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

• the compatibility of the flow approach with a green chemical manufacturing future. It is also not difficult to see how continuous manufacturing has implications for important green chemistry metrics such as atom economy, reaction mass efficiency, effective mass yield, carbon efficiency and

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• nitroalkanes, valuable precursors of amines. A variety of nitrostyrenes and alkyl-substituted nitroalkenes, including α- and β-substituted nitroolefins, were chemoselectively reduced to the nitroalkanes, with an atom economy-oriented, simple and convenient experimental procedure. A reliable and easily

• reproducible protocol to isolate the product without the use of any organic solvent was established, and the recyclability of the DES mixture was successfully investigated. Keywords: alternative solvents; atom economy; DES; nitro derivatives; reduction; Introduction The search for alternative solvents, not

• materials that can be used to form eutectic mixtures offers an incredibly high variety of combinations to generate new, safe and biodegradable DESs [5]. Another fundamental principle of green chemistry is the atom economy concept. In this context, ammonia borane (AB) is receiving increasing attention as

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• biguanides. This pathway is particularly convenient as cyanoguanidines are readily available, inexpensive, and safe [32]. Moreover, this reaction occurs with full atom economy and provides the desired biguanides with fairly high yields. A prior step of substituted cyanoguanidine preparation gives access to

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• enhanced yield and efficiency with microwave assistance. The highlights of MWA-MCRs are high yields, reduced reaction time, selectivity, atom economy and simpler purification techniques, such an approach can accelerate the drug discovery process. The present review focuses on the recent advances in MWA

• anticancer activities (72, Figure 6) [66][67][68][69] prompted chemists to develop newer methodologies for the synthesis of pyrimidinones with atom economy and high yields. The Biginelli reaction is one of the frequently employed MCRs for the synthesis of dihydropyrimidinones. The classical Biginelli

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• atom economy and reduces large amounts of waste generated by the unnecessary utilization of catalysts and solvents. Notably, this reaction is compatible with a gram scale, and further research is yet to be developed towards more sustainability. Benzylic addition of aldehydes to azaarenes using

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• find a green catalyst that could provide a wide substrate scope for the Hantzsch synthesis of 1,2-dihydropyridines in a short reaction time. In order to achieve a green method, apart from utilizing a multicomponent reaction as a route providing a high atom economy, heterogeneous catalysis should be

• green character of a reaction can be approximately quantified by calculating both the E-factor and the atom economy (AE), amongst other factors. The AE of the Hantzsch synthesis for the model reaction involving benzaldehyde (1a, 1 mol), ethyl acetoacetate (2, 2 mol) and ammonium acetate (3, 1 mol) is

A proposed sustainability index for synthesis plans based on input provenance and output fate: application to academic and industrial synthesis plans for vanillin as a case study

• John Andraos

Beilstein J. Org. Chem. 2020, 16, 2346–2362, doi:10.3762/bjoc.16.196

• defined in Equation 12 quantifies the mass fraction of reagents whose atoms do not contribute to the chemical structure of the final target product of the synthesis plan. Following the concept of atom economy [18], this attribute is important in designing syntheses that maximize the use of all atoms in

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• reported. Evaluation of the green chemistry metrics for the synthesis of benzimidazoles 3, dihydropyrimidinones 7, and highly functionalized pyridines 11 In order to evaluate the “greenness” of the proposed methodologies, the green chemistry metrics, such as the atom economy (AE), E-factor, process mass

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• sodium hydroxide (50%) in aqueous ethanol (Scheme 1). Although, these methods have specific merits, they sometimes suffer from drawbacks such as extended reaction temperatures, lengthy procedures, low yields and atom economy, which consume excess reagents. Extensive efforts have been devoted to adopting

• -amino-1,2,3,4-tetrazole (3) in excellent yields. The process proved to be an efficient synthetic route displaying high atom economy, short reaction times, and a simple work-up procedure. This protocol appeared to be general with a diversity of amines and aldehydes. Experimental All chemicals were

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• ]. Remarkable advances in the direct fluorination (F2/N2) of carbonyl compounds by Sandford and co-workers [14][15] are noteworthy in this regard, and mitigate the expense and poor atom economy associated with stoichiometric approaches. Moreover, this substructure provides a versatile entry point for subsequent

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• inexpensive starting materials. The purification of the hydrazono-dihydroberberines by sole filtration, avoiding any solvent-consuming steps, such as chromatography, extraction or recrystallization, determines a very simple workup. This aspect, together with the total efficiency in atom economy observed

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• Photocatalytic hydrogen atom transfer (HAT) represents a valuable strategy for accessing C(sp3) radicals. This method allows the direct cleavage of a C–H bond and the consequent generation of alkyl radicals without relying on the presence of redox-active functional groups. This results in a superior atom economy

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• achieved [14][15][16]. Such a strategy had already been used successfully in previous syntheses of o-, p-, and m-bis(arylazo)benzenes in our laboratory [14]. However, multiple protection/deprotection steps lowered the atom economy and increased the step count of this strategy. The second approach towards

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

• renaissance by virtue of its greenness, sustainability, atom economy, step economy and inherent safety. Achieving stereocontrol in such organic electrochemical reactions remains a major synthetic challenge and hence demands great expertise. This review provides a comprehensive discussion of the details of

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• isothiocyanate [48][49][50][51][52] showing better atom economy. Nonetheless, only a few examples can be found in the literature starting from thiocyanates, and regarding the isothiocyanates the preparation of the reagent is required as an additional reaction step before. The synthesis of isothiocyanates

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• was chemoselective, furnishing in good yields the products resulting from the transfer of the less hindered arene. However, this methodology exhibits two main limitations. First, arenes 86 with electron-withdrawing groups did not react under the optimized conditions and on the other hand, the atom

• economy is quite low, since a half of the diaryliodonium salt 87 is lost in the process. Replacing the arene substrate 86 by ketones, and keeping nearly equal reaction conditions, the same authors have achieved an efficient synthesis of 3-(2-oxopropyl)- or pentacyclic isoindolinones 90 or 92 (Scheme 26

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• presents several other advantages besides atom economy, such as higher overall yields, easiness of procedure and work-up [12], less solvent being used, fewer residues being produced, fewer purification steps and time-saving, contributing to a more sustainable process (Scheme 1). The Strecker synthesis of α

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• base led to a fused chromanyl-cyanopyridine. High selectivity, high atom economy, and good to high yields in addition to mild reaction conditions are the advantages of this approach. Keywords: chromane; domino reaction; fused heterocyclic skeletons; pyrazolopyridines; Introduction The synthesis of

• reaction conditions, the simplicity of operation, high atom-economy, and good to high yields. Experimental General information Reagents and solvents were purchased from various commercial sources and were used directly without any further purification unless otherwise stated. 1H and 13C NMR spectra were

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• a sticky resin on exposure to atmospheric moisture. This resin hinders the isolation of phosphonate 6 and stymies scale-up. Finally, several byproducts, including the ethyl ether of 4 and the hemi-dealkylated ester of 6, are produced during this reaction, further reducing the atom economy of this

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• , has good atom economy and has the notable advantage of giving volatile hydrolysis products, the small size of this group in some cases leaves the protected compound unnecessarily hydrophilic. This causes solubility problems and complicates isolation and purification steps in the synthetic procedures

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• extra synthetic steps that make the atom economy of this approach very low and the entire synthetic procedure time consuming. Structure elucidation of difunctionalized CDs is a challenging task, irrespective of the strategy used. In the direct difunctionalization approach, the disulfonyl-capped CD has

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• isolation of intermediates and creating chemical diversity with high atom economy [33][34][35][36]. In the last two decades, enzymes have found a privileged place in organic chemistry by virtue of its inherent selectivity and eco-friendly reaction conditions. Such properties, among other, make them