Solvent-free sonochemistry: Sonochemical organic synthesis in the absence of a liquid medium

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 1850–1856, doi:10.3762/bjoc.13.179

• . Keywords: mechanochemistry; organic; solvent-free; sonochemistry; synthesis; Introduction Mechanochemistry is typically regarded as the grinding of solid reagents in a ball mill (or mortar and pestle), to instigate and accelerate chemical reactions [1]. In recent years, mechanochemistry has evolved to

• of employing sonochemistry. Conclusion In conclusion, the first examples of ultrasound induced solvent-free condensation reactions are reported, forming a Schiff base 1 (which has significant applications in catalysis) and a 1,3-indandione 2. It was concluded that one of the key parameters in these

• reactions was the particle size of the starting materials, with a reduced particle size of <200 µm resulting in a homogeneous mixture leading to complete conversion to the product. This provides an excellent foundation for further investigations into solvent-free or solid-state sonochemistry, including

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• highlighted. While the literature is abundant on their preparation in conventional solution environment, it was not until the advent of solvent-free manual grinding using a mortar and pestle and automated ball milling that new synthetic opportunities have opened. The mechanochemical approach not only has

• and 1,2-phenylenediamine, benzimidazolidine-2-thiones 14a–c were isolated in 100% yields via cyclization of an unstable intermediate 13 (Scheme 3b,c). Compared to the solvent-free synthesis, the corresponding solution reactions resulted in lower yields (81–95%). Li and co-workers conducted a mortar

• were screened with electron-donating and electron-withdrawing groups attached to aromatic rings. The reactions were performed in a 1:1 stoichiometry by manual grinding in a mortar and by automated ball milling in a laboratory mixer mill. Also, the performance of solvent-free or neat grinding was

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• diameter) [9], demonstrated to efficiently mediate the enzymatic kinetic resolution of secondary alcohols under solvent-free conditions in both mixer and planetary ball mills (Scheme 1b) [10]. Interestingly, this latter lipase (a commercial preparation known as Novozyme 345, hereinafter referred as CALB

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

• . Reactions under solvent-free conditions in a ball mill gave good yields and could be put in place of the classical solution conditions. The method is general and can be applied to various imides and alkyl halides. Phthalimides prepared under ball milling conditions were used in a mechanochemical Gabriel

• time, important progress was made in the development of various solvent-free organic reactions [5], especially by the use of the ball milling technique [6][7][8]. In continuation of our interest in eco-friendly organic syntheses [9][10][11][12][13][14], we studied mechanochemical N-alkylation reactions

• inevitable formation of 4, prevented clean mono-alkylation. The optimized reaction conditions were used to establish the scope of this reaction. Firstly, other alkyl halides were employed (Scheme 2). These experiments revealed that the solvent-free N-alkylation could be effectively carried out with different

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

• -PEG1900-Im was heated with various organic bromides (2-(bromomethyl)pyridine, benzyl bromide and 1-(bromomethyl)naphthalene) to generate the corresponding imidazolium salts L1–L3 under solvent-free conditions. All imidazolium salts were water-soluble and air-stable. The resulted salts L1–L3 were

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• applications on a large scale [45][46]. Very recently, Hernández, Frings, and Bolm developed a method to carry out the kinetic resolution of secondary alcohols through selective acylation using Candida antarctica lipase B, under solvent-free ball-milling conditions [47][48]. Inspired by this ground-breaking

• quite acceptable. On the other hand, no product was detected after the third cycle. To evaluate the denaturalization of the enzyme provoked by the milling process, a sample of fresh catalyst was milled for 1 h at 15 Hz under solvent-free conditions and in the presence of a LAG additive, finding that

• presents a slight decrease in ee compared with the resolution reaction using the milled enzyme under solvent-free conditions. This observation suggests that the LAG additive increases to some extent the degree of denaturation of the enzyme, reducing the enantiodiscrimination (ee = 91%) although maintaining

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• heating, ultrasonication and solvent-free conditions alleviated the drawbacks to a major extent [56][57][58][59][60][61]. One such useful strategy include manganese dioxide (MnO2)-mediated oxidative aromatization of 1,4-DHP 45 to afford substituted pyridine derivatives 46 under microwave conditions

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• easily recovered and reused for at least five times without significant loss of catalytic activity. Keywords: ball milling; Heck reaction; layer double hydroxides; solvent-free; supported Pd catalyst; Introduction High-speed ball milling (HSBM)-assisted transition metal-catalyzed cross-coupling reactions

• such as Heck, Suzuki, Sonogashira and Glaser reactions are still unusual methods for the formation of C–C bonds [1][2][3][4][5][6][7], but the method arouse considerable attention because of an environmentally benign and solvent-free synthesis approach as well as high efficiency and good atom economy

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• silane procedure led to the single diastereomer 7a. In this case determination of the relative configuration as trans was based on a high coupling constant 3JP-H = 17.0 Hz, which evidenced retention of configuration during the desulfinylation process (Scheme 2). The reaction conducted under solvent-free

Mechanochemical borylation of aryldiazonium salts; merging light and ball milling

• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1463–1469, doi:10.3762/bjoc.13.144

• spectroscopy. This time trace quantities of product 3a were detected (Table 1, entry 5). This interesting result under solvent-free conditions encouraged performing the light irradiation accompanied by milling to improve mixing and to increase the surface exposure of the reaction mixture. In a following set of

• direct formation of 3a [26][27]. This observation is in agreement with the findings by Jacobi von Wangelin et al., who described that upon irradiation of a solution of 1a in MeCN direct heterolytic cleavage of the aryldiazonium salt occurred [23][25]. However, the formation of 3a under solvent-free

Mechanochemistry-assisted synthesis of hierarchical porous carbons applied as supercapacitors

• Desirée Leistenschneider,
• Nicolas Jäckel,
• Felix Hippauf,
• Volker Presser and
• Lars Borchardt

Beilstein J. Org. Chem. 2017, 13, 1332–1341, doi:10.3762/bjoc.13.130

• Engineering, Saarland University, Saarbrücken, Germany Fraunhofer Institute for Material and Beam Technology IWS, Dresden, Germany 10.3762/bjoc.13.130 Abstract A solvent-free synthesis of hierarchical porous carbons is conducted by a facile and fast mechanochemical reaction in a ball mill. By means of a

• . Keywords: electrochemical energy storage; mesoporous; microporous; solvent-free; supercapacitor; templated carbon; Introduction Porous carbons are key components in many energy and environmentally-relevant applications, such as catalysis [1], gas storage and separation [2][3], and electrochemical energy

• ]. For example, the preparation of nanocarbon structures such as graphene sheets or fullerenes [39][40][41] as well as porous carbonaceous polymers [42][43] have been conducted mechanochemically. Our work demonstrates that a templating approach can be transferred into the solvent-free environment of a

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• either using the Lindlar catalyst (84.6%) under smooth reaction conditions (298 K, 1 bar H2, Table 1, entry 1) or 16.2 wt % CeO2@TiO2 (97%), the latter resulting in a very high STY for 1a (18.86 kg L−1 h−1) under solvent-free conditions (Table 1, entry 2) [119]. Use of cerium oxide is certainly

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• achieved in the first two solvents (85–88%), the use of ethanol resulted in a low yield (47%). Thus the A3 coupling of salicylaldehyde, phenylacetylene and morpholine can be achieved under solvent-free conditions as well as in solvents like toluene or acetonitrile with the formation of the coupled product

• unusual but added role of the hydroxy group of salicylaldehyde, which paves the way to develop metal-free as well as solvent-free A3 coupling reactions leading to the formation of propargylamine – the useful synthetic intermediate and an important unit of many bio-active compounds. The reaction conditions

• only metal-catalyst-free approach from acetylene carboxylic acids that are difficultly accessible and with low atom economy. Thus the present reaction from easily available A3 components leading to the formation of propargylamine under metal-catalyst-free and solvent-free conditions could attract the

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• and α-aryl-α-aminophosphine oxides was synthesized by the microwave-assisted solvent-free addition of dialkyl phosphites and diphenylphosphine oxide, respectively, to imines formed from benzaldehyde derivatives and primary amines. After optimization, the reactivity was mapped, and the fine mechanism

• ][34][35][36][37][38], while in a few cases the catalysts, i.e., PTSA [39], Na [40], TEA [21] or MoO2Cl2 [41], were used under solvent-free conditions. As for the microwave (MW)-assisted additions, only two cases were reported, but the catalytic variations were carried out in kitchen MW ovens [32][42

• ], and thus, do lack of exact temperatures, these results cannot be reproduced. From a ’green chemical’ point of view, the solvent-free and catalyst-free additions are of interest, however, in these reactions, relatively long reaction times (1.5–10 h), and/or unreasonably large excesses (50–150 equiv) 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

• organic compounds are highlighted. Extrusion is a well-established technique that has a vital role in the manufacturing processes of polymers, pharmaceuticals and food products. Furthermore, this technique has recently been applied to the solvent-free continuous synthesis of co-crystals and coordination

• extensive amount of research into continuous organic transformations by extrusion and encourage them to consider the potential that extrusion holds for continuous chemical synthesis, particularly under solvent-free conditions. Reactive extrusion (REX) Extrusion is employed most frequently in the polymer

• polymerisation reactions are typically dependent on the solvent employed, temperature and concentration [17], however, when they are conducted by extrusion, they are carried out under solvent-free conditions, which is a major advantage. It must also be noted that to carry out a reaction solvent-free, when a

Supramolecular frameworks based on [60]fullerene hexakisadducts

• Andreas Kraft,
• Johannes Stangl,
• Ana-Maria Krause,
• Klaus Müller-Buschbaum and
• Florian Beuerle

Beilstein J. Org. Chem. 2017, 13, 1–9, doi:10.3762/bjoc.13.1

• retaining permanent porosity in the solvent-free state have been reported so far. Here, we report on the crystallization of three-dimensional hydrogen-bonding frameworks based on [60]fullerene hexakisadducts bearing twelve carboxylic acid groups icosahedrally arranged on the fullerene surface. By varying

• analysis of an activated sample is in perfect agreement with a solvent-free structure (see Experimental section). In order to activate HFF-3 and to utilize the channel system for porosity, the compound was activated for 48 hours at different stages of vacuum (10−3 to 10−6 mbar) from room temperature to 70

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• Montpellier Cedex 5, France 10.3762/bjoc.12.290 Abstract An efficient synthesis of a series of γ-ketoallylphosphonates through a direct conversion of both primary and secondary Morita–Baylis–Hillman (MBH) alcohols by trialkyl phosphites with or without DMAP, used as additive, and under solvent-free

• -ketoallylphosphonates from primary and secondary MBH alcohols, with or without DMAP used as additive, and under solvent-free conditions (Scheme 1, reaction 5 and Scheme 2, reaction 7). Taking into consideration the importance of aminophosphonates (vide infra), we developed in the second part of this study an efficient

• mixture conducted without any additive and under solvent-free conditions, at room temperature or at 80 °C, indicated that no reaction occurred and the starting materials were completely recovered (Table 1, entry 5). However, when 0.5 equiv of DMAP was employed under the previous conditions, the

Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

• Serena Traboni,
• Emiliano Bedini and
• Alfonso Iadonisi

Beilstein J. Org. Chem. 2016, 12, 2748–2756, doi:10.3762/bjoc.12.271

• conducted in short times with the requisite silyl chloride and a very limited excess of pyridine (2–3 equivalents). Under these conditions, that can be regarded as solvent-free conditions in view of the insolubility of the polyol substrates, the reactions are faster than in most examples reported in the

• of the silylation approach was significantly extended with the development of unprecedented “one-pot” and “solvent-free” sequences allowing the regioselective silylation/alkylation (or the reverse sequence) of saccharide polyols in short times. The developed methodologies represent a very useful and

• experimentally simple tool for the straightforward access to saccharide building-blocks useful in organic synthesis. Keywords: carbohydrates; one-pot synthesis; regioselective protection; silyl protecting group; solvent-free reaction; Introduction The application of an orthogonal set of protecting groups

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• alumina catalyst with a very low content in alumina gave excellent results in terms of both activity and selectivity also under solvent-free conditions. The reaction rate follows the electron density of the carbinol atom in the substrate alcohol and yields up to 99% and can be obtained for a wide range of

• thiols and benzylic alcohols under solvent-free conditions in excellent yields [21]. We already reported on the use of amorphous solid acid catalysts in organic synthesis. These solids are formed by dispersing a small amount of an inorganic oxide with Lewis acid nature onto the surface of silica [22]. In

• report that excellent yields can be obtained in the presence of an amorphous solid catalyst under solvent-free conditions. Results and Discussion In order to test our hypothesis we carried out the reaction of 1-(4-methoxyphenyl)ethanol (1a) and benzyl mercaptan (2a) in the presence of different solid

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• precursor of parylene D, from 2,5-dichloro-p-xylene. In the first bromination step, with H2O2–HBr as a bromide source, this procedure becomes organic-waste-free and organic-solvent-free and can appropriately replace the existing bromination methods. The Winberg elimination–dimerization step, using aqueous

• step, 1-(bromomethyl)-2,5-dichloro-4-methylbenzene was synthesized with high yield and selectivity from 2,5-dichloro-p-xylene by using a H2O2–HBr couple in water. The use of H2O2–HBr as a bromide source made this procedure organic-waste-free, organic-solvent-free and an appropriate replacement of the

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• -6-substituted cyclodextrin derivative syntheses have been effectively carried out in a planetary ball mill under solvent-free conditions. The preparation of Bridion® and important per-6-amino/thiocyclodextrin intermediates without polar aprotic solvents, a source of byproducts and persistent

• very strong complexes with not only the native but with the substituted CDs, too. Although a solvent-free synthetic method does not solve the problem of complexation but the reduced amount of reagents can simplify the purification. Heptakis(6-azido-6-deoxy)-β-CD is the precursor to per-6-amino-β-CD

• reaction of 6I-monotosyl-β-CD has been demonstrated in a previous article [22]. Most interestingly, the side reactions that appear to be unavoidable in the classical solution syntheses can be eliminated in the solvent-free method described for the preparation of various CD derivatives. HEBM was found to be

Solvent-free, visible-light photocatalytic alcohol oxidations applying an organic photocatalyst

• Martin Obst and
• Burkhard König

Beilstein J. Org. Chem. 2016, 12, 2358–2363, doi:10.3762/bjoc.12.229

• Martin Obst Burkhard Konig Institute of Organic Chemistry, University of Regensburg, Universitätsstraße 31, 93040 Regensburg, Germany 10.3762/bjoc.12.229 Abstract A method for the solvent-free photocatalytic conversion of solid and liquid substrates was developed, using a novel rod mill apparatus

• reaction mixture. The corresponding carbonyl compounds were obtained in moderate to good yields. Keywords: benzylic alcohol; oxidation; photocatalysis; solvent free; visible light; Introduction According to a classification made by Wilhelm Ostwald, one of the pioneers in the field of physical chemistry

• solvent-free conversion of solid reactants. The reaction is driven by mechanical energy, which is for instance realized by grinding in ball mills or pestle and mortar. Obviously, this method possesses several advantages compared to reactions, which are performed in solution: toxic solvents and wastes are

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

• of hydrophilic products and to obtain safe and stable pro-drugs. Results: A totally green, solvent-free and catalyst-free microwave (MW)-assisted method for peracetylation of natural products such as oleuropein, alpha-hederin, quercetin and rutin is presented. By simply tuning the MW heating program

• 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

• preferably acetic anhydride in solvent free conditions, in presence of non-toxic homogeneous catalysts such as environmental safe Lewis acids [13][14]. Moreover, the need to easily recover and reuse the catalyst, thus reducing the work-up procedure to a simple filtration, resulted in the growing use of

Silica-supported sulfonic acids as recyclable catalyst for esterification of levulinic acid with stoichiometric amounts of alcohols

• Raimondo Maggi,
• N. Raveendran Shiju,
• Veronica Santacroce,
• Giovanni Maestri,
• Franca Bigi and
• Gadi Rothenberg

Beilstein J. Org. Chem. 2016, 12, 2173–2180, doi:10.3762/bjoc.12.207

• sulfonated catalyst (1%), an equimolecular amount of reagents under solvent free conditions, and varying the temperature between 50–100 °C. Results are reported in Table 3. In all cases, the selectivity towards the esterification product 3a remained complete. A comparable yield of 3a was recovered reducing

• h) and provides good to excellent yields with various primary and secondary alcohols. The selectivity towards desired products remained complete in all cases. The coproduct of the reaction, namely water, did not hamper the efficiency of this solvent-free process. The selected catalyst is cheap, can

• chromatography on silica gel (eluent = hexane/ethyl acetate) and characterised by multinuclear NMR. Anchoring methodologies: a) impregnation; b) covalent binding. Activity of the supported sulfonic acid catalyst within the first six cycles. Reaction conditions: 1 mol % cat., acid:alcohol ratio = 1:1, solvent

Solvent-free synthesis of novel para-menthane-3,8-diol ester derivatives from citronellal using a polymer-supported scandium triflate catalyst

• Lubabalo Mafu,
• Ben Zeelie and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 2046–2054, doi:10.3762/bjoc.12.193

• environmentally friendly method for the synthesis of para-menthane-3,8-diol from natural citronellal oil in 96% yield, under solvent free aqueous conditions. The acylation of para-menthane-3,8-diol with various acid anhydrides over polymer-supported scandium triflate (PS-Sc(OTf)3) catalyst was subsequently

• developed, where both hydroxy groups of para-menthane-3,8-diol could be simultaneous acylated under mild reaction conditions to form the corresponding diesters in good yields. The advantages of this method include a simple procedure from natural resources, using solvent-free reaction conditions. Keywords

• was used. Moreover, all the reactions were carried-out under solvent-free conditions. Reaction parameters such as temperature, reaction time and reagent molar ratio were studied towards the substrate conversion and product selectivity. Effect of reaction temperature and reaction time In order to