LCST phase behavior of benzo-21-crown-7 with different alkyl chains

• Yan Deng,
• Xing Li,
• Qiao Zhang,
• Zheng Luo,
• Chengyou Han and
• Shengyi Dong

Beilstein J. Org. Chem. 2019, 15, 437–444, doi:10.3762/bjoc.15.38

• and molecular structures. Results and Discussion Two series of B21C7s, comprising carbamate-based linkers 3a–e and urea-based linkers 5a–e, were designed and synthesized, as shown in Scheme 1 and Scheme 2. All structures were confirmed by NMR spectroscopy and high-resolution mass spectrometry (details

• between the amine groups and isocyanate units (yields, 44.6–76.5%), or between hydroxy groups and isocyanate units (yields, 57.4–84.9%), respectively. We also investigated the role of linkages in LCST behavior by the introduction of urea-based and carbamate-based linkers. The water solubility of the

• ethers with urea-based linkers show higher water solubility (5a–e), compared to crown ethers with carbamate-based linkers (3a–e). As amide groups are more hydrophilic compared with ester groups, it is reasonable that 5a–e show stronger hydration effects and exhibit a larger water-accessible surface area

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• describe a method for alkene oxyamination and diamination that utilizes simple carbamate and urea groups as nucleophilic heteroatom donors. This method uses a tandem copper–photoredox catalyst system that is operationally convenient. The identity of the terminal oxidant is critical in these studies. Ag(I

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• with Cs2CO3 in anhydrous DMF, followed by the addition of an excess of pyrrolidine, produced urea 14f (24%) [48][49]. The moderate yield of 14f was attributed to the instability of the in situ-generated isocyanate 15f under the reaction conditions [50]. When trichloroacetamide 13f was treated with an

• excess of pyrrolidine and Cs2CO3 in bench grade (undried) DMF, the reaction followed a different pathway and delivered α-oxoacetamide 16f (58%) instead of urea 14f [48][49]. This type of transformation had already been reported [51] and interpreted by a Favorskii-type mechanism, presumably involving the

• isolation of urea 29 in good yield (78%). It is worth noting that alkylidenecyclopropane 29 was formed with high diastereoselectivity (E/Z ≥ 95:5) at low temperature (−78 °C) but a slight erosion of diastereoselectivity was observed (E/Z = 88:12) when the same sequence was performed at 0 °C. The

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• convenient chiral platform for such macrocycles [9][10]. Several of them, such as 5 (Figure 1), are able to differentiate enantiomers of α-phenylethylammonium salt [11][12]. Sucrose dimers containing two urea or thiourea units (6 or 7) are able to complex anions [13][14]. More complex derivatives with

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• present in the peptide spacer [38]. Therefore, it is pertinent to design a PSMA targeted conjugate that can pass through the tunnel smoothly and reach the active site as well as fit in hydrophobic pockets via hydrophobic interactions. Additionally, the carbonyl oxygen of the urea moiety of DUPA directly

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• was isolated as its p-toluensulfonic acid salt by recrystallization with Et2O in 70% yield (Scheme 2). L-valine (16) was protected as tert-butyl ester 17 by using perchloric acid in t-BuOAc in 75% yield. The unsymmetrical urea 18 was synthesized using triphosgene at room temperature in 50% yield. The

Bioinspired cobalt cubanes with tunable redox potentials for photocatalytic water oxidation and CO₂ reduction

• Zhishan Luo,
• Yidong Hou,
• Jinshui Zhang,
• Sibo Wang and
• Xinchen Wang

Beilstein J. Org. Chem. 2018, 14, 2331–2339, doi:10.3762/bjoc.14.208

• with Milli-Q ultrapure water (>18 MΩ) unless otherwise stated. Synthesis of p-C3N4: p-C3N4 was synthesized by annealing urea (10 g) at 550 °C for 2 h under the muffle furnace with the ramping rate at 5 °C/min, and the resulted buff powder was collected and denoted as PCN. Synthesis of ATCN/p-C3N4: The

• ATCN/p-C3N4 sample was synthesized according to the literature procedures [68]. 2-Aminothiophene-3-carbonitrile (ATCN, 10 mg) and 10 g urea were mixed with 10 mL pure water, and stirring at room temperature for 12 h and then stirring at 80 °C to remove water. The mixtures were ground into powder and

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• carbamates, urea and non-basic heterocycles (Scheme 11) [54]. The scope covers a multitude of electron-poor and electron-rich arenes which can be reacted with carbamates, urea, pyrazole and triazole derivatives to furnish aminated products. The authors address the various reactivities observed with respect

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• carbodiimide-promoted reactions [13][14]. As presented in Figure 2, step a, the first step of a carbodiimide-type conjugation involves the generation of an O-acylisourea intermediate, which is highly electrophilic and which bears the urea-based good leaving group. Such activation of carboxyl groups onto a

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• , possessing an urea backbone, forms a bis-copper complex with two equivalents of CuCl2 (Cu∙∙∙Cu distance = 4.291 Å) [53]. Tetraoxazoline ligand 13 undergoes formation of dinuclear complexes upon treatment with two equivalents of either ZnCl2, Ni(PPh3)2Br2, or Cu(OAc)2 (metal distances: Zn∙∙∙Zn = 8.963 Å; Ni

Graphitic carbon nitride prepared from urea as a photocatalyst for visible-light carbon dioxide reduction with the aid of a mononuclear ruthenium(II) complex

• Kazuhiko Maeda,
• Daehyeon An,
• Ryo Kuriki,
• Daling Lu and
• Osamu Ishitani

Beilstein J. Org. Chem. 2018, 14, 1806–1812, doi:10.3762/bjoc.14.153

• -ku, Tokyo 102-0083, Japan Suzukakedai Materials Analysis Division, Technical Department, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan 10.3762/bjoc.14.153 Abstract Graphitic carbon nitride (g-C3N4) was synthesized by heating urea at different temperatures

• (773–923 K) in air, and was examined as a photocatalyst for CO2 reduction. With increasing synthesis temperature, the conversion of urea into g-C3N4 was facilitated, as confirmed by X-ray diffraction, FTIR spectroscopy and elemental analysis. The as-synthesized g-C3N4 samples, further modified with Ag

• reactions [21][22]. Apart from mpg-C3N4 that is usually prepared by a hard-template method with multistep procedures [9][23], g-C3N4 having a relatively higher surface area can be readily prepared by heating urea, which is an inexpensive and readily available precursor, in air [14][24]. In fact, the urea

Synthesis of diamido-bridged bis-pillar[5]arenes and tris-pillar[5]arenes for construction of unique [1]rotaxanes and bis-[1]rotaxanes

• Ying Han,
• Li-Ming Xu,
• Cui-Yun Nie,
• Shuo Jiang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2018, 14, 1660–1667, doi:10.3762/bjoc.14.142

• ][55][56][57]. Recently, we have successfully constructed a couple of pseudo[1]rotaxane and [1]rotaxane both in solution and in solid state developed by using mono-functionalized pillar[5]arene Schiff base, urea and pyridylimine derivatives [58][59][60][61][62][63]. In continuation of our effort on the

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• both catalysts gave the Michael adduct in excellent yields, high ees were obtained only when 54b was used as organocatalyst (up to 94% ee, Scheme 16). During the last decade, squaramide catalysts have become a powerful alternative to the urea/thiourea and guanidine catalysts as multiple hydrogen bond

• through the enolate mechanism and complete noncovalent catalysis still needs further investigation. Biginelli reaction The catalysts 69f–j (Figure 8) were successfully applied to the enantioselective multicomponent Biginelli reaction of benzaldehyde, ethyl acetoacetate and urea [68]. The results show that

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• between heteroaryl bromides, chlorides or iodides and carbamate, sulfonamide or urea derivatives to be successfully realized in water using palladium-loaded TPGS-750-M (dl-α-tocopherol methoxypolyethylene glycol succinate) micelles (Scheme 1). Moreover, this micellar catalytic system allowed for catalyst

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• ) were solubilized in a total volume of 30 mL 20 mM Tris/HCl buffer, pH 8.0, containing 2 mM EDTA, 50 mM DTT and 8 M urea. After incubation on ice for 30 min, the solution was cleared by centrifugation (15 min at 15,000 rpm and 4 °C). The obtained supernatant was used as stock solution for the in vitro

• refolding. The PeAAOx was solubilized using 150 µg mL−1 protein in 20 mM Tris/HCl buffer, pH 9.0, containing 2.5 mM GSSG, 1 mM DTT, 0.02 mM FAD, 34% glycerol and 0.6 M urea at 4 °C for 80 h. After the incubation for PeAAOx activation/refolding, the refolding mixture was concentrated to 100 mL and the buffer

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• development of chiral bifunctional urea 1 [35], thiourea 2 and 3 [36][37], sulfonamide 4 [38][39][40] and squaramide 5 [38][39][40] catalysts derived from chloramphenicol base (Figure 1), which showed excellent reactivity and enantioselectivity for this asymmetric transformation. A typical example of the

• chloramphenicol-derived bifunctional amide organocatalysts and their application for enantioselective alcoholysis of meso-cyclic anhydrides. In the precedented urea- or thiourea-based organocatalytic methanolysis of anhydrides, one big problem is the homo-aggregation of the catalysts via hydrogen bonding, which

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• directly by fusion of thiourea/urea with 5-aminopyrazole 126 in an oil bath at 120 °C. N-Thiocarbamoyl pyrazole derivatives 180 and 183 underwent cyclization with hydrazine hydrate to give 5-(N-triazolyl)aminopyrazole derivative 182 and hydrazinopyrazolo[3,4-d]pyrimidines 185, respectively (Scheme 51). El

• -amines 198 possessing 4-(1H-benzimidazol-2-yl)phenylamine moiety at C4 position and primary as well as secondary amines at C6 position starting from 5-aminopyrazole-4-carboxamide (194). Compound 194 was treated with urea to give 1H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione (195) followed by chlorination

p-tert-Butylthiacalix[4]arenes functionalized by N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests

• Alena A. Vavilova and
• Ivan I. Stoikov

Beilstein J. Org. Chem. 2017, 13, 1940–1949, doi:10.3762/bjoc.13.188

• ][54][55][56][57]. Modified macrocycles with the amide fragments at the lower rim can form complexes with the anions by hydrogen bonds of the amide group with the guest. It was shown that (thia)calix[4]arene derivatives with urea and thiourea fragments at the lower rim can bind anions through hydrogen

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• variations are adopted to improve the efficiency of this reaction for practical application towards drug discovery [126][127][128]. Modifications have been done in substrates by replacing urea with substituted ureas and thio urea, use of various 1,3-dicarbonyl compounds etc. Reactions using ionic liquids as

• give benzaldehydes and H+ under solvent-free mechanochemical conditions within 30 min. Further, addition of 1,3-dicarbonyl compounds and urea derivatives within the same milling jar led to the desired products in 78–95% yield at 3 h (Scheme 32). Benzaldehydes with electron-donating or -withdrawing

• groups, heteroaromatic aldehydes, N-methyl urea and thio urea also resulted in good to excellent yield with high regioselectivity. It is interesting to note that the reaction was irreproducible in the solution of ethyl acetate at room temperature even after 24 h [133]. A mechanochemical asymmetric three

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• ; thioureas; ureas; Introduction The urea molecule played the central role in the development of organic chemistry since its first documented synthesis in 1828 when the German chemist Friedrich Wöhler prepared it starting from ammonium cyanate (Scheme 1) [1]. This simple, yet intriguing transformation of an

• years, molecules with incorporated (thio)urea and guanidine subunits, due to their ability to coordinate other molecules and ions via N–H hydrogen bonding, have also been considered as organocatalysts and anion sensors [7][8][9][10][11][12]. In Scheme 2, several examples of (thio)urea- and guanidine

• isocyanate provided the target urea sensor after milling for 60 minutes at 18 Hz (Scheme 13a). Monitoring the progress of the reaction by ex situ 1H NMR spectroscopy in DMSO-d6 revealed that the reaction reached completion after only 30 minutes of ball milling with a conversion greater than 90%. Although the

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• combination with an anthracenylmethyl quaternary ammonium group (resulting in catalyst A2) allows them to carry out the syntheses of products 3 with high enantioselectivities [76]. Our group has over the last years been interested in the design and development of bifunctional (thio)urea/ammonium salt

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• understand and model these biological pathways, oxidative aromatization of 1,4-DHP to their corresponding pyridine derivatives has acclaimed wide attention. A variety of oxidants such as urea nitrate, BrCCl3/hν, nitric acid, nitric oxide, N-methyl-N-nitroso-p-toluenesulfonamide, DDQ etc. has been used to

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• Ryota Miyaji Yuuki Wada Akira Matsumoto Keisuke Asano Seijiro Matsubara Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan 10.3762/bjoc.13.151 Abstract Bifunctional organocatalysts bearing amino and urea

• significantly contributed to the field of asymmetric synthesis [1][2][3][4][5][6]. In these catalysts, (thio)urea and tertiary amino functional groups cooperatively activate a nucleophile and an electrophile simultaneously, in a suitable spatial configuration. Thus, they enable various stereoselective addition

Detection of therapeutic radiation in three-dimensions

• John A. Adamovics

Beilstein J. Org. Chem. 2017, 13, 1325–1331, doi:10.3762/bjoc.13.129

• lab to create 3D images. Ionizing radiation reactions in the Fricke dosimeter. Sulfuric acid/urea promoted synthesis of LMG. Synthesized DTBs and their LMG (1) relative radiation dose sensitivity. Acknowledgements J. A. is grateful to the numerous students who have worked on this project and to Dr

Urea–hydrogen peroxide prompted the selective and controlled oxidation of thioglycosides into sulfoxides and sulfones

• Adesh Kumar Singh,
• Varsha Tiwari,
• Kunj Bihari Mishra,
• Surabhi Gupta and
• Jeyakumar Kandasamy

Beilstein J. Org. Chem. 2017, 13, 1139–1144, doi:10.3762/bjoc.13.113

• thioglycosides to corresponding glycosyl sulfoxides and sulfones is reported using urea–hydrogen peroxide (UHP). A wide range of glycosyl sulfoxides are selectively achieved using 1.5 equiv of UHP at 60 °C while corresponding sulfones are achieved using 2.5 equiv of UHP at 80 °C in acetic acid. Remarkably

• , oxidation susceptible olefin functional groups were found to be stable during the oxidation of sulfide. Keywords: monosaccharides; oxidation; sulfones; sulfoxides; thioglycosides; urea–hydrogen peroxide; Introduction Organosulfur compounds such as sulfides, sulfoxides and sulfones are useful intermediates

• [24]. Most of them are found to be stable which can be easily handled and stored. One such solid adduct is urea–hydrogen peroxide (UHP) which is considered to be a safer and efficient alternative to high concentrated aqueous hydrogen peroxide solution [25]. In addition, UHP is also commercially