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Search for "isocyanate" in Full Text gives 91 result(s) in Beilstein Journal of Organic Chemistry.
Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation
- Tereza Horáčková,
- Jan Budka,
- Vaclav Eigner,
- Wen-Sheng Chung,
- Petra Cuřínová and
- Pavel Lhoták
Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249
- atmosphere (5 atm) in an autoclave at room temperature provided compound 6 in 91% yield. The starting compound 5 was then reacted with commercially available isocyanates comprising p-nitrophenyl isocyanate, p-n-butylphenyl isocyanate, (S)-α-methylbenzyl isocyanate, and (R)-α-methylbenzyl isocyanate. The
- introduction of chiral isocyanate to form chiral urea moieties has not been accomplished yet. The formation of another chiral centre within the derivatives 7c and 7d led to the expected decrease [42] of the complexation constant values (by approximately one order of magnitude) due to the presence of alkyl
Graphical Abstract
Figure 1: Design of chiral calix[4]arene-based receptors for anions.
Scheme 1: Synthesis of the calix[4]arene-based chiral anionic receptors 7 and 8.
Figure 2: X-ray structure of 4a: (a) Top view into the cavity. (b) Side view of the same cavity.
Figure 3: X-ray structure of 7a: (a) Hydrogen bonding interactions (black) in a dimeric motif, chalcogen inte...
Figure 4: X-ray structure of 7d, showing hydrogen bonds between the ureido units (green) and hydrogen bonding...
Figure 5: 1H NMR titration of 7c with N-acetyl-ᴅ-phenylalaninate and N-acetyl-ʟ-phenylalaninate (as TBA salts...
Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation
- Alexander P. Molchanov,
- Mariia M. Efremova,
- Mariya A. Kryukova and
- Mikhail A. Kuznetsov
Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218
- assumption, we decided to study alternative methods for the generation of azomethine imines from adducts 3. For this purpose, pyrazolopyrazole 3g was heated in toluene at 110 °C for 3 hours under microwave irradiation in the presence of dipolarophiles such as maleimide 5, isocyanate 7, and isothiocyanate 9
Graphical Abstract
Scheme 1: The two types of azomethine imines (AMI).
Scheme 2: Reaction of 1,5-diazabicyclo[3.1.0]hexanes 1a–d with diarylpropenones 2a–l.
Figure 1: Single-crystal X-ray structure of compound 3e.
Figure 2: Single-crystal X-ray structure of compound 3g.
Scheme 3: Control experiments.
Scheme 4: Mechanistic hypothesis for cycloaddition and cycloreversion reactions of diazabicyclohexane 1a with...
Scheme 5: Experiments on the trapping of azomethine imine, generated from pyrazolopyrazole 3g.
One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway
- Esra Demir,
- Ozlem Sari,
- Yasin Çetinkaya,
- Ufuk Atmaca,
- Safiye Sağ Erdem and
- Murat Çelik
Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148
- Technology, Oltu Vocational School, Atatürk University, 25400 Oltu, Erzurum, Turkey Department of Chemistry, Faculty of Arts and Sciences, Marmara University, Goztepe Campus, 34722 Istanbul, Turkey 10.3762/bjoc.16.148 Abstract The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having
- isocyanate; computational modeling; cyclic carbonates; density functional theory; oxazolidinone; Introduction Oxazolidinones (1), five-membered heterocyclic rings containing an ester group adjacent to a nitrogen atom, are important compounds in synthetic and pharmaceutical chemistry because of their
- reaction with the metal complexes or catalysts, and the reaction of a diol with toxic phosgene are the most common processes [16][17][33][34][35][36]. CSI, a highly reactive and versatile isocyanate, reacts with epoxides to give five-membered cyclic carbonates and oxazolidinones [37][38][39]. In 1984
Graphical Abstract
Scheme 1: Oxazolidinone (1), five-membered cyclic carbonate (2) and some important compounds containing an ox...
Scheme 2: Proposed mechanisms by Keshava Murthy and Dhar [41] and De Meijere and co-workers [42].
Figure 1: Possible pathways for the formation of oxazolidinone intermediates 10 and 11. Optimized transition ...
Figure 2: Potential energy profile related to the formation of oxazolidinone intermediates 10 and 11 at the P...
Figure 3: IRC calculated for the formation of (a) 10 and (b) 11 at M06-2X/6-31+G(d,p) level. I-1, I-15, I-35, ...
Figure 4: Optimized geometries for the stationary points for the formation of 10 at PCM(DCM)/M06-2X/6-31+G(d,...
Scheme 3: Proposed mechanisms for the formation of oxazolidinone 9f.
Figure 5: Potential energy profiles for paths 1a (blue), 1b (red), 2 (green) and relative Gibbs free energies...
Figure 6: Optimized geometries for the stationary points of path 1b at PCM(DCM)/M06-2X/6-31+G(d,p)//M06-2X/6-...
Scheme 4: Proposed mechanism for the formation of five-membered cyclic carbonate 8f.
Figure 7: Potential energy profile and relative Gibbs free energies (kcal/mol) in DCM related to the formatio...
Figure 8: Optimized geometries for the stationary points of step 1 for the formation of 16 at PCM(DCM)/M06-2X...
Figure 9: Optimized geometries for the stationary points of step 2 for the formation of 17 at PCM(DCM)/M06-2X...
Figure 10: Optimized geometries for the stationary points of step 3 for the formation of PC8 at PCM(DCM)/M06-2...
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
- chemically reduced graphene oxide (CRGO)–OH. The CRGO–OH and 2-chloroethyl isocyanate (91) were magnetically stirred in anhydrous DMF under nitrogen atmosphere to afford Cl–graphene (92). The azide-functionalized GO 93 was synthesized by the reaction of 92 with sodium azide in DMSO and heating for 48 h. The
Graphical Abstract
Scheme 1: Chemical structure of the catalysts 1a and 1b and their catalytic application in CuAAC reactions.
Scheme 2: Synthetic route to the catalyst 11 and its catalytic application in CuAAC reactions.
Scheme 3: Synthetic route of dendrons, illustrated using G2-AMP 23.
Scheme 4: The catalytic application of CuYAu–Gx-AAA–SBA-15 in a CuAAC reaction.
Scheme 5: Synthetic route to the catalyst 36.
Scheme 6: Application of the catalyst 36 in CuAAC reactions.
Scheme 7: The synthetic route to the catalyst 45 and catalytic application of 45 in “click” reactions.
Scheme 8: Synthetic route to the catalyst 48 and catalytic application of 48 in “click” reactions.
Scheme 9: Synthetic route to the catalyst 58 and catalytic application of 58 in “click” reactions.
Scheme 10: Synthetic route to the catalyst 64 and catalytic application of 64 in “click” reactions.
Scheme 11: Chemical structure of the catalyst 68 and catalytic application of 68 in “click” reactions.
Scheme 12: Chemical structure of the catalyst 69 and catalytic application of 69 in “click” reactions.
Scheme 13: Synthetic route to, and chemical structure of the catalyst 74.
Scheme 14: Application of the cayalyst 74 in “click” reactions.
Scheme 15: Synthetic route to, and chemical structure of the catalyst 78 and catalytic application of 78 in “c...
Scheme 16: Synthetic route to the catalyst 85.
Scheme 17: Application of the catalyst 85 in “click” reactions.
Scheme 18: Synthetic route to the catalyst 87 and catalytic application of 87 in “click” reactions.
Scheme 19: Chemical structure of the catalyst 88 and catalytic application of 88 in “click” reactions.
Scheme 20: Synthetic route to the catalyst 90 and catalytic application of 90 in “click” reactions.
Scheme 21: Synthetic route to the catalyst 96 and catalytic application of 96 in “click” reactions.
Scheme 22: Synthetic route to the catalyst 100 and catalytic application of 100 in “click” reactions.
Scheme 23: Synthetic route to the catalyst 102 and catalytic application of 23 in “click” reactions.
Scheme 24: Synthetic route to the catalysts 108–111.
Scheme 25: Catalytic application of 108–111 in “click” reactions.
Scheme 26: Synthetic route to the catalyst 121 and catalytic application of 121 in “click” reactions.
Scheme 27: Synthetic route to 125 and application of 125 in “click” reactions.
Scheme 28: Synthetic route to the catalyst 131 and catalytic application of 131 in “click” reactions.
Scheme 29: Synthetic route to the catalyst 136.
Scheme 30: Application of the catalyst 136 in “click” reactions.
Scheme 31: Synthetic route to the catalyst 141 and catalytic application of 141 in “click” reactions.
Scheme 32: Synthetic route to the catalyst 144 and catalytic application of 144 in “click” reactions.
Scheme 33: Synthetic route to the catalyst 149 and catalytic application of 149 in “click” reactions.
Scheme 34: Synthetic route to the catalyst 153 and catalytic application of 153 in “click” reactions.
Scheme 35: Synthetic route to the catalyst 155 and catalytic application of 155 in “click” reactions.
Scheme 36: Synthetic route to the catalyst 157 and catalytic application of 157 in “click” reactions.
Scheme 37: Synthetic route to the catalyst 162.
Scheme 38: Application of the catalyst 162 in “click” reactions.
Scheme 39: Synthetic route to the catalyst 167 and catalytic application of 167 in “click” reactions.
Scheme 40: Synthetic route to the catalyst 169 and catalytic application of 169 in “click” reactions.
Scheme 41: Synthetic route to the catalyst 172.
Scheme 42: Application of the catalyst 172 in “click” reactions.
Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology
- Cloudius R. Sagandira and
- Paul Watts
Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251
- effort to address the safety concerns raised by the potentially explosive acyl azide 1a (Scheme 1), Hayashi and co-workers [14] demonstrated the handling of the Curtius rearrangement reaction (transformation from acyl azide 1a to isocyanate 1b) in a microreactor system (Scheme 1 and Figure 1). Acyl azide
- 1a is a potentially explosive compound because of its nitro and azide moieties [14] and its safety concerns need to be dealt with for large scale synthesis. Safety in this reaction was achieved by in situ formation and consumption in flow of the hazardous intermediates (azide 1a and isocyanate 1b
Graphical Abstract
Scheme 1: Handling of azide chemistry in Tamiflu synthesis by Hayashi and co-workers [14].
Figure 1: Synthesis of compound 2 from acyl chloride 1 via Curtius rearrangement using a continuous-flow syst...
Scheme 2: Azide chemistry in the synthesis of Tamiflu.
Scheme 3: Azidation of mesyl shikimate 5.
Figure 2: Continuous-flow system for C-3 azidation of mesyl shikimate using aqueous sodium azide.
Figure 3: Mesyl shikimate azidation conversion in a continuous-flow system using NaN3.
Figure 4: Desired azide 5 selectivity in a continuous-flow system using NaN3.
Figure 5: Effect of NaN3 concentration on mesyl shikimate 4 conversion and azide 5 selectivity.
Figure 6: Regio- and stereospecific nucleophilic -N3 group attack.
Figure 7: Continuous-flow system for C-3 azidation of mesyl shikimate using DPPA or TMSA.
Figure 8: Mesyl shikimate azidation conversion in a continuous-flow system using DPPA.
Figure 9: Desired azide 5 selectivity in a continuous-flow system using DPPA.
Scheme 4: DPPA azidating mechanism in the presence of a base.
Figure 10: Effect of TEA concentration on the reaction selectivity.
Figure 11: Mesyl shikimate azidation conversion in a continuous-flow system using TMSA.
Figure 12: Desired azide 5 selectivity in a continuous-flow system using TMSA.
Figure 13: Continuous-flow system for C-3 azidation of mesyl shikimate using TBAA.
Figure 14: Continuous-flow system for C-3 azidation of mesyl shikimate using TBAA.
Scheme 5: C-5 azidation of acetamide 6 in our proposed route.
Figure 15: Continuous flow system for C-5 azidation of acetamide 6 using NaN3.
Figure 16: Continuous-flow C-5 azidation of acetamide 6 using NaN3.
Figure 17: Continuous flow C-5 azidation of acetamide 6 using various azidating agents.
Figure 18: Continuous flow synthesis of azide 7 from acetamide 6 using various azidating agents.
Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids
- Jürgen Krauß,
- Monika Klimt,
- Markus Luber,
- Peter Mayer and
- Franz Bracher
Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206
- ][22]. For benzanilides Tu [21] proposed a mechanism involving protonation of the amide oxygen, followed by 1,3 proton shift to the ring carbon next to the amide carbonyl group, followed by elimination of protonated phenyl isocyanate under re-aromatization. For the pyrrole derived substrate
- ). A comparable fragmentation has been observed in the CID (collision-induced dissociation) mass spectrum of atorvastatin, where the base peak observed at m/z 440 clearly corresponds to a loss of phenyl isocyanate [22]. In contrast, refluxing 2 with concentrated aqueous hydrochloric acid (37%) led to
- indication for formation of 6. As the intermediate occurrence of a positive charge at C-2 of the pyrrole ring and a sp3-hybridized C-3 are most likely triggering the elimination of phenyl isocyanate from the pyrrole (see postulated mechanism shown in Scheme 2), we propose the formation of an intermediate C
Graphical Abstract
Figure 1: Atorvastatin calcium trihydrate (1) and previously published decomposition products arising from tr...
Scheme 1: Formation of novel artefacts 6 and 7 under extremely strong acidic conditions.
Figure 2: Top: Molecular structure of artefact 6. Shown here is the molecular structure of one of three indep...
Figure 3: Separation of atorvastatin (1; retention time: 5.8 min) from the four decomposition products 2 (ret...
Scheme 2: Proposed mechanism for the formation of desamidated product 7.
Scheme 3: Proposed mechanism for the formation of bridged product 6 under cyclization, isopropyl migration an...
A review of the total syntheses of triptolide
- Xiang Zhang,
- Zaozao Xiao and
- Hongtao Xu
Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194
- trifluoroacetate 60 by a known electrophilic substitution procedure that was developed by Tahara and co-workers [64]. Curtius rearrangement of 60 gave an isocyanate intermediate, which was reduced with LiAlH4 followed by reductive amination affording tertiary amine intermediate 61. Oxidation of 61 to its
Graphical Abstract
Figure 1: Structures of triptolide (1), triptonide (2), tripdiolide (3), 16-hydroxytriptolide (4), triptrioli...
Figure 2: Syntheses of triptolide.
Scheme 1: Berchtold’s synthesis of triptolide.
Scheme 2: Li’s formal synthesis of triptolide.
Scheme 3: van Tamelen’s asymmetric synthesis of triptonide and triptolide.
Scheme 4: Van Tamelen’s (method II) formal synthesis of triptolide.
Scheme 5: Sherburn’s formal synthesis of triptolide.
Scheme 6: van Tamelen’s biogenetic type total synthesis of triptolide.
Scheme 7: Yang’s total synthesis of triptolide.
Scheme 8: Key intermediates or transformations of routes J–N.
Installation of -SO2F groups onto primary amides
- Jing Liu,
- Shi-Meng Wang,
- Njud S. Alharbi and
- Hua-Li Qin
Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186
- fluorosulfonyl isocyanate (Scheme 1, (2)) [36]. The available procedures for the preparation of N-fluorosulfonyl amides are very limited which relied on using either the isocyanate approach, or the amidosulfofluoride (FSO2NH2) (Scheme 1, (2)) [37][38][39]. Therefore, the development of a new method for the
Graphical Abstract
Figure 1: Representative sulfonyl fluoride compounds applied in medicinal chemistry and chemical biology.
Scheme 1: Synthesis background of N-fluorosulfonyl amides and fluorosulfates.
Scheme 2: Screening of the substrate scope of amides. Reaction conditions: a mixture of amides 1 (1.0 mmol), ...
Scheme 3: Amide resonance model and X-ray single crystal structure of 4e (CCDC 1906002).
Scheme 4: The proposed reaction mechanism.
Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage
- Gagandeep Kour Reen,
- Ashok Kumar and
- Pratibha Sharma
Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165
Graphical Abstract
Figure 1: Various drugs having IP nucleus.
Figure 2: Participation percentage of various TMs for the syntheses of IPs.
Scheme 1: CuI–NaHSO4·SiO2-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 2: Experimental examination of reaction conditions.
Scheme 3: One-pot tandem reaction for the synthesis of 2-haloimidazopyridines.
Scheme 4: Mechanistic scheme for the synthesis of 2-haloimidazopyridine.
Scheme 5: Copper-MOF-catalyzed three-component reaction (3-CR) for imidazo[1,2-a]pyridines.
Scheme 6: Mechanism for copper-MOF-driven synthesis.
Scheme 7: Heterogeneous synthesis via titania-supported CuCl2.
Scheme 8: Mechanism involving oxidative C–H functionalization.
Scheme 9: Heterogeneous synthesis of IPs.
Scheme 10: One-pot regiospecific synthesis of imidazo[1,2-a]pyridines.
Scheme 11: Vinyl azide as an unprecedented substrate for imidazo[1,2-a]pyridines.
Scheme 12: Radical pathway.
Scheme 13: Cu(I)-catalyzed transannulation approach for imidazo[1,5-a]pyridines.
Scheme 14: Plausible radical pathway for the synthesis of imidazo[1,5-a]pyridines.
Scheme 15: A solvent-free domino reaction for imidazo[1,2-a]pyridines.
Scheme 16: Cu-NPs-mediated synthesis of imidazo[1,2-a]pyridines.
Scheme 17: CuI-catalyzed synthesis of isoxazolylimidazo[1,2-a]pyridines.
Scheme 18: Functionalization of 4-bromo derivative via Sonogashira coupling reaction.
Scheme 19: A plausible reaction pathway.
Scheme 20: Cu(I)-catalyzed intramolecular oxidative C–H amidation reaction.
Scheme 21: One-pot synthetic reaction for imidazo[1,2-a]pyridine.
Scheme 22: Plausible reaction mechanism.
Scheme 23: Cu(OAc)2-promoted synthesis of imidazo[1,2-a]pyridines.
Scheme 24: Mechanism for aminomethylation/cycloisomerization of propiolates with imines.
Scheme 25: Three-component synthesis of imidazo[1,2-a]pyridines.
Figure 3: Scope of pyridin-2(1H)-ones and acetophenones.
Scheme 26: CuO NPS-promoted A3 coupling reaction.
Scheme 27: Cu(II)-catalyzed C–N bond formation reaction.
Scheme 28: Mechanism involving Chan–Lam/Ullmann coupling.
Scheme 29: Synthesis of formyl-substituted imidazo[1,2-a]pyridines.
Scheme 30: A tandem sp3 C–H amination reaction.
Scheme 31: Probable mechanistic approach.
Scheme 32: Dual catalytic system for imidazo[1,2-a]pyridines.
Scheme 33: Tentative mechanism.
Scheme 34: CuO/CuAl2O4/ᴅ-glucose-promoted 3-CCR.
Scheme 35: A tandem CuOx/OMS-2-based synthetic strategy.
Figure 4: Biomimetic catalytic oxidation in the presence of electron-transfer mediators (ETMs).
Scheme 36: Control experiment.
Scheme 37: Copper-catalyzed C(sp3)–H aminatin reaction.
Scheme 38: Reaction of secondary amines.
Scheme 39: Probable mechanistic pathway.
Scheme 40: Coupling reaction of α-azidoketones.
Scheme 41: Probable pathway.
Scheme 42: Probable mechanism with free energy calculations.
Scheme 43: MCR for cyanated IP synthesis.
Scheme 44: Substrate scope for the reaction.
Scheme 45: Reaction mechanism.
Scheme 46: Probable mechanistic pathway for Cu/ZnAl2O4-catalyzed reaction.
Scheme 47: Copper-catalyzed double oxidative C–H amination reaction.
Scheme 48: Application towards different coupling reactions.
Scheme 49: Reaction mechanism.
Scheme 50: Condensation–cyclization approach for the synthesis of 1,3-diarylated imidazo[1,5-a]pyridines.
Scheme 51: Optimized reaction conditions.
Scheme 52: One-pot 2-CR.
Scheme 53: One-pot 3-CR without the isolation of chalcone.
Scheme 54: Copper–Pybox-catalyzed cyclization reaction.
Scheme 55: Mechanistic pathway catalyzed by Cu–Pybox complex.
Scheme 56: Cu(II)-promoted C(sp3)-H amination reaction.
Scheme 57: Wider substrate applicability for the reaction.
Scheme 58: Plausible reaction mechanism.
Scheme 59: CuI assisted C–N cross-coupling reaction.
Scheme 60: Probable reaction mechanism involving sp3 C–H amination.
Scheme 61: One-pot MCR-catalyzed by CoFe2O4/CNT-Cu.
Scheme 62: Mechanistic pathway.
Scheme 63: Synthetic scheme for 3-nitroimidazo[1,2-a]pyridines.
Scheme 64: Plausible mechanism for CuBr-catalyzed reaction.
Scheme 65: Regioselective synthesis of halo-substituted imidazo[1,2-a]pyridines.
Scheme 66: Synthesis of 2-phenylimidazo[1,2-a]pyridines.
Scheme 67: Synthesis of diarylated compounds.
Scheme 68: CuBr2-mediated one-pot two-component oxidative coupling reaction.
Scheme 69: Decarboxylative cyclization route to synthesize 1,3-diarylimidazo[1,5-a]pyridines.
Scheme 70: Mechanistic pathway.
Scheme 71: C–H functionalization reaction of enamines to produce diversified heterocycles.
Scheme 72: A plausible mechanism.
Scheme 73: CuI-promoted aerobic oxidative cyclization reaction of ketoxime acetates and pyridines.
Scheme 74: CuI-catalyzed pathway for the formation of imidazo[1,2-a]pyridine.
Scheme 75: Mechanistic pathway.
Scheme 76: Mechanistic rationale for the synthesis of products.
Scheme 77: Copper-catalyzed synthesis of vinyloxy-IP.
Scheme 78: Regioselective product formation with propiolates.
Scheme 79: Proposed mechanism for vinyloxy-IP formation.
Scheme 80: Regioselective synthesis of 3-hetero-substituted imidazo[1,2-a]pyridines with different reaction su...
Scheme 81: Mechanistic pathway.
Scheme 82: CuI-mediated synthesis of 3-formylimidazo[1,2-a]pyridines.
Scheme 83: Radical pathway for 3-formylated IP synthesis.
Scheme 84: Pd-catalyzed urea-cyclization reaction for IPs.
Scheme 85: Pd-catalyzed one-pot-tandem amination and intramolecular amidation reaction.
Figure 5: Scope of aniline nucleophiles.
Scheme 86: Pd–Cu-catalyzed Sonogashira coupling reaction.
Scheme 87: One-pot amide coupling reaction for the synthesis of imidazo[4,5-b]pyridines.
Scheme 88: Urea cyclization reaction for the synthesis of two series of pyridines.
Scheme 89: Amidation reaction for the synthesis of imidazo[4,5-b]pyridines.
Figure 6: Amide scope.
Scheme 90: Pd NPs-catalyzed 3-component reaction for the synthesis of 2,3-diarylated IPs.
Scheme 91: Plausible mechanistic pathway for Pd NPs-catalyzed MCR.
Scheme 92: Synthesis of chromenoannulated imidazo[1,2-a]pyridines.
Scheme 93: Mechanism for the synthesis of chromeno-annulated IPs.
Scheme 94: Zinc oxide NRs-catalyzed synthesis of imidazo[1,2-a]azines/diazines.
Scheme 95: Zinc oxide-catalyzed isocyanide based GBB reaction.
Scheme 96: Reaction pathway for ZnO-catalyzed GBB reaction.
Scheme 97: Mechanistic pathway.
Scheme 98: ZnO NRs-catalyzed MCR for the synthesis of imidazo[1,2-a]azines.
Scheme 99: Ugi type GBB three-component reaction.
Scheme 100: Magnetic NPs-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 101: Regioselective synthesis of 2-alkoxyimidazo[1,2-a]pyridines catalyzed by Fe-SBA-15.
Scheme 102: Plausible mechanistic pathway for the synthesis of 2-alkoxyimidazopyridine.
Scheme 103: Iron-catalyzed synthetic approach.
Scheme 104: Iron-catalyzed aminooxygenation reaction.
Scheme 105: Mechanistic pathway.
Scheme 106: Rh(III)-catalyzed double C–H activation of 2-substituted imidazoles and alkynes.
Scheme 107: Plausible reaction mechanism.
Scheme 108: Rh(III)-catalyzed non-aromatic C(sp2)–H bond activation–functionalization for the synthesis of imid...
Scheme 109: Reactivity and selectivity of different substrates.
Scheme 110: Rh-catalyzed direct C–H alkynylation by Li et al.
Scheme 111: Suggested radical mechanism.
Scheme 112: Scandium(III)triflate-catalyzed one-pot reaction and its mechanism for the synthesis of benzimidazo...
Scheme 113: RuCl3-assisted Ugi-type Groebke–Blackburn condensation reaction.
Scheme 114: C-3 aroylation via Ru-catalyzed two-component reaction.
Scheme 115: Regioselective synthetic mechanism.
Scheme 116: La(III)-catalyzed one-pot GBB reaction.
Scheme 117: Mechanistic approach for the synthesis of imidazo[1,2-a]pyridines.
Scheme 118: Synthesis of imidazo[1,2-a]pyridine using LaMnO3 NPs under neat conditions.
Scheme 119: Mechanistic approach.
Scheme 120: One-pot 3-CR for regioselective synthesis of 2-alkoxy-3-arylimidazo[1,2-a]pyridines.
Scheme 121: Formation of two possible products under optimization of the catalysts.
Scheme 122: Mechanistic strategy for NiFe2O4-catalyzed reaction.
Scheme 123: Two-component reaction for synthesizing imidazodipyridiniums.
Scheme 124: Mechanistic scheme for the synthesis of imidazodipyridiniums.
Scheme 125: CuI-catalyzed arylation of imidazo[1,2-a]pyridines.
Scheme 126: Mechanism for arylation reaction.
Scheme 127: Cupric acetate-catalyzed double carbonylation approach.
Scheme 128: Radical mechanism for double carbonylation of IP.
Scheme 129: C–S bond formation reaction catalyzed by cupric acetate.
Scheme 130: Cupric acetate-catalyzed C-3 formylation approach.
Scheme 131: Control experiments for signifying the role of DMSO and oxygen.
Scheme 132: Mechanism pathway.
Scheme 133: Copper bromide-catalyzed CDC reaction.
Scheme 134: Extension of the substrate scope.
Scheme 135: Plausible radical pathway.
Scheme 136: Transannulation reaction for the synthesis of imidazo[1,5-a]pyridines.
Scheme 137: Plausible reaction pathway for denitrogenative transannulation.
Scheme 138: Cupric acetate-catalyzed C-3 carbonylation reaction.
Scheme 139: Plausible mechanism for regioselective C-3 carbonylation.
Scheme 140: Alkynylation reaction at C-2 of 3H-imidazo[4,5-b]pyridines.
Scheme 141: Two-way mechanism for C-2 alkynylation of 3H-imidazo[4,5-b]pyridines.
Scheme 142: Palladium-catalyzed SCCR approach.
Scheme 143: Palladium-catalyzed Suzuki coupling reaction.
Scheme 144: Reaction mechanism.
Scheme 145: A phosphine free palladium-catalyzed synthesis of C-3 arylated imidazopyridines.
Scheme 146: Palladium-mediated Buchwald–Hartwig cross-coupling reaction.
Figure 7: Structure of the ligands optimized.
Scheme 147: Palladium acetate-catalyzed direct arylation of imidazo[1,2-a]pyridines.
Scheme 148: Palladium acetate-catalyzed mechanistic pathway.
Scheme 149: Palladium acetate-catalyzed regioselective arylation reported by Liu and Zhan.
Scheme 150: Mechanism for selective C-3 arylation of IP.
Scheme 151: Pd(II)-catalyzed alkenylation reaction with styrenes.
Scheme 152: Pd(II)-catalyzed alkenylation reaction with acrylates.
Scheme 153: A two way mechanism.
Scheme 154: Double C–H activation reaction catalyzed by Pd(OAc)2.
Scheme 155: Probable mechanism.
Scheme 156: Palladium-catalyzed decarboxylative coupling.
Scheme 157: Mechanistic cycle for decarboxylative arylation reaction.
Scheme 158: Ligand-free approach for arylation of imidazo[1,2-a]pyridine-3-carboxylic acids.
Scheme 159: Mechanism for ligandless arylation reaction.
Scheme 160: NHC-Pd(II) complex assisted arylation reaction.
Scheme 161: C-3 arylation of imidazo[1,2-a]pyridines with aryl bromides catalyzed by Pd(OAc)2.
Scheme 162: Pd(II)-catalyzed C-3 arylations with aryl tosylates and mesylates.
Scheme 163: CDC reaction for the synthesis of imidazo[1,2-a]pyridines.
Scheme 164: Plausible reaction mechanism for Pd(OAc)2-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 165: Pd-catalyzed C–H amination reaction.
Scheme 166: Mechanism for C–H amination reaction.
Scheme 167: One-pot synthesis for 3,6-di- or 2,3,6-tri(hetero)arylimidazo[1,2-a]pyridines.
Scheme 168: C–H/C–H cross-coupling reaction of IPs and azoles catalyzed by Pd(II).
Scheme 169: Mechanistic cycle.
Scheme 170: Rh-catalyzed C–H arylation reaction.
Scheme 171: Mechanistic pathway for C–H arylation of imidazo[1,2-a]pyridine.
Scheme 172: Rh(III)-catalyzed double C–H activation of 2-phenylimidazo[1,2-a]pyridines and alkynes.
Scheme 173: Rh(III)-catalyzed mechanistic pathway.
Scheme 174: Rh(III)-mediated oxidative coupling reaction.
Scheme 175: Reactions showing functionalization of the product obtained by the group of Kotla.
Scheme 176: Mechanism for Rh(III)-catalyzed oxidative coupling reaction.
Scheme 177: Rh(III)-catalyzed C–H activation reaction.
Scheme 178: Mechanistic cycle.
Scheme 179: Annulation reactions of 2-arylimidazo[1,2-a]pyridines and alkynes.
Scheme 180: Two-way reaction mechanism for annulations reaction.
Scheme 181: [RuCl2(p-cymene)]2-catalyzed C–C bond formation reaction.
Scheme 182: Reported reaction mechanism.
Scheme 183: Fe(III) catalyzed C-3 formylation approach.
Scheme 184: SET mechanism-catalyzed by Fe(III).
Scheme 185: Ni(dpp)Cl2-catalyzed KTC coupling.
Scheme 186: Pd-catalyzed SM coupling.
Scheme 187: Vanadium-catalyzed coupling of IP and NMO.
Scheme 188: Mechanistic cycle.
Scheme 189: Selective C3/C5–H bond functionalizations by mono and bimetallic systems.
Scheme 190: rGO-Ni@Pd-catalyzed C–H bond arylation of imidazo[1,2-a]pyridine.
Scheme 191: Mechanistic pathway for heterogeneously catalyzed arylation reaction.
Scheme 192: Zinc triflate-catalyzed coupling reaction of substituted propargyl alcohols.
Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams
- Edorta Martínez de Marigorta,
- Jesús M. de Los Santos,
- Ana M. Ochoa de Retana,
- Javier Vicario and
- Francisco Palacios
Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104
- excesses, which result, according to the authors, from a dynamic kinetic resolution of the initially formed Ugi adduct. Indeed, the plausible mechanism for the reaction implies the condensation of amine 2 and aldehyde 33 to form iminium salt intermediate 47 (Scheme 14). Next, addition of isocyanate 42
Graphical Abstract
Figure 1: γ-Lactam-derived structures considered in this review.
Figure 2: Alkaloids containing an isoindolinone moiety.
Figure 3: Alkaloids containing the 2-oxindole ring system.
Figure 4: Drugs and biological active compounds containing an isoindolinone moiety.
Figure 5: Drugs and biologically active compounds bearing a 2-oxindole skeleton.
Scheme 1: Three-component reaction of benzoic acid 1, amides 2 and DMSO (3).
Scheme 2: Copper-catalysed three-component reaction of 2-iodobenzoic acids 10, alkynylcarboxylic acids 11 and...
Scheme 3: Proposed mechanism for the formation of methylene isoindolinones 13.
Scheme 4: Copper-catalysed three-component reaction of 2-iodobenzamide 17, terminal alkyne 18 and pyrrole or ...
Scheme 5: Palladium-catalysed three-component reaction of ethynylbenzamides 21, secondary amines 22 and CO (23...
Scheme 6: Proposed mechanism for the formation of methyleneisoindolinones 24.
Scheme 7: Copper-catalysed three-component reaction of formyl benzoate 29, amines 2 and alkynes 18.
Scheme 8: Copper-catalysed three-component reaction of formylbenzoate 29, amines 2 and ketones 31.
Scheme 9: Non-catalysed (A) and phase-transfer catalysed (B) three-component reactions of formylbenzoic acids ...
Scheme 10: Proposed mechanism for the formation of isoindolinones 36.
Scheme 11: Three-component reaction of formylbenzoic acid 33, amines 2 and fluorinated silyl ethers 39.
Scheme 12: Three-component Ugi reaction of 2-formylbenzoic acid (33), diamines 41 and isocyanides 42.
Scheme 13: Non-catalysed (A, B) and chiral phosphoric acid promoted (C) three-component Ugi reactions of formy...
Scheme 14: Proposed mechanism for the enantioselective formation of isoindolinones 46.
Scheme 15: Three-component reaction of benzoic acids 33 or 54, amines 2 and TMSCN (52).
Scheme 16: Several variations of the three-component reaction of formylbenzoic acids 33, amines 2 and isatoic ...
Scheme 17: Proposed mechanism for the synthesis of isoindoloquinazolinones 57.
Scheme 18: Three-component reaction of isobenzofuranone 61, amines 2 and isatoic anhydrides 56.
Scheme 19: Palladium-catalysed three-component reaction of 2-aminobenzamides 59, 2-bromobenzaldehydes 62 and C...
Scheme 20: Proposed mechanism for the palladium-catalysed synthesis of isoindoloquinazolinones 57.
Scheme 21: Four-component reaction of 2-vinylbenzoic acids 67, aryldioazonium tetrafluoroborates 68, DABCO·(SO2...
Scheme 22: Plausible mechanism for the formation of isoindolinones 71.
Scheme 23: Three-component reaction of trimethylsilylaryltriflates 77, isocyanides 42 and CO2 (78).
Scheme 24: Plausible mechanism for the three-component synthesis of phthalimides 79.
Scheme 25: Copper-catalysed three-component reaction of 2-formylbenzonitriles 85, arenes 86 and diaryliodonium...
Scheme 26: Copper-catalysed three-component reaction of 2-formylbenzonitriles 85, diaryliodonium salts 87 and ...
Scheme 27: Proposed mechanism for the formation of 2,3-diarylisoindolinones 88, 89 and 92.
Scheme 28: Palladium-catalysed three-component reaction of chloroquinolinecarbaldehydes 97 with isocyanides 42...
Scheme 29: Palladium-catalysed three-component reaction of imines 99 with CO (23) and ortho-iodoarylimines 100....
Scheme 30: Palladium-catalysed three-component reaction of amines 2 with CO (23) and aryl iodide 105.
Scheme 31: Three-component reaction of 2-ethynylanilines 109, perfluoroalkyl iodides 110 and carbon monoxide (...
Scheme 32: Ultraviolet-induced three-component reaction of N-(2-iodoaryl)acrylamides 113, DABCO·(SO2)2 (69) an...
Scheme 33: Proposed mechanism for the preparation of oxindoles 115.
Scheme 34: Three-component reaction of acrylamide 113, CO (23) and 1,4-benzodiazepine 121.
Scheme 35: Multicomponent reaction of sulfonylacrylamides 123, aryldiazonium tetrafluoroborates 68 and DABCO·(...
Scheme 36: Proposed mechanism for the preparation of oxindoles 124.
Scheme 37: Three-component reaction of N-arylpropiolamides 128, aryl iodides 129 and boronic acids 130.
Scheme 38: Proposed mechanism for the formation of diarylmethylene- and diarylallylideneoxindoles 131 and 132.
Scheme 39: Three-component reaction of cyclohexa-1,3-dione (136), amines 2 and alkyl acetylenedicarboxylates 1...
Scheme 40: Proposed mechanism for the formation of 2-oxindoles 138.
A three-component, Zn(OTf)2-mediated entry into trisubstituted 2-aminoimidazoles
- Alexei Lukin,
- Anna Bakholdina,
- Anna Kryukova,
- Alexander Sapegin and
- Mikhail Krasavin
Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103
- from the respective isocyanates and propargylamine (or propagyl isocyanate and primary amines), thus could offer an opportunity to synthesize 2-aminoimidazoles 5 in a three-component format. Considering these premises, we started to explore the Zn(OTf)2-catalyzed reaction of 4 with primary amines
- . Herein, we present the preliminary results of these studies. Results and Discussion Urea 4a (prepared by reacting propargylamine with 4-(trifluoromethoxy)benzyl isocyanate) was reacted with an equivalent amount of benzylamine in refluxing toluene in the presence of various Lewis acids. To our delight
Graphical Abstract
Figure 1: Examples of imidazole (1 and 2) and oxazole (3) syntheses from propargylamides previously reported ...
Figure 2: Substrate scope for the three-component synthesis of 5.
Figure 3: Plausible mechanism for the formation of 5.
An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride
- Aytekin Köse,
- Aslı Ünal,
- Ertan Şahin,
- Uğur Bozkaya and
- Yunus Kara
Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89
- study, we developed a new addition reaction of chlorosulfonyl isocyanate (CSI), starting from 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione. The addition reaction of CSI with 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione resulted in the formation of ylidenesulfamoyl chloride, whose
- exact configuration was determined by X-ray crystal analysis. We explain the mechanism of product formation supported by theoretical calculations. Keywords: addition reaction; chlorosulfonyl isocyanate; sulfamoyl chloride; theoretical calculations; Introduction Since its identification in 1959 [1
- ], chlorosulfonyl isocyanate (CSI, 1) continues to be the most reactive isocyanate to date. CSI is relatively more reactive than alkylsulfonyl isocyanate in olefin additions [2]. Its highly reactive nature is due to the polarization of the allene double bond by the highly electronegative chlorosulfonyl group. CSI
Graphical Abstract
Scheme 1: The reaction of CSI with olefins.
Figure 1: The dipolar intermediate formed in the reaction of CSI with olefins.
Scheme 2: The synthesis of imide 9.
Scheme 3: The synthesis of ylidene sulfamoyl chloride 10.
Figure 2: (a) Molecular structure of racemic molecule 10 (asymmetric unit). Thermal ellipsoids are drawn at t...
Scheme 4: Mechanism for the formation of ylidenesulfamoyl chloride 10.
Figure 3: Relative energy profile of the reaction mechanism shown in Scheme 4.
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
- 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
Graphical Abstract
Scheme 1: Chemical structures of 3a–e and 5a–e, and the cartoon representation of LCST behavior.
Scheme 2: Synthetic routes and yields of 3a–e and 5a–e.
Figure 1: 1H NMR spectra (room temperature) of (a) 5a (5 mg/mL) in CDCl3; (b) 5a (5 mg/mL) in D2O; (c) 3a (5 ...
Figure 2: a) Water solubility of 3a–e and 5a–e at room temperature; b) concentration-dependent LCST behavior ...
Figure 3: Temperature-dependent 1H NMR spectra (400 MHz, D2O) of 3a–c and 5d. Measurement at temperature a) 2...
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
- resulting α-allenic carbocations 24a–c (Scheme 14) [48]. As a complementary strategy, our group examined the [3,3]-sigmatropic rearrangement of cyanates derived from cyclopropenylcarbinols [53]. The allyl cyanate to isocyanate rearrangement displays many interesting features such as the possibility to
- -disubstitution at C3 on the three-membered ring. Alcohol 25 was readily converted to carbamate 26 by reaction with trichloroacetyl isocyanate followed by cleavage of the trichloroacetyl group by alkaline hydrolysis. Dehydration of carbamate 26 was achieved by treatment with trifluoroacetic anhydride in the
Graphical Abstract
Scheme 1: Representative strategies for the formation of alkylidenecyclopropanes from cyclopropenes and scope...
Scheme 2: [2,3]-Sigmatropic rearrangement of phosphinites 2a–h.
Scheme 3: [2,3]-Sigmatropic rearrangement of a phosphinite derived from enantioenriched cyclopropenylcarbinol...
Scheme 4: Selective reduction of phosphine oxide (E)-3f.
Scheme 5: Attempted thermal [2,3]-sigmatropic rearrangement of phosphinite 6a.
Scheme 6: Computed activation barriers and free enthalpies.
Scheme 7: [2,3]-Sigmatropic rearrangement of phosphinites 6a–j.
Scheme 8: Proposed mechanism for the Lewis base-catalyzed rearrangement of phosphinites 6.
Scheme 9: [3,3]-Sigmatropic rearrangement of tertiary cyclopropenylcarbinyl acetates 10a–c.
Scheme 10: [3,3]-Sigmatropic rearrangement of secondary cyclopropenylcarbinyl esters 10d–h.
Scheme 11: [3,3]-Sigmatropic rearrangement of trichoroacetimidates 12a–i.
Scheme 12: Reaction of trichloroacetamide 13f with pyrrolidine.
Scheme 13: Catalytic hydrogenation of (arylmethylene)cyclopropropane 13f.
Scheme 14: Instability of trichloroacetimidates 21a–c derived from cyclopropenylcarbinols 20a–c.
Scheme 15: [3,3]-Sigmatropic rearrangement of cyanate 27 generated from cyclopropenylcarbinyl carbamate 26.
Scheme 16: Synthesis of alkylidene(aminocyclopropane) derivatives 30–37 from carbamate 26.
Scheme 17: Scope of the dehydration–[3,3]-sigmatropic rearrangement sequence of cyclopropenylcarbinyl carbamat...
Scheme 18: Formation of trifluoroacetamide 50 from carbamate 49.
Scheme 19: Formation of alkylidene[(N-trifluoroacetylamino)cyclopropanes] 51–54.
Scheme 20: Diastereoselective hydrogenation of alkylidenecyclopropane 51.
Scheme 21: Ireland–Claisen rearrangement of cyclopropenylcarbinyl glycolates 56a–l.
Scheme 22: Synthesis and Ireland–Claisen rearrangement of glycolate 61 possessing gem-diester substitution at ...
Scheme 23: Synthesis of alkylidene(gem-difluorocyclopropanes) 66a–h, and 66k–n from propargyl glycolates 64a–n....
Scheme 24: Ireland–Claisen rearrangement of N,N-diBoc glycinates 67a and 67b.
Scheme 25: Diastereoselective hydrogenation of alkylidenecyclopropanes 58a and 74.
Scheme 26: Synthesis of functionalized gem-difluorocyclopropanes 76 and 77 from alkylidenecyclopropane 66a.
Scheme 27: Access to oxa- and azabicyclic compounds 78–80.
Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step
- Pierre-Antoine Nocquet,
- Aurélie Macé,
- Frédéric Legros,
- Jacques Lebreton,
- Gilles Dujardin,
- Sylvain Collet,
- Arnaud Martel,
- Bertrand Carboni and
- François Carreaux
Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274
- synthesis of the carbamate-protected glycal of L-vancosamine 1 and L-saccharosamine 2 were prepared in two steps by treatment of alcohols with the trichloroacetyl isocyanate reagent (TCA-NCO) followed by basic hydrolysis. The spectroscopic properties of carbamates 17 were identical to those reported in the
Graphical Abstract
Figure 1: N,N-Dimethyl-L-vancosamine as substructure of kidamycin and pluramycin.
Figure 2: Glycals as relevant scaffolds for constructing aryl C-glycosidic linkage.
Figure 3: Strategy including a ring-closing metathesis of vinyl ethers as key step for the preparation of sev...
Scheme 1: Evans aldol reaction for the preparation of diastereomeric compounds 13a and 13b.
Scheme 2: Alternative preparation of 13b based on a diastereoselective allylboration.
Scheme 3: O-Vinylation-ring-closing metathesis sequence for access to 3-amino glycals.
Scheme 4: Synthesis of key intermediate 23 for the C-3 unbranched amino glycals preparation.
Scheme 5: Access to diastereoisomeric compounds 3 and 4 from 23.
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
- for 1.5 h at −50 °C and stirred for another 1.5 h at room temperature for the generation of isocyanate intermediate 2. Thereafter, a solution of L-glutamic-γ-benzyl-α-tert-butyl·HCl (0.159 g, 0.507 mmol) and triethylamine (0.14 mL, 1.014 mmol) in DCM was added to the reaction mixture and the progress
Graphical Abstract
Figure 1: (a) Structure of universal nova tag resin, (b) structure of H-L-Cys(Trt)-2-ClTrt resin.
Figure 2: (a) PSMA targeted DUPA rhodamine B chelating conjugate 13. (b) Folate receptor targeted pteroate rh...
Scheme 1: Synthesis of PSMA tris(tert-butoxy) protected DUPA ligand 4. Reagents and conditions: (a) Triphosge...
Scheme 2: Attempted synthesis of PSMA targeted DUPA rhodamine B chelating conjugate 13 using Fmoc-Lys(Mtt/Mmt...
Scheme 3: Synthesis of PSMA targeting DUPA rhodamine B chelating conjugate 13. Reagents and conditions: (a) F...
Scheme 4: Synthesis of folate receptor targeting pteroate rhodamine B chelating conjugate 17. Reagents and co...
Figure 3: (i) and (ix) DIC image of LNCaP cells (PSMA+); (ii) binding and internalization of DUPA-rhodamine B...
Hydroarylations by cobalt-catalyzed C–H activation
- Rajagopal Santhoshkumar and
- Chien-Hong Cheng
Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202
- hydroarylation of glyoxylate with pyrimidine containing indoles and pyrroles 7 to provide products 63 with high productivity (Scheme 40) [79]. Similar to the imine, isocyanate is also an efficient electrophile for hydroarylation of C=N bond. It provides a high atom- and step-economical method for the preparation
Graphical Abstract
Scheme 1: Cobalt-catalyzed C–H carbonylation.
Scheme 2: Hydroarylation by C–H activation.
Scheme 3: Pathways for cobalt-catalyzed hydroarylations.
Scheme 4: Co-catalyzed hydroarylation of alkynes with azobenzenes.
Scheme 5: Co-catalyzed hydroarylation of alkynes with 2-arylpyridines.
Scheme 6: Co-catalyzed addition of azoles to alkynes.
Scheme 7: Co-catalyzed addition of indoles to alkynes.
Scheme 8: Co-catalyzed hydroarylation of alkynes with imines.
Scheme 9: A plausible pathway for Co-catalyzed hydroarylation of alkynes.
Scheme 10: Co-catalyzed anti-selective C–H addition to alkynes.
Scheme 11: Co(III)-catalyzed hydroarylation of alkynes with indoles.
Scheme 12: Co(III)-catalyzed branch-selective hydroarylation of alkynes.
Scheme 13: Co(III)-catalyzed hydroarylation of terminal alkynes with arenes.
Scheme 14: Co(III)-catalyzed hydroarylation of alkynes with amides.
Scheme 15: Co(III)-catalyzed C–H alkenylation of arenes.
Scheme 16: Co-catalyzed alkylation of substituted benzamides with alkenes.
Scheme 17: Co-catalyzed switchable hydroarylation of styrenes with 2-aryl pyridines.
Scheme 18: Co-catalyzed linear-selective hydroarylation of alkenes with imines.
Scheme 19: Co-catalyzed linearly-selective hydroarylation of alkenes with N–H imines.
Scheme 20: Co-catalyzed branched-selective hydroarylation of alkenes with imines.
Scheme 21: Mechanism of Co-catalyzed hydroarylation of alkenes.
Scheme 22: Co-catalyzed intramolecular hydroarylation of indoles.
Scheme 23: Co-catalyzed asymmetric hydroarylation of alkenes with indoles.
Scheme 24: Co-catalyzed hydroarylation of alkenes with heteroarenes.
Scheme 25: Co(III)-catalyzed hydroarylation of activated alkenes with 2-phenyl pyridines.
Scheme 26: Co(III)-catalyzed C–H alkylation of arenes.
Scheme 27: Co(III)-catalyzed C2-alkylation of indoles.
Scheme 28: Co(III)-catalyzed switchable hydroarylation of alkyl alkenes with indoles.
Scheme 29: Co(III)-catalyzed C2-allylation of indoles.
Scheme 30: Co(III)-catalyzed ortho C–H alkylation of arenes with maleimides.
Scheme 31: Co(III)-catalyzed hydroarylation of maleimides with arenes.
Scheme 32: Co(III)-catalyzed hydroarylation of allenes with arenes.
Scheme 33: Co-catalyzed hydroarylative cyclization of enynes with carbonyl compounds.
Scheme 34: Mechanism for the Co-catalyzed hydroarylative cyclization of enynes with carbonyl compounds.
Scheme 35: Co-catalyzed addition of 2-arylpyridines to aromatic aldimines.
Scheme 36: Co-catalyzed addition of 2-arylpyridines to aziridines.
Scheme 37: Co(III)-catalyzed hydroarylation of imines with arenes.
Scheme 38: Co(III)-catalyzed addition of arenes to ketenimines.
Scheme 39: Co(III)-catalyzed three-component coupling.
Scheme 40: Co(III)-catalyzed hydroarylation of aldehydes.
Scheme 41: Co(III)-catalyzed addition of arenes to isocyanates.
Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing
- Françoise Debart,
- Christelle Dupouy and
- Jean-Jacques Vasseur
Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32
- with phenylsulfonyl isocyanate produces a caged ON unable to hybridize to its complementary RNA sequence until heat removal of the psc (Scheme 17) [65]. However, currently, this approach is limited to CPG-supported methylphosphonate ONs containing thymines and cytosines immobilized on a glass slide
Graphical Abstract
Scheme 1: Demasking under reducing agents of ON prodrugs modified as phosphotriesters with A) benzyl groups [13] ...
Scheme 2: A) Synthesis via phosphoramidite chemistry and B) demasking under the reducing environment of 2’-O-...
Scheme 3: Synthesis via phosphoramidite chemistry of various 2’-O-alkyldithiomethyl (RSSM)-modified RNAs bear...
Scheme 4: A) siRNA conjugates to cholesterol [19] and B) PNA conjugates to a triphenylphosphonium [20] through a disu...
Scheme 5: Synthesis via phosphoramidite chemistry and deprotection mediated by nitroreductase/NADH of hypoxia...
Scheme 6: Synthesis via phosphoramidite chemistry and conversion mediated by nitroreductase/NADH of hypoxia-a...
Scheme 7: Incorporation of O6-(4-nitrobenzyl)-2’-deoxyguanosine into an ON prone to form a G-quadruplex struc...
Scheme 8: Synthesis and mechanism for the demasking of ON prodrugs from A) S-acylthioethyl phosphotriester [29] a...
Figure 1: Oligothymidylates bearing A) 2,2-bis(ethoxycarbonyl)-3-(pivaloyloxy)propyl- and B) 2-cyano-2(2-phen...
Figure 2: Oligothymidylates containing esterase and thermo-labile (4-acetylthio-2,2-dimethyl-3-oxobutyl) phos...
Scheme 9: Phosphoramidites and the corresponding RNA prodrugs protected as A) t-Bu-SATE, B) OH-SATE and C) A-...
Scheme 10: Mechanism of the hydrolysis of 2’-O-acyloxymethyl ONs mediated by carboxyesterases [46]. The hydrolysis...
Scheme 11: Synthesis of partially 2’-O-PivOM-modified RNAs [49] and 2’-O-PiBuOM-modified RNAs [53] using their corresp...
Figure 3: A) 2’-O-amino and guanidino-containing acetal ester phosphoramidites and B) 2’-O-(amino acid) aceta...
Scheme 12: Prodrugs of tricyclo-ONs functionalized with A) ethyl (tcee-T) and B) hexadecyl (tchd-T) ester func...
Scheme 13: Demasking mechanism of fma thiophosphate triesters in CpG ODN upon heat action [58].
Scheme 14: Thermolytic cleavage of the hydroxy-alkylated thiophosphate and phosphato-/thiophosphato-alkylated ...
Scheme 15: Synthesis via phosphoramidite chemistry and thermolytic cleavage of alkylated (diisopropyl, diethyl...
Scheme 16: Synthesis of thermosensitive prodrugs of ODNs containing fma thiophosphate triesters combined to po...
Scheme 17: Caging of deoxycytidine in methylphosphonate ONs by using the thermolabile phenylsulfonylcarbamoyl ...
Figure 4: Biotinylated 1-(5-(aminomethyl)-2-nitrophenyl)ethyl phosphoramidite used to cage the 5’-end of a si...
Scheme 18: Introduction and cleavage of 1-(4,5-dimethoxy-2-nitrophenyl)ethyl (DMNPE) [74] and cyclododecyl-DMNPE (...
Scheme 19: Post-synthetic introduction of a thioether-enol phosphodiester (TEEP) linkage into a DNAzyme by the...
Scheme 20: A) NPP dT and dG phosphoramidites [91,92] and B) NPOM U and G phosphoramidites [83] used to introduce photocag...
Scheme 21: Introduction of the photocaged 3-NPOM nucleobase into phosphorothioate antisense and morpholino ant...
Scheme 22: Control of the activity of an antisense ODN using a photocaged hairpin [82]. Formation of the hairpin s...
Scheme 23: Control of alternative splicing using phosphorothioate (PS) 2’-OMe-photocaged ONs resulting from th...
Scheme 24: A) Light activation of a photocaged DNAzyme incorporating 3-NPOM thymidine in its catalytic site [87]; ...
Scheme 25: Incorporation of 3-(6-nitropiperonyloxymethyl) (NPOM) thymidine and 4-nitropiperonylethyl (NPE) deo...
Scheme 26: Synthesis of a photocaged DNA decoy from a 3-NPOM thymidine phosphoramidite and release of the NPOM...
Scheme 27: Synthesis of a caged DNA decoy hairpin containing a 7-nitroindole nucleotide and release of the mod...
Figure 5: Caged-2’-adenosines used by MacMillan et al [93,94] (X = O) and Piccirilli et al [95] (X = S) to study RNA mec...
Scheme 28: Synthesis of circular ODNs containing a photolabile linker as described by Tang et al. [101,104].
Scheme 29: Control of RNA digestion with RNase H using light activation of a photocaged hairpin [97].
Scheme 30: Photocontrol of RNA degradation using caged circular antisense ODNs containing a photoresponsive li...
Scheme 31: Control of RNA translation using an “RNA bandage” consisting of two short 2’-OMe ONs linked togethe...
Scheme 32: Control of alternative splicing using photocaged ONs resulting from the incorporation of an o-nitro...
Scheme 33: A) Light deactivation of a photocaged DNAzyme incorporating one photocleavable spacer in its cataly...
Scheme 34: Solid-phase synthesis of a caged vit E-siRNA conjugate and its release upon UV irradiation [106].
Scheme 35: Synthesis of a siRNA conjugated to a nanoparticle (NP) via a cyclooctene heterolinker from a siRNA-...
Recent developments in the asymmetric Reformatsky-type reaction
- Hélène Pellissier
Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21
- ). Finally, good to excellent enantioselectivities (76–94% ee) combined to moderate to quantitative yields (45–99%) were reported by Matsubara and Haraguchi in the enantioselective Reformatsky reaction of aldehydes 48b–e,g–i,r–w with enolate equivalent 55 prepared from phenyl isocyanate 56 and CH2(ZnI)2 in
- a stoichiometric amount of a chiral 1,2-amino alcohol ligand [45]. Reformatsky reaction of aldehydes with an enolate equivalent prepared from phenyl isocyanate and CH2(ZnI)2 performed in the presence of a chiral diarylprolinol ligand [46]. Domino aza-Reformatsky/cyclization reactions of imines with
Graphical Abstract
Scheme 1: Reformatsky-type reaction.
Scheme 2: First total synthesis of prunustatin A based on a Zn-mediated Reformatsky reaction [17].
Scheme 3: Synthesis of a γ-hydroxylysine derivative through a Zn-mediated nitrile Reformatsky-type reaction [18].
Scheme 4: Synthesis of apratoxin E and its C30 epimer through a Zn-mediated Reformatsky reaction. Fmoc = 9-fl...
Scheme 5: Synthesis of the eastern fragment of jatrophane diterpene Pl-3 through a SmI2-mediated Reformatsky ...
Scheme 6: First total synthesis of prebiscibactin through a SmI2-mediated Reformatsky reaction. Boc = tert-bu...
Scheme 7: Synthesis of prostaglandin E2 methyl ester through a SmI2-mediated Reformatsky reaction [23].
Scheme 8: Synthesis of the C1–C11 fragment of tedanolide C through a SnCl2-mediated Reformatsky reaction. PMB...
Scheme 9: Synthesis of β-trifluoromethyl β-(N-tert-butylsulfinyl)amino esters exhibiting a quaternary stereoc...
Scheme 10: Synthesis of α,α-difluoro-β-(N-tert-butylsulfinyl)amino esters through Zn(II)-mediated aza-Reformat...
Scheme 11: Synthesis of a common fragment to anti-apoptotic protein inhibitors through a Zn-mediated aza-Refor...
Scheme 12: Synthesis of α,α-difluoro-β-(N-tert-butylsulfinyl)amino ketones through a Zn-mediated aza-Reformats...
Scheme 13: Synthesis of (2-oxoindolin-3-yl)amino esters through a Zn-mediated aza-Reformatsky reaction [30].
Scheme 14: Synthesis of a precursor of sacubitril through a Zn-mediated aza-Reformatsky reaction [31].
Scheme 15: Synthesis of epothilone D through a Cr(II)-mediated Reformatsky reaction. TFA = trifluoroacetic aci...
Scheme 16: Synthesis of β-hydroxy-α-methyl-δ-trichloromethyl-δ-valerolactone through a Sm(II)- or Yb(II)-media...
Scheme 17: Synthesis of cebulactam A1 through a Sm(II)-mediated Reformatsky reaction. MOM = methoxymethyl [34].
Scheme 18: Synthesis of ansamacrolactams (+)-Q-1047H-A-A and (+)-Q-1047H-R-A through a Sm(II)-mediated Reforma...
Scheme 19: Reformatsky reaction of aldehydes with ethyl iodoacetate in the presence of a chiral 1,2-amino alco...
Scheme 20: Reformatsky reaction of aldehydes with ethyl bromoacetate in the presence of a chiral amide ligand [44]....
Scheme 21: Reformatsky reaction of cinnamaldehyde with ethyl bromozinc-α,α-difluoroacetate in the presence of ...
Scheme 22: Reformatsky reaction of aldehydes with an enolate equivalent prepared from phenyl isocyanate and CH2...
Scheme 23: Domino aza-Reformatsky/cyclization reactions of imines with ethyl dibromofluoroacetate in the prese...
Scheme 24: Domino aza-Reformatsky/cyclization reactions of imines with ethyl bromodifluoroacetate in the prese...
Scheme 25: Aza-Reformatsky reactions of cyclic imines with ethyl iodoacetate in the presence of a chiral diary...
Scheme 26: Mechanism for aza-Reformatsky reaction of cyclic imines with ethyl iodoacetate in the presence of a...
Scheme 27: Aza-Reformatsky reaction of dibenzo[b,f][1,4]oxazepines and dibenzo[b,f][1,4]thiazepine with ethyl ...
One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates
- Jun Ki Kim,
- Hwan Jung Lim,
- Kyung Chae Jeong and
- Seong Jun Park
Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16
- -acetal 7d, the formation of a resonance stabilized enaminate anion had a smaller contribution and this resulted in a reduced yield (34%, Table 1, entry 4) [70]. To identify the effects of sulfur, a reaction with the corresponding isocyanate was performed to introduce an oxygen atom. As a result, only O
Graphical Abstract
Figure 1: The selected examples of sulfur(IV) and sulfur(VI) ylides 1 [1], 2 [5-7], 3 [6,7,9], 4 [11,12], 5 [33,34], 6 [35-38].
Figure 2: Metal-free synthesis of thiophene-based heterocycles (A) [54,55], (B) [56].
Scheme 1: One-pot sequential synthesis of the trisubstituted 5-(pyridine-2-yl)thiophenes 8a. Substrate: amalo...
Figure 3: X-ray crystal structures of 8ad and 8an [68].
Figure 4: The proposed structure of sulfur ylide-like intermediates; resonance contributors (mesomeric struct...
Scheme 2: The substitution reaction with MeOH.
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
Graphical Abstract
Figure 1: Selected examples of drugs with fused pyrazole rings.
Figure 2: Typical structures of some fused pyrazoloazines from 5-aminopyrazoles.
Scheme 1: Regiospecific synthesis of 4 and 6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines.
Scheme 2: Synthesis of pyrazolo[3,4-b]pyridine-6-carboxylates.
Scheme 3: Synthesis of 1,4,6-triaryl-1H-pyrazolo[3,4-b]pyridines with ionic liquid .
Scheme 4: Synthesis of coumarin-based isomeric tetracyclic pyrazolo[3,4-b]pyridines.
Scheme 5: Synthesis of 6-substituted pyrazolo[3,4-b]pyridines under Heck conditions.
Scheme 6: Microwave-assisted palladium-catalyzed synthesis of pyrazolo[3,4-b]pyridines.
Scheme 7: Acid-catalyzed synthesis of pyrazolo[3,4-b]pyridines via enaminones.
Scheme 8: Synthesis of pyrazolo[3,4-b]pyridines via aza-Diels–Alder reaction.
Scheme 9: Synthesis of macrocyclane fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 10: Three-component synthesis of 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine derivatives.
Scheme 11: Ultrasonicated synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-diones.
Scheme 12: Synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]pyridine] derivatives under conventional heating co...
Scheme 13: Nanoparticle-catalyzed synthesis of pyrazolo[3,4-b]pyridine-spiroindolinones.
Scheme 14: Microwave-assisted multicomponent synthesis of spiropyrazolo[3,4-b]pyridines.
Scheme 15: Unexpected synthesis of naphthoic acid-substituted pyrazolo[3,4-b]pyridines.
Scheme 16: Multicomponent synthesis of variously substituted pyrazolo[3,4-b]pyridine derivatives.
Scheme 17: Three-component synthesis of 4,7-dihydropyrazolo[3,4-b]pyridines and pyrazolo[3,4-b]pyridines.
Scheme 18: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanediones.
Scheme 19: Ultrasound-mediated three-component synthesis of pyrazolo[3,4-b]pyridines.
Scheme 20: Multicomponent synthesis of 4-aryl-3-methyl-1-phenyl-4,6,8,9-tetrahydropyrazolo [3,4-b]thiopyrano[4...
Scheme 21: Synthesis of 2,3-dihydrochromeno[4,3-d]pyrazolo[3,4-b]pyridine-1,6-diones.
Scheme 22: FeCl3-catalyzed synthesis of o-hydroxyphenylpyrazolo[3,4-b]pyridine derivatives.
Scheme 23: Ionic liquid-mediated synthesis of pyrazolo[3,4-b]pyridines.
Scheme 24: Microwave-assisted synthesis of pyrazolo[3,4-b]pyridines.
Scheme 25: Multicomponent synthesis of pyrazolo[3,4-b]pyridine-5-carbonitriles.
Scheme 26: Unusual domino synthesis of 4,7-dihydropyrazolo[3,4-b]pyridine-5-nitriles.
Scheme 27: Synthesis of 4,5,6,7-tetrahydro-4H-pyrazolo[3,4-b]pyridines under conventional heating and ultrasou...
Scheme 28: L-Proline-catalyzed synthesis of of pyrazolo[3,4-b]pyridine.
Scheme 29: Microwave-assisted synthesis of 5-aminoarylpyrazolo[3,4-b]pyridines.
Scheme 30: Microwave-assisted multi-component synthesis of pyrazolo[3,4-e]indolizines.
Scheme 31: Synthesis of fluoropropynyl and fluoroalkyl substituted pyrazolo[1,5-a]pyrimidine.
Scheme 32: Acid-catalyzed synthesis of pyrazolo[1,5-a]pyrimidine derivatives.
Scheme 33: Chemoselective and regiospecific synthesis of 2-(3-methylpyrazol-1’-yl)-5-methylpyrazolo[1,5-a]pyri...
Scheme 34: Regioselective synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyrimidines.
Scheme 35: Microwave-assisted synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyrimidine carboxylates.
Scheme 36: Microwave and ultrasound-assisted synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyrimidines.
Scheme 37: Base-catalyzed unprecedented synthesis of pyrazolo[1,5-a]pyrimidines via C–C bond cleavage.
Scheme 38: Synthesis of aminobenzothiazole/piperazine linked pyrazolo[1,5-a]pyrimidines.
Scheme 39: Synthesis of aminoalkylpyrazolo[1,5-a]pyrimidine-7-amines.
Scheme 40: Synthesis of pyrazolo[1,5-a]pyrimidines from condensation of 5-aminopyrazole 126 and ethyl acetoace...
Scheme 41: Synthesis of 7-aminopyrazolo[1,5-a]pyrimidines.
Scheme 42: Unexpected synthesis of 7-aminopyrazolo[1,5-a]pyrimidines under solvent free and solvent-mediated c...
Scheme 43: Synthesis of N-(4-aminophenyl)-7-aryloxypyrazolo[1,5-a]pyrimidin-5-amines.
Scheme 44: Base-catalyzed synthesis of 5,7-diarylpyrazolo[1,5-a]pyrimidines.
Scheme 45: Synthesis of 6,7-dihydropyrazolo[1,5-a]pyrimidines in PEG-400.
Scheme 46: Synthesis of 7-heteroarylpyrazolo[1,5-a]pyrimidine-3-carboxamides.
Scheme 47: Synthesis of 7-heteroarylpyrazolo[1,5-a]pyrimidine derivatives under conventional heating and micro...
Scheme 48: Synthesis of N-aroylpyrazolo[1,5-a]pyrimidine-5-amines.
Scheme 49: Regioselective synthesis of ethyl pyrazolo[1,5-a]pyrimidine-7-carboxylate.
Scheme 50: Sodium methoxide-catalyzed synthesis of 3-cyano-6,7-diarylpyrazolo[1,5-a]pyrimidines.
Scheme 51: Synthesis of various pyrazolo[3,4-d]pyrimidine derivatives.
Scheme 52: Synthesis of hydrazinopyrazolo[3,4-d]pyrimidine derivatives.
Scheme 53: Synthesis of N-arylidinepyrazolo[3,4-d]pyrimidin-5-amines.
Scheme 54: Synthesis of pyrazolo[3,4-d]pyrimidinyl-4-amines.
Scheme 55: Iodine-catalyzed synthesis of pyrazolo[3,4-d]pyrimidinones.
Scheme 56: Synthesis of ethyl 6-amino-2H-pyrazolo[3,4-d]pyrimidine-4-carboxylate.
Scheme 57: Synthesis of 4-substituted-(3,6-dihydropyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidines.
Scheme 58: Synthesis of 1-(2,4-dichlorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl carboxamides.
Scheme 59: Synthesis of 5-(1,3,4-thidiazol-2-yl)pyrazolo[3,4-d]pyrimidine.
Scheme 60: One pot POCl3-catalyzed synthesis of 1-arylpyrazolo[3,4-d]pyrimidin-4-ones.
Scheme 61: Synthesis of 4-amino-N1,C3-dialkylpyrazolo[3,4-d]pyrimidines under Suzuki conditions.
Scheme 62: Microwave-assisted synthesis of pyrazolo[3,4-b]pyrazines.
Scheme 63: Synthesis and derivatization of pyrazolo[3,4-b]pyrazine-5-carbonitriles.
Scheme 64: Synthesis of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones.
Scheme 65: Synthesis of 2,3-dihydropyrazolo[1,5-a][1,3,5]triazin-4(1H)-one.
Scheme 66: Synthesis of pyrazolo[1,5-a][1,3,5]triazine-8-carboxylic acid ethyl ester.
Scheme 67: Microwave-assisted synthesis of 4,7-dihetarylpyrazolo[1,5-a][1,3,5]triazines.
Scheme 68: Alternative synthetic route to 4,7-diheteroarylpyrazolo[1,5-a][1,3,5]triazines.
Scheme 69: Synthesis of 4-aryl-2-ethylthio-7-methylpyrazolo[1,5-a][1,3,5]triazines.
Scheme 70: Microwave-assisted synthesis of 4-aminopyrazolo[1,5-a][1,3,5]triazine.
Scheme 71: Synthesis of pyrazolo[3,4-d][1,2,3]triazines from pyrazol-5-yl diazonium salts.
Scheme 72: Synthesis of 2,5-dihydropyrazolo[3,4-e][1,2,4]triazines.
Scheme 73: Synthesis of pyrazolo[5,1-c][1,2,4]triazines via diazopyrazolylenaminones.
Scheme 74: Synthesis of pyrazolo[5,1-c][1,2,4]triazines in presence of sodium acetate.
Scheme 75: Synthesis of various 7-diazopyrazolo[5,1-c][1,2,4]triazine derivatives.
Scheme 76: One pot synthesis of pyrazolo[5,1-c][1,2,4]triazines.
Scheme 77: Synthesis of 4-amino-3,7,8-trinitropyrazolo-[5,1-c][1,2,4]triazines.
Scheme 78: Synthesis of tricyclic pyrazolo[5,1-c][1,2,4]triazines by azocoupling reaction.
From dipivaloylketene to tetraoxaadamantanes
- Gert Kollenz and
- Curt Wentrup
Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1
- tetraoxaadamantanes. Inward-pointing isocyanate, urethane and carbamate groups in bisdioxines. The diisocyanate is obtained by Curtius and Hofmann rearrangements of the diazides and diamides [38][39]. Microwave-assisted tetraoxaadamantane formation. Cyclic bisdioxine ester derivative 34 forming a single mono
Graphical Abstract
Scheme 1: Synthetic routes to 2,4,6,8-tetraoxaadamantanes.
Scheme 2: Conversion of dipivaloylketene (2) to bisdioxines (2,6,9-trioxabicyclo[3.3.1]nona-3,7-dienes) 4 and...
Scheme 3: 2,6,9-Trioxabicyclo[3.3.1]nonadienes (bisdioxines, 9–13) derived from dipivaloylketene (2).
Scheme 4: Mechanisms of formation of bisdioxine acid derivatives from dimer 3.
Scheme 5: Recently reported synthesis of chromenobisdioxines.
Scheme 6: Formation of tetraoxaadamantanes.
Scheme 7: Decarboxylative hydrolysis and oxa-Michael-type ring closure.
Scheme 8: Oxime and hydrazine derivatives of bisdioxines and tetraoxaadamantanes.
Figure 1: Bistetraoxaadamantane derivatives.
Scheme 9: Inward-pointing isocyanate, urethane and carbamate groups in bisdioxines. The diisocyanate is obtai...
Scheme 10: Microwave-assisted tetraoxaadamantane formation.
Scheme 11: Cyclic bisdioxine ester derivative 34 forming a single mono-tetraoxaadamantane.
Figure 2: Cyclic bisdioxine derivative not forming a tetraoxaadamantane due to reduced cavity size.
Figure 3: The bisdioxine-calix[6]arene derivative 37 complexes Cs+ but does not form a tetraoxaadamantane der...
Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity
- Henryk Myszka,
- Patrycja Sokołowska,
- Agnieszka Cieślińska,
- Andrzej Nowacki,
- Maciej Jaśkiewicz,
- Wojciech Kamysz and
- Beata Liberek
Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227
- the condensation of saccharides with ureas or the reaction of glycosylamines, amino sugar, or aminoglycosides with isocyanates, or their equivalents such as carbamates [32][33]. Ureido saponins presented here were obtained in the reaction of ethyl isocyanate (8), chloroethyl isocyanate (9) and phenyl
- isocyanate (10) with the amino group of 4. Isocyanate was added to the 1:1 (v/v) chloroform–methanol solution of 4 and Et3N each time. The yields of these reactions were very good (90% for 8) or good (60% for 9). However, phenylurea derivative 10 was isolated with only 34% yield, and the formation of various
Graphical Abstract
Scheme 1: Synthesis of diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside (4).
Figure 1: Derivatives of diosgenyl glycosides 5–13.
Mechanochemical synthesis of thioureas, ureas and guanidines
- Vjekoslav Štrukil
Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178
- 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
- mono-urea 36 with phenyl isocyanate under the milling conditions used for the synthesis of bis-thioureas [35]. A known bis-urea anion sensor 35 was prepared in quantitative yield in 30 minutes by milling o-pda with phenyl isocyanate in a 1:2 molar ratio. However, in the 1:1 reaction, a mixture of mono
- milling for three hours, the addition of phenyl isocyanate (1 equiv) to mono-thioureas 19a–d quantitatively yielded the mixed urea–thioureas 37a–d (Scheme 15b), which could also be prepared by a ‘‘reverse’’ mechanosynthesis starting from the mono-urea 36. An interesting approach, published by Colacino et
Graphical Abstract
Scheme 1: a) Schematic representations of unsubstituted urea, thiourea and guanidine. b) Wöhler's synthesis o...
Figure 1: Antidiabetic (1–3) and antimalarial (4) drugs derived from ureas and guanidines currently available...
Scheme 2: The structures of some representative (thio)urea and guanidine organocatalysts 5–8 and anion sensor...
Scheme 3: Solid-state reactivity of isothiocyanates reported by Kaupp [30].
Scheme 4: a) Mechanochemical synthesis of aromatic and aliphatic di- and trisubstituted thioureas by click-co...
Figure 2: The supramolecular level of organization of thioureas in the solid-state.
Figure 3: The supramolecular level of organization of thioureas in the solid-state.
Scheme 5: Thiourea-based organocatalysts and anion sensors obtained by click-mechanochemical synthesis.
Scheme 6: Mechanochemical desymmetrization of ortho-phenylenediamine.
Scheme 7: Mechanochemical desymmetrization of para-phenylenediamine.
Scheme 8: a) Selected examples of a mechanochemical synthesis of aromatic isothiocyanates from anilines. b) O...
Scheme 9: In solution, aromatic N-thiocarbamoyl benzotriazoles 27 are unstable and decompose to isothiocyanat...
Scheme 10: Mechanosynthesis of a) bis-thiocarbamoyl benzotriazole 29 and b) benzimidazole thione 31. c) Synthe...
Figure 4: In situ Raman spectroscopy monitoring the synthesis of thiourea 28d in the solid-state. N-Thiocarba...
Scheme 11: a) The proposed synthesis of monosubstituted thioureas 32. b) Conversion of N-thiocarbamoyl benzotr...
Scheme 12: A few examples of mechanochemical amination of thiocarbamoyl benzotriazoles by in situ generated am...
Scheme 13: Mechanochemical synthesis of a) anion binding urea 33 by amine-isocyanate coupling and b) dialkylur...
Scheme 14: a) Solvent-free milling synthesis of the bis-urea anion sensor 35. b) Non-selective desymmetrizatio...
Scheme 15: a) HOMO−1 contours of mono-thiourea 19b and mono-urea 36. b) Mechanochemical synthesis of hybrid ur...
Scheme 16: Synthesis of ureido derivatives 38 and 39 from KOCN and hydrochloride salts of a) L-phenylalanine m...
Scheme 17: a) K2CO3-assisted synthesis of sulfonyl (thio)ureas. b) CuCl-catalyzed solid-state synthesis of sul...
Scheme 18: Two-step mechanochemical synthesis of the antidiabetic drug glibenclamide (2).
Scheme 19: Derivatization of saccharin by mechanochemical CuCl-catalyzed addition of isocyanates.
Scheme 20: a) Unsuccessful coupling of p-toluenesulfonamide and DCC in solution and by neat/LAG ball milling. ...
Scheme 21: a) Expansion of the saccharin ring by mechanochemical insertion of carbodiimides. b) Insertion of D...
Scheme 22: Synthesis of highly basic biguanides by ball milling.
Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates
- Anna Wrona-Piotrowicz,
- Marzena Witalewska,
- Janusz Zakrzewski and
- Anna Makal
Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102
- , although substitution at the 1-position prevails. For ethoxycarbonyl isothiocyanate, apart from the 1-substituted thioamide, 1,8-disubstituted thioamide and 2,7-di-tert-butylpyrene-1-carbonitrile are formed (especially at longer reaction times). Keywords: amide; Friedel–Crafts; isocyanate; isothiocyanate
- ). Results and Discussion The reaction was carried out at room temperature in dichloromethane using 1.7 equiv of isocyanate or isothiocyanate and 3.3 equiv of TfOH. For the isocyanates, the reaction was completed in less than 5 min, whereas the reaction with isothiocyanates required ≈30 min for completion
- spectra were recorded in CDCl3 at 600 MHz for 1H and 150 MHz for 13C at room temperature. Chemical shifts are reported in ppm and are referenced relative to solvent signals. 2,7-Di-tert-butylpyrene-1-carboxamides. General procedure Analogous as described in [12]. Isocyanate (1.2 mmol) and TfOH (348 μL, 4
Graphical Abstract
Figure 1: Sites of electrophilic attack in 1 and 2.
Scheme 1: Triflic acid promoted reaction of 2 with iso(thio)cyanates.
Scheme 2: Triflic acid promoted reaction of 2 with ethoxycarbonyl isothiocyanate.
Figure 2: Molecular structure of 4.
Scheme 3: Friedel–Crafts acylation of 2.
