Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• modulation of its amino groups at 3 and 8 positions of the phenanthridine ring [52][53]. Systematic changing of the ethidium bromide exocyclic amines into guanidine, pyrrole, urea, and various substituted ureas revealed importance of electron-donor properties of substituents at the 3- and 8-position of the

• the excited state between the 6-phenyl ring and the phenanthridinium chromophore, which controls the non-radiative relaxation [56]. Substituted phenanthridine derivatives In particular guanidine- and urea-substituted derivatives attracted a lot of attention due to the different interactions with

• polypurine tract by reverse transcriptase [65]. In a series of N5-protonated urea-substituted bis-phenanthridinium derivatives (Scheme 22, general structure 9), the variation of the linker length connecting two urea-phenanthridinium conjugates significantly influenced the efficiency of intramolecular

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• to the guest molecules [9][10]. These cyclodextrins linked by ester [11], thioether [12][13][14][15][16], urea [17][18][19], or triazole [20] moieties have been previously described. In addition, aromatic azobenzenes are excellent candidates as molecular switch linkers as they have two forms, namely

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• systems are sometimes required. Urea is the main industrial product for which CO2 is applied as a C1 building block in a reaction with ammonia, still requiring pressures around 200 bar to drive the equilibrium to acceptable yields [10][11]. Another important end product of CO2 are inorganic carbonates

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• room temperature and pH 9.0 (Figure 1a and 1b). The reaction was monitored by denaturing anion exchange chromatography. Addition of urea to the elution buffers and heating of the column to 70 °C causes non-linked duplex ODN to dissociate and elute as their respective single strands while the covalently

• performed on a Perseptive Poros HQ 10 column (10 × 100 mm, 10 µm) at a flow rate of 2 mL/min. Buffer A consist of 10 mM Tris/HCl, pH 7 and 5 M urea. Buffer B consists of 10 mM Tris/HCl, pH 7, 1 M potassium chloride and 5 M urea. The column was heated in a water bath to 70 °C. Before entering the column, the

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• (=C) hydrogen bond (Table 1). The conformational differences in the upper, polar hemisphere of 7a and 8 are also evident. In 7a, the three carbonyl groups point to the exterior and the three N–H bonds to the interior of the cavity formed by the three urea branches. In this way, the chloride anion is

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• degradation by a second-order reaction and forms LC as the major product along with some minor side-chain products [163]. LF is another degradation product of RF which is formed in alkaline solution [46][47] and is unstable at elevated temperatures [79]. Urea and a quinoxaline carboxylic acid has also been

Macrocyclic bis(ureas) as ligands for anion complexation

• Claudia Kretschmer,
• Gertrud Dittmann and
• Johannes Beck

Beilstein J. Org. Chem. 2014, 10, 1834–1839, doi:10.3762/bjoc.10.193

• rather weak complexing agent, the large ring of 2 binds anions with association constants up to log K = 7.93 for chloride ions. Keywords: anion binding; macrocyclic compounds; NMR spectra; supramolecular chemistry; template; urea; Introduction Supramolecular chemistry – the “chemistry beyond the

• molecule” – is an area of modern chemistry, which has grown exponentially in the last decades [1][2]. Among the many concepts of supramolecular interactions, anion coordination chemistry has always been an intensively explored field, which still offers substantial progress [3][4][5]. The urea group has

• proven to be an excellent anion receptor. The ability to form two directional hydrogen bonds through the highly polarized N−H groups towards different kinds of anions allows for building particular molecular arrangements. Incorporation of two or three urea groups into one molecular entity enables the

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• its epimer (Scheme 21) [87]. After completion of the synthesis of the urea dipeptide 53 bearing the cyclic moiety found in muraymycin D2, the four-component condensation was performed similarly as in [86] to yield the protected product 54 as a 1:1 diastereomeric mixture. Functional group manipulation

•  22) [89]. The urea dipeptide 55, 2,4-dimethoxybenzylamine, the protected (S)-2-(methylamino)propanal, and isonitrile 56 were simply combined in ethanol at ambient temperature for 48 h. The expected compound 57 and its epimer were obtained in reasonable yields, and were separated by column

• ) consists in the three-component condensation of a 1,3-dicarbonyl compound, an aldehyde, and a nitrogen component, i.e., urea (X = O, R3 = H) or thiourea (X = S, R3 = H) [29]. The use of N-substituted derivatives of urea or thiourea (R3 ≠ H) has also been reported. Recently numerous advances in the

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

• change of KI-starch test paper), which destroy product 1 during concentration and drying under vacuum. And neither addition of urea (reacting with HNO2 to release N2, CO2 and H2O) nor passing of crude product 1 through a short silica gel column can stop its decomposition. So three reductants were

• acid 6 at 0 °C followed by the addition of another 3 equiv of NaNO2 in water (40%). The resulting mixture was stirred for 40 h at room temperature, and urea in diluted HCl (1 M) was added dropwise until the mixture did not make potassium iodide starch test paper blue or purple. The resulting product 1

Homochiral BINOL-based macrocycles with π-electron-rich, electron-withdrawing or extended spacing units as receptors for C₆₀

• Marco Caricato,
• Silvia Díez González,
• Idoia Arandia Ariño and
• Dario Pasini

Beilstein J. Org. Chem. 2014, 10, 1308–1316, doi:10.3762/bjoc.10.132

• macrocycles [16], and urea-based structures [17] have all been exploited to develop the nanotube concept. Efficient supramolecular receptors for C60 and higher fullerenes have been already reported in the literature and research in this area is still very active [18][19]. Jasti and co-workers have

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• , acidic deprotection afforded the desired building blocks 13a,b suitable for N-derivatization, with the compounds not being fully purified. In order to demonstrate the synthetic versatility of these 3-hydroxyleucine derivatives, they were coupled with urea dipeptide 14 [36], thus providing protected

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

• , Oxone (Table 3, entry 2) shows 94% conversion of 1a in 2 h. In case of 50% Hydrogen peroxide (Table 3, entry 3), more than 7 equivalents of oxidant were required with successive addition. The urea hydrogen peroxide shows moderate conversion in 20 h (Table 3, entry 6). The other diperoxy acids like

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• couplings [16][23], the classical formation of ester [12][17], amide [25][26] or imide [27] bonds between CDs or amino CDs and acid- or anhydride-linkers, and finally urea/thiourea bonds [28][29]. However, the obvious advantages of the Staudinger ligation (high reaction rates, absence of a catalyst, aqueous

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• p-TsNCO 18 to generate the acyclic urea IV, and the alkyne moiety of IV coordinates to gold to form a new alkyne π-complex V. A 5-exo-dig cyclization by nucleophilic attack of the urea oxygen forms the vinylgold carbamimidinium ion VI (the minor 6-endo-dig 19 product is not shown), which undergoes

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

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

• and industrial explosive. Nitro derivatives of glycerine, urea and naphthalene also exhibit explosive properties. Some of the aniline based dyes were used for medical applications, too. The extension of the aniline based medicines led to hundreds of drugs [11], which were used for medication during

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• ] and enaminones [34]. On the other hand, as frequently utilized building blocks in organic synthesis, alkynes have been known to possess versatile reactivity in the synthesis of small molecules. For example, a previous protocol employing aryl alkynes, aldehydes and urea/thiourea has been found to

• scope. Various aldehydes of different properties have been subjected to react with thioureas/N-substituted thioureas/urea as well as different propiolates. Typical results were listed in Table 2. It can be seen from these reactions that aldehydes containing various functional groups tolerate the

• thiourea and alkyne were not successful. On the other hand, benzaldehydes with ortho- and meta-substitution could also react with thioureas and propiolates to give the corresponding DHPMs 5l–5p. However, compared with thiourea, urea has been found to undergo a similar transformation more toughly, and DHPMs

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• . DFT computations reveal high hydrogen-bonding strengths of cyclodiphosphazane PV-amides compared to urea-based catalysts. Experimental results and computations on the enantiodetermining step with cis-cyclodiphosphazane 14a suggest a strong bidentate H-bond activation of the nitrostyrene substrate by

• ) catalysts represent an ever growing class [6][7][8]. The majority of non-specific hydrogen-bonding catalysts are based on the (thio)urea motif (I, Figure 1) [9][10]. More recently squaramides (II, Figure 1) have emerged as complementing motif in HB catalysis [11]. Other H-bonding motifs are less established

• , e.g. sulfonamides [12], urea-N-sulfoxides [13], guanines [14] as well as protonated catalysts such as ammonium [15], 2-aminopyridinium [16] and guanidinium [17] motifs. Most catalysts can form two hydrogen bonds to a reactant, which further enhances their ability to activate and constrain it to a

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• -fused 7,8,10,11-tetraoxatrispiro[5.2.2.5.2.2]henicosane 227 (Scheme 64) [252]. 3.5. Synthesis of 1,2-dioxanes by the Kobayashi method The synthesis is based on the peroxidation of the carbonyl group of unsaturated ketones 228 with the urea–hydrogen peroxide complex followed by a Michael cyclization of

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• Haijun Qu Xuejian Li Fan Mo Xufeng Lin Department of Chemistry, Zhejiang University, Hangzhou 310027, China 10.3762/bjoc.9.320 Abstract A one-pot three-component synthesis of dihydropyrimidinones via a molecular iodine-catalyzed tandem reaction of simple readily available mono-substituted urea

• Biginelli [3][4]. Among them, the Biginelli multicomponent reaction, involving a multicomponent condensation of aldehyde, β-ketoester, and urea, provides an easy access to the preparation of DHPMs, because multicomponent reactions (MCRs) are considered with high facileness, efficiency and economy in organic

• Biginelli-type synthesis of DHPMs from simple readily available mono-substituted urea, alkylaldehyde, and arylaldehyde under mild reaction conditions [22][23][24]. The present method is suitable for a wide range of substrates, and especially for functionalized arylaldehydes. The first catalytic

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• type 11 were isolated by Toste in the intramolecular hydroamination of alkenyl urea 14 with a stoichiometric amount of phosphine–gold complex [(PPh3Au)3O]BF4 (Scheme 5a) [2]. The reaction proceeded at room temperature and was found being favoured by electron-withdrawing ligands. Finally, the use of the

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

• , University of Insubria, Via Valleggio 11, 22100 Como, Italy Department of Chemistry, Universidad Nacional del Sur, Av. Alem 1253, B8000CPB, Bahía Blanca, Buenos Aires, Argentina 10.3762/bjoc.9.274 Abstract A fast and efficient protocol for the synthesis of N,N'-disubstituted urea derivatives from alkyl

• : isocyanates; microwave-assisted reaction; one-pot reaction; tandem Staudinger–aza-Wittig reaction; urea derivatives; Introduction The industrial and commercial impact of isocyanates (R–NCO) is steadily growing. In particular, the polyurethane output has undergone yearly increases of 5% over the last decade

• [1]. Isocyanates play a relevant role as chemical intermediates in the manufacturing of thermoplastic foams, elastomers, adhesives, agrochemicals and pharmaceuticals. The isocyanate group is also widely used as a precursor to several bioactive compounds and drugs that contain urea and carbamate

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

• various robust routes (Scheme 31) [84][85]. Most of these transformations use condensation reactions between urea (3.6) and a bis-electrophile to generate the desired structures. For instance, ester 3.7 furnishes uracil (3.5), which in turn can be converted into cytosine (3.4) by selective amination with

• ammonia/ammonium chloride (Scheme 31). Alternatively, thymine (3.3) may be accessed by reacting methyl formylpropionate (3.8) which acts as a bis-electrophile with urea. Following construction of the pyrimidone core the linkage to the anomeric position of a ribose is best achieved using the Vorbrüggen

Creating Complexity

• Donald Craig

Beilstein J. Org. Chem. 2013, 9, 1881–1882, doi:10.3762/bjoc.9.220

• cyanate could be converted into urea [2]. Since that seminal finding, chemical synthesis has advanced to extents which must have been unimaginable to its early practitioners. The numerous paradigm-shifts which have taken place throughout the history of synthesis have been driven largely by a single

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• product conversions of 66−98% depending on how electron rich or deficient the aromatic ring of the aldehyde was (Table 3). The Biginelli reaction As our final reaction for study, we turned to the Biginelli reaction (Scheme 4) [43][44][45][46][47][48]. This acid-catalyzed cyclocondensation of urea, β

• reaction of benzaldehyde, ethyl acetoacetate and urea catalyzed by sulfuric acid (Figure 8). The calculated Raman spectrum of the product, 4a, shows a strong signal at 1598 cm−1 which was selected for monitoring. Using a catalyst loading of 10 mol % and a flow rate of 1 mL/min, we monitored the reaction

• volumetric flask was dissolved urea (3.003 g, 50 mmol, 1 equiv.) in methanol (~30 mL). Into the flask was then added benzaldehyde (1.306 g, 50 mmol, 1 equiv) and ethyl acetoacetate (6.507 g, 50 mmol, 1 equiv). Methanol was added to bring the total volume to 50 (1 M) and the reagents were thoroughly mixed. An