Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• and are uncorrected. X-ray crystallographic structure determinations were performed by using Rigaku Rapid II and Bruker X8 Prospector single crystal X-ray diffractometers. The X-ray crystal structure data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• Hammett analyses, have identified key determinants that are essential for reaction efficiency. X-ray crystal structure analysis of ketone 2 reveals a dihedral angle of φO=C-C-F = −3.7°. Although the origin of this specificity requires clarification, this fluorohydration reaction constitutes a rare case of

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• support. dMolecular representation of the X-ray crystal structure of 12. The unit cell of 12 contained two molecules of 12, with only one shown for clarity. Proposed mechanism. Optimization of the NHC-catalyzed formal [2 + 2] cycoaddition.a Supporting Information Supporting Information File 335

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• ; found, 501.20295. Crystal structure determination Single crystals of rotaxane 1a (C36H42FeN3O3) were obtained by slow evaporation of a dichloromethane solution. A suitable crystal was mounted on a cryoloop with paratone®-N oil on an AFC11 partial Chi goniometer. The data were collected at 120 K on

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• recrystallization. Compounds comprising a benzo[a]quinolizidine ring system. Representative NOE interactions in cis and trans-21–24 (only one enantiomer is shown). X-ray crystal structure of products 25 and 26. Representative NOE interactions in 28 and 29. Reactions between enolizable anhydrides and imines

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/structures. Supporting Information File 44: Experimental data for selected compounds 9, details of the crystal structure determination, and the original 1H and 13C NMR spectra for all products

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• atoms to engage the ammonium groups of TAPM (see the crystal structure of the F-1a phase). This structure was thermodynamically stable and hinted at a possible activation of water or methanol as nucleophiles by the sulfate anions during the ring opening of epoxides. When the coordinated water was

• frameworks could be tuned by varying the ratio of anion/cation multitopic components and the basicity of the cation component. View of the crystal structure of F-1 (F-1a phase), with representation of atoms by thermal ellipsoids at a 30% probability level. The hydrogen atoms, except for those in NH groups

• and solvate water molecules, were omitted for clarity. Only the labels of symmetry-independent heteroatoms are shown. View of the crystal structure of F-1 (F-1a’ phase), with representation of the atoms via thermal ellipsoids at a 30% probability level. The hydrogen atoms, except for those in NH

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• constant of 16 Hz between the two olefinic protons of the styryl fragment. Further characterization of the new oxazolones was provided by the determination of the crystal structure of oxazolone 2c. A molecular drawing of 2c is shown in Figure 4, where the (Z)-configuration of the exocyclic C=C bond (C7–C8

• )=C bond disappeared and two new signals appeared at around 68–69 ppm (quaternary C) and 51–60 ppm (CH). These facts are consistent with the expected hybridization change from Csp2 to Csp3 after formation of the cyclobutane ring. Determination of the crystal structure of complex 4a, which is shown in

• shorter than the sum of the van der Waals radii (2.67 Å) [51]. This suggest a close interaction between these two atoms, as observed in the crystal structure of 2c (see above). The analysis of other internal bond distances and angles in the coordination sphere of the Pd atom shows that they are similar to

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• -glycyrrhetinic acid derivative 18. The molecular structure of compound 18 in the crystalline state is shown in Figure 3. In this crystal structure, there is an orientational disorder of the m-fluorophenyl moiety due to the rotation of a single bond. Details for the crystal structure determinations are given in

• intermediate 6; b) Possible aminolysis process. Crystal structure of conpound 18. Synthesis of compound 4. Reagents and conditions: (a) Ac2O, NEt3, DMF (cat.), DCM, 25 °C, 1 day; (b) oxalyl chloride, NEt3, DMF (cat.), DCM, 25 °C, 5 h, then piperazine, DCM, NEt3, DMAP, 0/25 °C, 30 min. Synthesis of compound 4

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• 1 were obtained by slow evaporation from a carbon disulfide solution, allowing us to disclose the molecular structure by X-ray crystallography (Figure 2a). As shown in Figure 2a, the crystal structure of 1 clearly displayed a nonplanar conformation, resulting from steric repulsion between the phenyl

• . Hydrogen atoms and solvent molecules are omitted for clarity. (d) Selected bond lengths (from the crystal structure) and calculated NICS(1) values of rings A–I in 1. (e) Clar valence structure representation of 1 with three benzeneoid rings. (a) UV–vis absorption spectra of precursor 5 and 1 in CH2Cl2

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• molecule in the asymmetric unit with the bridgehead substituents being almost 180° to each other (Figure 2, for labelling see Figure S33 in Supporting Information File 1). Unlike the unsubstituted triptycene 1 crystal structure which exhibits a high degree of C–H···π interactions between the aromatic rings

• for C102H88N4O4Si2Zn, 1552.5636; found, 1552.5616. Crystal structure determinations Crystals were grown following the protocol developed by Hope by dissolving the compound in CH2Cl2 and layering with a MeOH for liquid–liquid diffusion [52]. Single crystal X-ray diffraction data for all compounds were

• (iii) of another triptycene molecule. Hydrogen atoms and minor disorder omitted for clarity (thermal displacement 50%). Single crystal X-ray structure of triptycene-linked zinc-nickel porphyrin dimer 16 showing the conformation within the crystal structure; (a) top-view of zinc porphyrin; (b) top-view

Synthesis of C₇₀-fragment buckybowls bearing alkoxy substituents

• Yumi Yakiyama,
• Shota Hishikawa and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2020, 16, 681–690, doi:10.3762/bjoc.16.66

• vapour diffusion method using CHCl3/hexane conditions. Figure 2 shows the crystal structure of 5a. The crystal was obtained as a racemic compound containing a pair of two enantiomers defined by bowl chirality [26], as a result of the rapid bowl inversion under the crystallization conditions. 5a formed a

• crystal structure of 5c, two crystallographically independent units were observed (Figure 5a). 5c also contained both of the enantiomers and formed a columnar structure along the b axis with the slipped stack manner, which was composed of only one side of the enantiomer (Figure 5b,c). The columns with the

• succeeded in synthesizing three different alkoxy-substituted C70-fragment buckybowls 5a–c. In particular, 5c was not an intended molecule, but was formed unexpectedly through the rearrangement through the Pd-catalyzed C–H bond activation reaction. The X-ray crystal structure analysis of 5a–c clearly

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• an essentially isoenergetic conformer is that found in the X-ray crystal structure. The first conformers where the terminal bispirocyclohexane ring lies axial are significantly higher in energy (ΔG = +1.25 kcal/mol−1 and ΔG = +1.19 kcal/mol−1) than the equatorial conformers as illustrated in Figure 3

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• possesses a −log(Kd) value of 8.36 suggesting that it too would be on a par with panobinostat (8.47). Our previous study showed that the hydroxamate tail of TOI1, TOI2, and TOI4 formed a bidentate interaction with the Zn2+ ion at the base of the HDAC8 receptor, which is consistent with the crystal structure

• Biotek Synergy HTX multimodal plate reader after incubation for 30 minutes. Preparation of the HDAC8 receptor for docking The HDAC8 crystal structure (protein database pdb: 1W22) [32] was utilized as the docking receptor for all compounds. This receptor is crystalized as a dimer thus only the A chain was

Six-fold C–H borylation of hexa-peri-hexabenzocoronene

• Mai Nagase,
• Kenta Kato,
• Akiko Yagi,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2020, 16, 391–397, doi:10.3762/bjoc.16.37

• -catalyzed six-fold C–H borylation of HBC was successfully achieved by screening solvents. The crystal structure of hexaborylated HBC was confirmed via X-ray crystallography. Optoelectronic properties of the thus-obtained hexaborylated HBC were analyzed with the support of density functional theory

• subjected to X-ray crystallographic analysis. Orange single crystals were formed by the diffusion of pentane vapor to a 1,1,1-trichloroethane solution of 1 synthesized by the C–H borylation method. The crystal structure confirmed that the C–H borylation proceeded regioselectively at the least hindered C–H

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• stacking distance of around 3.45 Å. It is noteworthy that both 4b and 4c pile up while minimizing the steric repulsion between the tert-butyl groups which occupy “staggered” orientations in their crystal structures (Figure 5c and 5d). Unfortunately, the crystal structure of 4a was not determined after

Absolute configurations of talaromycones A and B, α-diversonolic ester, and aspergillusone B from endophytic Talaromyces sp. ECN211

• Ken-ichi Nakashima,
• Junko Tomida,
• Takao Hirai,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 290–296, doi:10.3762/bjoc.16.28

• . Supporting Information File 266: Crystal structure information files for 1, 3, and 5. Acknowledgements The authors thank the Rigaku Corporation for the single-crystal X-ray structural analysis of talaromycone A. The authors are also grateful to Dr. Hiromi Ota at the Division of Instrumental Analysis for the

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• /methanol to afford a colorless transparent crystal. It crystallized in the monoclinic space group: P–1 (2), cell: a = 5.191(5) Å, b = 12.133(12) Å, c = 13.576(14) Å, α = 80.141(13)°, β = 81.978(12)°, γ = 79.496(12)°, temperature: 296 K. X-ray crystal structure of compound I18 and III4 are shown in Figure 3

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• , nitrogen, fluorine) and have been observed to govern the conformational structure of some molecules as well as the alignment of the molecules within a crystal structure [27][28][29]. Moreover, HBs have been reported to play a vital role in a ligand–receptor interaction that determines the biological

• crystal structure and solution-state NMR data of the coumarin 6 were studied to examine any C–F···H–C hydrogen bond interactions. DFT calculations were performed to determine the preferred conformations of the structure that might exhibit a C–F···H–C hydrogen bond. Results and Discussion Synthesis of 2

• the distances F–H5 and F–H3 fall inside the limit of ≈2.55 Å, although not simultaneously. For a fixed geometry like that of the crystal structure, this would suggest that through-space F–H coupling would be observed between F and H5 but not between F and H3, as in Figure 1, where there is an obvious

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• favor of 4cB. The resulting calculated equilibrium constant of 2.042, corresponding to a 67.1/32.9 ratio of the rotamers (4cB/4cA), was in good agreement with the experimentally by 1H NMR (CDCl3) observed ratio of 65/35. Significantly, the single crystal of 4c, which afforded the crystal structure shown

• of the final products were detected in the NMR spectra, and a representative DFT computational analysis conducted with 4c (this compound also yielded a crystal structure) was in agreement with the ratio of the two rotamers that were observed in the corresponding NMR spectra. A mechanism was proposed

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• been reviewed elsewhere [3][10][11][12][13][14][15][16][17]. The first crystal structure of a monoterpene cyclase [18] was reported in 2002. Subsequently, the first crystal structures of a sesquiterpene [19][20] and a triterpene [21] cyclase were published in 1997. Less than a decade ago, the first

• crystal structure of a diterpene cyclase was reported by Christianson and co-workers [22]. These structures, in conjunction with extensive biochemical work [10][13][14][23], have contributed to the understanding of mechanistic details of terpene cyclases and facilitated rational enzyme design [24

• relevant, i.e., that have a ligand bound in a reactive configuration and have a fully closed active site. Recently, a crystal structure of the CotB2 enzyme that met these criteria was published [42]. In the current work, we describe the crucial role of the amino acids in the active site on the reaction

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• characterize the formation of the 2,7-anhydro skeleton, triols 2 and 3 were treated with 2,2-dimethoxypropane in the presence of a catalytic amount of camphorsulfonic acid (CSA) in acetonitrile to afford compound 4 in 63% and azide acceptor 4a in quantitative yield (Scheme 1). The crystal structure of 4

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• , encoded by the gene fusA1) as their target [11][12]. The co-crystal structure of argyrin B (2) and P. aeruginosa EF-G1 provides structural information of the complex at atomic resolution as basis for further structure-based optimization [11]. Jones and colleagues analyzed possible resistance mechanisms to

• ’-methoxy group to halogens or other substituents in different positions led to a loss of antibacterial activity, whereas the 5’-methoxytryptophan regioisomer largely retained activity against P. aeruginosa PAO1. Inspection of the crystal structure of argyrin in complex with the bacterial elongation factor

• possibility resides in the dehydroalanine-sarcosine motif and modification seems possible as deduced from the crystal structure [11] of argyrin with elongation factor G1. Despite the successful implementation of total syntheses of argyrin derivatives, a more rapid access towards diversity in the argyrins and

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• -en-7-ol (23, Figure 7a) synthase, for which the active-site residues responsible for cationic intermediate stabilization were identified through analysis of the crystal structure [122] and structural modeling [123]. Mutations of the identified residues were shown to alter product profiles and yielded

Preparation of anthracene-based tetraperimidine hexafluorophosphate and selective recognition of chromium(III) ions

• Qing-Xiang Liu,
• Feng Yang,
• Zhi-Xiang Zhao,
• Shao-Cong Yu and
• Yue Ding

Beilstein J. Org. Chem. 2019, 15, 2847–2855, doi:10.3762/bjoc.15.278

• signal corresponding to the NCHN motif in perimidine was present at δ = 8.69 ppm [42]. Structure elucidation of compound 3 As can be seen in the crystal structure of 3 in Figure 1, the cationic moiety of the complex contained two (N-ethylperimidinyl–C2H4)2NCH2– arms attached to the 9- and 10-positions of