An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• . However, both of starting materials are expensive and unstable; especially, propargyl bromide is shock-sensitive and subjected to thermal explosive decomposition, which makes the preparation of 1 impractical with high cost and high risk of explosion. Herein, we report a simple, economical and safe

• hydroxylation of propargylic malonate 5 without work-up of any intermediate. Keywords: alkylation; ‘click’ chemistry; ‘clickable’ polylactide; decomposition; diethyl 2-acetamidomalonate; 2-hydroxy-4-pentynoic acid; one-pot; optimization; propargyl bromide; propargyl tosylate; safe and economical; Introduction

• risk of explosion. Thus, efforts were taken to develop a safe and practical synthetic route for precursor 1. Our first successful effort in the synthesis of 1 gave a good overall yield (50%) after removal of the trimethylsilyl protecting group and hydrolysis of ester 3, generated from diethylaluminum

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• stability against various conditions as well as easy and safe removal [29]. For SPPS, two major protecting groups for the Nα-amino function have been established: Boc (tert-butyloxycarbonyl) [30] and Fmoc [31]. The initial method applied by Merrifield was based on the use of the Boc group as temporary

• -bond formation as an alternative to the well-established HOBt. This introduction was essential because of the inherent explosive potential of HOBt. Moreover, COMU ((1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate) [61] has been identified as a safe and

Nonanebis(peroxoic acid): a stable peracid for oxidative bromination of aminoanthracene-9,10-dione

• Vilas Venunath Patil and
• Ganapati Subray Shankarling

Beilstein J. Org. Chem. 2014, 10, 921–928, doi:10.3762/bjoc.10.90

• bromination reaction proceeds under mild conditions with high yield and purity. The peracid used here is stable, safe and easy to handle and thus can be a good attractive alternative to the conventional peracids. Further study on nonanebis(peroxoic acid) is under progress. Experimental General information All

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• quenched in a tank containing cold water. In another study, Kulkarni et al. [35] showed that the nitration of benzaldehyde (16) can be carried out in a safe manner in a continuous mode using a microreactor system (Scheme 6). The performance of this two phase reaction critically depended on the choice of a

• step to isolate the product. However, since the large-scale synthesis of nitropyrazoles is not a safe reaction under batch conditions, the continuous flow synthesis is the process of choice. Henke and Winterbauer [46] reported a corrosion resistant microreactor built up of PTFE and tantalum for the

• by means of an ice condenser followed by a gas–liquid separator. Similar to the aforementioned study, Löwe et al. [38] reported the vapor phase nitration of propane in a multistep microreactor in a highly sophisticated and safe system. Different steps in the process are integrated in a single reactor

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• ][40]. Direct fluorination of aromatics in microreactor system took place cleanly [36]. As another splendid example for safe handling of hazardous fluorinating reagents, the flow microreactor synthesis using diethylaminosulfur trifluoride (Et2NSF3, abbreviated as DAST) was demonstrated. DAST is a

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• ]. More generally however, it seems safe to predict that the unique properties of stereoselectively fluorinated N-heterocycles will ensure that their importance and utility continue to grow in the future. Fluorination alters the reactivity of aziridines. The ring pucker in azetidine derivatives can be

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• rare sugar synthesis are from non-generally regarded as safe (GRAS) sources, which may stimulate an increasing demand for introducing related enzymes into GRAS microorganisms; 2) many biosynthetic methods involve a chemical equilibrium (isomerization or epimerization) between two or more sugars that

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

• results have been obtained under MW irradiation in a closed vessel also with gaseous reagents. The optimized procedure benefited from the use of a quasi-stoichiometric amount of PS-PPh2 and can be applied for the efficient, safe, rapid, and cost-effective production of urea derivative libraries

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• synthesized in 80% overall yield and 86% ee over 3 steps from geraniol. Nerol turned out to be less suitable as starting material as its asymmetric epoxidation provided a lower ee. It has been shown that (S)-1 with an ee of 92% is as active as enantiopure (S)-1 (99% ee), therefore it is probably safe to

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

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

• popular in organic and medicinal chemistry [4][5][6], mostly owing to the development of computer-controlled dedicated reactors [7][8][9][10] that allow safe and rapid heating to high temperatures and elevated pressures. Microwave radiation directly heats the reaction mixture through two mechanisms

Gold-catalyzed regioselective oxidation of propargylic carboxylates: a reliable access to α-carboxy-α,β-unsaturated ketones/aldehydes

• Kegong Ji,
• Jonathan Nelson and
• Liming Zhang

Beilstein J. Org. Chem. 2013, 9, 1925–1930, doi:10.3762/bjoc.9.227

• permits a safe and efficient access to α-oxo gold carbenes without resorting to the dediazotization strategy [3][4][5] using hazardous and potentially explosive diazo substrates (Scheme 1). Since then an array of versatile synthetic methods has been developed based on the general approach by us [2][6][7

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• used on lab scale. Its highly explosive nature, however, severely limits its use in industrial processes. The in-line coupling of microreactor synthesis and separation technology enables the synthesis of this compound in an inherently safe manner, thereby making it available on demand in sufficient

• chemical synthesis is performed. In particular continuous-flow microreactor technology offers multiple advantages over batch chemistry, including the inherently safe conducting of reactions due to the small reactor dimensions, efficient heat transport and excellent control over the reaction conditions [6

• variety of reactions e.g. cyclopropanation, X–H insertion, cycloaddition and ylide formation [13][15], and more recently, in the synthesis of valuable compound classes such as β-keto esters [16] and β-hydroxy-α-diazocarbonyl compounds [17], we aimed to develop an inherently safe continuous-flow EDA

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• safe and straightforward way. The obtained 1,2,3-triazole-substituted β-aminocyclohexanecarboxylates can be regarded as interesting precursors for drugs with possible biological effects. Keywords: β-amino acids; click chemistry; continuous-flow; copper; flow chemistry; triazoles; Introduction In

• to be environmentally benign technologies [48]. In consequence of these benefits, flow chemistry-based techniques have exerted a significant impact on modern synthetic chemistry, ranging from laboratory-based experiments to industrial-scale production. Here, we describe a safe and efficient CF

• setup is safe, even with unstable reactants such as azides (Figure 3). To maximize the CF triazole synthesis reaction rates, it appeared easiest to use high-temperature conditions initially. The application of elevated pressure in CuAAC is also beneficial, as it can promote the product formation in

Controlled synthesis of poly(3-hexylthiophene) in continuous flow

• Helga Seyler,
• Jegadesan Subbiah,
• David J. Jones,
• Andrew B. Holmes and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2013, 9, 1492–1500, doi:10.3762/bjoc.9.170

• mixing of reagents, boosting reaction rates, and safe handling of reactive intermediates. Using a commercial continuous-flow tube reactor [19], we have already demonstrated multigram synthesis of fullerene derivatives by cycloaddition reactions [11] as well as rapid conjugated-polymer synthesis using

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• the O2-mediated selective oxidation of organic compounds and looking for environmentally safe alternatives to metal catalysis. Keywords: autoxidation; free-radicals; metal-free; molecular oxygen; N-hydroxyphthalimide; Introduction The development of efficient and cheap catalytic systems for the

Simple and rapid hydrogenation of p-nitrophenol with aqueous formic acid in catalytic flow reactors

• Rahat Javaid,
• Shin-ichiro Kawasaki,
• Akira Suzuki and
• Toshishige M. Suzuki

Beilstein J. Org. Chem. 2013, 9, 1156–1163, doi:10.3762/bjoc.9.129

• catalyzed with core–shell Au–Pd NPs and Au NPs [23][24][25][26]. Formic acid is another attractive H2 source because it is safe, easy to handle, and requires no high-pressure equipment. Formic acid and formate have been used as effective H2 donors in the catalytic transfer hydrogenation of aromatic nitro

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• (2.9% ID/g at 2 min) and fast washout (0.2% ID/g at 60 min) in normal mice. These kinetic properties represented improvements over both 58a and 94 [92]. Safety, biodistribution, and dosimetry studies of [123I]IMPY, the [123I]-labeled counterpart of 140e, have indicated it may be a safe radiotracer with

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• have developed a new approach to key compounds 5a/5b for (−)-agelastatin A (1) synthesis, which features the iron(II)-mediated radical cyclization of N-tosyloxycarbamate, a safe azidoformate surrogate. Although somewhat moderate chemical yields of the compounds were obtained in this study, the

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• discussed for lack of space, but the interested reader is directed to a recent review for a more complete description [21]. Experimentally, the procedures are simple and safe, and the reagents are cheap and readily available. In the present context, two properties are especially noteworthy: (a) The reaction

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• swelling properties. The polarity and dimension of the polymer mesh can be easily tuned by varying the type of cross-linker and degree of cross-linking. Nanosponge functionalisation for site-specific targeting can be achieved by conjugating various ligands on their surface. They are a safe and

• safe between 500 and 5000 mg/kg in Swiss albino mice: they did not show any sign of toxicity or adverse reactions. Nanosponges were then injected intravenously into mice and monitored for 24 h. Oral administration of nanosponges was also tested in mice [20] with no apparent side effects. The nanoporous

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• pursued. The advantages of the MCR protocol are speed, variability, insensitivity to steric crowding, safe peptoid-moiety formation, and access to equally distributed stereoisomers (which can be a disadvantage though, once the most active isomer is identified). The improved classical approach gave the

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• weakly recognise Lex trisaccharide antigen [1][2][3][4][5][6]. With this in mind, we focus our research on the discovery of analogues of dimLex that can be used as safe vaccine candidates. Ideally, these analogues should display the internal epitopes that are recognized by anti-dimLex SH2-like antibodies

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• excellent reviews [6][7][8][9][10][11][12][13][14][15][16][17][18]. Review Glycopeptide-based vaccines Specific immune recognition, in which the glycan and the peptide backbone contribute to the binding epitope, is of particular interest for the development of safe immunotherapy and immunodiagnostics. Since