Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• compound 4. Established route for the synthesis of intermediate 4 [1]. Alternative route. Reaction conditions: a) TrCl, pyridine, rt, overnight, 100%; b) DMAP, imidazole, TBS, DCM, rt, 12 h, 65%; c) LDA, (R)-methyl p-tolyl sulfoxide, THF, −78 °C to rt, 2.5 h, 55% yield of 8. Sequence showing the source of

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• -closing metathesis (RCM), Clauson–Kaas and Ullmann-type coupling reactions as key steps. Moreover, we have also assembled some other interesting heterocyclic systems possessing oxazole, imidazole, benzimidazole, and benzoxazole in the framework of truxene. Additionally, the preliminary photophysical

• the bromination using Br2/CH2Cl2 and then subsequent alkylation followed by Ullmann-type copper-mediated cross-coupling reaction in overall good yield (Scheme 4). On the other hand, imidazole and benzimidazole containing C3-symmetric truxene-based molecules (14 and 16) have also been assembled from

• the hexaalkylated tribromotruxene 5 by means of Ullmann-type reaction in the presence of copper powder using pristine imidazole (13) and benzimidazole (15), respectively (Scheme 5). Moreover, we have successfully constructed the C3-symmetric oxazole containing truxene derivative 20 along with

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• furnished the desired products 105 in good to moderate yields. 7 Purines Purines are categorized as heterocyclic aromatic compounds, consisting of a pyrimidine ring fused to an imidazole ring. Adenine and guanine are purine nitrogenous bases found in nucleic acids. Utilizing purine analogs as isosteres are

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• substrates under 23 W CFL (compact fluorescent lamp) irradiation, affording the desired imidazole derivative 10 by utilizing DMSO as the solvent at room temperature (Scheme 4). It is worth noting that, unlike most reported intermolecular electron-transfer via an EDA complex pathway, this approach transfers

• quinoxaline derivative 7. Synthesis of imidazole derivative 10 initiated by an EDA complex. Synthesis of sulfamoylation product 12 initiated by an EDA complex. Mechanism of the synthesis of sulfamoylation product 12. Synthesis of indole derivative 22 initiated by an EDA complex. Synthesis of

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• protected by TBS (tert-butyldimethylsilane) using tert-butyldimethylsilyl chloride (9, TBSCl) and imidazole in CH2Cl2. The thus obtained derivative 10 was then subjected to an amidination by Al(Me)3 and NH4Cl to afford amidine 2 (Scheme 2). Compounds 3 and 4 were prepared from commercially available

• h, 44%. Synthesis of intermediate 2. Reagents and conditions: (i) Pd/C (wet), EtOAc/CH2Cl2, H2, 45 psi, rt, 2 h, 95%; (ii) imidazole, CH2Cl2, rt, 16 h, 46%; (iii) Al(Me)3, NH4Cl, CH2Cl2, 0 °C-rt, 40 h, 23%. Synthesis of intermediates 3–5. Reagents and conditions: (i) (Ac)2O, CH2Cl2, rt, 24 h, 95–99

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• , affording biaryl species 161. Using this strategy, several trifluoromethyl ketones 162 and alcohols 163 bearing heteroaryl substituents (i.e., benzothiazole, quinoline, isoquinoline, benzimidazole, or imidazole) prone to be protonated were elegantly converted into the corresponding alcohols 163 and biphenyl

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• protected with tert-butyldimethylsilyl chloride in the presence of 4-(dimethylamino)pyridine (DMAP) and imidazole (Scheme 2) according to a published procedure [20]. The thus obtained bis(silylether) 3 was then brominated with N-bromosuccinimide (NBS), where the utilization of acetonitrile as solvent [21

• . Biphenyl-derived mycotoxins. Synthesis of arylboronates 6. Conditions: a) TBSCl, DMAP, imidazole, DMF, 50 °C, 4 h (96%); b) NBS, MeCN, rt, 71 h (quant.); c) NBS, MeCN, rt, 72 h (R = TBS, 96%); d) BnBr, KI, K2CO3, DMF/acetone, 70 °C, 29 h, (R = Bn, 86%); e) R = TBS: BuLi, 2-isopropoxy-4,4,5,5-tetramethyl

• -1,3,2-dioxaborolane, THF, −78 °C, 0.45–2 h, rt, 18 h (57%); R = Bn: bis(pinacolato)diboron, Pd(dppf)Cl2·CH2Cl2 (cat.), KOAc, dioxane, 80 °C, 17 h (55%). Synthesis of aryl bromides 9. Conditions: f) BBr3, −78 °C to rt, 18 h (71%); g) R = TBS: TBSCl, DMAP, imidazole, DMF, 55 °C, 4 h (73%); R = Bn: BnBr

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• modulate the affinity of an aptamer towards its target. In particular, two artificial imidazole 2’-deoxyribonucleosides (Im) were incorporated into various positions of an established ATP-binding aptamer (ATP, adenosine triphosphate), resulting in the formation of three aptamer derivatives bearing Im:Im

• function opens new possibilities for applications of oligonucleotides. Keywords: aptamer; ATP; bioinorganic chemistry; DNA; imidazole; metal-mediated base pairs; Introduction Aptamers are oligonucleotides capable of recognizing and binding to specific molecules up to the size of proteins [1]. While

• versatility. The metal-mediated base pair chosen for this study is based on the artificial imidazole 2’-deoxyribonucleoside (Im). This nucleoside is well known to form highly stabilizing Ag(I)-mediated Im–Ag(I)–Im base pairs (Figure 1) [30][31][32][33] and has already been proposed for a use in various

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• -Cl, 5 equiv imidazole, DMF, 60 °C, overnight, 82%; (b) 5 equiv LDA, 1.8 equiv I2, 5 equiv acetic acid, THF, −75 °C, 9 h, 79%; (c) 6 equiv isobutyric anhydride, pyridine, 45 °C, overnight, 70%; (d) 3.5 equiv TEA·3HF, DMF, room temperature, overnight, 85%; (e) 1.2 equiv DMT-Cl, pyridine, room

• equiv di-tert-butylsilyl bis(trifluoromethanesulfonate), DMF, 0 °C, 45 min; ii) 5 equiv imidazole, 1.5 equiv TBDMS-Cl, DMF, room temperature, overnight, 83%; (b) 5 equiv LDA, 1.8 equiv I2, 5 equiv acetic acid, THF, −75 °C, 9 h, 83%; (c) 6 equiv isobutyric anhydride, pyridine, 45 °C, 24 h, 57%; (d) i) 4

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• 19713, USA DuPont Corporate Center for Analytical Sciences, Experimental Station, P.O. Box 80500, Wilmington, DE 19880-0500, USA 10.3762/bjoc.16.224 Abstract Several new derivatives of adenine, purine, and theophylline containing the (CF3)2CH group connected to a nitrogen atom of the imidazole ring

• were prepared by the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding substrates, resulting in the selective alkylation of one of the nitrogen atoms of the imidazole ring. The reaction proceeds under mild conditions in a polar solvent, giving the alkylated

• connected to a nitrogen atom of the imidazole segment are relatively rare. Known examples include benzimidazoles carrying NCF3 [10], NCF2H [11][12][13], NRf (Rf = CF2Cl, CF2Br, CF2CFClH, CF=CFClF) [14][15], and hexafluoroisopropyl groups attached to the nitrogen atom [16]. Recently, we reported a new method

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• -imidazol-1-yl)methane (5) was synthesized from imidazole (4) and CH2Br2 following a literature procedure [62][63] with slight modifications. Then, BImNs (N = 4, 10, 12, 14) were synthesized from 5 by mono-alkylation using the corresponding n-alkyl halides in DMF. Finally, PBImNs (N = 4, 10, 12, 14) were

• the nucleotides, 1-pyrenecarboxaldehyde, sodium borohydride, sodium hydride, phosphorus tribromide and 1-bromobutane, 1-bromodecane, 1-bromododecane and 1-bromotetradecane were purchased from Sigma-Aldrich. Imidazole, dibromomethane and tris(hydroxymethyl)aminomethane were purchased from TCI chemicals

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• both are 4-alkanoyl-5-aminoimidazoles with a 6-methyloctanoyl or decanoyl chain, respectively. Two possible positions of the amino group on the imidazole rings (C-2 and C-5) posed a challenge in the structure study, which was settled by the measurement of 1JC,H coupling constants for comparison with

• observed during the study of bulbimidazole A (5), which did not show sp2 carbon signals in neutral solutions due to the presence of multiple resonance structures for the imidazole moiety [22]. We envisaged that due to the presence of an imidazole ring, the UV spectra of 1 and 5 would obviously be different

• C3H4N3 with three double bond equivalents, composed in part by the two nonprotonated sp2 carbon atoms (C-4 and C-5) and an sp2 methine unit (CH-2) and exhibited HMBC correlations from H-2 to C-4 and C-5. These requirements were only satisfied by an amino-substituted imidazole ring. Indeed, a four-bond

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• the switchable ligand). This approach has been dubbed “record player” design for obvious reasons (Figure 1a). The Ni-porphyrin (“disk”) is low-spin if the azo-aryl unit (“tone arm”) is in trans configuration. Upon switching to the bent cis configuration, the lone pair of the pyridine (or imidazole

• substituents at the pyridine or imidazole part) to increase the Ni–ligand coordination strength. Strong coordination in turn improves the performance of the spin switch, namely the conversion rate to the cis isomer, the conversion rate to the high-spin state, as well as the thermal stability of the high-spin

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• monoacylated glucosamine building blocks. Conditions: (a) NaHCO3, TrocCl, H2O, 0 °C, 94% ; (b) Ac2O, pyridine, rt, 96%; (c) N2H4, AcOH, DMF, rt, 89%; (d) TBSCl, imidazole, DMF, rt, 93%; (e) guanidine hydrochloride buffer, rt; (f) NapC(OMe)2, camphorsulfonic acid, CH3CN, rt, 68% (2 steps); (g) acid 7, EDC·HCl

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• imidazole (32–98% yield) and pyrimidine derivatives (45–88% yield), with a broad substrate scope, when using deep eutectic solvents [choline chloride (ChCl)/glycerol (1:2 mol/mol) and ChCl/urea (1:2 mol/mol)] as environmentally benign and non-innocent reaction media, by modulating the temperature (25 or 80

• at 50 °C, we were able to isolate by column chromatography on silica gel a product which was characterized as 2-benzoyl-(4 or 5)-phenyl-(1H)-imidazole (3a/3a', Scheme 2). This adduct was formed as a mixture of two tautomers (3a and 3a'; 3a/3a' ratio: 57:43, Supporting Information File 1) [28][29] in

• chromatography on silica gel (hexane/EtOAc 5:1–4:1) to afford the desired α-azido ketone 2. Characterization data of the isolated 2-azido ketones are provided in Supporting Information File 1. Synthesis of 2-benzoyl-4-phenyl-1H-imidazole (3a) and 2-benzoyl-5-phenyl-1H-imidazole (3a'). Typical procedure Sodium

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• synthesis of 1-benzyl-2-phenyl-1H-benzo[d]imidazole (3a). At first, a control experiment was conducted by using model substrates, 1 and 2a, in H2O in the absence of catalyst under ultrasound irradiation for 60 min at 45–50 °C. It was found that the reaction did not proceed in the absence of a catalyst

Mechanochemical green synthesis of hyper-crosslinked cyclodextrin polymers

• Alberto Rubin Pedrazzo,
• Fabrizio Caldera,
• Marco Zanetti,
• Silvia Lucia Appleton,
• Nilesh Kumar Dhakar and
• Francesco Trotta

Beilstein J. Org. Chem. 2020, 16, 1554–1563, doi:10.3762/bjoc.16.127

• nanosponges with selected organic dyes that are used as probe molecules with different structures (methyl red, rhodamine B, and fluorescein). The simple functionalization of the cyclodextrin NS, in this case via reactive imidazole moieties, is particularly interesting for a variety of applications. For

• groups of CDs, forming a carbonate bond between two monomers and therefore releasing two imidazole molecules that are soluble in water and could be removed after synthesis. CDI, however, may react asymmetrically forming only one bond with cyclodextrin leaving one of the two moieties reactive. This is

• consistent with what was reported in the literature: the first activation of an alcohol by carbonyl imidazole showed faster kinetics than the second one, which needed longer reaction times and/or a higher temperature (from 60 °C to 80 °C) to obtain a significant yield [31][32]. To distinguish between the

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• oxazoles (17 examples, up to 87% yield) were difluoromethylated but a variety of other heteroarenes turned out to be suitable such as pyridine, imidazole, benzo[d]thiazole, benzo[b]thiophene, benzo[d]oxazole, thiazole and thiophene derivatives (Scheme 6). Copper-based CF2FG-containing reagents Besides the

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• -heterocyclic carbene) in multiple steps [28]. Initially, imidazole (28) was immobilized on the silica nanomaterial 27 by a nucleophilic attack of 28 on the iodopropylated silica nanomaterial 27 in acetonitrile under reflux for 48 h. The obtained 1-propylimidazole–nanosilica compound ImP–nSiO2 (29) was filtered

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• addition of chlorophosphine resulted in the desired ligand 58. However, the overall yield was lower than the yield obtained through the other method. Imidazole can be regioselectively deprotonated at the more acidic C2 position. The mono- and diphosphine imidazole ligands 62 and 63 were conveniently

• synthesized by Milde et al. (Scheme 11) [8]. The imidazole intermediates 61 were obtained by coupling iodoaniline (59) with the dialdehyde 60. Selective metalation of the imidazole ring and subsequent treatment with the phosphine gave the imidazolylphosphine ligands 62 and 63 (46–64%). The fast and clean

• sterically crowded biaryl ligands as they showed outstanding performances [8]. Phosphines with imidazole and imidazoline functional groups present some interesting features. The imidazolium functionality mimics active sites in biological molecules [83][84]. The ionic nature adds another dimension to the

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• in moderate to good yields (28–85%) with remarkable regio- (>95%) and enantioselectivities (91–95% ee) [39]. Interestingly, DFT calculations supported the crucial role of the imidazole moiety towards the 1,4-addition (vs 1,6 or 1,8) [39]. Thanks to the efficient post-transformation of the

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• compounds have frequently been employed as modules, e.g., to control protein–DNA interactions. However, their use in conjunction with minor groove-binding imidazole/pyrrole (Im/Py) polyamides is yet unprecedented. Dervan-type Im/Py polyamides were equipped with an azobenzene unit, i.e., 3-(3-(aminomethyl

• acted as a building block inducing a reverse turn, which favored hydrogen bonds between the pyrrole/imidazole amide and the DNA bases. In contrast, the E-configured polyamides did not induce any ICD characteristic for minor groove binding. The incorporation of the photoswitchable azobenzene unit is a

• . A major breakthrough concerning selective small DNA-targeting molecules was the use of pyrrole/imidazole hairpin polyamides. They are conceptually derived from the natural products netropsin and distamycin A, which selectively bind to particular sequences of the DNA duplex [2][3][4]. Covalent

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• , n = 7 cells, *** indicates P < 0.001 in paired t-test. Synthesis of 4FABTA. a) Reagents and conditions: (a) 3-Butynol, PdCl2(PPh3)2, CuI, THF, rt, 93%; (b) H2, PtO2, EtOH, rt, 71%; (c) TBDMS-Cl, imidazole, DCM, rt, 96%; (d) n-BuLi, THF, −78 °C to −50 °C; (e) NBS, ACN, rt, 89%; (f) CuCN, NMP, 202 °C