A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• new entries into these valuable structures [6]. However, common to the majority of these indole syntheses is the use of hazardous entities such as hydrazines (Fischer), diazonium species (Japp–Klingemann) or azides (Hemetsberger–Knittel) or the necessity to construct specifically functionalised

Mechanically induced oxidation of alcohols to aldehydes and ketones in ambient air: Revisiting TEMPO-assisted oxidations

• Andrea Porcheddu,
• Evelina Colacino,
• Giancarlo Cravotto,
• Francesco Delogu and
• Lidia De Luca

Beilstein J. Org. Chem. 2017, 13, 2049–2055, doi:10.3762/bjoc.13.202

• to the respective carboxylic acid [11][12]. In addition, the appeal of this reaction is reduced by the need to use stoichiometric amounts of strong oxidising agents that are extremely toxic, hazardous, and expensive [13][14][15][16][17]. The use of the stable tetraalkylnitroxyl radical TEMPO (2,2,6,6

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• global warming, it is important to minimize the usage of hazardous chemicals in both academic and industrial research, elimination of waste, and possibly recycle them to obtain better results in greener fashion. The studies under the area of mechanochemistry which cover the grinding chemistry to ball

• ][83][84]. During the synthetic application of these molecules protection of -NH2 and -COOH group are needed. The traditional protection chemistry involves hazardous solvents, direct handling of corrosive reagents, longer reaction time, and tedious purification processes, etc. Therefore, methodologies

• reaction time, hazardous organic solvent, and tedious isolation procedure are implemented. Dekamin and co-workers have demonstrated the synthesis of pyrans using potassium phthalimide (POPI) as a catalyst under ball-milling which is found to be advantageous over solution phase synthesis [158]. Malonitrile

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• equiv) for 40 minutes, followed by the click-coupling reaction of the second equivalent of an aniline with the intermediate isothiocyanate. In this way, non-symmetrical thioureas 25a–d were synthesized and isolated in high 87–94% yields. Instead of using thiophosgene and CS2 as corrosive and hazardous

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• hazardous hydrazine hydrate was replaced by 1,2-diaminoethane [39] and conversion to the corresponding benzylamines was quantitative within 1 h. As a proof of concept of reaction, p-methylbenzylamine was isolated in 41% yield in the form of acetamide 42. In this way, a three-step, two-pot (A and B, Scheme 5

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• often volatile, toxic, flammable and expensive as well as might introduce a bulk of hazardous waste treatment issues. Thus, great efforts have been put into reducing or eliminating those organic solvents by replacing them with more environmentally acceptable alternatives [3]. It is beyond doubt that

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• ), the use of water or aqueous systems as solvent in organic synthesis to replace hazardous and expensive organic solvents have been explored [39][40]. Various catalytic systems have been reported for the Mizoroki–Heck reaction in aqueous medium [41][42][43]. However, a drawback of using water is related

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• /bjoc.13.117 Abstract In this paper we report an efficient and mild procedure for the conversion of organic thiocyanates to thiols in the presence of phosphorus pentasulfide (P2S5) in refluxing toluene. The method avoids the use of expensive and hazardous transition metals and harsh reducing agents, as

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• acetate as a viable, greener, inexpensive and easily available alternative to the highly hazardous chlorinated solvent which is a traditionally and most frequently used solvent for RCM reactions. To check the effect of purity of the cycloadduct on the rate and feasibility of subsequent RCM reactions and

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• volatile or the process stream is a two-phase mixture. Recently, Movsisyan et al. have reviewed the application of flow reactors for hazardous reactions [1]. Although the flow reactors allow such reactions to be carried in a safer manner controlling such reactors at production scale could be challenging

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• dyes were freshly synthesized starting from fluorescein (Flu, 1). Although the described synthetic procedures for the preparation of eosin dyes commonly use Br2, herein the less hazardous N-bromosuccinimide (NBS) was used as the source of bromine. Thus, eosin Y (2) was prepared in a single step from 1

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• chemistry could play an important role in the development of green and sustainable synthetic processes. In this review, some recent relevant examples in the field of flash chemistry, catalysis, hazardous chemistry and continuous flow processing are described. Selected examples highlight the role that flow

• becoming a new technique for fulfilling several of the twelve green chemistry principles. The microreactor approach, could provide protection, preserves atom economy, guarantees less hazardous chemical synthesis and allows the use of safer solvents and auxiliaries. Furthermore, it pushes towards designing

• synthesis. Hazardous chemistry by using green and sustainable continuous-flow microreactors We have already shown how continuous-flow technology could play an important role in improving chemical processes [5][71], providing different advantages over traditional batch mode. However, the hazardous nature of

Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• pyrophoric reagent, such as s-BuLi, is involved is quite remarkable, and it is carried out as a continuous process and not on a small scale. This suggests that solvent-free extrusion can be on par with continuous flow technology, allowing a wider range of hazardous reagents to be used continuously and on

• materials can be used in the extruder, through the use of s-Buli by Höcker et al., reagents that are potentially explosive or can be ignited when dry or exposed to friction are too hazardous to be used in an extrusion process, therefore chemistry involving azides or hydrazines for example, would need to be

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

• . Flow chemistry has recently emerged as a powerful technology in synthetic chemistry [12] as it can reduce risks associated to the use of hazardous chemicals and favors reaction scale-up [13][14][15][16][17]. The possibility to efficiently perform nitro reduction in continuo would make the

• demonstrated. The use of extremely inexpensive and non-hazardous chemicals, the very high chemoselectivity and the possibility to realize a completely automated reduction/work-up/isolation process are distinctive features that make the protocol suitable for the reduction of a large variety of products and

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• hazardous reagents and intermediates in small quantities, in situ, and transferred directly into a reaction stage without operator handling [21][22][23][24][25][26]. As rapid heat transfer (steps 1 and 3) and greater reaction control (steps 2 and 3) were identified as the key challenges to be overcome, we

Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

• Natividad Herrera Cano,
• Jorge G. Uranga,
• Mónica Nardi,
• Antonio Procopio,
• Daniel A. Wunderlin and
• Ana N. Santiago

Beilstein J. Org. Chem. 2016, 12, 2410–2419, doi:10.3762/bjoc.12.235

• -disubstituted benzimidazoles (b). Therefore, the main drawbacks of current protocols for the synthesis of benzimidazoles include the use of expensive reagents, difficulties in the preparation of the catalyst, long reaction times, a narrow scope of substrates, tedious work-up procedures, the use of hazardous

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• principles of green chemistry [1][2] such as less hazardous chemical synthesis, efficient atom economy, reduction of waste produced, some alternative cleaner methods for the synthesis of azo dyes have been developed. These methods are however only representative of particular coupling agents and diazotized

• be changed or modified to achieve the above mentioned green benefits in addition to other advantages. For example, isolated diazonium salts are known to be hazardous due to their explosive and unstable nature. However, microreactor technology makes it possible to safely perform reactions with

• unstable intermediates [17] such as these, as well as those that give rise to explosive [18] and hazardous products [19]. The small reagent volumes used in microreactors also reduce the amount of acidic and alkaline waste associated with the synthesis of azo compounds during research and development. In

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• ][9][11][12]. Over the past decade, various reactor types and technical specifications have been developed to address the intricate challenges of many chemical reactions, including the handling of hazardous [13][14] or explosive [15][16] reagents, advanced concentration and temperature gradients [17

Amidofluorene-appended lower rim 1,3-diconjugate of calix[4]arene: synthesis, characterization and highly selective sensor for Cu²⁺

• Rahman Hosseinzadeh,
• Mohammad Nemati,
• Reza Zadmard and
• Maryam Mohadjerani

Beilstein J. Org. Chem. 2016, 12, 1749–1757, doi:10.3762/bjoc.12.163

• amounts of Cu2+ are hazardous, due to generate reactive oxygen species (ROS) that disturbs cellular metabolism [10][11]. On the other hand, its deficiency may cause haematological and neurological diseases [12]. Therefore, the selective and sensitive measurement of Cu2+ ions – either as significant

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• these atoms are expected (cf. [19]). Trimethylsilyldiazomethane (7c) is widely applied as a practical and useful synthetic equivalent of the hazardous diazomethane [24][25]. In our earlier publications, its reactions with thiofluorenone (1b) and S-methyl (phosphonyl)dithioformate, leading to the

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

• properties, making it highly hazardous and operationally difficult to use. In addition, the hydrochloric acid byproduct requires additional processing to neutralise and separate it. N-Chlorosuccinimide is used frequently in the laboratory because it is a relatively stable solid that is easily weighed and

• added to reactions [3][17], however, it has a low atom economy, poor economics, and requires separation of the succinimide byproduct [18]. The tert-butyl hypochlorite (t-BuOCl) reagent is also used regularly, but is similarly expensive, wasteful and hazardous [14][19][20][21]. On the other hand sodium

• of hazardous or unstable products. Furthermore smaller volumes with higher surface areas enable faster heat removal and better temperature control to limit unwanted side reactions. Further kinetic control is achieved with reactant concentrations, feed rates, mixing regime and residence time resulting

Coupling of α,α-difluoro-substituted organozinc reagents with 1-bromoalkynes

• Artem A. Zemtsov,
• Alexander D. Volodin,
• Vitalij V. Levin,
• Marina I. Struchkova and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2015, 11, 2145–2149, doi:10.3762/bjoc.11.231

• , unique stereoelectronic properties of the CF2-unit may be exploited in conformational analysis [3][4][5], carbohydrate and peptide research [6][7], and reaction engineering [8][9]. Typically, the difluoromethylene fragment is created by deoxyfluorination, which requires harsh or hazardous conditions [10

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• reaction with styrene, avoiding the use of hazardous diazo compound 7 [82]. Towards the end of 2013, a report by Olszewski, Skowerski and co-workers showed how a variety of commercially available catalysts (Figure 12) could be employed in air with nondegassed ACS grade green solvents. Their results were in

Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• combination of a wide range of substrates and solvents [9][10][11][12]. Over the past decade, Ru–alkylidene based olefin metathesis in aqueous media has become increasingly important [13]. Benefits such as the non-hazardous, vastly abundant and commercially highly attractive of water coupled with a high heat

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• of such processes, but also enables the chemist to perform more potentially hazardous and otherwise forbidden transformations in a safer and more reliable fashion [16][17][18][19][20][21]. The main advantages cited for improved operational safety are principally the reduced inventories of reactive

• inventory of the reactive intermediate reduced the safety concerns associated with the use of the azide. The choice of flow when handling hazardous materials like azides is a very frequently encountered driver and several publications detailing the associated benefits have emerged over the years [88][89][90