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Search for "benzyl chloride" in Full Text gives 23 result(s) in Beilstein Journal of Organic Chemistry.
Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides
- Kan Tang,
- Megan R. Brown,
- Chad Risko,
- Melissa K. Gish,
- Garry Rumbles,
- Phuc H. Pham,
- Oana R. Luca,
- Stephen Barlow and
- Seth R. Marder
Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142
- process (given the reduction potentials in Table 2). As shown in Scheme 1, we found 2-iodobenzyl chloride is cleanly converted to benzyl chloride under the standard conditions used in Table 2 (see Supporting Information File 1, Table S4 for more details). This selectivity is not typically achievable using
Graphical Abstract
Figure 1: (a, b) Schematics of previous approaches to dehalogenation-based reactions using molecular reductan...
Scheme 1: Selective deiodination of 2-iodobenzyl chloride.
Scheme 2: Reaction mechanisms for the reactions of dimeric reductants (D2) such as (Y-DMBI)2 derivatives with...
Figure 2: (a) A representative temporal evolution of % conversion (blue squares), % toluene yield (red diamon...
Figure 3: Top: UV–vis absorption spectra for the two dimeric reductants in THF emphasizing (a) the different ...
Figure 4: Transient absorption spectra of (a) (N-DMBI)2 in MeCN, (b) (N-DMBI)2 in toluene, and (c) (Cyc-DMBI)2...
Photoredox catalysis harvesting multiple photon or electrochemical energies
- Mattia Lepori,
- Simon Schmid and
- Joshua P. Barham
Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81
Graphical Abstract
Figure 1: Oxidative and reductive activations of organic compounds harvesting photoredox catalysis.
Figure 2: General catalytic cycles of radical ion conPET (left) and radical ion e-PRC (right).
Figure 3: “Beginner’s guide”: comparison between advantages, capacities, and prospectives of conPET and PEC.
Figure 4: A) conPET reductive dehalogenation of aryl halides with PDI. B) Reductive C–H arylation with pyrrol...
Figure 5: A) Chromoselective mono- and disubstitution or polybrominated pyrimidines with pyrroles. B) Sequent...
Figure 6: A) Synthesis of pyrrolo[1,2-a]quinolines. B) Synthesis of ullazines.
Figure 7: A) Reductive phosphorylation of aryl halides via conPET. B) Selected examples from the substrate sc...
Figure 8: A) Reductive dehalogenation of aryl halides via conPET and selected examples from the substrate sco...
Figure 9: A) Reductive C–H arylation of aryl halides via conPET (top) and selected examples from the substrat...
Figure 10: A) Reductive hydrodehalogenation of aryl halides with Mes-Acr-BF4. B) Selected examples from the su...
Figure 11: A) Reductive hydrodechlorination of aryl chlorides with 4-DPAIPN. B) Proposed formation of CO2•−. C...
Figure 12: A) Reductive conPET borylation with 3CzEPAIPN (top) and selected examples from the substrate scope ...
Figure 13: Scale-up of conPET phosphorylation with 3CzEPAIPN.
Figure 14: A) Borylation of 1d. B) Characteristics and structure of PC1 with green and red parts showing the l...
Figure 15: A) Reductive C–H arylation scope with polysulfide conPET (top) and selected examples from the subst...
Figure 16: Scale-up of A) C–H arylation and B) dehaloborylation with polysulfide photocatalysis in continuous-...
Figure 17: A) Formation of [Ir1]0 and [Ir2]0 upon PET between [Ir1]+ and Et3N. B) Mechanism of multi-photon ta...
Figure 18: A) Reductive hydrodehalogenation of aryl halides via multi-photon tandem photocatalysis. B) Selecte...
Figure 19: A) Carbonylative amidation of aryl halides in continuous flow. B) Selected examples from the substr...
Figure 20: A) General scheme for reductive (RQ) and oxidative quenching (OQ) protocols using [FeIII(btz)3](PF6)...
Figure 21: A) Carbonylative amidation of alkyl iodides with [IrIII(ppy)2(dtbbpy)]PF6. B) Selected examples fro...
Figure 22: A) Carboxylative C–N bond cleavage in cyclic amines. B) Selected examples from the substrate scope....
Figure 23: A) Formal reduction of alkenes to alkanes via transfer hydrogenation. B) Selected examples from the...
Figure 24: A) Birch-type reduction of benzenes with PMP-BPI. B) Selected examples from the substrate scope (sc...
Figure 25: Proposed mechanism of the OH− mediated conPET Birch-type reduction of benzene via generation of sol...
Figure 26: Reductive detosylation of N-tosylated amides with Mes-Acr-BF4. B) Selected examples from the substr...
Figure 27: A) Reductive detosylation of N-tosyl amides by dual PRC. B) Selected examples from the substrate sc...
Figure 28: A) Mechanism of the dual PRC based on PET between [Cu(dap)2]+ and DCA. B) Mechanism of the dual PRC...
Figure 29: A) N–O bond cleavage in Weinreb amides with anthracene. B) N–O bond cleavage in Weinreb amides rely...
Figure 30: A) Pentafluorosulfanylation and fluoride elimination. B) Mechanism of the pentafluorosulfanylation ...
Figure 31: A) α-Alkoxypentafluorosulfanylation (top) and selected examples from the substrate scope (bottom). ...
Figure 32: A) Oxidative amination of arenes with azoles catalyzed by N-Ph PTZ. B) Selected examples from the s...
Figure 33: A) C(sp3)–H bond activation by HAT via chloride oxidation by *N-Ph PTZ•+. B) Proposed mechanism for...
Figure 34: A) Recycling e-PRC C–H azolation of electron-rich arenes with pyrazoles using Mes-Acr+ as a photoca...
Figure 35: A) Radical ion e-PRC direct oxidation of unactivated arenes using TAC+ as an electro-activated phot...
Figure 36: A) Radical ion e-PRC direct oxidation of unactivated arenes using TPA as an electro-activated photo...
Figure 37: Proposed mechanism (top) and mode of preassembly (bottom).
Figure 38: A) Possible preassemblies of reactive (left) vs unreactive (right) arenes. B) Calculated spin densi...
Figure 39: A) Recycling e-PRC C(sp2 )–H acetoxylation of arenes using DDQ as a photocatalyst. B) Proposed cata...
Figure 40: Gram scale hydroxylation of benzene in a recirculated flow setup.
Figure 41: A) Radical ion e-PRC vicinal diamination of alkylarenes using TAC+ as an electro-activated photocat...
Figure 42: A) Sequential oxygenation of multiple adjacent C–H bonds under radical ion e-PRC using TAC+ as an e...
Figure 43: A) Enantioselective recycling e-PRC cyanation of benzylic C–H bonds using ADQS as photocatalyst. B)...
Figure 44: Proposed tandem mechanism by Xu and co-workers.
Figure 45: A) Enantioselective recycling e-PRC decarboxylative cyanation using Cu(acac)2, Ce(OTf)3 and a box l...
Figure 46: A) Enantioselective recycling e-PRC benzylic cyanation using Cu(MeCN)4BF4, box ligand and anthraqui...
Figure 47: A) Radical ion e-PRC acetoxyhydroxylation of aryl olefins using TAC+ as an electro-activated photoc...
Figure 48: Selected examples from the substrate scope.
Figure 49: Photoelectrochemical acetoxyhydroxylation in a recirculated flow setup.
Figure 50: A) Radical ion e-PRC aminooxygenation of aryl olefins using TAC+ as an electro-activated photocatal...
Figure 51: A) Recycling e-PRC C–H alkylation of heteroarenes with organic trifluoroborates using Mes-Acr+ as p...
Figure 52: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using CeCl3·7H2O as catalyst. B) ...
Figure 53: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using Fe(NH4)2(SO4)2·6H2O as cata...
Figure 54: A) Recycling e-PRC C–H alkylation of heteroarenes with alkyl oxalates and 4CzIPN as photocatalyst. ...
Figure 55: A) Recycling e-PRC decarboxylative C–H carbamoylation of heteroarenes using 4CzIPN as photocatalyst...
Figure 56: A) Photoelectrochemical HAT-mediated hydrocarbon activation via the chlorine radical. B) Proposed m...
Figure 57: A) Selected examples from the substrate scope. B) Gram and decagram scale semi-continuous flow PEC ...
Figure 58: A) Photoelectrochemical HAT-mediated dehydrogenative coupling of benzothiazoles with aliphatic C–H ...
Figure 59: A) Photoelectrochemical HAT activation of ethers using electro-activated TAC+ as photocatalyst. B) ...
Figure 60: Selected examples from the substrate scope.
Figure 61: A) Photoelectrochemical HAT-mediated synthesis of alkylated benzimidazo-fused isoquinolinones using...
Figure 62: A) Decoupled photoelectrochemical cerium-catalyzed oxydichlorination of alkynes using CeCl3 as cata...
Figure 63: Proposed decoupled photoelectrochemical mechanism.
Figure 64: A) Decoupled photoelectrochemical ring-opening bromination of tertiary cycloalkanols using MgBr2 as...
Figure 65: A) Recycling e-PRC ring-opening functionalization of cycloalkanols using CeCl3 as catalyst. B) Prop...
Figure 66: Selected examples from the substrate scope of the PEC ring-opening functionalization.
Figure 67: A) Radical ion e-PRC reduction of chloro- and bromoarenes using DCA as catalyst and various accepto...
Figure 68: A) Screening of different phthalimide derivatives as catalyst for the e-PRC reduction of aryl halid...
Figure 69: Screening of different organic catalysts for the e-PRC reduction of trialkylanilium salts.
Figure 70: A) e-PRC reduction of phosphonated phenols and anilinium salts. B) Selected examples from the subst...
Figure 71: A) ConPET and e-PRC reduction of 4-bromobenzonitrile using a naphthalene diimide (NDI) precatalyst ...
Figure 72: A) Radical ion e-PRC reduction of phosphinated aliphatic alcohols with n-BuO-NpMI as catalyst. B) C...
Figure 73: Selected examples from the substrate scope.
Figure 74: A) Recycling e-PRC reductive dimerization of benzylic chlorides using a [Cu2] catalyst. B) Proposed...
Figure 75: A) Decoupled photoelectrochemical C–H alkylation of heteroarenes through deamination of Katritzky s...
Figure 76: Proposed mechanism by Chen and co-workers.
An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates
- Timur O. Zanakhov,
- Ekaterina E. Galenko,
- Mikhail S. Novikov and
- Alexander F. Khlebnikov
Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74
- pyridone 2n can be quantitatively benzylated by benzyl chloride to give derivative 17. Conclusion A method has been developed for the preparation of 2-alkyl-6-aryl-, 2-aryl-6-aryl and 2,6-diaryl-5-aryl/hetaryl-substituted derivatives of 4-oxo-1,4-dihydropyridine-3-carboxylic acid 2 via Mo(CO)6-mediated
Graphical Abstract
Scheme 1: Approaches to the synthesis of alkyl 4-oxo-1,4-dihydropyridine-3-carboxylates.
Scheme 2: Synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates.
Scheme 3: Synthesis of Isoxazoles 11–13.
Scheme 4: Synthesis of isoxazoles 1.
Scheme 5: Synthesis of pyridones 2.
Scheme 6: Transformations of pyridones 2.
Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide
- Dongming Zhang,
- Bin Lv,
- Pan Gao,
- Xiaodong Jia and
- Yu Yuan
Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65
- )benzene was treated with 2a. Moreover, benzyl chloride and benzyl bromide tolerated the reaction conditions, affording the aryl-phthalimidated products of which the ortho and para products were the major isomers. It is also shown that disubstituted and trisubstituted arenes successfully reacted to give
Graphical Abstract
Scheme 1: Amination of arenes with phthalimides.
Scheme 2: Substrate scope of the copper-catalyzed C–H imidation of arenes. Reaction conditions: 1 (2.0 mL as ...
Scheme 3: Substrate scope of the copper-catalyzed C–H imidation of N-hydroxyphthalimide. Reaction conditions: ...
Scheme 4: A plausible reaction mechanism.
Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides
- Mateo Berton,
- Kevin Sheehan,
- Andrea Adamo and
- D. Tyler McQuade
Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115
- chlorobenzene, considered a deactivated species, was converted to PhMgCl in an excellent yield (2.32 M, 93%, Table 1, entry 10), heating the column to 100 °C. For benzyl chloride, a 2-MeTHF/THF, 9:1 mixture [57] was found to be optimal to reduce the formation of a Wurtz-type side product, 1,2-diphenylethane
Graphical Abstract
Figure 1: Comparing on-demand coffee and turbo Grignard pod-style machines.
Figure 2: Ranking of the 20 most cited Grignard reagents (SciFinder March 26, 2019).
Figure 3: On-demand prototype. A) Inside view of the pump with a flexible bag containing a yellow liquid layi...
Figure 4: Temperature evolution measured with thermocouples along the column outer surface at three different...
Figure 5: Stratified bicomponent column (Diba Omnifit EZ Solvent Plus) composed of magnesium (chips/powder, 1...
Scheme 1: Continuous flow synthesis of TMPMgCl⋅LiCl with a stratified packed-bed column of activated magnesiu...
Scheme 2: Continuous flow synthesis of TMPMgCl⋅LiBr with a stratified packed-bed column of activated magnesiu...
Scheme 3: Continuous flow synthesis of t-AmylOMgCl⋅LiCl with a stratified packed-bed column of activated magn...
Figure 6: Steady-state concentration stability during the conversion of iPrCl in THF (56 mL, 2.2 M) into iPrM...
Scheme 4: Synthesis of iPrMgCl⋅LiCl on the ODR prototype.
Scheme 5: Synthesis of HMDSMgCl⋅LiCl on the ODR prototype.
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
- , washed with THF and dichloromethane, and dried. Different organic halides (benzyl bromides, benzyl chloride, allyl bromide, aliphatic epoxides, and aromatic epoxides) were treated with sodium azide and phenylacetylene in the presence of a catalytic amount of the copper catalyst 121 in water at 70 °C
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.
KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones
- Qiao Lin,
- Shiling Zhang and
- Bin Li
Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44
- evaluated for the ring-opening N-alkylation with benzyl chloride derivatives 4 under similar conditions but at 80 °C, as the chlorides are expected to be less reactive than the corresponding benzyl bromides (Scheme 3). Only 26% yield of 2-aminoethyl acetate compound 3a were observed, however, the addition
- % yields from the corresponding benzyl bromides. The electron-donating and the electron-withdrawing groups did not affect these N-alkylation reactions. Interestingly, the reaction tolerates a cyano functional group on the aryl ring of benzyl chloride, and the corresponding thiazolidone 5i (80%), was
- mmol), benzyl chloride (1.0 mmol) and DMC (2 mL) were introduced in a tube, equipped with magnetic stirring bar and the mixture was stirred at 80 °C. After 16 h, the progress of the reaction was analyzed by gas chromatography. The solvent was then evaporated under vacuum and the desired product was
Graphical Abstract
Scheme 1: Comparison of different ring-opening reactions of 2-oxazolines and thiazolidinones synthesis.
Scheme 2: KOt-Bu-promoted selective ring-opening N-alkylation of 2-methyl-2-oxazoline with benzyl bromides. C...
Scheme 3: KOt-Bu-promoted selective ring-opening N-alkylation of 2-methyl-2-oxazoline with benzyl chlorides. ...
Scheme 4: KOt-Bu-promoted selective ring-opening N-alkylation of 2,4,4-trimethyl-4,5-dihydrooxazole (2b) with...
Scheme 5: KOt-Bu/I2-promoted selective N-alkylation to synthesis of thiazolidone derivatives. Conditions: KOt...
Scheme 6: Transformation of 2-aminoethyl acetate derivative to 2-(dibenzylamino)ethanol.
Scheme 7: Control experiments and 18O-labeling experiment.
Scheme 8: Control experiments with radical scavengers.
Scheme 9: Proposed mechanism.
Friedel–Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts
- Kenta Tanaka,
- Yuta Tanaka,
- Mami Kishimoto,
- Yujiro Hoshino and
- Kiyoshi Honda
Beilstein J. Org. Chem. 2019, 15, 2105–2112, doi:10.3762/bjoc.15.208
- is a more easily available substrate in comparison with benzyl chloride, the desired product was obtained in good yield. It was found that the reaction can be applied to not only benzoyl chloride but also to benzoic acid. With the optimized conditions in hand, we investigated the generality of diaryl
Graphical Abstract
Scheme 1: The representative synthesis of thioxanthylium salts.
Figure 1: The generality of diaryl sulfide 1 and benzoyl chloride 2. aThe reaction was carried out with 1a (2...
Figure 2: The UV–vis spectra of thioxanthylium salt (0.1 mM) in CH3CN.
Figure 3: Frontier orbitals of thioxanthylium salts, calculated by DFT at the B3LYP/6-31G(d,p) level of Orca....
Figure 4: UV–vis spectra of thioxanthylium salts 3b and 4b (0.1 mM) in CH3CN.
Figure 5: Structure of thioxanthylium salt 4.
Figure 6: Cyclic voltammograms of thioxanthylium salts 3b and 4b.
Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source
- Tetsuaki Fujihara and
- Yasushi Tsuji
Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221
- Negishi coupling with aryl bromide, affording the corresponding sterically congested alkene 17b-Ar in 56% yield after two steps. The Negishi coupling with benzyl chloride and the Cu-catalyzed allylation of allyl bromide also afforded the corresponding products 17b-Bn and 17b-Allyl, respectively, in good
Graphical Abstract
Scheme 1: Optimization of the Co-catalyzed carboxylation of 1a.
Scheme 2: Co-catalyzed carboxylation of propargyl acetates 1.
Scheme 3: Plausible reaction mechanism for the Co-catalyzed carboxylation of propargyl acetates 1.
Scheme 4: Optimization of the Co-catalyzed carboxylation of 3a.
Scheme 5: Co-catalyzed carboxylation of vinyl triflates 3.
Scheme 6: Co-catalyzed carboxylation of a sterically hindered aryl triflate 5.
Scheme 7: Optimization of the Co-catalyzed carboxylation of 7a.
Scheme 8: Scope of the reductive carboxylation of α,β-unsaturated nitriles 7.
Scheme 9: Scope of the carboxylation of α,β-unsaturated carboxamides 9.
Scheme 10: Optimization of the Co-catalyzed carboxylation of 11a.
Scheme 11: Scope of the carboxylation of allylarenes 11.
Scheme 12: Scope of the carboxylation of 1,4-diene derivatives 14.
Scheme 13: Plausible reaction mechanism for the Co-catalyzed C(sp3)–H carboxylation of allylarenes.
Scheme 14: Optimization of the Co-catalyzed carboxyzincation of 16a.
Scheme 15: Derivatization of the carboxyzincated product.
Scheme 16: Co-catalyzed carboxyzincation of alkynes 16.
Scheme 17: Plausible reaction mechanism for the Co-catalyzed carboxyzincation of alkynes 16.
Scheme 18: Co-catalyzed four-component coupling of alkynes 16, acrylates 18, CO2, and zinc.
Scheme 19: Proposed reaction mechanism for the Co-catalyzed four-component coupling.
Scheme 20: Visible-light-driven hydrocarboxylation of alkynes.
Scheme 21: Visible-light-driven synthesis of γ-hydroxybutenolides from ortho-ester-substituted aryl alkynes.
Scheme 22: One-pot synthesis of coumarines and 2-quinolones via hydrocarboxylation/alkyne isomerization/cycliz...
Scheme 23: Proposed reaction mechanism for the Co-catalyzed carboxylative cyclization of ortho-substituted aro...
Scheme 24: Rh-catalyzed carboxylation of arylboronic esters 25.
Scheme 25: Rh-catalyzed carboxylation of alkenylboronic esters 27.
Scheme 26: Plausible reaction mechanism for the Rh-catalyzed carboxylation of arylboronic esters 25.
Scheme 27: Ligand effect on the Rh-catalyzed carboxylation of 2-phenylpyridine 29a.
Scheme 28: Rh-catalyzed chelation-assisted C(sp2)–H bond carboxylation with CO2.
Scheme 29: Reaction mechanism for the Rh-catalyzed C(sp2)–H carboxylation of 2-pyridylarenes 29.
Scheme 30: Carboxylation of C(sp2)–H bond with CO2.
Scheme 31: Carboxylation of C(sp2)–H bond with CO2.
Scheme 32: Reaction mechanism for the Rh-catalyzed C(sp2)–H carboxylation of 2-arylphenols 34.
Scheme 33: Hydrocarboxylation of styrene derivatives with CO2.
Scheme 34: Hydrocarboxylation of α,β-unsaturated esters with CO2.
Scheme 35: Asymmetric hydrocarboxylation of α,β-unsaturated esters with CO2.
Scheme 36: Proposed reaction mechanism for the Rh-catalyzed hydrocarboxylation of C–C double bonds with CO2.
Scheme 37: Visible-light-driven hydrocarboxylation with CO2.
Scheme 38: Visible-light-driven Rh-catalyzed hydrocarboxylation of C–C double bonds with CO2.
Scheme 39: Optimization of reaction conditions on the Rh-catalyzed [2 + 2 + 2] cycloaddition of diyne 42a and ...
Scheme 40: [2 + 2 + 2] Cycloaddition of diyne and CO2.
Scheme 41: Proposed reaction pathways for the Rh-catalyzed [2 + 2 + 2] cycloaddition of diyne and CO2.
CF3SO2X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF3SO2Na
- Hélène Guyon,
- Hélène Chachignon and
- Dominique Cahard
Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272
Graphical Abstract
Scheme 1: Trifluoromethylation of enol acetates by Langlois.
Scheme 2: Trifluoromethylation of (het)aryl enol acetates.
Scheme 3: Mechanism for the trifluoromethylation of enol acetates.
Scheme 4: Oxidative trifluoromethylation of unactivated olefins and mechanistic pathway.
Scheme 5: Oxidative trifluoromethylation of acetylenic substrates.
Scheme 6: Metal free trifluoromethylation of styrenes.
Scheme 7: Synthesis of α-trifluoromethylated ketones by oxytrifluoromethylation of heteroatom-functionalised ...
Scheme 8: Catalysed photoredox trifluoromethylation of vinyl azides.
Scheme 9: Oxidative difunctionalisation of alkenyl MIDA boronates.
Scheme 10: Synthesis of β-trifluoromethyl ketones from cyclopropanols.
Scheme 11: Aryltrifluoromethylation of allylic alcohols.
Scheme 12: Cascade multicomponent synthesis of nitrogen heterocycles via azotrifluoromethylation of alkenes.
Scheme 13: Photocatalytic azotrifluoromethylation of alkenes with aryldiazonium salts and CF3SO2Na.
Scheme 14: Copper-promoted intramolecular aminotrifluoromethylation of alkenes with CF3SO2Na.
Scheme 15: Oxytrifluoromethylation of alkenes with CF3SO2Na and hydroxamic acid.
Scheme 16: Manganese-catalysed oxytrifluoromethylation of styrene derivatives.
Scheme 17: Oxytrifluoromethylation of alkenes with NMP/O2 and CF3SO2Na.
Scheme 18: Intramolecular oxytrifluoromethylation of alkenes.
Scheme 19: Hydrotrifluoromethylation of styrenyl alkenes and unactivated aliphatic alkenes.
Scheme 20: Hydrotrifluoromethylation of electron-deficient alkenes.
Scheme 21: Hydrotrifluoromethylation of alkenes by iridium photoredox catalysis.
Scheme 22: Iodo- and bromotrifluoromethylation of alkenes by CF3SO2Na/I2O5 or CF3SO2Na / NaBrO3.
Scheme 23: N-methyl-9-mesityl acridinium and visible-light-induced chloro-, bromo- and SCF3 trifluoromethylati...
Scheme 24: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na / TBHP by Lipshutz.
Scheme 25: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/TBHP reported by Lei.
Scheme 26: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/(NH4)2S2O8.
Scheme 27: Metal-free carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/K2S2O8 reported by Wang.
Scheme 28: Metal-free carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/PIDA reported by Fu.
Scheme 29: Metal-free cascade trifluoromethylation/cyclisation of N-arylmethacrylamides (a) and enynes (b) wit...
Scheme 30: Trifluoromethylation/cyclisation of N-arylcinnamamides: Synthesis of 3,4-disubstituted dihydroquino...
Scheme 31: Trifluoromethylation/cyclisation of aromatic-containing unsaturated ketones.
Scheme 32: Chemo- and regioselective cascade trifluoromethylation/heteroaryl ipso-migration of unactivated alk...
Scheme 33: Copper-mediated 1,2-bis(trifluoromethylation) of alkenes.
Scheme 34: Trifluoromethylation of aromatics with CF3SO2Na reported by Langlois.
Scheme 35: Baran’s oxidative C–H trifluoromethylation of heterocycles.
Scheme 36: Trifluoromethylation of acetanilides and anilines.
Scheme 37: Trifluoromethylation of heterocycles in water.
Scheme 38: Trifluoromethylation of coumarins in a continuous-flow reactor.
Scheme 39: Oxidative trifluoromethylation of coumarins, quinolines and pyrimidinones.
Scheme 40: Oxidative trifluoromethylation of pyrimidinones and pyridinones.
Scheme 41: Phosphovanadomolybdic acid-catalysed direct C−H trifluoromethylation.
Scheme 42: Oxidative trifluoromethylation of imidazopyridines and imidazoheterocycles.
Scheme 43: Oxidative trifluoromethylation of imidazoheterocycles and imidazoles in ionic liquid/water.
Scheme 44: Oxidative trifluoromethylation of 8-aminoquinolines.
Scheme 45: Oxidative trifluoromethylation of various 8-aminoquinolines using the supported catalyst CS@Cu(OAc)2...
Scheme 46: Oxidative trifluoromethylation of the naphthylamide 70.
Scheme 47: Oxidative trifluoromethylation of various arenes in the presence of CF3SO2Na and sodium persulfate.
Scheme 48: Trifluoromethylation of electron-rich arenes and unsymmetrical biaryls with CF3SO2Na in the presenc...
Figure 1: Trifluoromethylated coumarin and flavone.
Scheme 49: Metal-free trifluoromethylation catalysed by a photoredox organocatalyst.
Scheme 50: Quinone-mediated trifluoromethylation of arenes and heteroarenes.
Scheme 51: Metal- and oxidant-free photochemical trifluoromethylation of arenes.
Scheme 52: Copper-mediated trifluoromethylation of arenediazonium tetrafluoroborates.
Scheme 53: Oxidative trifluoromethylation of aryl- and heteroarylboronic acids.
Scheme 54: Oxidative trifluoromethylation of aryl- and vinylboronic acids.
Scheme 55: Oxidative trifluoromethylation of unsaturated potassium organotrifluoroborates.
Scheme 56: Oxidative trifluoromethylation of (hetero)aryl- and vinyltrifluoroborates.
Scheme 57: Copper−catalysed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 58: Iron-mediated decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids.
Scheme 59: Cu/Ag-catalysed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 60: I2O5-Promoted decarboxylative trifluoromethylation of cinnamic acids.
Scheme 61: Silver(I)-catalysed denitrative trifluoromethylation of β-nitrostyrenes.
Scheme 62: Copper-catalysed direct trifluoromethylation of styrene derivatives.
Scheme 63: Transition-metal-free synthesis of β-trifluoromethylated enamines.
Scheme 64: I2O5-mediated iodotrifluoromethylation of alkynes.
Scheme 65: Silver-catalysed tandem trifluoromethylation/cyclisation of aryl isonitriles.
Scheme 66: Photoredox trifluoromethylation of 2-isocyanobiphenyls.
Scheme 67: Trifluoromethylation of potassium alkynyltrifluoroborates with CF3SO2Na.
Scheme 68: N-trifluoromethylation of nitrosoarenes with CF3SO2Na (SQ: semiquinone).
Scheme 69: Trifluoromethylation of disulfides with CF3SO2Na.
Scheme 70: Trifluoromethylation of thiols with CF3SO2Na/I2O5.
Scheme 71: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/(EtO)2P(O)H/CuCl/DMSO.
Scheme 72: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/(EtO)2P(O)H/TMSCl.
Scheme 73: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PPh3/N-chlorophthalimide.
Scheme 74: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PCl3.
Scheme 75: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PCl3.
Scheme 76: Trifluoromethylsulfenylation of aryl iodides with in situ generated CuSCF3 (DMI: 1,3-dimethyl-2-imi...
Scheme 77: Pioneering trifluoromethylsulfinylation of N, O, and C-nucleophiles.
Scheme 78: Trifluoromethylsulfinylation of (1R,2S)-ephedrine (Im: imidazole; DIEA: N,N-diisopropylethylamine).
Scheme 79: Trifluoromethylsulfinylation of substituted benzenes with CF3SO2Na/CF3SO3H.
Scheme 80: Trifluoromethylsulfinylation of indoles with CF3SO2Na/P(O)Cl3.
Scheme 81: Trifluoromethylsulfinylation of indoles with CF3SO2Na/PCl3.
Scheme 82: Formation of triflones from benzyl bromides (DMA: dimethylacetamide).
Scheme 83: Formation of α-trifluoromethylsulfonyl ketones, esters, and amides.
Scheme 84: Allylic trifluoromethanesulfonylation of aromatic allylic alcohols.
Scheme 85: Copper-catalysed couplings of aryl iodonium salts with CF3SO2Na.
Scheme 86: Palladium-catalysed trifluoromethanesulfonylation of aryl triflates and chlorides with CF3SO2Na.
Scheme 87: Copper-catalysed coupling of arenediazonium tetrafluoroborates with CF3SO2Na.
Scheme 88: Synthesis of phenyltriflone via coupling of benzyne with CF3SO2Na.
Scheme 89: Synthesis of 1-trifluoromethanesulfonylcyclopentenes from 1-alkynyl-λ3-bromanes and CF3SO2Na.
Scheme 90: One-pot synthesis of functionalised vinyl triflones.
Scheme 91: Regioselective synthesis of vinyltriflones from styrenes.
Scheme 92: Trifluoromethanesulfonylation of alkynyl(phenyl) iodonium tosylates by CF3SO2Na.
Scheme 93: Synthesis of thio- and selenotrifluoromethanesulfonates.
New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions
- Daily Rodríguez-Padrón,
- Alina M. Balu,
- Antonio A. Romero and
- Rafael Luque
Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194
- potential from an environmental point-of-view since it is able to reduce solvent issues in chemical syntheses. The catalytic activity of the obtained nanocatalysts was investigated in both the oxidation of benzyl alcohol to benzaldehyde and in the alkylation of toluene with benzyl chloride. The microwave
- in both the oxidation and alkylation reaction reveals a potential method for the valorization of lignocellulosic biomass. Keywords: alkylation; benzyl alcohol; benzyl chloride; iron oxide; mechanochemistry; microwave-assisted oxidation; polysaccharide; toluene; Introduction Heterogeneous catalysis
- mesostructured zeolitic materials. In particular, in this study, our research group has focused attention on the alkylation of toluene with benzyl chloride, since is promoted by the presence of Lewis acids such as iron oxides [49]. These two reactions in particular (oxidation and alkylation of benzyl alcohol and
Graphical Abstract
Figure 1: Overview of the preparation of the nanocomposites based on iron oxide and polysaccharide.
Figure 2: XPS spectra of A: Fe2O3-PS4, B: Fe2O3-PS4-MNP and C: TiO2-Fe2O3-PS4 nanohybrids.
Figure 3: A and B: SEM and TEM images of TiO2-Fe2O3-PS4; C and D: SEM and TEM images of Fe2O3-PS4. E and F: S...
Figure 4: DRIFT spectra of A: TiO2-Fe2O3-PS4 and B: Fe2O3-PS4-MNP nanohybrids.
Scheme 1: Oxidation of benzyl alcohol to benzaldehyde.
Figure 5: Conversion and selectivity of the oxidation of benzyl alcohol for the three catalytic systems.
Scheme 2: Microwave-assisted alkylation of toluene with benzyl chloride.
Figure 6: Conversion and selectivity of the microwave-assisted alkylation of toluene for the three catalytic ...
Scheme 3: Alkylation of toluene with benzyl chloride with conventional heating.
Figure 7: Conversion and selectivity of the alkylation of toluene with conventional heating for the three cat...
Figure 8: Reusability of the iron oxide/polysaccharide nanohybrids.
Stimuli-responsive HBPS-g-PDMAEMA and its application as nanocarrier in loading hydrophobic molecules
- Yongsheng Chen,
- Li Wang,
- Haojie Yu,
- Zain-Ul-Abdin,
- Ruoli Sun,
- Guanghui Jing,
- Rongbai Tong and
- Zheng Deng
Beilstein J. Org. Chem. 2016, 12, 939–949, doi:10.3762/bjoc.12.92
- by benzyl chloride of VBC. It was found that each polymer chain was tethered with a double bond and chloride groups. Each monomer inserted into the polymer chain has one initiate site to start propagation of the side chains, which leads to the formation of hyperbranched topology. The broad peak from
- and benzyl chloride (BC) were used as received. Water was deionized before use. CuBr was purified by using acetic acid and methanol before use. Alkaline alumina, CuCl, 2,2-bipyrene (bpy) and N,N,N′,N″,N″-pentamethyldimethylenetriamine (PMDETA) were used as received. Preparation of HBPS and HBPS-g
- -PDMAEMA [26] The synthetic routes to HBPS and HBPS-g-PDMAEMA are shown in Figure 1A. The synthesis of HBPS was done by using a Schlenk line system under argon atmosphere. The solution of monomer was prepared by the addition of 3.0 mL VBC (21.1 mmol) in 8.4 mL benzyl chloride followed by deoxygenation by
Graphical Abstract
Figure 1: (A) The synthetic routes to HBPS and HBPS-g-PDMAEMA; (B) 1H NMR spectra of HBPS and HBPS-g-PDMAEMA ...
Figure 2: (A) The transmittance of HBPS-g-PDMAEMA aqueous solution of 10 mg/mL (pH 7); (B) pictures of aqueou...
Figure 3: (A) The effect of HBPS-g-PDMAEMA concentration on the size of aggregates (pH 7); (B) photographs of...
Figure 4: The sizes of 1 mg/mL HBPE-g-PDMAEMA aggregates in aqueous solutions with different concentration of...
Figure 5: (A) Photographs of phase inversion of 1 mg/mL HBPS-g-PDMAEMA in aqueous solution with different pH ...
Figure 6: The effect of pH on: (A) the size of 1 mg/mL HBPS-g-PDMAEMA aggregates; (B) the DLS results of 1 mg...
Figure 7: (A) The UV–vis spectra of HBPS-g-PDMAEMA/pyrene solution with different polymer concentrations; (B)...
Figure 8: (A) Photographs of HBPS-g-PDMAEMA/NR in aqueous solution with different polymer concentrations; (B)...
Figure 9: (A) Plot of the concentration of NR as a function of the UV–vis absorbance at a wavelength of 520 n...
Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors
- Morgan Hans,
- Jan Lorkowski,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252
- two-step synthesis of 1,3-dibenzylimidazolium halides via the formation of 1-benzylimidazole [50][51][52][53]. In our hands, however, the quaternization of this intermediate with benzyl chloride or bromide was often sluggish, which led to incomplete conversions and residues of unpleasant, lachrymatory
- procedure allowed us [48] and others [49] to isolate ICy·HBF4 as a well-behaved, non-hygroscopic solid that could be easily purified by recrystallization from isopropanol. Typical yields were in the 70–80% range (Scheme 3). Synthesis of 1,3-dibenzylimidazolium tetrafluoroborate At first sight, benzyl
- chloride or benzyl bromide seem to be ideal candidates to prepare 1,3-dibenzylimidazolium salts via a double alkylation of imidazole. Indeed, these primary alkyl halides are highly reactive toward nucleophiles and do not undergo elimination reactions. Accordingly, numerous procedures were reported for the
Graphical Abstract
Scheme 1: Various synthetic paths leading to the formation of NHCs.
Scheme 2: Retrosynthetic path for the preparation of symmetrical imidazolium and imidazolinium salts from sim...
Figure 1: Structures of the imidazolium and imidazolinium salts discussed in this study and their acronyms.
Scheme 3: Synthesis of 1,3-dicyclohexylimidazolium tetrafluoroborate (ICy·HBF4).
Scheme 4: Synthesis of 1,3-dibenzylimidazolium tetrafluoroborate (IBn·HBF4).
Scheme 5: Synthesis of 1,3-dimesitylimidazolium salts (IMes·HCl and IMes·HBF4).
Scheme 6: Synthesis of 1,3-dimesitylimidazolinium chloride (SIMes·HCl).
Scheme 7: Synthesis of 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (IDip·HCl).
Scheme 8: Synthesis of 1,3-bis(2,6-diisopropylphenyl)imidazolinium chloride (SIDip·HCl).
Scheme 9: Synthesis of 1,3-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazolium chloride (IDip*·HCl).
Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids
- Roman Matthessen,
- Jan Fransaer,
- Koen Binnemans and
- Dirk E. De Vos
Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260
- cyanoacetic acid product have similar oxidation potentials. On top of that, some halogenation of the solvent to chloroacetonitrile was observed as a side reaction [147]. This reaction setup was also tested with propionitrile, butyronitrile, benzyl chloride and toluene in the anolyte compartment. Adjacent
Graphical Abstract
Scheme 1: Synthesis of salicylic acid and p-hydroxybenzoic acid via Kolbe–Schmidt reaction [16-20].
Scheme 2: Electroreduction of carbon dioxide to formic acid, methanol or methane.
Scheme 3: Electrochemical fixation of CO2 in olefins.
Scheme 4: Electrohydrodimerisation of acrylonitrile to adiponitrile [32].
Scheme 5: Parallel paired electrosynthesis of phthalide and tert-butylbenzaldehyde dimethylacetal [34].
Scheme 6: Overview of electrocarboxylation setups using (a) a sacrificial anode, (b) an inert anode, generati...
Scheme 7: General mechanism of the electrochemical dicarboxylation of conjugated dienes [49].
Scheme 8: Reported anodic reactions for the electrocarboxylation of 1,3-butadiene.
Scheme 9: General mechanism for electrocarboxylation of alkynes.
Scheme 10: Electrocarboxylation of ethyl cinnamate [70].
Scheme 11: General electrocarboxylation mechanism for carbonyl compounds (Y = O) and imines (Y = NH) [75-77].
Scheme 12: Electrocarboxylation mechanism of butyraldehyde proposed by Doherty [78].
Scheme 13: Electrocarboxylation of AMN to HN using a sacrificial aluminum anode [86].
Scheme 14: Electrocarboxylation of benzalaniline using a sacrificial aluminum anode [105].
Scheme 15: Electrocarboxylation of p-isobutylacetophenone with stable electrodes [94,95].
Scheme 16: Electrochemical carboxylation of MMP to MHA [110,111].
Scheme 17: General mechanism for electrocarboxylation of alkyl halides [122,124-126,128].
Scheme 18: Electrocarboxylation of benzylic chlorides as synthesis route for NSAIDs.
Scheme 19: Electrocarboxylation of 1,4-dibromo-2-butene [144].
Scheme 20: Convergent paired electrosynthesis of cyanoacetic acid, with X− = F4B−, ClO4−, HSO4−, Cl−, Br− [147].
Scheme 21: General scheme of carboxylation of weak acidic hydrocarbons with electrogenerated bases. RH: weakly...
Scheme 22: Electrocarboxylation of N-methyldiglycolimide to methoxymethane-1,1,1’-tricarboxylate precursors. R1...
Scheme 23: Electrochemical dimerization of CO2 with stable electrodes [153].
New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones
- Emilian Georgescu,
- Alina Nicolescu,
- Florentina Georgescu,
- Florina Teodorescu,
- Daniela Marinescu,
- Ana-Maria Macsim and
- Calin Deleanu
Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248
- obtained from corresponding benzimidazoles and benzyl chloride, respectively ethyl bromide. 1-Benzylbenzimidazolium bromides (6) were obtained from 1-benzylbenzimidazole, respectively 1-benzyl-5,6-dimethylbenzimidazole, and alkyl bromoacetate in acetone, according previously reported methods [8
Graphical Abstract
Scheme 1: Synthesis of pyrrolo[1,2-a]quinoxalin-4-ones 4 and pyrrolo[1,2-a]benzimidazoles 5.
Scheme 2: Reaction pathway leading to the formation of pyrrolo[1,2-a]quinoxalin-4-ones 4 and pyrrolo[1,2-a]be...
Scheme 3: Novel synthetic pathway towards pyrrolo[1,2-a]quinoxalin-4-ones 10.
Figure 1: Undecoulpled H,C-HSQC spectrum for compound 5h.
Figure 2: Individual 1H signal assignments based on 13C traces from H,C-undecoulpled-HSQC spectrum around the...
Figure 3: NOE response as cross peaks between carbethoxy group protons and protons from positions 2 and 8 of ...
Pd/C-catalyzed aerobic oxidative esterification of alcohols and aldehydes: a highly efficient microwave-assisted green protocol
- Marina Caporaso,
- Giancarlo Cravotto,
- Spyros Georgakopoulos,
- George Heropoulos,
- Katia Martina and
- Silvia Tagliapietra
Beilstein J. Org. Chem. 2014, 10, 1454–1461, doi:10.3762/bjoc.10.149
- electron-deficient ligands [9][31] have all been added to the catalyst in an attempt to improve conversion and selectivity. Other examples refer to the use of Pd(II) species in the presence of a cooxidant such as benzyl chloride or desyl chloride [34][44]. The optimized procedures are therefore limited
Graphical Abstract
Scheme 1: Reaction pathway of aerobic oxidative esterification of alcohols.
Figure 1: Screening of different catalysts and bases in the catalytic oxidative esterification of benzylalcoh...
Scheme 2: Catalyst regeneration and oxidative esterification of benzaldehyde (2nd cycle).
Silver and gold-catalyzed multicomponent reactions
- Giorgio Abbiati and
- Elisabetta Rossi
Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46
- between acyl chloride and imine, to give the propargylamide III. The proton released during the formation of the acetylide I activates the triple bond of propargylamide III which undergoes the attack from the amide oxygen atom. The benzyl group of the resultant iminium ion IV is lost as benzyl chloride by
Graphical Abstract
Scheme 1: General reaction mechanism for Ag(I)-catalyzed A3-coupling reactions.
Scheme 2: A3-coupling reaction catalyzed by polystyrene-supported NHC–silver halides.
Figure 1: Various NHC–Ag(I) complexes used as catalysts for A3-coupling.
Scheme 3: Proposed reaction mechanism for NHC–AgCl catalyzed A3-coupling reactions.
Scheme 4: Liu’s synthesis of pyrrole-2-carboxaldehydes 4.
Scheme 5: Proposed reaction mechanism for Liu’s synthesis of pyrrole-2-carboxaldehydes 4.
Scheme 6: Gold-catalyzed synthesis of propargylamines 1.
Scheme 7: A3-coupling catalyzed by phosphinamidic Au(III) metallacycle 6.
Scheme 8: Gold-catalyzed KA2-coupling.
Scheme 9: A3-coupling applied to aldehyde-containing oligosaccharides 8.
Scheme 10: A3-MCR for the preparation of propargylamine-substituted indoles 9.
Scheme 11: A3-coupling interceded synthesis of furans 12.
Scheme 12: A3/KA2-coupling mediated synthesis of functionalized dihydropyrazoles 13 and polycyclic dihydropyra...
Scheme 13: Au(I)-catalyzed entry to cyclic carbamimidates 17 via an A3-coupling-type approach.
Scheme 14: Proposed reaction mechanism for the Au(I)-catalyzed synthesis of cyclic carbamimidates 17.
Figure 2: Chiral trans-1-diphenylphosphino-2-aminocyclohexane–Au(I) complex 20.
Scheme 15: A3-coupling-type synthesis of oxazoles 21 catalyzed by Au(III)–salen complex.
Scheme 16: Proposed reaction mechanism for the synthesis of oxazoles 21.
Scheme 17: Synthesis of propargyl ethyl ethers 24 by an A3-coupling-type reaction.
Scheme 18: General mechanism of Ag(I)-catalyzed MCRs of 2-alkynylbenzaldehydes, amines and nucleophiles.
Scheme 19: General synthetic pathway to 1,3-disubstituted-1,2-dihydroisoquinolines.
Scheme 20: Synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 29.
Scheme 21: Synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 35 and 36.
Scheme 22: Rh(II)/Ag(I) co-catalyzed synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 40.
Scheme 23: General synthetic pathway to 2-amino-1,2-dihydroquinolines.
Scheme 24: Synthesis of 2-amino-1,2-dihydroquinolines 47.
Scheme 25: Synthesis of tricyclic H-pyrazolo[5,1-a]isoquinoline 48.
Scheme 26: Synthesis of tricyclic H-pyrazolo[5,1-a]isoquinolines 48.
Scheme 27: Cu(II)/Ag(I) catalyzed synthesis of H-pyrazolo[5,1-a]isoquinolines 48.
Scheme 28: Synthesis of 2-aminopyrazolo[5,1-a]isoquinolines 53.
Scheme 29: Synthesis of 1-(isoquinolin-1-yl)guanidines 55.
Scheme 30: Ag(I)/Cu(I) catalyzed synthesis of 2-amino-H-pyrazolo[5,1-a]isoquinolines 58.
Scheme 31: Ag(I)/Ni(II) co-catalyzed synthesis of 3,4-dihydro-1H-pyridazino[6,1-a]isoquinoline-1,1-dicarboxyla...
Scheme 32: Ag(I) promoted activation of the α-carbon atom of the isocyanide group.
Scheme 33: Synthesis of dihydroimidazoles 65.
Scheme 34: Synthesis of oxazoles 68.
Scheme 35: Stereoselective synthesis of chiral butenolides 71.
Scheme 36: Proposed reaction mechanism for the synthesis of butenolides 71.
Scheme 37: Stereoselective three-component approach to pirrolidines 77 by means of a chiral auxiliary.
Scheme 38: Stereoselective three-component approach to pyrrolidines 81 and 82 by means of a chiral catalyst.
Scheme 39: Synthesis of substituted five-membered carbocyles 86.
Scheme 40: Synthesis of regioisomeric arylnaphthalene lactones.
Scheme 41: Enantioselective synthesis of spiroacetals 96 by Fañanás and Rodríguez [105].
Scheme 42: Enantioselective synthesis of spiroacetals 101 by Gong [106].
Scheme 43: Synthesis of polyfunctionalized fused bicyclic ketals 103 and bridged tricyclic ketals 104.
Scheme 44: Proposed reaction mechanism for the synthesis of ketals 103 and 104.
Scheme 45: Synthesis of β-alkoxyketones 108.
Scheme 46: Synthesis of N-methyl-1,4-dihydropyridines 112.
Scheme 47: Synthesis of tetrahydrocarbazoles 115–117.
Scheme 48: Plausible reaction mechanism for the synthesis of tetrahydrocarbazoles 115–117.
Scheme 49: Carboamination, carboalkoxylation and carbolactonization of terminal alkenes.
Scheme 50: Oxyarylation of alkenes with arylboronic acids and Selectfluor as reoxidant.
Scheme 51: Proposed reaction mechanism for oxyarylation of alkenes.
Scheme 52: Oxyarylation of alkenes with arylsilanes and Selectfluor as reoxidant.
Scheme 53: Oxyarylation of alkenes with arylsilanes and IBA as reoxidant.
An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles
- Marcus Baumann and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265
- ) followed by alkylation with benzyl chloride to give the chain elongated adduct [27]. The tert-butylamide 1.24 is then dehydrated with phosphorous oxychloride at elevated temperatures to yield the nitrile derivative 1.25. Introduction of the piperidine ring is achieved by utilisation of the appropriately
Graphical Abstract
Scheme 1: Scaled industrial processes for the synthesis of simple pyridines.
Scheme 2: Synthesis of nicotinic acid from 2-methyl-5-ethylpyridine (1.11).
Scheme 3: Synthesis of 3-picoline and nicotinic acid.
Scheme 4: Synthesis of 3-picoline from 2-methylglutarodinitrile 1.19.
Scheme 5: Picoline-based synthesis of clarinex (no yields reported).
Scheme 6: Mode of action of proton-pump inhibitors and structures of the API’s.
Scheme 7: Hantzsch-like route towards the pyridine rings in common proton pump inhibitors.
Figure 1: Structures of rosiglitazone (1.40) and pioglitazone (1.41).
Scheme 8: Synthesis of rosiglitazone.
Scheme 9: Syntheses of 2-pyridones.
Scheme 10: Synthesis and mechanism of 2-pyrone from malic acid.
Scheme 11: Polymer-assisted synthesis of rosiglitazone.
Scheme 12: Synthesis of pioglitazone.
Scheme 13: Meerwein arylation reaction towards pioglitazone.
Scheme 14: Route towards pioglitazone utilising tyrosine.
Scheme 15: Route towards pioglitazone via Darzens ester formation.
Scheme 16: Syntheses of the thiazolidinedione moiety.
Scheme 17: Synthesis of etoricoxib utilising Negishi and Stille cross-coupling reactions.
Scheme 18: Synthesis of etoricoxib via vinamidinium condensation.
Figure 2: Structures of nalidixic acid, levofloxacin and moxifloxacin.
Scheme 19: Synthesis of moxifloxacin.
Scheme 20: Synthesis of (S,S)-2,8-diazabicyclo[4.3.0]nonane 1.105.
Scheme 21: Synthesis of levofloxacin.
Scheme 22: Alternative approach to the levofloxacin core 1.125.
Figure 3: Structures of nifedipine, amlodipine and clevidipine.
Scheme 23: Mg3N2-mediated synthesis of nifedipine.
Scheme 24: Synthesis of rac-amlodipine as besylate salt.
Scheme 25: Aza Diels–Alder approach towards amlodipine.
Scheme 26: Routes towards clevidipine.
Figure 4: Examples of piperidine containing drugs.
Figure 5: Discovery of tiagabine based on early leads.
Scheme 27: Synthetic sequences to tiagabine.
Figure 6: Structures of solifenacin (2.57) and muscarine (2.58).
Scheme 28: Enantioselective synthesis of solifenacin.
Figure 7: Structures of DPP-4 inhibitors of the gliptin-type.
Scheme 29: Formation of inactive diketopiperazines from cis-rotameric precursors.
Figure 8: Co-crystal structure of carmegliptin bound in the human DPP-4 active site (PDB 3kwf).
Scheme 30: Improved route to carmegliptin.
Figure 9: Structures of lamivudine and zidovudine.
Scheme 31: Typical routes accessing uracil, thymine and cytosine.
Scheme 32: Coupling between pyrimidones and riboses via the Vorbrüggen nucleosidation.
Scheme 33: Synthesis of lamivudine.
Scheme 34: Synthesis of raltegravir.
Scheme 35: Mechanistic studies on the formation of 3.22.
Figure 10: Structures of selected pyrimidine containing drugs.
Scheme 36: General preparation of pyrimidines and dihydropyrimidones.
Scheme 37: Synthesis of imatinib.
Scheme 38: Flow synthesis of imatinib.
Scheme 39: Syntheses of erlotinib.
Scheme 40: Synthesis of erlotinib proceeding via Dimroth rearrangement.
Scheme 41: Synthesis of lapatinib.
Scheme 42: Synthesis of rosuvastatin.
Scheme 43: Alternative preparation of the key aldehyde towards rosuvastatin.
Figure 11: Structure comparison between nicotinic acetylcholine receptor agonists.
Scheme 44: Syntheses of varenicline and its key building block 4.5.
Scheme 45: Synthetic access to eszopiclone and brimonidine via quinoxaline intermediates.
Figure 12: Bortezomib bound in an active site of the yeast 20S proteasome ([114], pdb 2F16).
Scheme 46: Asymmetric synthesis of bortezomib.
Figure 13: Structures of some prominent piperazine containing drugs.
Figure 14: Structural comparison between the core of aplaviroc (4.35) and a type-1 β-turn (4.36).
Scheme 47: Examplary synthesis of an aplaviroc analogue via the Ugi-MCR.
Scheme 48: Syntheses of azelastine (5.1).
Figure 15: Structures of captopril, enalapril and cilazapril.
Scheme 49: Synthesis of cilazapril.
Figure 16: Structures of lamotrigine, ceftriaxone and azapropazone.
Scheme 50: Synthesis of lamotrigine.
Scheme 51: Alternative synthesis of lamotrigine (no yields reported).
Figure 17: Structural comparison between imiquimod and the related adenosine nucleoside.
Scheme 52: Conventional synthesis of imiquimod (no yields reported).
Scheme 53: Synthesis of imiquimod.
Scheme 54: Synthesis of imiquimod via tetrazole formation (not all yields reported).
Figure 18: Structures of various anti HIV-medications.
Scheme 55: Synthesis of abacavir.
Figure 19: Structures of diazepam compared to modern replacements.
Scheme 56: Synthesis of ocinaplon.
Scheme 57: Access to zaleplon and indiplon.
Scheme 58: Different routes towards the required N-methylpyrazole 6.65 of sildenafil.
Scheme 59: Polymer-supported reagents in the synthesis of key aminopyrazole 6.72.
Scheme 60: Early synthetic route to sildenafil.
Scheme 61: Convergent preparations of sildenafil.
Figure 20: Comparison of the structures of sildenafil, tadalafil and vardenafil.
Scheme 62: Short route to imidazotriazinones.
Scheme 63: Alternative route towards vardenafils core imidazotriazinone (6.95).
Scheme 64: Bayer’s approach to the vardenafil core.
Scheme 65: Large scale synthesis of vardenafil.
Scheme 66: Mode of action of temozolomide (6.105) as methylating agent.
Scheme 67: Different routes to temozolomide.
Scheme 68: Safer route towards temozolomide.
Figure 21: Some unreported heterocyclic scaffolds in top market drugs.
The synthesis of well-defined poly(vinylbenzyl chloride)-grafted nanoparticles via RAFT polymerization
- John Moraes,
- Kohji Ohno,
- Guillaume Gody,
- Thomas Maschmeyer and
- Sébastien Perrier
Beilstein J. Org. Chem. 2013, 9, 1226–1234, doi:10.3762/bjoc.9.139
- number of functionalizable benzyl chloride groups present. Additionally, having a large amount of polymer grown from the particle will allow fine control over the effective diameter of the particle by merely tuning the polymerization conditions to dictate the size of the polymer shell. This cannot be
Graphical Abstract
Scheme 1: RAFT polymerization and silica-supported RAFT polymerization of vinylbenzyl chloride (VBC).
Figure 1: Evolution of number-average molecular weight (Mn) and Mw/Mn values of the poly(VBC) chains obtained...
Figure 2: Conversion and ln([M]0/[M]) versus time for AIBN-initiated, PABTC-mediated polymerization of VBC at...
Figure 3: AIBN-initiated, PABTC-mediated polymerization of VBC with (triangles, DP 4,400) and without (circle...
Figure 4: Evolution of molecular weights of free and grafted poly(VBC) chains with conversion.
Figure 5: Plot of the average diameter and PDI of particles recovered from silica-supported RAFT polymerizati...
Figure 6: TEM micrographs of particles (A) after 2 hours and (B) after 21 hours of VBC polymerization. Scale ...
Volatile organic compounds produced by the phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria 85-10
- Teresa Weise,
- Marco Kai,
- Anja Gummesson,
- Armin Troeger,
- Stephan von Reuß,
- Silvia Piepenborn,
- Francine Kosterka,
- Martin Sklorz,
- Ralf Zimmermann,
- Wittko Francke and
- Birgit Piechulla
Beilstein J. Org. Chem. 2012, 8, 579–596, doi:10.3762/bjoc.8.65
- -methylundecan-2-one (34) and 9-methylundecan-2-one (35) proceeded straightforwardly, following a conventional alkyne approach (Scheme 1). Commercially available (Aldrich) 4-pentyne-2-ol was reacted with benzyl chloride to yield the corresponding benzyl ether A. Subsequently, A was coupled to commercially
Graphical Abstract
Figure 1: Cocultivation of Xanthomonas campestris pv. vesicatoria 85-10 with three fungi on different media. ...
Figure 2: GC/MS-chromatogram (total ion current) of the headspace of X. c. pv. vesicatoria 85-10 grown in 10 ...
Figure 3: Structures of compounds emitted by Xanthomonas campestris pv. vesicatoria 85-10. Compound labels ar...
Scheme 1: Synthesis of 10-methylundecan-2-one (34) and 9-methylundecan-2-one (35).
Scheme 2: Suggested biosynthesis of methylketones found in Xanthomonas campestris pv. vesicatoria 85-10.
Figure 4: PTR–MS mass spectra of Xanthomonas campestris pv. vesicatoria 85-10 volatiles after three days of i...
Figure 5: GC/MS analysis of volatiles emitted by Xanthomonas campestris pv. vesicatoria 85-10 grown on differ...
Figure 6: Testing synthetic volatiles on the growth of Rhizoctonia solani. Synthetic commercially available a...
Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis
- Inhee Cho,
- Labros Meimetis,
- Lee Belding,
- Michael J. Katz,
- Travis Dudding and
- Robert Britton
Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154
- , benzaldehyde), trimethylsilyl chloride, or allyl/benzyl chloride/bromide failed to provide the desired products in reasonable yield. For example, treatment of the tetralithio intermediate 8 with benzyl chloride resulted in recovery of (R,R)-hydrobenzoin along with 1-chloro-1,2-diphenylethane, the latter of
- which arises through the deprotonation of benzyl chloride by 8 and reaction of the resulting benzyl anion with a second equivalent of benzyl chloride. Likewise, attempts to effect a reductive coupling of the tetralithio intermediate to afford the dihydrophenanthrenediol 23 [22] with the aid of various
Graphical Abstract
Figure 1: Chiral diols useful for asymmetric synthesis and the tetralithio intermediate 8.
Scheme 1: Directed ortho,ortho'-dimetalation of (R,R)-hydrobenzoin (3).
Figure 2: Percentage of (R,R)-hydrobenzoin (3) (○), monodeuterohydrobenzoin (13) (■), and dideuterohydrobenzo...
Figure 3: Percentage of methylhydrobenzoin (14) (■), and dimethylhydrobenzoin (15) (Δ) as determined by 1H NM...
Scheme 2: Formation of the tetralithio intermediate 8 and the X-ray crystal structure of the bis(siloxane) 19....
Scheme 3: Reaction of the tetralithio intermediate 8 with various electrophiles.
Scheme 4: Reactions of the diiodohydrobenzoin 12 and X-ray crystal structure of the dihydrosilepin 31.
Scheme 5: Cross coupling reactions of the bis(benzoxaborol) 20 and a short formal synthesis of (R,R)-Vivol (4...
A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis
- Magnus Rueping and
- Boris J. Nachtsheim
Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6
- authors explained this observation with a chlorination of 1-phenylethanol 1 and subsequent FC alkylation of the formed benzyl chloride and toluene. However, more surprisingly the reaction yield could be improved to 93% if only catalytic amounts (10 mol%) of TeCl4 were present (Scheme 3) [2]. Although the
Graphical Abstract
Scheme 1: AlCl3-mediated reaction between amyl chloride and benzene as developed by Friedel and Crafts.
Figure 1: Most often used metal salts for catalytic FC alkylations and hydroarylations of arenes.
Figure 2: 1,1-diarylalkanes with biological activity.
Scheme 2: Alkylating reagents and side products produced.
Scheme 3: Initially reported TeCl4-mediated FC alkylation of 1-penylethanol with toluene.
Scheme 4: Sc(OTf)3-catalyzed FC benzylation of arenes.
Scheme 5: Reductive FC alkylation of arenes with arenecarbaldehydes.
Scheme 6: Iron(III)-catalyzed FC benzylation of arenes and heteroarenes.
Scheme 7: A gold(III)-catalyzed route to beclobrate.
Scheme 8: Catalytic FC-type alkylations of 1,3-dicarbonyl compounds.
Scheme 9: Iron(III)-catalyzed synthesis of phenprocoumon.
Scheme 10: Bi(OTf)3-catalyzed FC alkylation of benzyl alcohols developed by Rueping et al.
Scheme 11: (A) Bi(OTf)3-catalyzed intramolecular FC alkylation as an efficient route to substituted fulvenes. ...
Scheme 12: FC-type glycosylation of 1,2-dimethylindole and trimethoxybenzene.
Scheme 13: FC alkylation with highly reactive ferrocenyl- and benzyl alcohols. The reaction proceeds even with...
Scheme 14: Reductive FC alkylation of arenes with benzaldehyde and acetophenone catalyzed by the Ir-carbene co...
Scheme 15: Formal synthesis of 1,1-diarylalkanes from benzyl alcohols and styrenes.
Scheme 16: (A) Mo-catalyzed hydroarylation of styrenes and cyclohexenes. (B) Hydroalkylation–cyclization casca...
Scheme 17: Bi(III)-catalyzed hydroarylation of styrenes with arenes and heteroarenes.
Scheme 18: BiCl3-catalyzed ene/FC alkylation reaction cascade – A fast access to highly arylated dihydroindene...
Scheme 19: Au(I)/Ag(I)-catalyzed hydroarylation of indoles with styrenes, aliphatic and cyclic alkenes.
Scheme 20: First transition-metal-catalyzed ortho-hydroarylation developed by Beller et al.
Scheme 21: (A) Ti(IV)-mediated rearrangement of an N-benzylated aniline to the corresponding ortho-alkylated a...
Scheme 22: Dibenzylation of aniline gives potentially useful amine-based ligands in a one-step procedure.
Scheme 23: FC-type alkylations with allyl alcohols as alkylating reagents – linear vs. branched product format...
Scheme 24: (A) First catalytic FC allylation and cinnamylation using allyl alcohols and its derivatives. (B) E...
Scheme 25: FC allylation/cyclization reaction yielding substituted chromanes.
Scheme 26: Synthesis of (all-rac)-α-tocopherol utilizing Lewis- and strong Brønsted-acids.
Scheme 27: Au(III)-catalyzed cinnamylation of arenes.
Scheme 28: “Exhaustive” allylation of benzene-1,3,5-triol.
Scheme 29: Palladium-catalyzed allylation of indole.
Scheme 30: Pd-catalyzed synthesis of pyrroloindoles from L-tryptophane.
Scheme 31: Ru(IV)-catalyzed allylation of indole and pyrroles with unique regioselectivity.
Scheme 32: Silver(I)-catalyzed intramolecular FC-type allylation of arenes and heteroarenes.
Scheme 33: FC-type alkylations of arenes using propargyl alcohols.
Scheme 34: (A) Propargylation of arenes with stoichiometric amounts of the Ru-allenylidene complex 86. (B) Fir...
Scheme 35: Diruthenium-catalyzed formation of chromenes and 1H-naphtho[2,1-b]pyrans.
Scheme 36: Rhenium(V)-catalyzed FC propargylations as a first step in the total synthesis of podophyllotoxin, ...
Scheme 37: Scandium-catalyzed arylation of 3-sulfanyl- and 3-selanylpropargyl alcohols.
Scheme 38: Synthesis of 1,3-diarylpropynes via direct coupling of propargyl trichloracetimidates and arenes.
Scheme 39: Diastereoselective substitutions of benzyl alcohols.
Scheme 40: (A) First diastereoselective FC alkylations developed by Bach et al. (B) anti-Selective FC alkylati...
Scheme 41: Diastereoselective AuCl3-catalyzed FC alkylation.
Scheme 42: Bi(OTf)3-catalyzed alkylation of α-chiral benzyl acetates with silyl enol ethers.
Scheme 43: Bi(OTf)3-catalyzed diastereoselective substitution of propargyl acetates.
Scheme 44: Nucelophilic substitution of enantioenriched ferrocenyl alcohols.
Scheme 45: First catalytic enantioselective propargylation of arenes.
EcoScale, a semi- quantitative tool to select an organic preparation based on economical and ecological parameters
- Koen Van Aken,
- Lucjan Strekowski and
- Luc Patiny
Beilstein J. Org. Chem. 2006, 2, No. 3, doi:10.1186/1860-5397-2-3
- indicated. In this way, it can be used as a convenient tool in education (students learn to analyze a reaction protocol), and is valuable in research as an effective way to compare different sets of preparations of the same product. Reduction of nitrobenzene to aniline [23] Oxidation of benzyl chloride to
Graphical Abstract
Scheme 1: Reduction of nitrobenzene to aniline [23]
Scheme 2: Oxidation of benzyl chloride to benzoic acid [24]
Scheme 3: Synthesis of benzamide [25]
Scheme 4: Synthesis of benzamide using HMDS [26]
