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

• (C–X), etc. is documented. Mechanochemical syntheses of heterocyclic rings, multicomponent reactions and organometallic molecules including their catalytic applications are also highlighted. Keywords: ball-milling; green chemistry; mechanochemistry; solid-phase synthesis; solvent-free synthesis

• techniques like ball-milling or hand grinding are considered to be promising candidates in solvent-free synthesis [10][11]. Mechanochemical methods deal with chemical transformations induced by mechanical energy, such as compression, shear, or friction [12]. Wilhelm Ostwald, a Russian-German chemist who

• ]. Nevertheless, this subject needs more attention to the both experimental and theoretical chemists [21]. The sophisticated technique of ball-milling or mechanomilling is the adaptation from the traditional grinding methods using a mortar and pestle. These mechanomillings methods are generally conducted in

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

• employed to explain the processes occurring in ball milling [7]. It must also be noted that there is a similar technology available to sonochemistry, that is considered to be less harsh than mechanochemistry, and this is resonant acoustic mixing (RAM). The RAM mixes by controlling the vibration applied to

• that alternative products can be formed using this technique, as with ball milling. The Knoevenagel condensation [18], Michael addition [19] and Biginelli reactions [20] amongst others have been instigated by ultrasonic irradiation in the presence of solvents such as pyridine and methanol, resulting in

• sonochemical reactions being carried out in the absence of solvent, or a liquid reagent [8][9]. Herein, we report two condensation reactions (investigated extensively by ball milling), one to form salen ligand 1 by sonicating o-vanillin and 1,2-phenylenediamine, and the second to form 1,3-indandione 2 from

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• Vjekoslav Strukil Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia 10.3762/bjoc.13.178 Abstract In this review, the recent progress in the synthesis of ureas, thioureas and guanidines by solid-state mechanochemical ball milling is

• 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

• phase to a mixture treated by manual grinding or ball milling [19]. What was in the beginning termed as "solvent-drop grinding" (SDG) eventually became "liquid-assisted grinding" or LAG, now a well-established method for improving the outcome of mechanochemical reactions [20]. In continuation of this

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

• biocatalyst for these transformations. Noteworthy, various acyl donors of different chain lengths were tolerated under the mechanochemical conditions. Keywords: ball milling; enzymes; esterification; lignin derivatization; mechanochemistry; Introduction Mechanochemical reactions, particularly those carried

• out by ball milling, have recently attracted attention of a wider scientific community, owing to the many advantages the excellent mixing inside the ball mill can offer [1]. Besides avoiding or minimizing the use of organic solvents as reaction media, chemical transformations by ball milling very

• products or materials [2][3]. In organic chemistry, amino acids and short peptides are not only known for being stable under automated ball milling conditions during their preparation [4], but also when applied as catalysts to perform stereoselective transformations [5][6][7]. Encouraged by these facts, we

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

• synthesis of amines by their reaction with 1,2-diaminoethane. Keywords: ball milling; Gabriel reaction; imides; mechanochemistry; N-alkylation; Introduction The development of environmentally friendly organic reactions is a growing area of interest [1]. The reduction of the impact of chemical reactions on

• 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

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

• . Several chiral organocatalysts and even enzymes have proved to be resistant to milling conditions, which allows for rather efficient enantioselective transformations under ball-milling conditions. The present article reports the first example of a liquid-assisted grinding (LAG) mechanochemical enzymatic

• resolution of racemic β3-amino esters employing Candida antarctica lipase B (CALB) to afford highly valuable enantioenriched N-benzylated-β3-amino acids in good yields. Furthermore the present protocol is readily scalable. Keywords: ball-milling; β3-amino acid; Candida antarctica lipase B; enzymatic

• ][40][41][42][43][44], so this converts mechanochemistry into a green technique, whose field of application is still very wide. In this context, the use of a minimal amount of solvent (LAG) enable the development of convenient ball-milling protocols. In particular, LAG facilitates mechanochemical

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

• of the coupled products with unacceptable Pd species led to a hard separation and recycling of homogeneous catalyst systems. In our previous study [4] we reported a ball-milling Heck reaction catalyzed by Pd(OAc)2. Although the catalyst showed the satisfactory reactivity, it was difficult to recover

• Information File 1). The Heck coupling reaction under HSBM conditions m-Bromoacetophenone (1a) and styrene (2a) were chosen as the model reactants (Scheme 2), catalyzed by Pd/MgAl-LDHs under ball-milling conditions with silica gel (5 g) and stainless-steel balls (ΦMB = 0.2, dMB = 14 mm) at 800 rpm. Based on

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

• to enable external light irradiation of the reaction mixture while having simultaneously the high-speed ball milling acting on the mixture of reactants and PC (Figure 1; for details, see Supporting Information File 1). Subsequently, with the aim to determine the role of the light, PC and the

• the diazonium salt 1a and B2pin2 (2) was milled for 2 h at 25 Hz in a mixer mill, using a Teflon milling jar and ZrO2 ball bearings. The safe use of diazonium salt under ball milling conditions has been previously reported in the literature [19]. The analysis of the reaction mixture by 1H NMR

• milling conditions (vide supra) could have been indeed the result of a photoredox transformation where the organic photocatalyst eosin Y played a key role in triggering the SET process. Conclusion In summary, simultaneous activation of an organic system by light and ball milling techniques has been

Mechanochemical synthesis of graphene oxide-supported transition metal catalysts for the oxidation of isoeugenol to vanillin

• Ana Franco,
• Sudipta De,
• Alina M. Balu,
• Araceli Garcia and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1439–1445, doi:10.3762/bjoc.13.141

• catalytic support, RGO, a graphene derived material are normally produced by chemical reduction of graphene oxide (GO) [22][23]. The materials were prepared using a simple and effective ball milling approach and were characterized by different techniques. Results and Discussion The supported RGO materials

• with a pore diameter of 39 nm and pore volume of 0.74 cm3 g−1 (Table 1). After the ball milling with metal precursors, the mesoporous structure of RGO was found to be partially collapsed as observed from BET isotherms in Figure 1b and c. BET surface areas of metal supported RGO materials consequently

• decrease in the catalytic activity due to material deactivation. Conclusion A simple mechanochemical ball milling process was used to prepare highly active transition-metal-supported reduced graphene oxide catalysts. The catalysts were used to produce the highly useful aromatic compound vanillin, by

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

• mechanochemical ball-milling approach, we obtained titanium(IV) citrate-based polymers, which have been processed via high temperature chlorine treatment to hierarchical porous carbons with a high specific surface area of up to 1814 m2 g−1 and well-defined pore structures. The carbons are applied as electrode

• ball mill, and thus simplify the synthesis of hierarchical porous carbons drastically. Moreover, it is the first proof that even well-defined carbon pore structures can be derived making use of solid-state conditions like ball-milling. In detail, we apply the Pechini method, an approach commonly used

• involving two synthesis steps: firstly, the mechanochemical synthesis of a polymeric composite, received by ball-milling within five minutes only, and secondly, the conversion of this precursor to a hierarchical carbon by a carbochlorination reaction. The received carbons exhibit specific surface areas of

Kinetic analysis of mechanoradical formation during the mechanolysis of dextran and glycogen

• Naoki Doi,
• Yasushi Sasai,
• Yukinori Yamauchi,
• Tetsuo Adachi,
• Masayuki Kuzuya and
• Shin-ichi Kondo

Beilstein J. Org. Chem. 2017, 13, 1174–1183, doi:10.3762/bjoc.13.116

• were also investigated. Results and Discussion Figure 3 shows the progressive changes in the ESR spectra of amylose [5], Dx, and Gly mechanically fractured by vibratory ball milling at 60 Hz at room temperature for various periods of time under anaerobic conditions, together with the corresponding

• way to Dx. Mechanolysis methods Analogous to the description in [19], powdered samples (100 mg) were mechanically fractured under a nitrogen atmosphere in a vibratory ball-milling apparatus (Shofu Co., Ltd., Kyoto, Japan) equipped with a stainless steel twin-shell blender (7.8 mm diameter, 24 mm

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• University, Department of Chemistry, Lower Mountjoy, Stockton Road, Durham DH1 3LE, UK 10.3762/bjoc.13.11 Abstract Vibration ball-milling in a zirconia-lined vessel afforded clean and quantitative nucleophilic displacement reactions between 4-methoxybenzylthiolate salts and nucleoside 5′-halides or 5

• ball-milling chemistry on nucleoside substrates has not, to the authors’ knowledge, been demonstrated, despite reports of similar chemistry on glycoside derivatives [16][23] and α-amino acid analogues [24]. We describe here the efficient displacement of 5'-chloride, iodide or tosylate leaving groups

• from nucleosides by 4-methoxybenzylthiolate using vibration ball milling (VBM) where competing intramolecular cyclisation reactions are completely avoided. We further demonstrate the application of liquid-assisted grinding to related displacements using potassium selenocyanate. Results and Discussion

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

• formation In 2009, Alvarez-Nunez et al. of Amgen used TSE to scale up the synthesis of a cocrystal which had already been reported to be synthesised successfully by ball milling (employing liquid-assisted grinding (LAG)). This was the first example demonstrating that mechanochemical synthesis could be

• and usage of MOFs increases, the manufacture of these materials, which typically require solvothermal techniques, has become a key research area. Mechanochemical synthesis of several MOFs has been reported typically by ball milling [48], and James et al. have scaled up the synthesis of HKUST-1, ZIF-8

• avoided. In summary, extrusion is a technique that has great potential for use in organic synthesis. It has already been demonstrated as a method to scale up synthesis carried out by ball milling, therefore there is very little preventing its use for the organic reactions that have been reported to be

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

• agents. In general, cleaner reaction profiles were observed in the presence of PEGs, compared to dry-grinding procedures. Keywords: ball-milling; 1,1’-carbonyldiimidazole (CDI); hydantoins; mechanochemistry; liquid-assisted grinding (LAG); poly(ethylene) glycols (PEGs); Introduction Poly(ethylene

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

• , which is an important component of DNA sequencing equipment [4]. p-Toluenesulfonyl (Ts) esters are still an irreplaceable leaving group for carbohydrates as well. The Ts → azide exchange in Ts-β-CD is effective in both solution and under high-energy ball milling (HEBM) conditions, whereas it is

• because of the high boiling polar aprotic solvents used; their complete removal is a difficult task under laboratory conditions, even at high vacuum. Ball milling is an effective method for the preparation of inclusion complexes which has recently begun to be appreciated by organic chemists for its

• heptakis(6-chloro-6-deoxy)-β-CD being produced in good yields [20]. Not unexpectedly, per-6-chlorinated-β-CD showed very poor reactivity, not only under classic solvent reaction conditions (entry 14 in Table 1), but also under ball milling (entries 5 and 15 in Table 1). Mechanochemical syntheses from 6I-O

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• reactions, is acknowledged as an acute inhalation hazard and carcinogen [65][66]. To date, only a few studies of glycosylation under neat conditions have been published. In these methods either the need of heating [67][68][69] or the use of ball milling [70][71][72] was demanded. Moreover, the selectivity

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• the thiourea derived from (L)-valine and 1,6-hexanediamine. The catalysts can be used in only 2 mol % loading, and reused for at least four cycles in neat conditions. The ball milling promoted additions also worked very well. Keywords: bifunctional organocatalysts; organocatalysis; stereoselective

• decreasing the yield (compare Table 4, entries 5, 9, and 11). The recent interest in alternative activation modes [32] for promoting C–C bond formations, led us to consider the catalytic addition of α-nitrocyclohexanone (6a) to nitrostyrene derivatives 1a, 1b, and 1d under ball milling conditions [33]. We

• enantiomeric excess was determined by chiral-phase HPLC analysis using mixtures of hexane/isopropanol as eluent. Method B, under ball-milling conditions: Catalyst VI (15 mg, 0.015 mmol, 0.05 equiv), 2-nitrocyclohexanone (43 mg, 0.3 mmol) and nitroalkene (0.45 mmol, 1.5 equiv) were transferred to a clean, dry

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

• CD derivatives, CD grafted materials and polymers. Mechanochemical methods have successfully furnished greener, solvent-free syntheses and efficient complexation, while flow microreactors may well improve the repeatability and optimization of critical synthetic protocols. Keywords: ball milling

• -conventional techniques, the largest number of papers is dealing with US-assisted CD solubilization or re-dissolution and in a minor extends CD derivatization. Analogously, ball milling is mostly used in the preparation of CD complexes rather than synthetic preparations. MW-assisted CD chemistry covers 1/4–1/5

• achieve a homogeneous solid mixture is ball milling. By this method extremely fine powders can be achieved in mineral dressing processes, paints and pyrotechnics, etc. [79]. It is suitable for both batch and continuous operation, it is similarly suitable also for open and closed circuit grinding as well

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• reaction of N-aryltetrahydroisoquinolines and alkynes can be accomplished under high-speed ball-milling conditions with copper balls (Scheme 9) [31]. Under these solvent-free reaction conditions, isoquinolines 28 were formed more quickly than the in-solvent reactions previously reported, but the ee’s are

• azomethine imines. Su’s CDC of tetrahydroisoquinolines and alkynes under ball milling conditions. Ma’s A3-coupling. Li’s CDC reaction using photoredox catalysis. Liu’s CDC reaction of N-carbamoyltetrahydroisoquinolines. T+BF4– = 2,2,6,6-tetramethylpiperidine N-oxide tetrafluoroborate. Aponick’s alkynylation

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• Pankaj Chauhan Swapandeep Singh Chimni U.G.C. Sponsored Centre for Advance Studies in Chemistry, Department of Chemistry Guru Nanak Dev University, Amritsar, 143005, India, Fax: (+)91-183-2258820 10.3762/bjoc.8.240 Abstract Ball-milling and pestle and mortar grinding have emerged as powerful

• : ball-milling; enantioselective synthesis; mechanochemistry; organocatalysis; solvent-free; Introduction Green chemistry involves innovation in chemical research and engineering that encourages the design of processes to minimize the use and production of hazardous materials and also reduce the use of

• . To address many of these issues mechanochemical methods such as ball-milling and grinding with pestle and mortar have emerged as powerful techniques [5][6][7][8][9][10][11][12]. The mechanical energy generated by grinding two solids or one solid and one liquid substance results in the formation of

Solvent-free and time-efficient Suzuki–Miyaura reaction in a ball mill: the solid reagent system KF–Al₂O₃ under inspection

• Franziska Bernhardt,
• Ronald Trotzki,
• Tony Szuppa,
• Achim Stolle and
• Bernd Ondruschka

Beilstein J. Org. Chem. 2010, 6, No. 7, doi:10.3762/bjoc.6.7

• the above mentioned parameters on the results of coupling reactions. The results from ball milling experiments led to the conclusion that self-prepared and commercially available KF–Al2O3 differ in water content. The higher the residual water content, the higher are the product yields. Keywords: ball

• couplings applying ball milling conditions [55][56], respectively, the reaction times were substantially reduced from several hours to a few minutes following the present reaction protocol. A comparison of the results from the Suzuki–Miyaura coupling of 1 with p-bromoacetophenone (2a) assisted by pure

• titanium silicalite, TiSiO4, showed moderate conversions in the range of basic γ-Al2O3 SRS3. Contrary to microwave-assisted reactions, MgO showed only little conversion when used as a base under ball milling conditions [34], whereas neutral oxides SiO2 and CeO2 did not show any conversion. Since the