Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• reaction was carried out without any solvent (Table 5, entry 8). Again, catalyst C6 (10 mol %) decreased the yield under solvent-free conditions from 95 to 73% (Table 5, entries 8 vs 9). The Ireland–Claisen rearrangement of cinnamyl isobutyrate (1d) gave under solvent-free conditions only 17% of the acid

• hand, catalyst-free Ireland–Claisen rearrangements proceed well in green solvents such as CpOMe or under solvent-free conditions. NMR kinetic measurements supported the notion that thiourea and squaramide organocatalysts bind strongly to the starting silyl ketene acetals and prevent the Ireland–Claisen

One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines

• Valeriya G. Melekhina,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Vitaly S. Mityanov,
• Artem N. Fakhrutdinov,
• Arkady A. Dudinov,
• Vasily A. Migulin,
• Yulia V. Nelyubina,
• Elizaveta K. Melnikova and
• Michail M. Krayushkin

Beilstein J. Org. Chem. 2019, 15, 2840–2846, doi:10.3762/bjoc.15.277

• -one (4), arylglyoxals 5, and acetamide (6) using SnCl2–SiO2 nanoparticles as heterogeneous catalyst under solvent-free conditions [10]. However, as we found out, the use of a catalyst was unnecessary for this transformation. In turn, refluxing the reaction mixture in acetonitrile was sufficient for

Probing of local polarity in poly(methyl methacrylate) with the charge transfer transition in Nile red

• Aydan Yadigarli,
• Qimeng Song,
• Sergey I. Druzhinin and
• Holger Schönherr

Beilstein J. Org. Chem. 2019, 15, 2552–2562, doi:10.3762/bjoc.15.248

• techniques, and (ii) different theoretical models of solvatochromic effects were employed, some of them take inductive solute–solvent interactions and solute polarizability into account, others neglect them, and (iii) different definitions of the molecular dipole moment in solvent-free conditions in vacuum

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• dihydrotetrazolopyrimidines one may concern carrying out these reactions under solvent-free conditions [15][16][17] or using water as a “green solvent” [18]. Results and Discussion Synthesis Due to the small number of reports available for dihydroazolopyrimidines with aliphatic substituents, we aimed by this work to

Reaction of oxiranes with cyclodextrins under high-energy ball-milling conditions

• László Jicsinszky,
• Federica Calsolaro,
• Katia Martina,
• Fabio Bucciol,
• Maela Manzoli and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2019, 15, 1448–1459, doi:10.3762/bjoc.15.145

• substitution, which results in products having some DS-dependent solubilisation properties [8][9][10][11]. In solvent-free conditions, although the nature of the reaction means that they are not absolutely water free, not only the PG formation can be optimised but also the reagent use. As previously

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• polymerization efficiency and good chain-length control under solvent-free conditions. When compared to the very low rate obtained under solution conditions, this demonstrates that mechanochemical reactions can improve reaction efficiency and greenness. The use of TBD truly enhanced the efficiency, and all

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• acetic acid (for liquid-assisted grinding, LAG) led to the regioselective C–H activation (Figure 5) [58]. In 2008, the mechanochemical synthesis of both [2]- and [4]rotaxanes was reported by Chiu and co-workers. The reactions led to high yields of the products 12 and 13 under solvent-free conditions at a

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• nucleophiles [36]. Moreover, salen complexes endure mechanochemical conditions, as proven during their preparation in ball mills [37]. In addition, various related Jacobsen salen complexes have shown catalytic activity under solvent-free conditions [38]. Collectively, these precedents made this synthetic route

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• (Scheme 2, Table 1) in a sealed tube in the presence of Et3N and under solvent-free conditions. From green chemistry point of view, this enhanced procedure appears to be a good alternative of the precedents for the synthesis of hydrazides 3a–m [26][27][28][29]. Moreover, the phenylglycine phenylhydrazide

• -imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones. Synthesis of the starting (L)-α-amino acid phenylhydrazides and 4-chlorophenylhydrazides 3a–m under solvent-free conditions. Cyclocondensation of 2-formylbenzoic acid (4) with (L)-alanine phenylhydrazide (3a). Synthesis of the nitrogenated tricyclic compounds 5a

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• synthesis of tetrahydrobenzo[a]xanthenone derivatives 48a and the four component synthesis of tetrahydrobenzo[a]acridinone derivatives 48b were performed with good to excellent yields under solvent-free conditions at 75–85 °C within short reaction times using the higher acidic/stable ILs containing

• 110 °C under solvent-free conditions. The products were produced in very short reaction times and recrystallized in ethanol to give pure 1-amidoalkyl-2-naphthols 50 (Scheme 8). The reusability of the ionic liquid catalyst 3 was also studied. For this purpose, warm acetone was used to extract the

• , catalyst 53 was utilized for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione derivatives 55 via a one-pot, three-component reaction of phthalhydrazide (54), aldehydes 7, and dimedone (20) or cyclohexane-1,3-dione (for R3 = H, 20) under solvent-free conditions (Scheme 9). To check the

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• .14.246 Abstract A new metal-free one-pot three-component procedure towards fully substituted triazolochromenes has been developed, starting from commercially available materials. Salicylaldehydes and nitroalkenes were reacted under solvent-free conditions, followed by a 1,3-dipolar cycloaddition of the

• -nitrochromenes. Because our first step is best performed solvent-free, we opted to try our own optimized solvent-free conditions for the in situ syntheses of 3-nitro-2H-chromenes, followed by the 1,3-dipolar cycloaddition in a reaction vial. Despite being a two-pot procedure, purification of the intermediate 3

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

• amounts of both reactants. The reaction between 2-ABA and 2-nitrohalobenzenes was chosen for the initial optimization of the experimental conditions, whose results are collected in Table 1. No reaction was observed with 2-nitrochlorobenzene after 8 h either in solvent-free conditions at 125 °C or using

The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX

• Md Toufique Alam,
• Saikat Maiti and
• Prasenjit Mal

Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216

• ; contact explosive; IBX; mechanochemical synthesis; quinazolin-4(3H)-one; Introduction An iodine and ammonia mixture is a well-known contact explosive due to formation of NI3 [1]. Similarly, hypervalent iodines as oxidizing compounds [2] react violently with amines under solvent-free conditions [3

• may take place between hypervalent iodine reagents and electron-rich amines. For this reason, synthetic methods based on hypervalent iodine reagents and primary amines under solvent-free conditions or constrained media are limited [8]. Recently, we have described a method for the successful reaction

• ). Melting points (mp) of the compounds were determined using a digital melting point apparatus and are uncorrected. Caution. When aniline and IBX are mixed under solvent-free conditions or at maximum contact, immediate explosion was observed. However, no explosion could be observed under similar conditions

Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation

• Mrunesh Koli,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2018, 14, 2198–2203, doi:10.3762/bjoc.14.193

• Barbier-type allylations of carbonyls have been reported in organic solvents [28][29][30], water [31] or under solvent-free conditions [32][33]. The solvent free synthetic procedure required a large excess (4–8 equiv) of Bi metal [33] whereas, the reactions in water or in organic solvents required either

Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases

• Svetlana O. Kasatkina,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Ivan G. Mokrushin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147

• 3-acylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones react regioselectively with Schiff bases under solvent-free conditions to form pyrimido[1,6-a]quinoxaline derivatives in good yields. Keywords: acyl(quinoxalin-2-yl)ketenes; cycloaddition; pyrimido[1,6-a]quinoxalines; Schiff bases; thermolysis

• compounds deemed to be reversible. Performing the reaction under solvent-free conditions at the onset decarbonylation temperature (Table 1) exceeded our expectations and gave the best yields of the target compound 3a (Table 2, entry 6). Being inspired by the optimization results obtained, we examined the

• , Figure 6; CCDC 1834012, Figure 7). Conclusion We have developed a facile synthesis of pyrimido[1,6-a]quinoxaline derivatives via the intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases. The reaction proceeds under solvent-free conditions without any additives and

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• the thiolysis of alkyl and aryl epoxides under solvent-free conditions with 5 mol % of catalyst loading, the activity was highly dependent of the nature of the acid or base catalyst employed. The Lewis acid InCl3 and the Brønsted base K2CO3 provided superior yields and reaction rates in comparison to

• thiols under solvent-free conditions as shown in Scheme 6 [26]. The reaction is compatible with both alkyl and arylthiols, with the nature of the substituent on the aromatic ring (electron donating/withdrawing) not having any influence on the reaction. Moreover, the reaction is compatible with

• epoxides using ionic liquids under solvent free conditions [27]. The reaction is compatible with the presence of alkyl halides (R1 = CH2Cl), alkyls (R1 = CH3), aryloxy (R1 = ArO) and aryls on the epoxide ring as well as a wide range of thiophenols bearing a variety of substituents (Scheme 8). The nature of

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• of Boc group gave the target compounds 69. The catalytic activities of these prolinamide organocatalysts based on the calix[4]arene scaffold were evaluated for the model reaction between 21 and 70. The results showed that under solvent-free conditions at −25 °C, 2 mol % catalyst 69b with two

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• . Currently, the Heck reaction is usually carried out by adding an excess of phase-transfer catalyst such as tetrabutylammonium bromide (TBAB) or tetrabutylammonium iodide (TBAI) to increase the reaction yield under both solvent-heating [19][20][21][22][23] and solvent-free conditions [24][25][26][27

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• the reaction in comparison to completely solvent-free conditions. Finally, we observed that there was an effect of the dielectric constant of the solvent used in LAG on the stereochemistry of the product [27]. Although previously we were able to generate high yields of Wittig products under liquid

• the same rationale could be used in the case of our solvent-free conditions. In solution, ions are separated and stabilized by solvent molecules. Mechanistically we envision ions to start out as contact ion pairs, then solvent separated ion pairs (i.e., loose ion pairs) followed by free ion pairs

• . However, this pathway is shut down under solvent-free conditions, making everything in the system a contact ion pair. The traditional solution-based mechanism of the Wittig reaction proceeds via a four-membered oxaphosphetane intermediate. However, by incorporating the halide anion and the alkali metal

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• -assisted reactions, solvent-free conditions and the reusability of the catalyst (Table 1). Procedures are carried out as one-pot multicomponent transformations without the isolation of the intermediates formed. Therefore, with the application of nontoxic, readily available and inexpensive reagents, both

• , Samant et al. reported an ultrasound-promoted condensation catalysed by sulfamic acid [44]. As shown in Table 1, entries 39 and 40, both dichloroethane (DCE) and solvent-free conditions were tested. The catalyst worked at low temperature (28–30 °C) and the products were formed in short reaction times in

• -hydroxypropanals and cyclic secondary amines, Jha et al. achieved the synthesis of 2,2-dialkyl-3-dialkylamino-2,3-dihydro-1H-naphtho[2,1-b]pyrans under solvent-free conditions using pTSA as catalyst [75]. It is important to note, that during the reaction, 2,2-disubstituted 3-hydroxypropanals 26 decompose to

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• acetic acid (Scheme 1). In the same report the other regioisomers 6-trifluoromethylpyrazolo[3,4-b]pyridines 20 were obtained under multicomponent solvent-free conditions by the reaction of hydrazine 14, β-ketonitrile 15 and β-diketone 17 as an exclusive product. The structures of both the regioisomers

• have been confirmed unambiguously by HMBC, HMQC and 19F NMR studies. The authors proposed that trifluoromethyl-β-diketone exists mainly in keto form 17 under solvent-free conditions whereas under solvent-mediated conditions the enolic form 21 towards the carbonyl carbon that carries the CF3 group is

Mechanochemistry

• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 2372–2373, doi:10.3762/bjoc.13.234

• of achieving chemical reactivity under solvent-free conditions. Additionally, the utilization of mechanochemical technology can often further simplify the posterior work-up procedures, having a deeper impact on the sustainability of the global synthetic process (reduction of waste, lower energy

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• . Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline–proline dipeptides under solvent-free conditions. A deprotection–cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be

• filtration of the catalytic system. 12 was engaged without further purification in a coupling reaction with Z-proline (5) and Boc-proline (6), in the solvent-free conditions described above. In both cases, the dipeptides 13 and 14 were obtained in good yields (78 and 61%, respectively). Deprotection followed

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

• solvent is the main component of the reaction system and, thus, the main source of waste in organic synthesis [35]. By far, performing the oxidation of alcohols under solvent-free conditions represents the best strategy to radically eliminate possible drawbacks in regard to waste disposal [36][37]. In

• amounts of the catalyst as well as molecular oxygen instead of air did not result in a significant improvement (Scheme 2, left side). To our great surprise, using Stahl’s catalyst, the mechanically activated oxidation of the model substrate 1a under solvent-free conditions proceed so quickly and

Mechanochemical Knoevenagel condensation investigated in situ

• Sebastian Haferkamp,
• Franziska Fischer,
• Werner Kraus and
• Franziska Emmerling

Beilstein J. Org. Chem. 2017, 13, 2010–2014, doi:10.3762/bjoc.13.197

• .13.197 Abstract The mechanochemical Knoevenagel condensation of malononitrile with p-nitrobenzaldehyde was studied in situ using a tandem approach. X-ray diffraction and Raman spectroscopy were combined to yield time-resolved information on the milling process. Under solvent-free conditions, the reaction