Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• ethyl xanthate in ethanol under reflux. Bromination of 1 led to the key intermediate 2-bromo-5,6-dimethylbenzimidazole (2), which reacted smoothly with 3-aminopropanol to give the amine 3 in high yield and purity after extraction. The solvent-free microwave process employed was superior to traditional

Expeditious, mechanochemical synthesis of BODIPY dyes

• Laramie P. Jameson and
• Sergei V. Dzyuba

Beilstein J. Org. Chem. 2013, 9, 786–790, doi:10.3762/bjoc.9.89

• Laramie P. Jameson Sergei V. Dzyuba Department of Chemistry, Texas Christian University, Fort Worth, TX 76129, USA 10.3762/bjoc.9.89 Abstract BODIPY dyes have been synthesized under solvent-free or essentially solvent-free conditions, within about 5 minutes in an open-to-air setup by using a

• pestle and mortar, with yields that are comparable to those obtained via traditional routes that typically require reaction times of several hours to days. Keywords: BODIPY; condensation; fluorescent dye; mechanochemistry; solvent-free; Introduction BODIPY dyes are fluorescent organic molecules, which

• air-sensitive nature of DBU (Table 1, entry 5). Et3N, however, appeared to give reproducible results. In contrast, inorganic bases added as solids (K2CO3 and NaOH, Table 1, entries 6 and 7, respectively) failed to give the desired product. Overall, this essentially solvent-free, 5-minute procedure can

A facile, rapid, one-pot regio/stereoselective synthesis of 2-iminothiazolidin-4-ones under solvent/scavenger-free conditions

• Murugan Sathishkumar,
• Sangaraiah Nagarajan,
• Poovan Shanmugavelan,
• Murugan Dinesh and
• Alagusundaram Ponnuswamy

Beilstein J. Org. Chem. 2013, 9, 689–697, doi:10.3762/bjoc.9.78

• based on the relative magnitude of the allylic strains developed during the course of the reaction. This is the first report wherein the impact of allylic strains in directing the regiocyclization has been noted. Keywords: 2-iminothiazolidin-4-ones; regioselective; stereoselective; solvent-free

• environmentally friendly methodologies for the synthesis of 2-iminothiazolidin-4-ones is worth attempting. In this regard, and in continuation of our recent reports on the solvent-free synthesis of amides [19][20], thioamides [21], cyclic imides [22], thiazolidin-4-ones [23], spirothiazolidin-4-ones [24], 1,2,3

• are presented below. Results and Discussion At the outset, optimization of the one-pot reaction was attempted by varying the solvents and using triethylamine as the acid scavenger (Table 1). The reaction was also attempted under solvent-free conditions. The latter was more promising in the sense that

1-n-Butyl-3-methylimidazolium-2-carboxylate: a versatile precatalyst for the ring-opening polymerization of ε-caprolactone and rac-lactide under solvent-free conditions

• Astrid Hoppe,
• Faten Sadaka,
• Claire-Hélène Brachais,
• Gilles Boni,
• Jean-Pierre Couvercelle and
• Laurent Plasseraud

Beilstein J. Org. Chem. 2013, 9, 647–654, doi:10.3762/bjoc.9.73

• of ε-caprolactone (ε-CL) and rac-lactide (rac-LA) under solvent-free conditions and using 1-n-butyl-3-methylimidazolium-2-carboxylate (BMIM-2-CO2) as precatalyst is described. Linear and star-branched polyesters were synthesized by successive use of benzyl alcohol, ethylene glycol, glycerol and

• concept was extended to the synthesis of aliphatic polycarbonates, involving the transesterification of DMC with linear alkane diols under solvent-free conditions, and based on a two-step polymerization process [50]. The high reactivity of imidazolium-2-carboxylates can be explained by their facile

• decarboxylation, thus generating active carbene species, which occurs either by heating [51] or by the addition of Na+ or K+ (NaBPh4, KPF6) [47]. In this paper, we apply this dual approach to the solvent-free ROP of ε-caprolactone and rac-lactide using 1-n-butyl-3-methylimidazolium-2-carboxylate (BMIM-2-CO2) as a

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• Pawel Borowiecki Malgorzata Milner-Krawczyk Jan Plenkiewicz Warsaw University of Technology, Faculty of Chemistry, Noakowskiego St. 3, 00-664 Warsaw, Poland 10.3762/bjoc.9.56 Abstract Racemic 1-(β-hydroxypropyl)azoles were prepared by solvent-free direct regioselective ring opening of 1,2

• oxide (1) under solvent-free conditions. The epoxide ring-opening reactions were carried for 24 h at elevated temperature (32 °C) and resulted in the formation of the appropriate alcohols (±)-3a and (±)-3b in high yields (Scheme 1). In the next step, the influence of crucial parameters in enzyme

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors

• El Sayed H. El Ashry,
• El Sayed H. El Tamany,
• Mohy El Din Abdel Fattah,
• Mohamed R. E. Aly,
• Ahmed T. A. Boraei and
• Axel Duerkop

Beilstein J. Org. Chem. 2013, 9, 135–146, doi:10.3762/bjoc.9.16

• signals at δc 176.10–177.40 ppm. Anomeric carbons in both types were observed at δ 83.20–84.00 ppm. Thermal rearrangement of the S-glycosides 5–7 under solvent-free and atmospheric conditions afforded the corresponding 3-N-glycosides 8–10. The conversion was achieved in a few minutes with good to

• type II (from the four glycosylthiosemicarbazide structural isomers I–IV shown in Scheme 1) were synthesized from 3-N-(glycosyl)oxadiazolinethiones, which were accessed by new regioselective glycosylations. Additionally, 3-N-(glycosyl)oxadiazolinethiones may be prepared by a mild solvent-free thermal S

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• (aq) in ethanol as reported by Mazimba and co-workers. Chalcone 9 was then oxidatively cyclized in the presence of iodine and in a solvent-free environment to give flavone (11) in 72% yield. Methyl-, methoxy- and chloro-substituted acetophenones were also well tolerated in the reaction to give the

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

• : 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

• synthetic organic chemistry has increased considerably, due to the need for development of sustainable methodologies, and has been widely used in solvent-free non-asymmetric transformations. On the other hand, demands for the development of stereoselective synthesis of organic molecules have noticeably

• transformations assisted by mechanochemical techniques proved to be an excellent alternative to atom-economical stereoselective transformations under solvent-free reaction conditions. This review gives an overview of the solvent-free asymmetric organocatalytic transformation assisted by mechanochemical techniques

Catalyst-free and solvent-free Michael addition of 1,3-dicarbonyl compounds to nitroalkenes by a grinding method

• Zong-Bo Xie,
• Na Wang,
• Ming-Yu Wu,
• Ting He,
• Zhang-Gao Le and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2012, 8, 534–538, doi:10.3762/bjoc.8.61

• yields by a grinding method under catalyst- and solvent-free conditions. Keywords: catalyst-free; grinding; Michael addition; solvent-free; Introduction Nowadays, chemists are vigorously taking on the challenge of developing green synthetic methodologies to meet the criteria of sustainable

• , environmentally conscious development. As a result, catalyst- and solvent-free synthetic methods have attracted much interest not only for laboratory synthesis but also in chemical industry, because of reduced pollution, lower costs, mild conditions, and ease of purification. Recently, practical procedures in the

• absence of solvents and catalysts have been accomplished for greener and cleaner syntheses [1][2][3][4][5][6]. As the typical representative of solvent-free reactions, the grinding technique has been widely used in organic synthesis [7][8][9][10][11][12][13]. Compared to traditional methods, some organic

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• [19][21] was tested, since it is known to be an efficient promoter of aldol condensations and Michael additions under solvent-free conditions [22][23]. Nevertheless, the treatment of furanyl-substituted aldehydes 1, 3 and 15 did not yield the targeted diketo-intermediates, but instead the chalcones 5

• hydroxide or barium hydroxide. More recently, another one-pot two-steps procedure using the environmentally benign solvent ethanol was described [24]. The reaction is based on the same mechanism as the solvent-free synthesis described above, but provides better yields. This protocol was recently used to

• ) American Chemical Society). Structure of pyrrolyl (66), thienyl (67) and bithienyl (68)-substituted complexes analogous to compound 43. PF6− counter-anions are omitted. Synthesis of furanyl-substituted terpyridines 12–14 by using Kröhnke’s method. Synthesis of terpyridines under solvent-free conditions

Dioxane dibromide mediated bromination of substituted coumarins under solvent-free conditions

• Subrata Kumar Chaudhuri,
• Sanchita Roy and
• Sanjay Bhar

Beilstein J. Org. Chem. 2012, 8, 323–329, doi:10.3762/bjoc.8.35

• /bjoc.8.35 Abstract An efficient solvent-free protocol for regioselective bromination of substituted coumarins has been developed by using dioxane dibromide as the solid brominating agent. The efficacy of the solvent-free protocol has been established. The effects of the electronic nature and location

• of the substituents on the outcome of the reaction have been rationalized with a proposed mechanism. Keywords: coumarins; solvent-free reaction; substituents; vinylic bromination; Introduction Brominated coumarins have immense synthetic, biological and industrial importance due to their occurance

• ], and for the selective synthesis of α-bromo and α,α-dibromoalkanones supported on silica gel under solvent-free conditions and microwave irradiation [13]. As a part of our endeavor to develop novel solvent-free protocols for important organic transformations, we have reported the efficient synthesis of

Continuous-flow hydration–condensation reaction: Synthesis of α,β-unsaturated ketones from alkynes and aldehydes by using a heterogeneous solid acid catalyst

• Magnus Rueping,
• Teerawut Bootwicha,
• Hannah Baars and
• Erli Sugiono

Beilstein J. Org. Chem. 2011, 7, 1680–1687, doi:10.3762/bjoc.7.198

• ). However, the best result was achieved when the reaction was conducted under solvent-free conditions (Table 1, entry 4). To probe the influence of microwave heating on this transformation, we examined the same transformation under batch conditions and without microwave irradiation. As shown in Table 1

Structural conditions required for the bridge lithiation and substitution of a basic calix[4]arene

• Conrad Fischer,
• Wilhelm Seichter and
• Edwin Weber

Beilstein J. Org. Chem. 2011, 7, 1602–1608, doi:10.3762/bjoc.7.188

• solvent-free crystals featuring two crystallographically independent molecules within the asymmetric unit (Figure 3). Unlike the findings relating to the conformational behaviour in solution, both structurally different calixarene molecules display a partial cone conformation with an anti-arrangement of

A novel and facile synthesis of 3-(2-benzofuroyl)- and 3,6-bis(2-benzofuroyl)carbazole derivatives

• Wentao Gao,
• Meiru Zheng and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 1533–1540, doi:10.3762/bjoc.7.180

• initial investigation towards the synthesis of 3a according to reported methods under solvent-free [49] or solvent-free, microwave-irradiation conditions [50]. Unfortunately, it was found that the Rap–Stoermer reaction did not occur or gave intractable, complex mixtures (as observed by TLC), according to

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• and solvent-free environment [38]. In the first noncatalyzed thermal aza-Michael addition performed at 80 °C, the racemic ester rac-46 is formed from cheap starting materials benzylamine (44) and trans-ethylcrotonate (45) (Scheme 14). Subsequently, Novozym 435 is applied for the kinetic resolution of

• enzyme membrane reactors. E1: GDP-mannose pyrophosphorylase; E2: Pyrophosphatase [36]. Continuous solvent-free chemo-enzymatic synthesis of ethyl (S)-3-(benzylamino)butanoate (48) in a sequence of a plug-flow reactor (PFR) and a packed-bed reactor containing Novozym 435 (E) [38]. Continuous chemo

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• very well suited to work under flow conditions [76][77]. Both catalysts were studied in flow conditions with scCO2 (40 °C, 8 MPa), with conventional solvents and under solvent-free conditions [74][78][79]. One of the main outcomes of the results obtained was the observation of a significant improvement

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• as well. The lower yield obtained in these cases probably results from stirring problems under these solvent-free conditions. To circumvent the problems caused by the α,β-unsaturated aldehyde, we hydrogenated 4 before oxidation to obtain the saturated aldehyde 7. And indeed, under our optimized

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• required position (o,o-disubstituted) we employed a copper- and solvent-free methodology for the Sonogashira coupling that uses tetrabutylammonium fluoride as base [42] (Table 2, method A). Subsequently, we checked that the selective coupling could be carried out under standard Pd–Cu catalysis by

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• also engages in longer, weaker secondary contacts with both the ipso-carbon and nitrogen atom of the anilide unit (Na(1)···C(6A) 2.9231(15) and Na(1)···N(1A) 2.6749(14) Å). The Na(1)–C(1A) distance is comparable to similar distances in the solvent-free sodium aryl derivative (NaC6H3–2,6-Mes2)2 prepared

Novel synthesis of pseudopeptides bearing a difluoromethyl group by Ugi reaction and desulfanylation

• Jingjing Wu,
• Hui Li and
• Song Cao

Beilstein J. Org. Chem. 2011, 7, 1070–1074, doi:10.3762/bjoc.7.123

• , we tried to use it as one of the components in the preparations of the difluoromethylene-containing pseudopeptides by Ugi reaction. Indeed, the reaction of aniline, benzaldehyde, (isocyanomethyl)benzene with 2 proceeded efficiently under solvent-free conditions. Finally, we removed the protecting

• building block 2 were subjected to Ugi reaction under solvent-free conditions, followed by reductive cleavage of the phenylsulfanyl group. It was found that both Ugi reaction and desulfanylation proceeded smoothly for all substrates used to give the corresponding difluoromethylene-containing and

• methanol or under solvent-free conditions. Synthesis of 2,2-difluoro-2-(phenylthio)acetic acid (2). Synthesis of difluoromethylene-containing pseudopeptides (3a–m) and difluoromethyl-containing pseudopeptides (4a–m). Supporting Information Supporting Information File 310: Experimental procedures and

SbCl₃-catalyzed one-pot synthesis of 4,4′-diaminotriarylmethanes under solvent-free conditions: Synthesis, characterization, and DFT studies

• Ghasem Rezanejade Bardajee

Beilstein J. Org. Chem. 2011, 7, 135–144, doi:10.3762/bjoc.7.19

• Ghasem Rezanejade Bardajee Department of Chemistry, Payame Noor University, Qazvin Branch, P.O. Box 878, Qazvin, Iran, Tel.: 982813336366, Fax: 982813344081 10.3762/bjoc.7.19 Abstract A simple, efficient, and mild procedure for a solvent-free one-step synthesis of various 4,4

• performing theoretical calculations at the HF and DFT levels of theory by standard 6-31G*, 6-31G*/B3LYP, and B3LYP/cc-pVDZ methods and good agreement was obtained between experimental and theoretical results. Keywords: diaminotriarylmethane; SbCl3; solvent-free reactions; synthesis; vibrational analysis

• inconvenience in handling the reagents. Considering these restrictions, the development of new and simple synthetic methods for the efficient preparation of DTMs is therefore an interesting challenge. In this contribution, we describe a new route for the preparation of DTM derivatives under solvent-free

Synthesis of 3-(quinolin-2-yl)- and 3,6-bis(quinolin-2-yl)-9H-carbazoles

• Yang Li and
• Wentao Gao

Beilstein J. Org. Chem. 2010, 6, 966–972, doi:10.3762/bjoc.6.108

• )carbazoles under solvent-free conditions by the reaction of β-nitrovinylcarbazole or bis(β-nitrovinyl)carbazole with salicylaldehydes. In light of these findings, and in view of the prominent role structural diversity plays in medicinal and combinatorial chemistry, we felt that there was a real need for the

Formation of epoxide-amine oligo-adducts as OH-functionalized initiators for the ring-opening polymerization of ε-caprolactone

• Julia Theis and
• Helmut Ritter

Beilstein J. Org. Chem. 2010, 6, 938–944, doi:10.3762/bjoc.6.105

• solvent. Surprisingly, in this process only reduction of the nitro groups took place, but no formation of oligomers was observed. Performing the solvent-free one-pot synthesis with reaction times up to 1 h did not lead to higher molecular weights. The formation of low molecular weight adducts 4 here is

Poly(glycolide) multi-arm star polymers: Improved solubility via limited arm length

• Florian K. Wolf,
• Anna M. Fischer and
• Holger Frey

Beilstein J. Org. Chem. 2010, 6, No. 67, doi:10.3762/bjoc.6.67

• environment when core–shell topologies for encapsulation are desired. Here we present a solvent-free synthetic strategy for multi-arm star block copolymers with a hyperbranched polyether core and PGA arms, systematically varying arm length. The combination of glycolide with a multifunctional initiator studied

Synthesis of spiroannulated and 3-arylated 1,2,4-trioxanes from mesitylol and methyl 4-hydroxytiglate by photooxygenation and peroxyacetalization

• Axel G. Griesbeck,
• Lars-Oliver Höinck and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2010, 6, No. 61, doi:10.3762/bjoc.6.61

• sensitization of triplet oxygen with meso-tetraphenylporphyrin (TPP) were performed in polystyrene beads under solvent-free conditions (Scheme 1) [18][19]. Numerous applications of the hydroperoxides 4 and 7, that result from the singlet oxygen ene reactions, have already been reported [20][21]. In context with