, it is certain that many more applications will be developed

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

• higher degree of safety [1][2][3][4][5][6][7][8][9][10][11][12]. Alcohol oxidations are well suited for microreactors due to high by-product formation, catalyst contamination and safety concerns often associated with scale-up in batch reactors [13]. Recent developments in microreactor technology and

• run continuously and sampled periodically to monitor its activity. As seen in Figure 3, the activity of the catalyst bed remained high even after hours of use. Furthermore, the work-up of this simplified oxidation scale-up comprised only of phase separation followed by concentration, yielding a white

Synthesis of imidazol- 1-yl-acetic acid hydrochloride: A key intermediate for zoledronic acid

• Santosh Kumar Singh,
• Narendra Manne,
• Purna Chandra Ray and
• Manojit Pal

Beilstein J. Org. Chem. 2008, 4, No. 42, doi:10.3762/bjoc.4.42

• methods, the most critical one being the isolation of imidazol-1-yl-acetic acid, a key precursor of Z, from aqueous media (see later for a discussion). We then decided to develop a more straightforward and practical route to generate Z, also suitable for its scale-up. Herein we report our detailed study

The first preparative solution phase synthesis of melanotan II

• Vladimir V. Ryakhovsky,
• Georgy A. Khachiyan,
• Nina F. Kosovova,
• Elena F. Isamiddinova and
• Andrey S. Ivanov

Beilstein J. Org. Chem. 2008, 4, No. 39, doi:10.3762/bjoc.4.39

• 55–60% overall yield [18][24]. The yield dropped to 30% when lactamization of the linear heptapeptide sequence, synthesized on the resin, was performed in DMF solution using DPPA/K2HPO4. Despite the high overall yield in the described solid phase approach, it has several drawbacks for the scale-up

Large- scale ruthenium- and enzyme- catalyzed dynamic kinetic resolution of (rac)-1-phenylethanol

• Krisztián Bogár,
• Belén Martín-Matute and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2007, 3, No. 50, doi:10.1186/1860-5397-3-50

• Krisztian Bogar Belen Martin-Matute Jan-E. Backvall Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden 10.1186/1860-5397-3-50 Abstract The scale-up of the ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) of (rac)-1

• . Herein, we address some of the scale-up issues of the ruthenium- and enzyme-catalyzed DKR of (rac)-1-phenylethanol under mild conditions. Results and Discussions The DKR of 1-phenylethanol has been tested under different reaction conditions with the aim of decreasing the catalyst loading. When the

• obtained in 87% yield (corresponds to 1.43 kg). The remaining alcohol had an ee of 19%, demonstrating the high racemization ability activity of ruthenium complex 1. Conclusion In this article, some of the scale-up issues in the ruthenium- and enzyme-catalyzed DKR of (rac)-1-phenylethanol were investigated

Expedient syntheses of the N-heterocyclic carbene precursor imidazolium salts IPr·HCl, IMes·HCl and IXy·HCl

• Lukas Hintermann

Beilstein J. Org. Chem. 2007, 3, No. 22, doi:10.1186/1860-5397-3-22

• acetate fulfilled these requirements and gave optimal results in all imidazolium salt syntheses (entries 6,8,14). In the course of scale-up, the reactant concentration was identified as another important parameter (entry 2 vs 3; entries 5,10). The final, recommended procedure for the synthesis of 1,3