Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• °C in dimethyl propylene urea (DMPU) gave dione 235 (72%). An RCM sequence of compound 235 in the presence of G-I (12) catalyst gave the RCM product 236. A subsequent catalytic hydrogenation generated the saturated dione 237. Finally, the pyridine ring has been introduced by reacting dione 237 with

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• system maintained at 0 °C in order to generate the urea adduct 90 in quantitative yield (Scheme 15). In order to prepare the target compound this flow stream was then combined with an additional stream of bromoacetophenone (91) and passed through a heated tubular reactor unit (100 °C, 15 min) furnishing

Glycoluril–tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests

• Yoann Cotelle,
• Marie Hardouin-Lerouge,
• Stéphanie Legoupy,
• Olivier Alévêque,
• Eric Levillain and
• Piétrick Hudhomme

Beilstein J. Org. Chem. 2015, 11, 1023–1036, doi:10.3762/bjoc.11.115

• from diphenylglycoluril 5 (Scheme 1). The key building-block 5 is available in multigram scale by reaction of benzil with urea [20]. The first approach leading to molecular clips 1 and 2 is based on a straightforward double nucleophilic substitution leading to a seven-membered ring using 4,5-bis

• (bromomethyl)-2-thioxo-1,3-dithiole (6) [21]. In order to determine the optimized experimental procedure to carry out the urea N-alkylation of compound 5, we took advantage from literature of previous works realized on glycoluril for such reaction using a 2,3-bis(halogenomethyl)aryl derivative. Reported

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• creates the opportunity to synthesize new analogues with an enhanced activity. In this way, many of the N-acyl [41][42][43] as well as urea and thiosemicarbazone [44] analogues of 7 have been obtained and evaluated. Their characteristic feature is that their amine group is bound with the carbonyl or

CO₂ Chemistry

• Thomas E. Müller and
• Walter Leitner

Beilstein J. Org. Chem. 2015, 11, 675–677, doi:10.3762/bjoc.11.76

• [3]. Remarkably, 110 million metric tons of CO2 per year for producing urea, methanol and salicylic acid are industrial reality today. These applications clearly illustrate the path forward. Due to the abundant availability of pure CO2 gas streams [1], it is only logical to promote a more widespread

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• corresponding amine at room temperature in dichloromethane [31] was sufficient for ureas 2a,c–e, heating (40 °C) and the addition of triethylamine [32] were required for condensation with N-methylbenzylamine to obtain urea 2b. The Vilsmeier salt was then generated in situ with oxalyl chloride from the

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• direct conjugation, whereby a third such system is excluded from interaction [3]. Typical examples are 2-vinyl-buta-1,3-diene ([3]dendralene, 3-methylene-penta-1,4-diene), benzophenone or urea. Whereas the hydrocarbon parent systems, the [n]dendralenes, have long been a neglected class of oligoenes [4

TEMPO-derived spin labels linked to the nucleobases adenine and cytosine for probing local structural perturbations in DNA by EPR spectroscopy

• Dnyaneshwar B. Gophane and
• Snorri Th. Sigurdsson

Beilstein J. Org. Chem. 2015, 11, 219–227, doi:10.3762/bjoc.11.24

• deoxyoligonucleotides using the phosphoramidite method. All three nucleosides contain 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) connected to the exocyclic amino group; TA directly and UA as well as UC through a urea linkage. TA and UC showed a minor destabilization of a DNA duplex, as registered by a small decrease

• formation of TAH+•C and TAH+•G, in which protonation of N1 of A allows the formation of an additional hydrogen bond to N3 of C and N7 of G, respectively, with G in a syn-conformation. The urea-based spin labels UA and UC were more mobile than TA, but still showed a minor variation in their EPR spectra when

• prepared urea-linked spin-labeled derivatives of 2´-deoxycytidine (UC) and 2´-deoxyadenosine (UA) and incorporated them into DNA duplexes (Figure 1C and D). These labels provide additional possibilities for hydrogen-bonding through the urea linkage but are also more flexible than TA or TC. In spite of the

Molecular cleft or tweezer compounds derived from trioxabicyclo[3.3.1]nonadiene diisocyanate and diacid dichloride

• Gert Kollenz,
• Ralf Smounig,
• Ferdinand Belaj,
• David Kvaskoff and
• Curt Wentrup

Beilstein J. Org. Chem. 2015, 11, 1–8, doi:10.3762/bjoc.11.1

• = 0.0942. In each molecule there is one H atom (H31, H81) bonded to the nitrogen atom, which is cis to the O atom of the urea subunit. These H atoms are not involved in hydrogen bonding. The other H atoms of the same urea subunit (H(N32) and H(N82)) show intramolecular hydrogen bonds to O40 and O90 of

Synthesis and characterization of pH responsive D-glucosamine based molecular gelators

• Navneet Goyal,
• Hari P. R. Mangunuru,
• Bargav Parikh,
• Sonu Shrestha and
• Guijun Wang

Beilstein J. Org. Chem. 2014, 10, 3111–3121, doi:10.3762/bjoc.10.328

• benzylidene acetal group, we synthesized a small library of amide and urea derivatives of head group 3 (Scheme 1) and screened their gelation properties. Similar solvent systems used for our previous small molecular gelators were used, and selected representative hydrophobic functional groups were studied. We

• expect that other C-2 analogs with similar polarities exhibit similar self-assembling properties. Scheme 1 shows the preparation of the headgroup 3, the amide I and urea II analogs by a similar method as reported previously [36]. Several alkyl and aryl derivatives are synthesized for the amide and urea

• substituted 3. These include the short chain alkyl, phenyl, and naphthyl groups. The gelation properties of the amide and urea derivatives are shown in Table 1. We found that nearly all analogs synthesized and screened are effective gelators for ethanol, ethanol/water (1:2 by volume), and DMSO/water (1:2 by

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• , Světlik et al. studied the Biginelli-type condensation of 2-hydroxybenzaldehyde with urea (thiourea) and dialkyl acetone-1,3-dicarboxylates as active methylene components [16]. Unexpectedly, the reaction with salicylaldehyde furnished two different products depending on the ester alkyl group (Scheme 2

• derivatives from salicylaldehyde, various dicarbonyl compounds, and urea (thiourea) using PdO as a catalyst (Scheme 2). Heterocyclizations involving both, salicylaldehyde and aminoazoles, are intriguing as well. Thus, for example in the course of the study on the application of 3-amino-1,2,4-triazole and

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