Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• other approaches such as visible light, microwaves, heterogeneous catalysis, and ultrasound [12][13][14][15]. Due to its versatility, one of the most prevalent of these MCRs is the Ugi reaction [16]. This reaction generally combines an isocyanide with an acid, an amine, and an aldehyde or ketone to

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• acrylamide derivatives [140]. Using the same directing group, a panel of α-arylacrylamide derivatives 39a–f was successfully functionalized with a high Z-selectivity (yields up to 98%, Scheme 18). Both, thermal reaction conditions (DMSO at 70 °C for 16 h) and microwave irradiation (100 °C using microwaves in

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• , temperature) [32], and introduces various effects of microwaves [33], cyclodextrines [34], or tetrabutylammonium fluoride on the N7/N9-product ratio [35]. It is therefore of interest to collect complementary data on analogous acylation reactions, which are required for a future comparative study. Intrinsic

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• temperature and microwave power, although requiring much longer time. A possible mechanism for the cyclization is presented, and further functionalization of the newly created pyrrole ring in the dihydropyrrolizine core is described. Keywords: dihydropyrrolizines; enaminones; microwaves; silica gel

• ) Lawesson’s reagent, toluene, 80 °C, 18 h; (iii) BrCH2COPh, MeCN, rt, overnight; (iv) P(OEt)3, NEt3, MeCN, rt, 18 h; (v) AcOH, microwaves (150 W, 140 °C), 10 min; (vi) SiO2, xylene, microwaves (150 W, 150 °C), 3.5 min. Proposed mechanism for the formation of pyrrolizidine 19a from enaminone (E)-15a. Synthesis

• of tetrahydroindolizines 26a–c from lactam 23 via enaminones 25a–c. Reagents and conditions: (i) NaH, THF, rt, 2.3 h, then BrCH2CO2Et, 0 °C–rt, 16 h; (ii) Lawesson’s reagent, PhMe, 80 °C, 18 h; (iii) BrCH2COAr, MeCN, rt, overnight; (iv) P(OEt)3, NEt3, MeCN, rt, 18 h; (v) SiO2, EtOH, microwaves (50 W

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

• understood about the role of microwaves on this specific conversion, i.e., thermal or non-thermal effects. Therefore, further investigations in this direction would be of great interest. Another optimization was also attempted by the replacement of HCl with other similar reagents. For example, to exacerbate

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

• organic synthesis (2000–10), witnessed microwaves with optic fibre or IR pyrometers for temperature detection along with specific glass reaction vessels that can withstand pressure and temperature in the reaction generated especially by low boiling solvents. Microwave-assisted heating reduces reaction

• seems to be compromised imposing restrictions on using microwaves at a scale-up level. However, the batch process and continuous flow process seem to provide an entry into scale-up standards with safety. The microwave reactors serving the purpose of batch and parallel approach are designed in various

• approach delivered the desired product in 62% yield after 6 h which reveals the efficiency of microwaves in increasing the yield and reducing the reaction time. The studies for the anticancer activity of the synthesized molecules revealed them to be more potent than the standard doxorubicin against AGS

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

• , variations in the absorption, an inadequate penetrating ability of the radiation into the reaction medium, and further reflection of the microwaves. Nevertheless, the solvent was water, which required long extraction processes compared to solvent-free conditions. Castro and co-workers have also reported the

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• and affords good to excellent yields of the desired heterocycles in very short reaction times. Keywords: cyclodehydration; medium-size heterocycles; microwaves; PPSE; tetrahydrothiazepines; Introduction Thiazolines (4,5-dihydrothiazoles) are widely studied heterocycles due to their multiple

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• for each isomer. In these reactions, we attribute no special effect due to microwaves. This has been a subject of some debate in the literature [37][38]. As we have demonstrated earlier, the microwave reactor simply provides a safe and reliable way to heat samples with superacids at temperatures well

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

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

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• reaction promoted by trimethylsilyl polyphosphate (PPSE) is also proposed on the basis of literature data and our experimental observations. Keywords: cyclodehydrations; dihydroquinazolines; microwaves; nitrilium ions; PPSE; SNAr; Introduction Dihydroquinazolines (DHQs) represent heterocyclic cores of

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• thiodibenzosuberone (1i) were prepared from the corresponding ketones by treatment with Lawesson’s reagent (L.R.) in toluene upon irradiation with microwaves (150 W) over 2 min [32]. The most efficient method for the preparation of thiofluorenone (1c) was the thionation of fluorenone by simultaneous passing of dry

• hydrogen chloride and hydrogen sulfide streams through the ethanolic solution at 0–5 °C (ice bath cooling) [33]. In analogy to 1a, hetaryl thioketones 1b,d–g were prepared from the corresponding ketones [34] by treatment with L.R. in toluene solution upon irradiation with microwaves over 2 min [32

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

• -assisted ring closure of the corresponding aminoamides promoted by ethyl polyphosphate (PPE). Keywords: dihydroquinazolines; microwaves; N-acylations; N-alkylations; PPE; Introduction Nitrogen heterocycles are part of many drugs and represent structures with wide therapeutic potential. Therefore, much

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• 2-bromo-6-methoxy-3-phenyl-1-indanone (130, Scheme 41). An efficient microwave-assisted synthesis of 1-indanones 132a–s related to combretastatin A-4 has been proposed by Lawrence et al. [68]. Two of the indanones were obtained via a Nazarov cyclization of chalcones 131 without using microwaves, in

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• ) glycols (PEGs) are eco-friendly solvents [1][2], finding applications in the biomedical field and for pharmaceutical formulations [3] and catalysis [4]. PEG-based reaction media [1] are safe reaction environments, efficiently heated by microwaves [5], but their use in organic transformations activated by

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• green acetylation of hydrophilic biological molecules, potentially easily scalable for industrial applications, including pharmaceutical, cosmetic and food industry. Keywords: catalyst-free; microwaves; peracetylation; polyhydroxylated compounds; solvent-free; Introduction Peracetylation of alcohols

• balanced by the absence of catalyst and by the reaction speed due to microwaves. The applied P-program was compatible with the N-Boc protecting group already present on the tyrosine methyl ester 8. Concerning salbutamol (9) the reported yield was referred to the peracetylated product 9a even if a

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• synthesis. Keywords: cyclic amidines; medium size heterocycles; microwaves; PPE; PPSE; Introduction The synthesis of new nitrogen heterocycles has a great interest in medicinal chemistry since they are part of many drugs and represent structures with a wide therapeutic potential [1][2]. 2

Superstructures with cyclodextrins: chemistry and applications III

• Gerhard Wenz and
• Eric Monflier

Beilstein J. Org. Chem. 2016, 12, 937–938, doi:10.3762/bjoc.12.91

• highly dangerous substances to be trapped and hydrolyzed before they reach their biological target. G. Cravotto et al. have reported on the recent advances in enabling technologies and green processes in CD chemistry [15]. By increasing heat and mass transfer, the protocols (assisted by microwaves

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• green strategies for the selective modification of cyclodextrins (CDs) is still a challenging task. Outstanding results have been achieved in recent years by means of so-called enabling technologies, such as microwaves, ultrasound and ball mills, that have become irreplaceable tools in the synthesis of

• ; cyclodextrin; microwaves; synthesis; ultrasound; Review The last decade has witnessed the development of highly efficient alternative synthetic methods which make use of new enabling technologies. The need for a more rational approach to the synthesis of cyclodextrin (CD) derivatives has led to several energy

• sources been tested for their ability to activate C–C and C–X bond formation. In recent years non-conventional energy sources, such as microwaves (MW), ultrasound (US), ball mills (BM) and microreactors have made access to CD derivatives much simpler, as have heterogeneous catalysts and greener solvents

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• 29a–c, 30a and 30b, Scheme 6), required modified conditions. The use of non-conventional activation methodologies (i.e., ultra-sound or microwaves) proved to be valuable to access some of these challenging CD derivatives [85]. Introduction of an oxime group at the C-2 position was also performed with

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• temperature could afford divalent and tetravalent glycocalixarenes in very high yields and regioselectivity. Following these studies, a wide series of other examples appeared in the literature [18][36][37][38][39] also exploiting the use of microwaves, ionic liquids and protected or even deprotected [17

Pd/C-catalyzed aerobic oxidative esterification of alcohols and aldehydes: a highly efficient microwave-assisted green protocol

• Marina Caporaso,
• Giancarlo Cravotto,
• Spyros Georgakopoulos,
• George Heropoulos,
• Katia Martina and
• Silvia Tagliapietra

Beilstein J. Org. Chem. 2014, 10, 1454–1461, doi:10.3762/bjoc.10.149

• enhanced by mild dielectric heating. Furthermore, it is a versatile green procedure which generally enables the isolation of esters to be carried out by simple filtration in almost quantitative yields. Keywords: aerobic oxidation; alcohol; esterification; heterogeneous catalysis; microwaves; Introduction

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• . Gratifyingly, yield and purity of pyrrole 7a increased when 6a was heated with microwaves to 250 °C under air cooling of the reaction vessel without any additive under solvent-free conditions. The results of the application of these conditions to cyanopyrrolines 6a–j are summarized in Table 1. This compound

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• high purity products [21]. So called “enabling techniques”, mainly non-conventional energy sources such as microwaves (MW) and ultrasound (US), can dramatically enhance reaction rates in organic synthesis [22][23]. Kinetics and yields of any chemical modification are strongly improved by the optimal

Temperature measurements with two different IR sensors in a continuous-flow microwave heated system

• Jonas Rydfjord,
• Fredrik Svensson,
• Magnus Fagrell,
• Jonas Sävmarker,
• Måns Thulin and
• Mats Larhed

Beilstein J. Org. Chem. 2013, 9, 2079–2087, doi:10.3762/bjoc.9.244

• mixture is typically heated from the outside, via the walls of the vessel. An internal temperature probe such as a thermometer or a thermocouple can in that case determine the temperature of the reaction mixture. In the last few decades the use of microwaves as a mode of heating has become increasingly