Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships
- Sabyasachi Chakraborty,
- Eduardo Mayo Yanes and
- Renana Gershoni-Poranne
Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160
Graphical Abstract
Figure 1: A) The building blocks used in the COMPAS-2 datasets. B) Possible annulation types formed when comb...
Figure 2: Roadmap of the work described in this article. Three main criteria are defined in increasing struct...
Figure 3: Comparison between COMPAS-1 (blue) and COMPAS-2 (purple). A) Principal Moments of Inertia shape dis...
Figure 4: Distributions of electronic properties of the dataset. KDE plots of HOMO, LUMO, Gap, AIP, and AEA c...
Figure 5: KDE distributions of the HOMO, LUMO, and Gap separated and colored by the longest L for: A) all 9-r...
Figure 6: Distributions of molecular properties for 4n and (4n + 2) π-electron count systems, divided by the ...
Figure 7: Stacked histograms showing the prevalence of the different heteroatoms across different areas of th...
Figure 8: Distributions of electronic properties of the dataset. KDE plots of A) HOMO, B) LUMO, C) Gap, D) AI...
Figure 9: A) Scatter plot of the HOMO (x-axis) and LUMO (y-axis) values of the molecules in COMPAS-2. In each...
Figure 10: The effect of multiple heterocycles of a certain type on the A) HOMO, B) LUMO, and C) Gap. For all ...
A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts
- Ivana Weisheitelová,
- Radek Cibulka,
- Marek Sikorski and
- Tetiana Pavlovska
Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161
Graphical Abstract
Figure 1: (A) The general structures of isoalloxazine (flavin, Fl), alloxazine (All), 5-deazaisoalloxazine (5...
Scheme 1: Three-component condensation of anilines, aldehydes and N,N-dimethylbarbituric acid. aReaction was ...
Figure 2: UV–vis absorption spectra of 5-arydeazaalloxazines 2f, 2j and 2n in DMF (l = 1 cm, c = 2.50 × 10−5 ...
Scheme 2: Control experiments related to bulky substituted aldehydes.
The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)
- Cristina Martini,
- Muhammad Idham Darussalam Mardjan and
- Andrea Basso
Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162
Graphical Abstract
Scheme 1: Mechanism of the GBB reaction.
Scheme 2: Comparison of the performance of Sc(OTf)3 with some RE(OTf)3 in a model GBB reaction. Conditions: a...
Scheme 3: Comparison of the performance of various Brønsted acid catalysts in the synthesis of GBB adduct 6. ...
Scheme 4: Synthesis of Brønsted acidic ionic liquid catalyst 7. Conditions: a) neat, 60 °C, 24 h; b) TfOH, DC...
Scheme 5: Aryliodonium derivatives as organic catalysts in the GBB reaction. In the box the proposed binding ...
Scheme 6: DNA-encoded GBB reaction in micelles made of amphiphilic polymer 13. Conditions: a) 13 (50 equiv), ...
Scheme 7: GBB reaction catalyzed by cyclodextrin derivative 14. Conditions: a) 14 (1 mol %), water, 100 °C, 4...
Scheme 8: Proposed mode of activation of CALB. a) activation of the substrates; b) activation of the imine; c...
Scheme 9: One-pot GBB reaction–Suzuki coupling with a bifunctional hybrid biocatalyst. Conditions: a) Pd(0)-C...
Scheme 10: GBB reaction employing 5-HMF (23) as carbonyl component. Conditions: a) TFA (20 mol %), EtOH, 60 °C...
Scheme 11: GBB reaction with β-C-glucopyranosyl aldehyde 26. Conditions: a) InCl3 (20 mol %), MeOH, 70 °C, 2–3...
Scheme 12: GBB reaction with diacetylated 5-formyldeoxyuridine 29, followed by deacetylation of GBB adduct 30....
Scheme 13: GBB reaction with glycal aldehydes 32. Conditions: a) HFIP, 25 °C, 2–4 h.
Scheme 14: Vilsmeier–Haack formylation of 6-β-acetoxyvouacapane (34) and subsequent GBB reaction. Conditions: ...
Scheme 15: GBB reaction of 4-formlyl-PCP 37. Conditions: a) HOAc or HClO4, MeOH/DCM (2:3), rt, 3 d.
Scheme 16: GBB reaction with HexT-aldehyde 39. Conditions: a) 39 (20 nmol) and amidine (20 μmol), MeOH, rt, 6 ...
Scheme 17: GBB reaction of 2,4-diaminopirimidine 41. Conditions: a) Sc(OTf)3 (20 mol %), MeCN, 120 °C (MW), 1 ...
Scheme 18: Synthesis of N-edited guanine derivatives from 3,6-diamine-1,2,4-triazin-5-one 44. Conditions: a) S...
Scheme 19: Synthesis of 2-aminoimidazoles 49 by a Mannich-3CR followed by a one-pot intramolecular oxidative a...
Scheme 20: On DNA Suzuki–Miyaura reaction followed by GBB reaction. Conditions: a) CsOH, sSPhos-Pd-G2; b) AcOH...
Scheme 21: One-pot cascade synthesis of 5-iminoimidazoles. Conditions: a) Na2SO4, DMF, 220 °C (MW).
Scheme 22: GBB reaction of 5-amino-1H-imidazole-4-carbonile 57. Conditions: a) HClO4 (5 mol %), MeOH, rt, 24 h....
Scheme 23: One-pot cascade synthesis of indole-imidazo[1,2,a]pyridine hybrids. In blue the structural motif in...
Scheme 24: One-pot cascade synthesis of fused polycyclic indoles 67 or 69 from indole-3-carbaldehyde. Conditio...
Scheme 25: One-pot cascade synthesis of linked- and bridged polycyclic indoles from indole-2-carbaldehyde (70)...
Scheme 26: One-pot cascade synthesis of pentacyclic dihydroisoquinolines (X = N or CH). In blue the structural...
Scheme 27: One-pot stepwise synthesis of imidazopyridine-fused benzodiazepines 85. Conditions: a) p-TsOH (20 m...
Scheme 28: One-pot stepwise synthesis of benzoxazepinium-fused imidazothiazoles 89. Conditions: a) Yb(OTf)3 (2...
Scheme 29: One-pot stepwise synthesis of fused imidazo[4,5,b]pyridines 95. Conditions: a) HClO4, MeOH, rt, ove...
Scheme 30: Synthesis of heterocyclic polymers via the GBB reaction. Conditions: a) p-TsOH, EtOH, 70 °C, 24 h.
Scheme 31: One-pot multicomponent reaction towards the synthesis of covalent organic frameworks via the GBB re...
Scheme 32: One-pot multicomponent reaction towards the synthesis of covalent organic frameworks via the GBB re...
Scheme 33: GBB-like multicomponent reaction towards the synthesis of benzothiazolpyrroles (X = S) and benzoxaz...
Scheme 34: GBB-like multicomponent reaction towards the formation of imidazo[1,2,a]pyridines. Conditions: a) I2...
Scheme 35: Post-functionalization of GBB products via Ugi reaction. Conditions a) HClO4, DMF, rt, 24 h; b) MeO...
Scheme 36: Post-functionalization of GBB products via Click reaction. Conditions: a) solvent-free, 150 °C, 24 ...
Scheme 37: Post-functionalization of GBB products via cascade alkyne–allene isomerization–intramolecular nucle...
Scheme 38: Post-functionalization of GBB products via metal-catalyzed intramolecular N-arylation. In red and b...
Scheme 39: Post-functionalization of GBB products via isocyanide insertion (X = N or CH). Conditions: a) HClO4...
Scheme 40: Post-functionalization of GBB products via intramolecular nucleophilic addition to nitriles. Condit...
Scheme 41: Post-functionalization of GBB products via Pictet–Spengler cyclization. Conditions: a) 4 N HCl/diox...
Scheme 42: Post-functionalization of GBB products via O-alkylation. Conditions: a) TFA (20 mol %), EtOH, 120 °...
Scheme 43: Post-functionalization of GBB products via macrocyclization (X = -CH2CH2O-, -CH2-, -(CH2)4-). Condi...
Figure 1: Antibacterial activity of GBB-Ugi adducts 113 on both Gram-negative and Gram-positive strains.
Scheme 44: GBB multicomponent reaction using trimethoprim as the precursor. Conditions: a) Yb(OTf)3 or Y(OTf)3...
Figure 2: Antibacterial activity of GBB adducts 152 against MRSA and VRE; NA = not available.
Figure 3: Antibacterial activity of GBB adduct 153 against Leishmania amazonensis promastigotes and amastigot...
Figure 4: Antiviral and anticancer evaluation of the GBB adducts 154a and 154b. In vitro antiproliferative ac...
Figure 5: Anticancer activity of the GBB-furoxan hybrids 145b, 145c and 145d determined through antiprolifera...
Scheme 45: Synthesis and anticancer activity of the GBB-gossypol conjugates. Conditions: a) Sc(OTf)3 (10 mol %...
Figure 6: Anticancer activity of polyheterocycles 133a and 136a against human neuroblastoma. Clonogenic assay...
Figure 7: Development of GBB-adducts 158a and 158b as PD-L1 antagonists. HTRF assays were carried out against...
Figure 8: Development of imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines as TDP1 inhibitors. The SMM meth...
Figure 9: GBB adducts 164a–c as anticancer through in vitro HDACs inhibition assays. Additional cytotoxic ass...
Figure 10: GBB adducts 165, 166a and 166b as anti-inflammatory agents through HDAC6 inhibition; NA = not avail...
Scheme 46: GBB reaction of triphenylamine 167. Conditions: a) NH4Cl (10 mol %), MeOH, 80 °C (MW), 1 h.
Scheme 47: 1) Modified GBB-3CR. Conditions: a) TMSCN (1.0 equiv), Sc(OTf)3 (0.2 equiv), MeOH, 140 °C (MW), 20 ...
Scheme 48: GBB reaction to assemble imidazo-fused heterocycle dimers 172. Conditions: a) Sc(OTf)3 (20 mol %), ...
Figure 11: Model compounds 173 and 174, used to study the acid/base-triggered reversible fluorescence response...
2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space
- Carlos Nieto,
- Alejandro Manchado,
- Ángel García-González,
- David Díez and
- Narciso M. Garrido
Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163
Graphical Abstract
Scheme 1: Description of the 2-heteroarylethylamine scope of the present review featuring appropriate heteroa...
Scheme 2: 2-Aminoethylpyridine derivatives with therapeutic activity.
Scheme 3: 2-Aminoethylfuran derivatives with therapeutic activity.
Scheme 4: 2-Aminoethylthiophene derivatives with therapeutic activity, part 1.
Scheme 5: 2-Aminoethylthiophene derivatives with therapeutic activity, part 2.
Scheme 6: 2-Aminoethylthiophene derivatives with therapeutic activity, part 3.
Scheme 7: 2-Aminoethylpyrrole derivatives with therapeutic activity.
Scheme 8: Histamine metabolic pathway.
Scheme 9: 2-Aminoethylimidazole derivatives with therapeutic activity, part 1. Krel is referred as histamine ...
Scheme 10: Conformationally restricted 2-aminoethylimidazole derivatives with therapeutic activity, part 2.
Scheme 11: 2-Aminoethylimidazole derivatives with therapeutic activity, part 3.
Scheme 12: 2-Aminoethylimidazole derivatives with therapeutic activity, part 4.
Scheme 13: 2-Aminoethylpyrazole derivatives with therapeutic activity.
Scheme 14: 2-Aminoethylisoxazole derivatives with therapeutic activity.
Scheme 15: 2-Aminoethylthiazole derivatives with therapeutic activity.
Scheme 16: 2-Aminoethyloxadiazole derivatives with therapeutic activity.
Scheme 17: 2-Aminoethyltriazole derivatives with therapeutic activity.
Scheme 18: 2-Aminoethyloxadiazole derivatives with therapeutic activity.
Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles
- Ivan Lyutin,
- Vasilisa Krivovicheva,
- Grigory Kantin and
- Dmitry Dar’in
Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164
Graphical Abstract
Scheme 1: Synthetic routes to 2-oxoazetidine-3-carboxylic acid derivatives.
Scheme 2: Scope of diazotetramic acids 1 thermolysis in the presence of various nucleophiles. PMP = p-methoxy...
Scheme 3: Negative results with several N-, O-, and C-nucleophiles and with diazo reagent 1m.
Scheme 4: Preparation of acids 4 by hydrogenolysis of benzyl esters and examples of acid 4a amidation.
Electrochemical radical cation aza-Wacker cyclizations
- Sota Adachi and
- Yohei Okada
Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165
Graphical Abstract
Scheme 1: Radical and ionic intramolecular cyclizations.
Scheme 2: Electrochemical and photochemical aza-Wacker cyclizations.
Scheme 3: Scope of electrochemical aza-Wacker cyclization. Reaction conditions: the alkene (0.20 mmol), Bu4NO...
Scheme 4: Mechanistic studies of aza-Wacker cyclization. A: Electrochemical (Bu4NOTf in CH3CN/1,2-DCE), B: no...
Figure 1: Cyclic voltammograms for aryl sulfonamides.
Novel oxidative routes to N-arylpyridoindazolium salts
- Oleg A. Levitskiy,
- Yuri K. Grishin and
- Tatiana V. Magdesieva
Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166
Graphical Abstract
Scheme 1: Pyridoindazolium salts known to date and obtained in the present work.
Scheme 2: Synthesis of S1–S3 salts using PIFA as an oxidant and the resonance structures demonstrating the el...
Figure 1: CV curves for salt S2 and corresponding amine A2 (left, Figure 1a) and salt S3 with and without diethyl malo...
Scheme 3: Redox-interconversion between diarylamines A1–A3 and N-arylpyridoindazoliums S1–S3.
Scheme 4: Electrochemical approach to pyridoindazolium salts.
Figure 2: CV curves for amine A1 without the lutidine additive (black curve) and after addition of 2 equiv (r...
Figure 3: Semi-differential CV curves for the mediators (TEMPO, bis(4-tert-butylphenyl)nitroxide and tris(4-b...
Figure 4: CV curves of bis(4-tert-butylphenyl)nitroxide (a) and TEMPO (b) with amine A3 and 2,6-lutidine adde...
Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA
- Ze-Nan Hu,
- Yan-Hui Wang,
- Jia-Bing Wu,
- Ze Chen,
- Dou Hong and
- Chi Zhang
Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167
Graphical Abstract
Figure 1: Selected natural products, pharmaceuticals, and biologically active compounds having an isoquinolin...
Scheme 1: Chemoselective and PISA-mediated, solvent-controlled synthesis of different isoquinolinone derivati...
Scheme 2: Substrate scope for the synthesis of 4-substituted isoquinolinones 2. Reaction conditions: 1 (0.3 m...
Scheme 3: Optimal reaction conditions for the synthesis of 3-substituted isoquinolinone 3a.
Scheme 4: Substrate scope for the synthesis of 3-substituted isoquinolinones 3. Reaction conditions: 1 (0.3 m...
Scheme 5: Control experiment to test for radical intermediates.
Scheme 6: Proposed mechanism for the reaction between 1a and PISA in anhydrous acetonitrile.
Scheme 7: Two other resonance structures of the intermediate 1CC.
Scheme 8: Proposed mechanism for the reaction between 1a and PISA in wet HFIP.
Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications
- Matteo Gasparetto,
- Balázs Fődi and
- Gellért Sipos
Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168
Graphical Abstract
Scheme 1: Known and improved synthetic strategies to access α-(hetero)aryl-amino acids.
Scheme 2: Reformatsky reagent production.
Scheme 3: Scope of ethyl heteroarylacetates. Isolated yields are given. *Dark reactions were carried out for ...
Scheme 4: Telescoped flow synthesis of heteroarylacetates.
Scheme 5: Potential routes for the preparation of oximes.
Scheme 6: Oxime group insertion step.
Scheme 7: Amino ester production: general scheme, scope and gram scale experiment. The numbers in brackets re...
Scheme 8: Reactions scheme and results for the on-DNA experiments. The reported values represent the normaliz...
A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions
- Vitor A. S. Almodovar and
- Augusto C. Tomé
Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169
Graphical Abstract
Scheme 1: Synthesis of new diketopyrrolopyrroles via nucleophilic aromatic substitution.
Figure 1: (A) Absorption and (B) fluorescence spectra of compounds 3a–f, 4a, 4d and 4f, in DMF. Different con...
Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations
- Pengcheng Lu,
- Luis Juarez,
- Paul A. Wiget,
- Weihe Zhang,
- Krishnan Raman and
- Pravin L. Kotian
Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170
Graphical Abstract
Figure 1: Indazole-containing bioactive molecules.
Figure 2: Tautomerism of indazole.
Scheme 1: NMR, NOE, and yield data of compounds 8 and 9.
Scheme 2: Synthesis of compounds P1 and P2.
Figure 3: DFT-calculated deprotonation of 6 with Cs2CO3 in implicit THF with the temperature of the calculati...
Figure 4: DFT-calculated Cs+-coordinated complexes with different enolate forms of 6(N-H) calculated as isola...
Figure 5: DFT-calculated reaction coordinate diagram for the reaction of 6 under conditions A. Concerning con...
Figure 6: DFT-calculated energy for the deprotonation of 6 by the DMAD anion.
Figure 7: DFT-calculations concerning a coordinated Mitsunobu reaction pathway.
Figure 8: Reaction coordinate diagram of 6(N-H) reacting under conditions B. All calculated energies in kcal/...
Figure 9: Reaction of 18 under conditions A and B (top), and proposed chelation/coordination pathways to acco...
Figure 10: DFT-calculated reaction coordinate diagram for the reaction of 18 under conditions A.
Figure 11: DFT-calculated reaction coordinate diagram for the reaction of 18 under conditions B. Ball-and-stic...
Scheme 3: Reaction of 21 under conditions A and B; amultiple purifications; bdetermined by LC–MS.
Figure 12: DFT-calculated transition-state structures and energies of 21 under conditions A (top) and conditio...
1,2-Difluoroethylene (HFO-1132): synthesis and chemistry
- Liubov V. Sokolenko,
- Taras M. Sokolenko and
- Yurii L. Yagupolskii
Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171
Graphical Abstract
Scheme 1: 1,2-Difluoroethylene synthesis from HFO-1123.
Scheme 2: 1,2-Difluoroethylene synthesis from CFC-112 and HCFC-132.
Scheme 3: 1,2-Difluoroethylene synthesis from HFC-143.
Scheme 4: 1,2-Difluoroethylene synthesis from HCFC-142 via HCFC-142a.
Scheme 5: 1,2-Difluoroethylene synthesis from CFO-1112.
Scheme 6: 1,2-Difluoroethylene synthesis from 1,2-dichloroethylene.
Scheme 7: 1,2-Difluoroethylene synthesis from perfluoropropyl vinyl ether.
Scheme 8: Deuteration reaction of 1,2-difluoroethylene.
Scheme 9: Halogen addition to 1,2-difluoroethylene.
Scheme 10: Hypohalite addition to 1,2-difluoroethylene.
Scheme 11: N-Bromobis(trifluoromethyl)amine addition to 1,2-difluoroethylene.
Scheme 12: N-Chloroimidobis(sulfonyl fluoride) addition to 1,2-difluoroethylene.
Scheme 13: Trichlorosilane addition to 1,2-difluoroethylene.
Scheme 14: SF5Br addition to 1,2-difluoroethylene.
Scheme 15: PCl3/O2 addition to 1,2-difluoroethylene.
Scheme 16: Reaction of tetramethyldiarsine with 1,2-difluoroethylene.
Scheme 17: Reaction of trichlorofluoromethane with 1,2-difluoroethylene.
Scheme 18: Addition of perfluoroalkyl iodides to 1,2-difluoroethylene.
Scheme 19: Cyclopropanation of 1,2-difluoroethylene.
Scheme 20: Diels–Alder reaction of 1,2-difluoroethylene and hexachlorocyclopentadiene.
Scheme 21: Cycloaddition reaction of 1,2-difluoroethylene and fluorinated ketones.
Scheme 22: Cycloaddition reaction of 1,2-difluoroethylene and perfluorinated aldehydes.
Scheme 23: Photochemical cycloaddition of 1,2-difluoroethylene and hexafluorodiacetyl.
Scheme 24: Reaction of 1,2-difluoroethylene with difluorosilylene.
Scheme 25: Reaction of 1,2-difluoroethylene with aryl iodides.
Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators
- Siham Asyiqin Shafie,
- Ryo Nozawa,
- Hideaki Takano and
- Hiroshi Shinokubo
Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172
Graphical Abstract
Figure 1: Reactivities of norcorroles with various reagents.
Scheme 1: Reaction of norcorrole 1 with AIBN.
Figure 2: Top and side views of the X-ray structures of a) 2a and b) 1 [2]. Mesityl groups and hydrogen atoms we...
Scheme 2: Reaction of norcorrole 1 with V-40.
Figure 3: UV–vis–NIR absorption spectra of 1 and 2a in CH2Cl2.
Figure 4: Cyclic voltammogram of 2a in CH2Cl2. Supporting electrolyte: 0.1 M Bu4NPF6; working electrode: glas...
Scheme 3: Plausible reaction mechanism.
Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate
- Masahiro Terada,
- Zen Iwasaki,
- Ryohei Yazaki,
- Shigenobu Umemiya and
- Jun Kikuchi
Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173
Graphical Abstract
Scheme 1: (a) Sequential π-Lewis acidic metal-catalyzed cyclization/photochemical radical addition for the fo...
Scheme 2: The reaction with benzyltrimethylsilane derivatives 2. aFlow rate was 6 mL/h and premixing zone was...
Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384
- Marwa Elsbaey,
- Naoya Oku,
- Mohamed S. A. Abdel-Mottaleb and
- Yasuhiro Igarashi
Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174
Graphical Abstract
Figure 1: Structures of allostreptopyrroles A–E (1–5) and related metabolites.
Figure 2: COSY, 15N-HMBC and key HMBC correlations of compounds 1–5 and 1a.
Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations
- Aurélie Claraz
Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175
Graphical Abstract
Scheme 1: Synthesis of triazolopyridinium salts [34-36].
Scheme 2: Synthesis of pyrazoles [37].
Scheme 3: Synthesis of indazoles from ketone-derived hydrazones [38].
Scheme 4: Intramolecular C(sp2)–H functionalization of aldehyde-derived N-(2-pyridinyl)hydrazones for the syn...
Scheme 5: Synthesis of pyrazolo[4,3-c]quinoline derivatives [40].
Scheme 6: Synthesis of 1,3,4-oxadiazoles and Δ3-1,3,4-oxadiazolines [41].
Scheme 7: Synthesis of 1,3,4-oxadiazoles [43].
Scheme 8: Synthesis of 2-(1,3,4-oxadiazol-2-yl)anilines [44].
Scheme 9: Synthesis of fused s-triazolo perchlorates [45].
Scheme 10: Synthesis of 1-aryl and 1,5-disubstitued 1,2,4-triazoles [49].
Scheme 11: Synthesis of 1,3,5-trisubstituted 1,2,4-triazoles [50].
Scheme 12: Alternative synthesis of 1,3,5-trisubstituted 1,2,4-triazoles [51].
Scheme 13: Synthesis of 5-amino 1,2,4-triazoles [55].
Scheme 14: Synthesis of 1-arylpyrazolines [58].
Scheme 15: Synthesis of 3‑aminopyrazoles [60].
Scheme 16: Synthesis of [1,2,4]triazolo[4,3-a]quinolines [61].·
Scheme 17: Synthesis of 1,2,3-thiadiazoles [64].
Scheme 18: Synthesis of 5-thioxo-1,2,4-triazolium inner salts [65].
Scheme 19: Synthesis of 1-aminotetrazoles [66].
Scheme 20: C(sp2)–H functionalization of aldehyde-derived hydrazones: general mechanisms.
Scheme 21: C(sp2)–H functionalization of benzaldehyde diphenyl hydrazone [68,69].
Scheme 22: Phosphorylation of aldehyde-derived hydrazones [70].
Scheme 23: Azolation of aldehyde-derived hydrazones [72].
Scheme 24: Thiocyanation of benzaldehyde-derived hydrazone 122 [73].
Scheme 25: Sulfonylation of aromatic aldehyde-derived hydrazones [74].
Scheme 26: Trifluoromethylation of aromatic aldehyde-derived hydrazones [76].
Scheme 27: Electrooxidation of benzophenone hydrazones [77].
Scheme 28: Electrooxidative coupling of benzophenone hydrazones and alkenes [77].
Scheme 29: Electrosynthesis of α-diazoketones [78].
Scheme 30: Electrosynthesis of stable diazo compounds [80].
Scheme 31: Photoelectrochemical synthesis of alkenes through in situ generation of diazo compounds [81].
Scheme 32: Synthesis of nitriles [82].
Scheme 33: Electrochemical oxidation of ketone-derived NH-allylhydrazone [83].
Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies
- Beatrice E. Jones,
- Camille Blayo,
- Jake L. Greenfield,
- Matthew J. Fuchter,
- Nathan Cowieson and
- Rachel C. Evans
Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176
Graphical Abstract
Figure 1: E–Z isomerisation of (a) AzoTAB and (b) AAPTAB under UV light (365 nm) results in a change in shape...
Figure 2: SAXS curves for AzoTAB (50 mM in water) showing the transition from the Z-rich PSS to the E-rich st...
Figure 3: SAXS curves for the Z-rich PSS of AAPTAB (50 mM) in (a) water (H2O) and (b) deuterium dioxide (D2O)...
Figure 4: Addition of excess acid (pH = 0.4) induces Z–E isomerisation in AzoTAB and AAPTAB. UV–vis absorbanc...
Figure 5: Effect of X-ray exposure time on high-concentration samples of AAPTAB in water, (a) 10 wt % and (b)...
Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates
- Deepa Nair,
- Abhishek Tiwari,
- Banamali Laha and
- Irishi N. N. Namboothiri
Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177
Graphical Abstract
Figure 1: Biologically active derivatives of cyclohexanones.
Scheme 1: The Michael donor–acceptor reactivity of curcumin: previous vs present work.
Scheme 2: A plausible reaction mechanism.
Figure 2: X-ray structure of 4a (CCDC 2351387).
Figure 3: Origin of stereoselectivity in the double Michael addition.
Scheme 3: Scale-up reaction.
Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps
- Ignaz Betcke,
- Alissa C. Götzinger,
- Maryna M. Kornet and
- Thomas J. J. Müller
Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178
Graphical Abstract
Scheme 1: Consecutive three-component synthesis of pyrazoles 1 via in situ-formed 1,3-diketones 2 [44].
Scheme 2: Consecutive three-component synthesis of 4-ethoxycarbonylpyrazoles 5 via SmCl3-catalyzed acylation ...
Scheme 3: Consecutive four-component synthesis of 1-(thiazol-2-yl)pyrazole-3-carboxylates 8 [51].
Scheme 4: Three-component synthesis of thiazolylpyrazoles 17 via in situ formation of acetoacetylcoumarins 18 ...
Scheme 5: Consecutive pseudo-four-component and four-component synthesis of pyrazoles 21 from sodium acetylac...
Scheme 6: Consecutive three-component synthesis of 1-substituted pyrazoles 24 from boronic acids, di(Boc)diim...
Scheme 7: Consecutive three-component synthesis of N-arylpyrazoles 25 via in situ formation of aryl-di(Boc)hy...
Scheme 8: Consecutive three-component synthesis of 1,3,4-substituted pyrazoles 27 and 28 from methylhydrazine...
Scheme 9: Consecutive three-component synthesis of 4-allylpyrazoles 32 via oxidative allylation of 1,3-dicarb...
Scheme 10: Pseudo-five-component synthesis of tris(pyrazolyl)methanes 35 [61].
Scheme 11: Pseudo-three-component synthesis of 5-(indol-3-yl)pyrazoles 39 from 1,3,5-triketones 38 [64].
Scheme 12: Three-component synthesis of thiazolylpyrazoles 43 [65].
Scheme 13: Three-component synthesis of triazolo[3,4-b]-1,3,4-thiadiazin-3-yl substituted 5-aminopyrazoles 47 [67]....
Scheme 14: Consecutive three-component synthesis of 5-aminopyrazoles 49 via formation of β-oxothioamides 50 [68].
Scheme 15: Synthesis of 3,4-biarylpyrazoles 52 from aryl halides, α-bromocinnamaldehyde, and tosylhydrazine vi...
Scheme 16: Consecutive three-component synthesis of 3,4-substituted pyrazoles 57 from iodochromones 55 by Suzu...
Scheme 17: Pseudo-four-component synthesis of pyrazolyl-2-pyrazolines 59 by ring opening/ring closing cyclocon...
Scheme 18: Consecutive three-component synthesis of pyrazoles 61 [77].
Scheme 19: Three-component synthesis of pyrazoles 62 from malononitrile, aldehydes, and hydrazines [78-90].
Scheme 20: Four-component synthesis of pyrano[2,3-c]pyrazoles 63 [91].
Scheme 21: Three-component synthesis of persubstituted pyrazoles 65 from aldehydes, β-ketoesters, and hydrazin...
Scheme 22: Three-component synthesis of pyrazol-4-carbodithioates 67 [100].
Scheme 23: Regioselective three-component synthesis of persubstituted pyrazoles 68 catalyzed by ionic liquid [...
Scheme 24: Consecutive three-component synthesis of 4-halopyrazoles 69 and anellated pyrazoles 70 [102].
Scheme 25: Three-component synthesis of 2,2,2-trifluoroethyl pyrazole-5-carboxylates 72 [103].
Scheme 26: Synthesis of pyrazoles 75 in a one-pot process via carbonylative Heck coupling and subsequent cycli...
Scheme 27: Copper-catalyzed three-component synthesis of 1,3-substituted pyrazoles 76 [105].
Scheme 28: Pseudo-three-component synthesis of bis(pyrazolyl)methanes 78 by ring opening-ring closing cyclocon...
Scheme 29: Three-component synthesis of 1,4,5-substituted pyrazoles 80 [107].
Scheme 30: Consecutive three-component synthesis of 3,5-bis(fluoroalkyl)pyrazoles 83 [111].
Scheme 31: Consecutive three-component synthesis of difluoromethanesulfonyl-functionalized pyrazole 88 [114].
Scheme 32: Consecutive three-component synthesis of perfluoroalkyl-substituted fluoropyrazoles 91 [115].
Scheme 33: Regioselective consecutive three-component synthesis of 1,3,5-substituted pyrazoles 93 [116].
Scheme 34: Three-component synthesis of pyrazoles 96 mediated by trimethyl phosphite [117].
Scheme 35: One-pot synthesis of pyrazoles 99 via Liebeskind–Srogl cross-coupling/cyclocondensation [118].
Scheme 36: Synthesis of 1,3,5-substituted pyrazoles 101 via domino condensation/Suzuki–Miyaura cross-coupling ...
Scheme 37: Consecutive three-component synthesis of 1,3,5-trisubstituted pyrazoles 102 and 103 by Sonogashira ...
Scheme 38: Polymer analogous consecutive three-component synthesis of pyrazole-based polymers 107 [132].
Scheme 39: Synthesis of 1,3,5-substituted pyrazoles 108 by sequentially Pd-catalyzed Kumada–Sonogashira cycloc...
Scheme 40: Consecutive four-step one-pot synthesis of 1,3,4,5-substituted pyrazoles 110 [137].
Scheme 41: Four-component synthesis of pyrazoles 113, 115, and 117 via Sonogashira coupling and subsequent Suz...
Scheme 42: Consecutive four- or five-component synthesis for the preparation of 4-pyrazoly-1,2,3-triazoles 119...
Scheme 43: Four-component synthesis of pyrazoles 121 via alkynone formation by carbonylative Pd-catalyzed coup...
Scheme 44: Preparation of 3-azulenyl pyrazoles 124 by glyoxylation, decarbonylative Sonogashira coupling, and ...
Scheme 45: Four-component synthesis of a 3-indoloylpyrazole 128 [147].
Scheme 46: Two-step synthesis of 5-acylpyrazoles 132 via glyoxylation-Stephen–Castro sequence and subsequent c...
Scheme 47: Copper on iron mediated consecutive three-component synthesis of 3,5-substituted pyrazoles 136 [150].
Scheme 48: Consecutive three-component synthesis of 3-substituted pyrazoles 141 by Sonogashira coupling and su...
Scheme 49: Consecutive three-component synthesis of pyrazoles 143 initiated by Cu(I)-catalyzed carboxylation o...
Scheme 50: Consecutive three-component synthesis of benzamide-substituted pyrazoles 146 starting from N-phthal...
Scheme 51: Consecutive three-component synthesis of 1,3,5-substituted pyrazoles 148 [156].
Scheme 52: Three-component synthesis of 4-ninhydrin-substituted pyrazoles 151 [158].
Scheme 53: Consecutive four-component synthesis of 4-(oxoindol)-1-phenylpyrazole-3-carboxylates 155 [159].
Scheme 54: Three-component synthesis of pyrazoles 160 [160].
Scheme 55: Consecutive three-component synthesis of pyrazoles 165 [162].
Scheme 56: Consecutive three-component synthesis of 3,5-disubstituted and 3-substituted pyrazoles 168 and 169 ...
Scheme 57: Three-component synthesis of 3,4,5-substituted pyrazoles 171 via 1,3-dipolar cycloaddition of vinyl...
Scheme 58: Three-component synthesis of pyrazoles 173 and 174 from aldehydes, tosylhydrazine, and vinylidene c...
Scheme 59: Three-component synthesis of pyrazoles 175 from glyoxyl hydrates, tosylhydrazine, and electron-defi...
Scheme 60: Pseudo-four-component synthesis of pyrazoles 177 from glyoxyl hydrates, tosylhydrazine, and aldehyd...
Scheme 61: Consecutive three-component synthesis of pyrazoles 179 via Knoevenagel-cycloaddition sequence [179].
Scheme 62: Three-component synthesis of 5-dimethylphosphonate substituted pyrazoles 182 from aldehydes, the Be...
Scheme 63: Consecutive three-component synthesis of 5-(dimethyl phosphonate)-substituted pyrazoles 185 from al...
Scheme 64: Three-component synthesis of 5-(dimethyl phosphonate)-substituted pyrazoles 187 from aldehydes, the...
Scheme 65: Three-component synthesis of 5-diethylphosphonate/5-phenylsulfonyl substituted pyrazoles 189 from a...
Scheme 66: Pseudo-three-component synthesis of 3-(dimethyl phosphonate)-substituted pyrazoles 190 [185].
Scheme 67: Three-component synthesis of 3-trifluoromethylpyrazoles 193 [186].
Scheme 68: Consecutive three-component synthesis of 5-stannyl-substituted 4-fluoropyrazole 197 [191,192].
Scheme 69: Pseudo-three-component synthesis of 3,5-diacyl-4-arylpyrazoles 199 [195].
Scheme 70: Three-component synthesis of pyrazoles 204 via nitrilimines [196].
Scheme 71: Three-component synthesis of 1,3,5-substituted pyrazoles 206 via formation of nitrilimines and sali...
Scheme 72: Pseudo four-component synthesis of pyrazoles 209 from acetylene dicarboxylates 147, hydrazonyl chlo...
Scheme 73: Consecutive three-component synthesis of pyrazoles 213 via syndnones 214 [200].
Scheme 74: Consecutive three-component synthesis of pyrazoles 216 via in situ-formed diazomethinimines 217 [201].
Scheme 75: Consecutive three-component synthesis of 3-methylthiopyrazoles 219 from aldehydes, hydrazine, and 1...
Scheme 76: Three-component synthesis of 1,3,5-substituted pyrazoles 220 from aldehydes, hydrazines, and termin...
Scheme 77: Three-component synthesis of 1,3,4,5-substituted pyrazoles 222 from aldehydes, hydrazines, and DMAD ...
Scheme 78: Pseudo three-component synthesis of pyrazoles 224 from sulfonyl hydrazone and benzyl acrylate under...
Scheme 79: Titanium-catalyzed consecutive four-component synthesis of pyrazoles 225 via enamino imines 226 [211]. a...
Scheme 80: Titanium-catalyzed three-component synthesis of pyrazoles 227 via enhydrazino imine complex interme...
Scheme 81: Pseudo-three-component synthesis of pyrazoles 229 via Glaser coupling of terminal alkynes and photo...
Scheme 82: Copper(II)acetate-mediated three-component synthesis of pyrazoles 232 [216].
Scheme 83: Copper-catalyzed three-component synthesis of 1,3,4-substituted pyrazole 234 from oxime acetates, a...
Scheme 84: Three-component synthesis of 3-trifluoroethylpyrazoles 239 [218].
Scheme 85: Pseudo-three-component synthesis of 1,4-bisulfonyl-substituted pyrazoles 242 [219].
Scheme 86: Three-component synthesis of 4-hydroxypyrazole 246 [221].
Cage-like microstructures via sequential Ugi reactions in aqueous emulsions
- Rita S. Alqubelat,
- Yaroslava A. Menzorova and
- Maxim A. Mironov
Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179
Graphical Abstract
Scheme 1: Synthesis of cross-linked microgel labelled with aminofluorescein.
Figure 1: Single droplets of the Pickering emulsion attached to a glass surface.
Figure 2: Cage-like microstructure obtained via sequential Ugi reactions.
Figure 3: AFM images of A) single domains and B) cross-linked CMC/chitosan polymer particles.
Figure 4: Variations of microstructures obtained via sequential Ugi reactions. A) Cap-like structures at 5 mo...
Computational toolbox for the analysis of protein–glycan interactions
- Ferran Nieto-Fabregat,
- Maria Pia Lenza,
- Angela Marseglia,
- Cristina Di Carluccio,
- Antonio Molinaro,
- Alba Silipo and
- Roberta Marchetti
Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180
Graphical Abstract
Figure 1: Carbohydrate conformational variability. a) Illustration of Φ, Ψ and ω dihedral angles for a repres...
Figure 2: Monosaccharides diversity in eukaryotes and bacteria. a) Eukaryotic monosaccharides. b) Examples of...
Figure 3: Different glycan representations. The 3’-sialyllactosamine is depicted according to the a) IUPAC no...
Figure 4: Visualisation programs. Different representation of a protein–ligand complex by using the most used...
Figure 5: A schematic representation of useful computational methods to study protein–glycan interactions. a)...
