Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• developed the pyroglutamic acid-derived triazolium salt 10 which mediated benzoin reactions in similar enantioselectivities [14]. The chiral triazolium catalyst 11 transfers chiral information to the benzoin products by engaging in hydrogen-bonding interactions [15]. Waser’s chiral bifunctional (thio)urea

• a cross-benzoin reaction of the latter to furnish the spirocyclic product 84 (Scheme 46). Conclusion The first report of a benzoin reaction by Wöhler and Liebig appeared merely four years after the former disclosed the paradigm-changing urea synthesis. However, detailed investigations of this

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

• preliminary study on sonochemical Staudinger-aza-Wittig tandem reactions [20] proving that isocyanate and urea formation is strongly favored. However, the applied power must be optimised for the best conversions of azido-CD into urea to be obtained and if lower efficiency in the second step is to be avoided

Asymmetric α-amination of β-keto esters using a guanidine–bisurea bifunctional organocatalyst

• Minami Odagi,
• Yoshiharu Yamamoto and
• Kazuo Nagasawa

Beilstein J. Org. Chem. 2016, 12, 198–203, doi:10.3762/bjoc.12.22

• presence of a guanidine–bisurea bifunctional organocatalyst was investigated. The α-amination products were obtained in up to 99% yield with up to 94% ee. Keywords: α-amination; bifunctional catalyst; guanidine; hydrogen-bonding catalyst; urea; Introduction Asymmetric α-amination of β-keto esters is an

• particular, catalytic asymmetric α-amination of β-keto esters has been widely explored, using both metal catalysts and organocatalysts [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. We have developed a series of guanidine–bis(thio)urea bifunctional organocatalysts, and have used them in a variety of

• expected that guanidine–bisurea bifunctional organocatalyst 1 would be effective in promoting α-amination of β-keto esters as a result of interactions between guanidine and enolate of the β-keto ester, and between urea and azodicarboxylate (Figure 1b). Herein, we describe the catalytic asymmetric α

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• [26]. The now familiar glycoluril motif of 16 clearly has the rigid C-shaped required, and a subsequent report showed it to be capable of complexing dihydroxybenzenes using a combination of aromatic stacking and hydrogen bonding to the urea carbonyl groups [27]. The aromatic stacking surface can be

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• trimers as shown by Lincoln et al. [77].) The longer succinamide linker in 66β-CD2su engenders higher viscosities than does the shorter urea linker in 66β-CD2ur probably because steric hindrance between the adjacent adamantyl-substituted poly(acrylate) chains is greater when 66β-CD2ur forms a cross-link

• [76]. (The 66 prefix in 66β-CD2su and 66β-CD2ur indicates that the succinamide and urea linkers are attached to the C6 carbon in a D-glucopyranose subunit of each β-CD.) The increasing length of the adamantyl tether from amido to hexylamido in PAAAD and PAAADhn progressively decreases steric hindrance

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• already discussed [21][22][23], the bifunctional nature of organocatalysts plays an important role in this reaction to attain satisfactory levels of enantioselectivity. The presence of additional hydrogen donors such as urea groups positively affected the enantioselectivity both in the presence of chiral

• base organo-catalysts and when using quaternary ammonium salts. In the latter case, however, only 46% ee was obtained using the bifunctional urea-containing ammonium salt catalyst introduced by Dixon's group [30]. Readily available commonly used quaternary ammonium salt catalysts gave racemic mixtures

• the urea and ammonium sides of the catalyst (Table 1, entries 16, 17, and 21). Electron-neutral or bulky aryl groups on the ammonium side, as well as the introduction of a naphthyl group, did not result in any improvement of the enantioselectivity. Also, the presence of aliphatic groups on the urea

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• [4]arenes are sulfur-bridged analogs of calix[4]arenes, which have potential application in the molecular recognition of cationic, anionic or neutral molecules. In this regard, Yamato et al. incorporated two urea moieties possessing various aryl groups and two pyrene-appended triazole rings at the

• opposite side of the thiacalix[4]arene cavity [38]. The authors found that receptor 52 (Scheme 18) could selectively bind Cl− through hydrogen bonding interaction with the urea NH protons, and 52 can also bind with Ag+ through complexation with the pyrene-appended bistriazole. In homogeneous catalysis

Urethane tetrathiafulvalene derivatives: synthesis, self-assembly and electrochemical properties

• Xiang Sun,
• Guoqiao Lai,
• Zhifang Li,
• Yuwen Ma,
• Xiao Yuan,
• Yongjia Shen and
• Chengyun Wang

Beilstein J. Org. Chem. 2015, 11, 2343–2349, doi:10.3762/bjoc.11.255

• intermolecular interactions in molecular self-assembly systems. Therefore, molecules containing urea, amide and other similar groups have been investigated because these molecules can easily generate intermolecular hydrogen bonds [7][8][9]. Tetrathiafulvalene (TTF) derivatives have been widely investigated in

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• existence of life. It is also present in many small molecules acting as an intramolecular configurational lock. This is realized in hydrazones [1], heterocyclic urea derivatives [2], molecules exhibiting photoexcited proton transfer [3] and other compounds [4][5][6] reported also by us [7][8][9][10]. The

• studied by MS [44] while its interaction preferences with anions in solution are not known. On the other hand the tris-urea derivatives with a spacer between NHCONH groups were used in several supramolecular complexes including those with encapsulated anions [45][46], sensing nerve agents [47] or in self

• other hand understanding the behaviour of non-rigid molecules may also be useful and a challenging task. Experimental Synthesis Compound 1 was obtained by heating urea (1.0 g, 16.7 mmol) and n-butyl isocyanate (3.3 g, 33.4 mmol, 1:2 molar ratio) for 24 h under reflux in pyridine (20 mL). Then pyridine

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• ], one of the greatest physical organic chemists in China, my small group survived until I returned to the institute. I was so impressed by the work of Professor Zimmerman on the folding of linear urea derivatives driven by intramolecular hydrogen bonding [21], that in 2001, our group started several

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• described for nagelamide B (8) [15]. The structure of citrinamine C (3) was elucidated to be the 2,2´-didebromo derivative of nagelamide B (8) with an additional methylation of the hydroxy group at C-9 (80.8 ppm) and an oxidation of the imidazole ring at position C-13 (154.6 ppm) (an urea instead of a

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• heterocyclic compounds with cyclic urea core, are widely used as intermediates in industrial production of α-amino acids [1]. They exhibit various biological activities making them attractive candidates for drug discovery [2][3][4][5][6][7][8][9][10][11]. In the most cases, the observed biological activities

Why base-catalyzed isomerization of N-propargyl amides yields mostly allenamides rather than ynamides

• Armando Navarro-Vázquez

Beilstein J. Org. Chem. 2015, 11, 1441–1446, doi:10.3762/bjoc.11.156

• for the corresponding isomers for a selected combination of starting amides or carbamates and a final urea example (Figure 1) were computed using ab initio and DFT methods. Results and Discussion Computational procedures It is known that ab initio prediction of cumulene–polyynes isomerization energies

• position. A final and more demanding test is the Hsung observation that whereas only ynamide 12 was observed upon isomerization of the corresponding N-propargylamide, the related carbamate 13 only evolves to the allenamide stage [18]. Furthermore, urea 14 (see page 5069 of [3], we thank one of the referees

• for highlighting this example) again furnished only the ynamide compound. The ωB97 computations predict the ynamide 12c to be more stable than allenamide 12b by 1.7 kcal/mol (Table 2). On the other hand, the yncarbamate 13c is nearly degenerate with the allencarbamate 13b. For the urea 14 this trend

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• ]. Even so, industrial processes using CO2 as chemical feedstock are limited to the production of few large scale chemicals such as urea, methanol, salicylic acid as well as inorganic and organic carbonates [5]. Since CO2 is captured in huge amounts from the flue gases of fossil fuel combustion, it would

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