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Search for "safe" in Full Text gives 189 result(s) in Beilstein Journal of Organic Chemistry.
Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors
- Sedat Ünal,
- Gamze Varan,
- Juan M. Benito,
- Yeşim Aktaş and
- Erem Bilensoy
Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14
- in cancer-related deaths. With the current treatment possibilities, a definitive, safe, and effective treatment approach for CRC has not been presented yet. However, new drug delivery systems show promise in this field. Amphiphilic cyclodextrin-based nanocarriers are innovative and interesting
Graphical Abstract
Figure 1: In vitro release profile of CPT from nanoparticle formulations (n = 3, ± SD).
Figure 2: Results for release kinetics obtained automatically by the DDSolver software for SGF release medium...
Figure 3: Results for release kinetics obtained automatically by the DDSolver software for SIF release medium...
Figure 4: Results for release kinetics obtained automatically by the DDSolver software for SCoF release mediu...
Figure 5: Anticancer effect of blank or CPT-loaded CD nanoparticles and camptothecin solution against 2D CT26...
Figure 6: Live/dead analysis of CT26 and HT29 cells using double staining with calcein AM and ethidium homodi...
Figure 7: Murine (CT26) and human (HT29) colon cancer spheroid was formed by scaffold-based method, and the m...
Figure 8: Anticancer effect of blank or drug-loaded cyclodextrin nanoparticles and CPT solution against 3D CT...
Figure 9: Chemical structures of 6-O-capro-β-CD, poly-β-CD-C6, and chitosan.
New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling
- Elenilson F. da Silva,
- Krist Helen Antunes Fernandes,
- Denise Diedrich,
- Jessica Gotardi,
- Marcia Silvana Freire Franco,
- Carlos Henrique Tomich de Paula da Silva,
- Ana Paula Duarte de Souza and
- Simone Cristina Baggio Gnoatto
Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161
- , selective, and potent anti-HIV activity, however, it failed in phase IIb clinical trials due to viral resistance [28][29][30][31]. Even so, this class of natural products has great antiviral potential and its chemical modification could lead to new, efficient, and safe therapeutic resources. In this
Graphical Abstract
Figure 1: Structures of RBV, betulinic acid (1), and ursolic acid (2).
Scheme 1: Synthesis of 1-azido-3-nitrobenzene (c).
Scheme 2: Synthesis of the triazole-substituted triterpene derivatives 7 and 8.
Figure 2: (A) Activity of compound 8 in A549 cells infected with RSV. MTT assay 96 h after treatment. DMSO (0...
Figure 3: Superposition of the top-ranked docking solution of compound 8 (carbon atoms in yellow, in stick re...
A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH4I
- Shang-Feng Yang,
- Pei Li,
- Zi-Lin Fang,
- Sen Liang,
- Hong-Yu Tian,
- Bao-Guo Sun,
- Kun Xu and
- Cheng-Chu Zeng
Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130
- . Organic electrosynthesis has been recognized as a green, modern, and safe technique, since electrons can be used as an alternative for oxidants or reductants [30][31][32][33][34][35][36][37][38]. During our continuous interests in halide-mediated indirect electrolysis [39][40][41][42], we have achieved
Graphical Abstract
Scheme 1: Methods for the synthesis of thiazoles using active methylene ketones as starting materials.
Scheme 2: Substrate scope. Reaction conditions: 1 (2 mmol), 2 (1 mmol), NH4I (0.1 mmol), ᴅʟ-alanine (1 mmol),...
Scheme 3: Up-scaling experiment.
Scheme 4: Control experiments.
Scheme 5: The proposed mechanism for the one-pot electrochemical synthesis of 2-aminothiazoles mediated by NH4...
Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes
- Mana Kitano,
- Tsuyoshi Saitoh,
- Shigeru Nishiyama,
- Yasuaki Einaga and
- Takashi Yamamoto
Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119
- , where the BDD’s wide potential window enables the direct anodic oxidation of cumene into the cumyl cation. Since electricity is directly employed as the oxidizing and reducing reagents, the present protocol is easy to use, suitable for scale-up, and inherently safe. Keywords: aromatic alkyl; boron
Graphical Abstract
Figure 1: (a) Cyclic voltammograms of a BDD electrode in MeCN solution containing cumene (1; 5 mM) and Et4NClO...
Figure 2: Proposed reaction mechanism of electro-conversion of cumene (1) into acetophenone (3).
A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH4/I2 system
- Lin Chen,
- Xuan Zhou,
- Zhiyong Chen,
- Changxu Wang,
- Shunjie Wang and
- Hanbing Teng
Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104
- materials including amines, carboxylic acids and isocyanates under mild and safe reaction conditions. Results and Discussion Initially, N-phenethyl-1H-imidazole-1-carboxamide (1b) was chosen as a model substrate to react with 3.0 equiv of NaBH4 and 1.0 equiv of I2 in THF at reflux temperature, as expected
Graphical Abstract
Scheme 1: The synthesis of formamides and monomethylamines.
Scheme 2: The possible reaction mechanism. RDS = rate determining step.
Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides
- Dharmendra Das,
- Akhil A. Bhosle,
- Amrita Chatterjee and
- Mainak Banerjee
Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100
- (X = Br, Cl) suffers from low atom economy (<50%), formation of corrosive byproducts (e.g., HBr) [15][16], which cause serious environmental issues. To mitigate the problem, several mild and operationally safe halogenating agents have been successfully introduced to replace X2 [17][18][19][20][21][22
Graphical Abstract
Figure 1: Representative examples of important halogen-containing aryl derivatives.
Scheme 1: Strategies for halogenation of aromatic compounds using NXS.
Scheme 2: General scheme of PEG-400-assisted halogenation of phenols and anilines in an automated grinder usi...
Scheme 3: Monohalogenation of phenols and anilines by automated grinding with NXS. All yields refer to the is...
Scheme 4: Dihalogenation of phenols and anilines with NXS by automated grinding. All yields refer to the isol...
Scheme 5: Gram-scale monobromination of p-cresol by NBS in the automated grinder.
Synthesis of odorants in flow and their applications in perfumery
- Merlin Kleoff,
- Paul Kiler and
- Philipp Heretsch
Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76
- safe two-step synthesis of 56 from cyclohexanone. In the first step, a solution of cyclohexanone in dodecane is mixed in a Q-piece with hydrogen peroxide, nitric acid, and formic acid and subsequently pumped at room temperature through a PTFE tube reactor with a residence time of 93 min. The resulting
Graphical Abstract
Figure 1: The olfactory spectrum wheel ordering different types of odorants from fruity to musky.
Figure 2: Classification of odorants as “top note”, “middle note” and “base note” depending on their substant...
Scheme 1: Synthesis of raspberry ketone (5) and raspberry ketone methyl ether (6) in two steps in flow.
Scheme 2: Autoxidation of (+)-valencene (7) to (+)-nootkatone (8) under catalyst and solvent-free conditions ...
Scheme 3: Enzyme-catalyzed acetylation of isoamyl alcohol (9) in a biphasic n-heptane/water mixture utilizing...
Scheme 4: Esterification of alcohols by transesterification, catalyzed by immobilized acyltransferase in a pa...
Scheme 5: Synthesis of homologated alcohols 20 by iterative homologation of terpenyl boronate esters 17 follo...
Scheme 6: Sequential three-step synthesis of (S)-α-phellandrene (30) from (R)-carvone (25) via selective hydr...
Scheme 7: Selective hydrogenation of alkyne 31 to “leaf alcohol” 32 employing a solid-supported palladium cat...
Scheme 8: A) Synthesis of jasmonal (35) by crossed aldol condensation of benzaldehyde (33) and heptanal (34) ...
Scheme 9: Synthesis of thymol (41) from m-cresol (39) and isopropyl alcohol via Fries-type rearrangement of e...
Scheme 10: Preparation of coumarin (46) by reaction of salicylaldehyde (44) with potassium acetate, acetic aci...
Scheme 11: Synthesis of phthalide (50) by photoinduced decatungstate catalysis.
Scheme 12: Synthesis of woody acetate (54) by reduction of cyclohexanone 51 and subsequent acetylation; ADH200...
Scheme 13: Synthesis of juniper lactone (56) by pyrolysis of triperoxide 55 generated by oxidation of cyclohex...
Scheme 14: Synthesis of macrocyclic olefine 60 by ring-closing metathesis of diene 58 in a continuously stirre...
Scheme 15: Synthesis of macrocycles 65 and 66 by ring-closing metathesis of dienes 62 or 63, respectively, in ...
Scheme 16: Z-Selective synthesis of civetone (69) enabled by metathesis catalyst 68 in a tube-in-tube reactor.
Scheme 17: Synthesis of macrocyclic olefine 72 by ring-closing metathesis of diene 70.
Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide
- Kyoko Mandai,
- Tetsuya Yamamoto,
- Hiroki Mandai and
- Aiichiro Nagaki
Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67
- for safe, low-cost, and environmentally benign operations. Initially, we decided to maintain the key flow conditions such as the flow rate since it severely affects the fluidic interaction inside a flow reactor and thus the reaction efficiency of this type of gas–liquid reaction. Thus, the flow rate
Graphical Abstract
Scheme 1: Synthesis of cyclochexene oxide via epoxidation with air in the presence of isobutyraldehyde.
Figure 1: Epoxidation of cyclohexene with air bubbling in batch at various temperature.
Figure 2: Schematic diagram (a) and photo (b) of the flow reactor used for cyclohexene epoxidation with air. ...
Figure 3: Investigation of reaction temperature in flow epoxidation of cyclohexene at residence time of 0.35 ...
Figure 4: Investigation of residence time in flow epoxidation of cyclohexene at 100 °C.
Scheme 2: Plausible reaction pathway of the epoxidation of cyclohexene with air in the flow system.
Figure 5: Continuous production of cyclohexene oxide.
Figure 6: Effect of concentration of cyclohexene and eqivalent of aldehyde.
Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives
- Martin Pošta,
- Václav Zima,
- Lenka Poštová Slavětínská,
- Marika Matoušová and
- Petr Beier
Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57
- unknown, that could have untapped potential in medicine. The study of the relationship between the components of plant-derived smoke and MAO and/or AChE can lead to safe and efficient drugs and drug scaffolds from a yet unexploited resource. One very important bioactive constituent of smoke of burning
Graphical Abstract
Figure 1: Structures of naturally occurring karrikins.
Scheme 1: i) P4S10, THF; ii) 2-chloropropionyl chloride, Et3N; iii) Ph3P, NaOAc, Ac2O.
Figure 2: Target compounds with highlighted positions of oxygen to sulfur exchange.
Scheme 2: i) Lawesson’s reagent, HMDO, toluene, MW irradiation, 120 °C, 60 min.
Scheme 3: i) P4S10 or Lawesson’s reagent, see table for conditions; ii) 2-chloropropionyl chloride, Et3N, DCM...
Scheme 4: i) LiHMDS, MeI, THF, −78 °C.
Scheme 5: i) a) NaOH, MeOH/H2O, rt, Amberlyst 15 [H+], b) AcOH 70% aq, reflux, 2 h; ii) a) EtOCOCl, pyridine,...
Scheme 6: i) Lawesson’s reagent, HMDO, toluene, MW irradiation (120 °C), 60 min.
Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
- Irina Kuznetcova,
- Felix Bacher,
- Daniel Vegh,
- Hsiang-Yu Chuang and
- Vladimir B. Arion
Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15
- was observed by TLC. However, the acid chloride reacted very sluggishly with (CH3)3SiCHN2, which is a safe alternative to the highly explosive diazomethane [34]. Another attempt to synthesize the open-chain precursor from indole and 2-bromo-N-(2-bromophenyl)acetamide by regioselective palladium
Graphical Abstract
Figure 1: Paullone related indolobenzazepinone isomers. 7,12-Dihydroindolo[3,2-d][1]benzazepin-6(5H)-one or p...
Scheme 1: Investigated retrosynthetic pathways to scaffold C.
Scheme 2: Attempted synthesis of scaffold C by route (a).
Scheme 3: Attempted synthesis of C by route (b).
Scheme 4: Attempted synthesis of N-benzylated indole-2-acetic acid.
Scheme 5: Attempt to obtain open-chain precursor N-(2-bromophenyl)-2-(1H-indol-2-yl)acetamide.
Scheme 6: Synthesis of scaffold C and analogues by route (c).
Figure 2: ORTEP view of 1a with thermal ellipsoids drawn at the 50% probability level.
Figure 3: ORTEP view of 3a with thermal ellipsoids drawn at the 50% probability level.
Scheme 7: Attempted Ullmann cross-coupling of 23 with o-bromo-nitrobenzene.
Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol
- Lin Zhang,
- Jun Zheng,
- Guangyan Luo,
- Xiaoyue Li,
- Yunqian Zhang,
- Zhu Tao and
- Qianjun Zhang
Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194
- cucurbit[n]urils can be used as non-toxic and safe drug carriers [29][30][31], among which cucurbit[8]uril (Q[8]) [32] has a large cavity. Q[8] interacts with a variety of small drug molecules such as chrysin, oroxin A and B, baicalein, etc., which can enhance the solubility, stability, antioxidant and
Graphical Abstract
Figure 1: The structures of chloramphenicol (A) and cucurbit[n]urils (B).
Figure 2: (A) CPE and Q[8] structural model diagram, (B) interaction between CPE and Q[8], (C) CPE@Q[8] stack...
Figure 3: UV–vis absorption spectra of CPE with Q[8] in aqueous solution (A) or hydrochloric acid solution (C...
Figure 4: ITC data obtained for the binding of Q[8] with CPE in an aqueous solution at 25 °C.
Figure 5: 1H NMR spectra of CPE, CPE@Q[8] and Q[8] (VD2O/VDCl = 3:2).
Figure 6: IR spectra recorded for Q[8] (a), CPE (b), a physical mixture of Q[8] and CPE (c), and the CPE@Q[8]...
Figure 7: UV absorption intensity of CPE and CPE@Q[8] changes with time in the artificial gastrointestinal ju...
Figure 8: Release curve of CPE and CPE@Q[8] in artificial gastrointestinal juice (pH 1.2, pH 6.8).
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing
- Luke O. Jones,
- Leah Williams,
- Tasmin Boam,
- Martin Kalmet,
- Chidubem Oguike and
- Fiona L. Hatton
Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171
- injecting through a conventional needle [18]. Gelatin was chosen for its inherent peptide sequences that facilitate cell adhesion and enzymatic degradation. Gelatin is also low cost and safe to use in human testing as shown in a work done by Nichol et al. [77]. The bulk mechanical behaviour, structure, and
- effective but is below the level considered toxic [85]. Drug-delivery systems (DDS) demand safe and effective treatment, and in the majority of cases a long-term target specific treatment would be favoured over general multi-dose pharmaceuticals. Cryogels have been identified as a good material of choice
Graphical Abstract
Figure 1: Schematic representation of the process of aqueous cryogel formation, using (a) monomers/small mole...
Figure 2: Microarchitecture of gelatin cryogels. (A) Surface and cross-sectional SEM micrographs of highly po...
Figure 3: Principle of 3D-cryogel printing. A) Illustration of 3D-printing of cryogels. B) Illustration of th...
Figure 4: Illustration of the production of the injectable multifunctional composite, comprised of alginate c...
Figure 5: Digital and SEM photographs of PETEGA cryogel at 20 °C (top) and 50 °C (bottom), synthesised via UV...
Figure 6: Cell morphology of T47D breast cancer cells cultured in HA cryogels. (A) Schematic representation o...
Figure 7: Preparation of PDMA/β-CD cryogel via cryogenic treatment and photochemical crosslinking in frozen s...
Figure 8: (A) Healing rate of wounds treated with autoclaved CG11 cryogels and those treated with 70% ethanol...
Figure 9: In vivo haemostatic capacity evaluation of the cryogels. Blood loss (a) and haemostatic time (b) in...
Towards new NIR dyes for free radical photopolymerization processes
- Haifaa Mokbel,
- Guillaume Noirbent,
- Didier Gigmes,
- Frédéric Dumur and
- Jacques Lalevée
Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133
- and safe near-infrared (NIR) light is still the subject of intense research efforts but remains a huge challenge due to the associated low photon energy (wavelength from 0.78 to 2.5 µm). In this study, a series of 17 NIR dyes mainly based on a well-established cyanine scaffold is proposed. Remarkably
- ][4][5][6][7][8]. In this context, the use of NIR light is very attractive, i.e., such a long wavelength is quite safe and characterized by an excellent penetration in materials. Interestingly, NIR curing technology exhibit several advantages: i) an efficient process: a high polymerization rate
Graphical Abstract
Scheme 1: Investigated NIR dyes.
Scheme 2: Other used chemicals.
Scheme 3: Synthetic routes to compounds Ca, Cb, and CNa.
Scheme 4: Synthetic routes to CI1, CI3, CI4, and CI6–CI9.
Scheme 5: The metathesis reaction enabling the formation of “soft” salts CBPh1-CBPh4.
Figure 1: Visible–NIR spectra of NIR dyes in ACN. A) (1) CBPh1, (2) CBPh2, (3) CBPh3, (4) CBPh4, (5) Ca, (6) ...
Figure 2: Photopolymerization profiles of PETIA monomer under air (acrylate functions conversion vs irradiati...
Figure 3: Photopolymerization profiles of PETIA monomer under air (acrylate functions conversion vs irradiati...
Scheme 6: Pictures of polymers obtained for a thickness of 1.4 mm, using a NIR dye/iod/amine 0.1:3:2, %w/w/w ...
Scheme 7: Proposed mechanism for the photochemical reactivity of NIR dyes in a three-component PIS.
Figure 4: A) Photopolymerization profiles of PETIA/epoxy blend 1:1, w/w under air (acrylate and epoxy functio...
Development of N-F fluorinating agents and their fluorinations: Historical perspective
- Teruo Umemoto,
- Yuhao Yang and
- Gerald B. Hammond
Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123
- agents for many years. However, these reagents have significant risks for safe handling. Although XeF2 [15] was considered as a safer alternative, it is expensive because of the scarcity of Xe in nature. The appearance of the safe and easy-to-handle N-F fluorinating agents described in this review have
Graphical Abstract
Scheme 1: Fluorination with N-F amine 1-1.
Scheme 2: Preparation of N-F amine 1-1.
Scheme 3: Reactions of N-F amine 1-1.
Scheme 4: Synthesis of N-F perfluoroimides 2-1 and 2-2.
Scheme 5: Synthesis of 1-fluoro-2-pyridone (3-1).
Scheme 6: Fluorination with 1-fluoro-2-pyridone (3-1).
Figure 1: Synthesis of N-F sulfonamides 4-1a–g.
Scheme 7: Fluorination with N-F reagent 4-1b,c,f.
Scheme 8: Fluorination of alkenyllithiums with N-F 4-1h.
Scheme 9: Synthesis of N-fluoropyridinium triflate (5-4a).
Scheme 10: Synthetic methods for N-F-pyridinium salts.
Figure 2: Synthesis of various N-fluoropyridinium salts. Note: athis yield was the one by the improved method...
Scheme 11: Fluorination power order of N-fluoropyridinium salts.
Scheme 12: Fluorinations with N-F salts 5-4.
Scheme 13: Fluorination of Corey lactone 5-7 with N-F-bis(methoxymethyl) salt 5-4l.
Scheme 14: Fluorination with NFPy.
Scheme 15: Synthesis of the N-F reagent, N-fluoroquinuclidinium fluoride (6-1).
Scheme 16: Fluorinations achieved with N-F fluoride 6-1.
Scheme 17: Synthesis of N-F imides 7-1a–g.
Scheme 18: Fluorination with (CF3SO2)2NF, 7-1a.
Scheme 19: Fluorination reactions of various substrates with 7-1a.
Scheme 20: Synthesis of N-F triflate 8-1.
Scheme 21: Synthesis of chiral N-fluoro sultams 9-1 and 9-2.
Scheme 22: Fluorination with chiral N-fluoro sultams 9-1 and 9-2.
Scheme 23: Synthesis of saccharin-derived N-fluorosultam 10-2.
Scheme 24: Fluorination with N-fluorosultam 10-2.
Scheme 25: Synthesis of N-F reagent 11-2.
Scheme 26: Fluorination with N-F reagent 11-2.
Scheme 27: Synthesis and reaction of N-fluorolactams 12-1.
Scheme 28: Synthesis of NFOBS 13-2.
Scheme 29: Fluorination with NFOBS 13-2.
Scheme 30: Synthesis of NFSI (14-2).
Scheme 31: Fluorination with NFSI 14-2.
Scheme 32: Synthesis of N-fluorosaccharin (15-1) and N-fluorophthalimide (15-2).
Scheme 33: Synthesis of N-F salts 16-3.
Scheme 34: Fluorination with N-F salts 16-3.
Figure 3: Monofluorination with Selectfluor (16-3a).
Figure 4: Difluorination with Selectfluor (16-3a).
Scheme 35: Transfer fluorination of Selectfluor (16-3a).
Scheme 36: Fluorination of substrates with Selectfluor (16-3a).
Scheme 37: Synthesis of chiral N-fluoro-sultam 17-2.
Scheme 38: Asymmetric fluorination with chiral 17-2.
Figure 5: Synthesis of Zwitterionic N-fluoropyridinium salts 18-2a–h.
Scheme 39: Fluorinating power order of zwitterionic N-fluoropyridinium salts.
Scheme 40: Fluorination with zwitterionic 18-2.
Scheme 41: Activation of salt 18-2h with TfOH.
Scheme 42: Synthesis of NFTh, 19-2.
Scheme 43: Fluorination with NFTh, 19-2.
Scheme 44: Synthesis of 3-fluorobenzo-1,2,3-oxathiazin-4-one 2,2-dioxide (20-2).
Scheme 45: Fluorination with 20-2.
Scheme 46: Synthesis of N-F amide 21-3.
Scheme 47: Fluorination with N-F amide 21-2.
Scheme 48: Synthesis of N,N’-difluorodiazoniabicyclo[2.2.2]octane salts 22-1.
Scheme 49: One-pot synthesis of N,N’-difluoro-1,4-diazoniabicyclo[2.2.2]octane bistetrafluoroborate salt (22-1d...
Figure 6: Fluorination of anisole with 22-1a, d, e.
Scheme 50: Fluorination with N,N’-diF bisBF4 22-1d.
Scheme 51: Synthesis of bis-N-F reagents 23-1–5.
Scheme 52: Fluorination with 23-2, 4, 5.
Figure 7: Synthesis of N,N’-difluorobipyridinium salts 24-2.
Figure 8: Controlled fluorination of N,N’-diF 24-2.
Scheme 53: Fluorinating power of N,N’-diF salts 24-2 and N-F salt 5-4a.
Scheme 54: Fluorination reactions with SynfluorTM (24-2b).
Scheme 55: Additional fluorination reactions with SynfluorTM (24-2b).
Scheme 56: Synthesis of N-F 25-1.
Scheme 57: Fluorination of polycyclic aromatics with 25-1.
Scheme 58: Synthesis of 26-1 and dimethyl analog 26-2.
Scheme 59: Fluorination with reagents 26-1, 26-2, 1-1, and 26-3.
Scheme 60: Synthesis of N-F reagent 27-2.
Scheme 61: Synthesis of chiral N-F reagents 27-6.
Scheme 62: Synthesis of chiral N-F 27-7–9.
Scheme 63: Asymmetric fluorination with 27-6.
Scheme 64: Synthesis of chiral N-F reagents 28-3.
Scheme 65: Asymmetric fluorination with 28-3.
Scheme 66: Synthesis of chiral N-F reagents 28-7.
Figure 9: Asymmetric fluorination with 28-7.
Scheme 67: In situ formation of N-fluorinated cinchona alkaloids with SelectfluorTM.
Scheme 68: Asymmetric fluorination with N-F alkaloids formed in situ.
Scheme 69: Synthesis of N-fluorocinchona alkaloids with Selectfluor.
Scheme 70: Asymmetric fluorination with 30-1–4.
Scheme 71: Transfer fluorination from various N-F reagents.
Figure 10: Asymmetric fluorination of silyl enol ethers.
Scheme 72: Synthesis of N-fluoro salt 32-2.
Scheme 73: Reactivity of N-fluorotriazinium salt 32-2.
Scheme 74: Synthesis of bulky N-fluorobenzenesulfonimide NFBSI 33-3.
Scheme 75: Comparison of NFSI and NFBSI.
Scheme 76: Synthesis of p-substituted N-fluorobenzenesulfonimides 34-3.
Figure 11: Asymmetric fluorination with 34-3 and a chiral catalyst 34-4.
Scheme 77: 1,4-Fluoroamination with Selecfluor and a chiral catalyst.
Figure 12: Asymmetric fluoroamination with 35-5a, b.
Scheme 78: Synthesis of Selectfluor analogs 35-5a, b.
Scheme 79: Synthesis of chiral dicationic DABCO-based N-F reagents 36-5.
Scheme 80: Asymmetric fluorocyclization with chiral 36-5b.
Scheme 81: Synthesis of chiral 37-2a,b.
Scheme 82: Asymmetric fluorination with chiral 37-2a,b.
Scheme 83: Asymmetric fluorination with chiral 37-2b.
Scheme 84: Reaction of indene with chiral 37-2a,b.
Scheme 85: Synthesis of Me-NFSI, 38-2.
Scheme 86: Fluorination of active methine compounds with Me-NFSI.
Scheme 87: Fluorination of malonates with Me-NFSI.
Scheme 88: Fluorination of keto esters with Me-NFSI.
Scheme 89: Synthesis of N-F 39-3 derived from the ethylene-bridged Tröger’s base.
Scheme 90: Fluorine transfer from N-F 39-3.
Scheme 91: Fluorination with N-F 39-3.
Scheme 92: Synthesis of SelectfluorCN.
Scheme 93: Bistrifluoromethoxylation of alkenes using SelectfluorCN.
Figure 13: Synthesis of NFAS 41-2.
Scheme 94: Radical fluorination with different N-F reagents.
Scheme 95: Radical fluorination of alkenes with NFAS 41-2.
Scheme 96: Radical fluorination of alkenes with NFAS 41-2f.
Scheme 97: Decarboxylative fluorination with NFAS 41-2a,f.
Scheme 98: Fluorine plus detachment (FPD).
Figure 14: FPD values of representative N-F reagents in CH2Cl2 and CH3CN (in parentheses). Adapted with permis...
Scheme 99: N-F homolytic bond dissociation energy (BDE).
Figure 15: BDE values of representative N-F reagents in CH3CN. Adapted with permission from ref. [127]. Copyright 2...
Figure 16: Quantitative reactivity scale for popular N-F reagents. Adapted with permission from ref. [138], publish...
Scheme 100: SET and SN2 mechanisms.
Scheme 101: Radical clock reactions.
Scheme 102: Reaction of potassium enolate of citronellic ester with N-F reagents, 10-1, NFSI, and 8-1.
Scheme 103: Reaction of compound IV with Selectfluor (OTf) and NFSI.
Scheme 104: Reaction of TEMPO with Selecfluor.
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
- commercial flow reactors allow for the safe simulation of larger scale processes within the lab environment, facilitating and expediting the process optimisation experience. While some of the implications of the flow chemistry are more obvious than others, i.e., greener processes with potential cost
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
Nitroalkene reduction in deep eutectic solvents promoted by BH3NH3
- Chiara Faverio,
- Monica Fiorenza Boselli,
- Patricia Camarero Gonzalez,
- Alessandra Puglisi and
- Maurizio Benaglia
Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83
- safe as well as economically and environmentally sustainable alternative to the traditional organic solvents. Here, we report the combination of an atom-economic, very convenient and inexpensive reagent, such as BH3NH3, with bio-based eutectic mixtures as biorenewable solvents in the synthesis of
- whole research community concerned with the concept of a circular economy [3]. In this context, deep eutectic solvents (DESs) have attracted an increasing attention as green, safe, economically and environmentally sustainable alternative to the traditional organic solvents [4]. They are combinations of
- materials that can be used to form eutectic mixtures offers an incredibly high variety of combinations to generate new, safe and biodegradable DESs [5]. Another fundamental principle of green chemistry is the atom economy concept. In this context, ammonia borane (AB) is receiving increasing attention as
Graphical Abstract
Scheme 1: AB-mediated reductions of nitrostyrenes 3a–h.
Scheme 2: AB-mediated reductions of nitrostyrenes 1, 3a, and 3c using DESs B and D.
Scheme 3: AB-mediated reductions of nitroalkenes 5a–f.
Scheme 4: Recovery and recycling experiments in the AB-mediated reduction of nitrostyrene 3h to afford nitroa...
Synthetic accesses to biguanide compounds
- Oleksandr Grytsai,
- Cyril Ronco and
- Rachid Benhida
Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82
- biguanides. This pathway is particularly convenient as cyanoguanidines are readily available, inexpensive, and safe [32]. Moreover, this reaction occurs with full atom economy and provides the desired biguanides with fairly high yields. A prior step of substituted cyanoguanidine preparation gives access to
Graphical Abstract
Figure 1: Tautomeric forms of biguanide.
Figure 2: Illustrations of neutral, monoprotonated, and diprotonated structures biguanide.
Figure 3: The main approaches for the synthesis of biguanides. The core structure is obtained via the additio...
Scheme 1: The three main preparations of biguanides from cyanoguanidine.
Scheme 2: Synthesis of butylbiguanide using CuCl2 [16].
Scheme 3: Synthesis of biguanides by the direct fusion of cyanoguanidine and amine hydrochlorides [17,18].
Scheme 4: Synthesis of ethylbiguanide and phenylbiguanide as reported by Smolka and Friedreich [14].
Scheme 5: Synthesis of arylbiguanides through the reaction of cyanoguanidine with anilines in water [19].
Scheme 6: Synthesis of aryl- and alkylbiguanides by adaptations of Cohn’s procedure [20,21].
Scheme 7: Microwave-assisted synthesis of N1-aryl and -dialkylbiguanides [22,23].
Scheme 8: Synthesis of aryl- and alkylbiguanides by trimethylsilyl activation [24,26].
Scheme 9: Synthesis of phenformin analogs by TMSOTf activation [27].
Scheme 10: Synthesis of N1-(1,2,4-triazolyl)biguanides [28].
Scheme 11: Synthesis of 2-guanidinobenzazoles by addition of ortho-substituted anilines to cyanoguanidine [30,32] and...
Scheme 12: Synthesis of 2,4-diaminoquinazolines by the addition of 2-cyanoaniline to cyanoguanidine and from 3...
Scheme 13: Reactions of anthranilic acid and 2-mercaptobenzoic acid with cyanoguanidine [24,36,37].
Scheme 14: Synthesis of disubstituted biguanides with Cu(II) salts [38].
Scheme 15: Synthesis of an N1,N2,N5-trisubstituted biguanide by fusion of an amine hydrochloride and 2-cyano-1...
Scheme 16: Synthesis of N1,N5-disubstituted biguanides by the addition of anilines to cyanoguanidine derivativ...
Scheme 17: Microwave-assisted additions of piperazine and aniline hydrochloride to substituted cyanoguanidines ...
Scheme 18: Synthesis of N1,N5-alkyl-substituted biguanides by TMSOTf activation [27].
Scheme 19: Additions of oxoamines hydrochlorides to dimethylcyanoguanidine [49].
Scheme 20: Unexpected cyclization of pyridylcyanoguanidines under acidic conditions [50].
Scheme 21: Example of industrial synthesis of chlorhexidine [51].
Scheme 22: Synthesis of symmetrical N1,N5-diarylbiguanides from sodium dicyanamide [52,53].
Scheme 23: Synthesis of symmetrical N1,N5-dialkylbiguanides from sodium dicyanamide [54-56].
Scheme 24: Stepwise synthesis of unsymmetrical N1,N5-trisubstituted biguanides from sodium dicyanamide [57].
Scheme 25: Examples for the synthesis of unsymmetrical biguanides [58].
Scheme 26: Examples for the synthesis of an 1,3-diaminobenzoquinazoline derivative by the SEAr cyclization of ...
Scheme 27: Major isomers formed by the SEAr cyclization of symmetric biguanides derived from 2- and 3-aminophe...
Scheme 28: Lewis acid-catalyzed synthesis of 8H-pyrrolo[3,2-g]quinazoline-2,4-diamine [63].
Scheme 29: Synthesis of [1,2,4]oxadiazoles by the addition of hydroxylamine to dicyanamide [49,64].
Scheme 30: Principle of “bisamidine transfer” and analogy between the reactions with N-amidinopyrazole and N-a...
Scheme 31: Representative syntheses of N-amidino-amidinopyrazole hydrochloride [68,69].
Scheme 32: First examples of biguanide syntheses using N-amidino-amidinopyrazole [66].
Scheme 33: Example of “biguanidylation” of a hydrazide substrate [70].
Scheme 34: Example for the synthesis of biguanides using S-methylguanylisothiouronium iodide as “bisamidine tr...
Scheme 35: Synthesis of N-substituted N1-cyano-S-methylisothiourea precursors.
Scheme 36: Addition routes on N1-cyano-S-methylisothioureas.
Scheme 37: Synthesis of an hydroxybiguanidine from N1-cyano-S-methylisothiourea [77].
Scheme 38: Synthesis of an N1,N2,N3,N4,N5-pentaarylbiguanide from the corresponding triarylguanidine and carbo...
Scheme 39: Reactions of N,N,N’,N’-tetramethylguanidine (TMG) with carbodiimides to synthesize hexasubstituted ...
Scheme 40: Microwave-assisted addition of N,N,N’,N’-tetramethylguanidine to carbodiimides [80].
Scheme 41: Synthesis of N1-aryl heptasubstituted biguanides via a one-pot biguanide formation–copper-catalyzed ...
Scheme 42: Formation of 1,2-dihydro-1,3,5-triazine derivatives by the reaction of guanidine with excess carbod...
Scheme 43: Plausible mechanism for the spontaneous cyclization of triguanides [82].
Scheme 44: a) Formation of mono- and disubstituted (iso)melamine derivatives by the reaction of biguanides and...
Scheme 45: Reactions of 2-aminopyrimidine with carbodiimides to synthesize 2-guanidinopyrimidines as “biguanid...
Scheme 46: Non-catalyzed alternatives for the addition of 2-aminopyrimidine derivatives to carbodiimides. A) h...
Scheme 47: Addition of guanidinomagnesium halides to substituted cyanamides [90].
Scheme 48: Microwave-assisted synthesis of [11C]metformin by the reaction of 11C-labelled dimethylcyanamide an...
Scheme 49: Formation of 4-amino-6-dimethylamino[1,3,5]triazin-2-ol through the reaction of Boc-guanidine and d...
Scheme 50: Formation of 1,3,5-triazine derivatives via the addition of guanidines to substituted cyanamides [92].
Scheme 51: Synthesis of biguanide by the reaction of O-alkylisourea and guanidine [93].
Scheme 52: Aromatic nucleophilic substitution of guanidine on 2-O-ethyl-1,3,5-triazine [95].
Scheme 53: Synthesis of N1,N2-disubstituted biguanides by the reaction of guanidine and thioureas in the prese...
Scheme 54: Cyclization reactions involving condensations of guanidine(-like) structures with thioureas [97,98].
Scheme 55: Condensations of guanidine-like structures with thioureas [99,100].
Scheme 56: Condensations of guanidines with S-methylisothioureas [101,102].
Scheme 57: Addition of 2-amino-1,3-diazaaromatics to S-alkylisothioureas [103,104].
Scheme 58: Addition of guanidines to 2-(methylsulfonyl)pyrimidines [105].
Scheme 59: An example of a cyclodesulfurization reaction to a fused 3,5-diamino-1,2,4-triazole [106].
Scheme 60: Ring-opening reactions of 1,3-diaryl-2,4-bis(arylimino)-1,3-diazetidines [107].
Scheme 61: Formation of 3,5-diamino-1,2,4-triazole derivatives via addition of hydrazines to 1,3-diazetidine-2...
Scheme 62: Formation of a biguanide via the addition of aniline to 1,2,4-thiadiazol-3,5-diamines, ring opening...
Figure 4: Substitution pattern of biguanides accessible by synthetic pathways a–h.
Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides
- Roslyn M. Ray,
- Anders Højgaard Hansen,
- Maria Taskova,
- Bernhard Jandl,
- Jonas Hansen,
- Citra Soemardy,
- Kevin V. Morris and
- Kira Astakhova
Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75
- this LNP formulation may not induce cytokine release syndrome in vivo [60][61]. Conclusion Taken together, we have shown that the LNP B9 formulation is safe, can traverse the BBB, and is readily taken up in multiple cell types. In the future, it will be interesting to explore whether increased uptake
Graphical Abstract
Figure 1: Components of the LNPs. A) Lipid species and lipidated cell-penetrating peptides applied by postins...
Figure 2: LNPs with T7 pass through the transwell cell barrier and are taken up by target cells. HeLa (CCR5-n...
Figure 3: LNPs with Tat pass through the transwell cell barrier and are taken up by target cells. A) Percenta...
Figure 4: LNPs do not stimulate secretion of proinflammatory cytokines. A) GMCSF-primed MDMs were treated wit...
Figure 5: LNPs modestly affect cell viability in a cell-specific manner. HeLa (A) or HEK293T cells (B) were t...
Valorisation of plastic waste via metal-catalysed depolymerisation
- Francesca Liguori,
- Carmen Moreno-Marrodán and
- Pierluigi Barbaro
Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53
- monobutyltin oxide, using substoichiometric amounts of isosorbide and succinic acid and no solvent at 230 °C reaction temperature. Isosorbide is a safe chemical [246] that is obtainable on the large scale from renewable glucose [247][248]. Because of this and due to the inherent rigid structure, conferring the
- hydrogenolysis to give PD in 99% yield at 160 °C, 54 bar H2 and in anisole/THF solvent [182][188]. PD is a safe chemical that is mainly produced from propylene oxide or catalytically from lactic acid intermediate, and it serves in the polymer and food industry or as antifreezing agent [276][277]. Under milder
Graphical Abstract
Figure 1: Potential classification of plastic recycling processes. The area covered by the present review is ...
Figure 2: EG produced during glycolytic depolymerisation of PET using DEG + DPG as solvent and titanium(IV) n...
Scheme 1: Simplified representation of the conversion of 1,4-PBD to C16–C44 macrocycles using Ru metathesis c...
Figure 3: Main added-value monomers obtainable by catalytic depolymerisation of PET via chemolytic methods.
Scheme 2: Hydrogenolytic depolymerisation of PET by ruthenium complexes.
Scheme 3: Depolymerisation of PET via catalytic hydrosilylation by Ir(III) pincer complex.
Scheme 4: Catalytic hydrolysis (top) and methanolysis (bottom) reactions of PET.
Scheme 5: Depolymerisation of PET by glycolysis with ethylene glycol.
Figure 4: Glycolysis of PET: evolution of BHET yield over time, with and without zinc acetate catalyst (196 °...
Scheme 6: Potential activated complex for the glycolysis reaction of PET catalysed by metallated ILs and evol...
Scheme 7: One-pot, two-step process for PET repurposing via chemical recycling.
Scheme 8: Synthetic routes to PLA.
Scheme 9: Structures of the zinc molecular catalysts used for PLA-methanolysis in various works. a) See [265], b) ...
Scheme 10: Depolymerisation of PLLA by Zn–N-heterocyclic carbene complex.
Scheme 11: Salalen ligands.
Scheme 12: Catalytic hydrogenolysis of PLA.
Scheme 13: Catalytic hydrosilylation of PLA.
Scheme 14: Hydrogenative depolymerisation of PBT and PCL by molecular Ru catalysts.
Scheme 15: Glycolysis reaction of PCT by diethylene glycol.
Scheme 16: Polymerisation–depolymerisation cycle of 3,4-T6GBL.
Scheme 17: Polymerisation–depolymerisation cycle of 2,3-HDB.
Scheme 18: Hydrogenative depolymerisation of PBPAC by molecular Ru catalysts.
Scheme 19: Catalytic hydrolysis (top), alcoholysis (middle) and aminolysis (bottom) reactions of PBPAC.
Scheme 20: Hydrogenative depolymerisation of PPC (top) and PEC (bottom) by molecular Ru catalysts.
Scheme 21: Polymerisation-depolymerisation cycle of BEP.
Scheme 22: Hydrogenolysis of polyamides using soluble Ru catalysts.
Scheme 23: Catalytic depolymerisation of epoxy resin/carbon fibres composite.
Scheme 24: Depolymerisation of polyethers with metal salt catalysts and acyl chlorides.
Scheme 25: Proposed mechanism for the iron-catalysed depolymerisation reaction of polyethers. Adapted with per...
The preparation and properties of 1,1-difluorocyclopropane derivatives
- Kymbat S. Adekenova,
- Peter B. Wyatt and
- Sergazy M. Adekenov
Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25
Graphical Abstract
Scheme 1: Synthesis of 1,1-difluoro-2,3-dimethylcyclopropane (2).
Scheme 2: Cyclopropanation via dehydrohalogenation of chlorodifluoromethane.
Scheme 3: Difluorocyclopropanation of methylstyrene 7 using dibromodifluoromethane and zinc.
Scheme 4: Synthesis of difluorocyclopropanes from the reaction of dibromodifluoromethane and triphenylphosphi...
Scheme 5: Generation of difluorocarbene in a catalytic two-phase system and its addition to tetramethylethyle...
Scheme 6: The reaction of methylstyrene 7 with chlorodifluoromethane (11) in the presence of a tetraarylarson...
Scheme 7: Pyrolysis of sodium chlorodifluoroacetate (12) in refluxing diglyme in the presence of alkene 13.
Scheme 8: Synthesis of boron-substituted gem-difluorocyclopropanes 16.
Scheme 9: Addition of sodium bromodifluoroacetate (17) to alkenes.
Scheme 10: Addition of sodium bromodifluoroacetate (17) to silyloxy-substituted cyclopropanes 20.
Scheme 11: Synthesis of difluorinated nucleosides.
Scheme 12: Addition of butyl acrylate (26) to difluorocarbene generated from TFDA (25).
Scheme 13: Addition of difluorocarbene to propargyl esters 27 and conversion of the difluorocyclopropenes 28 t...
Scheme 14: The generation of difluorocyclopropanes using MDFA 30.
Scheme 15: gem-Difluorocyclopropanation of styrene (32) using difluorocarbene generated from TMSCF3 (31) under...
Scheme 16: Synthesis of a gem-difluorocyclopropane derivative using HFPO (41) as a source of difluorocarbene.
Scheme 17: Cyclopropanation of (Z)-2-butene in the presence of difluorodiazirine (44).
Scheme 18: The cyclopropanation of 1-octene (46) using Seyferth's reagent (45) as a source of difluorocarbene.
Scheme 19: Alternative approaches for the difluorocarbene synthesis from trimethyl(trifluoromethyl)tin (48).
Scheme 20: Difluorocyclopropanation of cyclohexene (49).
Scheme 21: Synthesis of difluorocyclopropane derivative 53 using bis(trifluoromethyl)cadmium (51) as the diflu...
Scheme 22: Addition of difluorocarbene generated from tris(trifluoromethyl)bismuth (54).
Scheme 23: Addition of a stable (trifluoromethyl)zinc reagent to styrenes.
Scheme 24: The preparation of 2,2-difluorocyclopropanecarboxylic acids of type 58.
Scheme 25: Difluorocyclopropanation via Michael cyclization.
Scheme 26: Difluorocyclopropanation using N-acylimidazolidinone 60.
Scheme 27: Difluorocyclopropanation through the cyclization of phenylacetonitrile (61) and 1,2-dibromo-1,1-dif...
Scheme 28: gem-Difluoroolefins 64 for the synthesis of functionalized cyclopropanes 65.
Scheme 29: Preparation of aminocyclopropanes 70.
Scheme 30: Synthesis of fluorinated methylenecyclopropane 74 via selenoxide elimination.
Scheme 31: Reductive dehalogenation of (1R,3R)-75.
Scheme 32: Synthesis of chiral monoacetates by lipase catalysis.
Scheme 33: Transformation of (±)-trans-81 using Rhodococcus sp. AJ270.
Scheme 34: Transformation of (±)-trans-83 using Rhodococcus sp. AJ270.
Scheme 35: Hydrogenation of difluorocyclopropenes through enantioselective hydrocupration.
Scheme 36: Enantioselective transfer hydrogenation of difluorocyclopropenes with a Ru-based catalyst.
Scheme 37: The thermal transformation of trans-1,2-dichloro-3,3-difluorocyclopropane (84).
Scheme 38: cis–trans-Epimerization of 1,1-difluoro-2,3-dimethylcyclopropane.
Scheme 39: 2,2-Difluorotrimethylene diradical intermediate.
Scheme 40: Ring opening of stereoisomers 88 and 89.
Scheme 41: [1,3]-Rearrangement of alkenylcyclopropanes 90–92.
Scheme 42: Thermolytic rearrangement of 2,2-difluoro-1-vinylcyclopropane (90).
Scheme 43: Thermal rearrangement for ethyl 3-(2,2-difluoro)-3-phenylcyclopropyl)acrylates 93 and 95.
Scheme 44: Possible pathways of the ring opening of 1,1-difluoro-2-vinylcyclopropane.
Scheme 45: Equilibrium between 1,1-difluoro-2-methylenecyclopropane (96) and (difluoromethylene)cyclopropane 97...
Scheme 46: Ring opening of substituted 1,1-difluoro-2,2-dimethyl-3-methylenecyclopropane 98.
Scheme 47: 1,1-Difluorospiropentane rearrangement.
Scheme 48: Acetolysis of (2,2-difluorocyclopropyl)methyl tosylate (104) and (1,1-difluoro-2-methylcyclopropyl)...
Scheme 49: Ring opening of gem-difluorocyclopropyl ketones 106 and 108 by thiolate nucleophiles.
Scheme 50: Hydrolysis of gem-difluorocyclopropyl acetals 110.
Scheme 51: Ring-opening reaction of 2,2-difluorocyclopropyl ketones 113 in the presence of ionic liquid as a s...
Scheme 52: Ring opening of gem-difluorocyclopropyl ketones 113a by MgI2-initiated reaction with diarylimines 1...
Scheme 53: Ring-opening reaction of gem-difluorocyclopropylstannanes 117.
Scheme 54: Preparation of 1-fluorovinyl vinyl ketone 123 and the synthesis of 2-fluorocyclopentenone 124. TBAT...
Scheme 55: Iodine atom-transfer ring opening of 1,1-difluoro-2-(1-iodoalkyl)cyclopropanes 125a–c.
Scheme 56: Ring opening of bromomethyl gem-difluorocyclopropanes 130 and formation of gem-difluoromethylene-co...
Scheme 57: Ring-opening aerobic oxidation reaction of gem-difluorocyclopropanes 132.
Scheme 58: Dibrominative ring-opening functionalization of gem-difluorocyclopropanes 134.
Scheme 59: The selective formation of (E,E)- and (E,Z)-fluorodienals 136 and 137 from difluorocyclopropyl acet...
Scheme 60: Proposed mechanism for the reaction of difluoro(methylene)cyclopropane 139 with Br2.
Scheme 61: Thermal rearrangement of F2MCP 139 and iodine by CuI catalysis.
Scheme 62: Synthesis of 2-fluoropyrroles 142.
Scheme 63: Ring opening of gem-difluorocyclopropyl ketones 143 mediated by BX3.
Scheme 64: Lewis acid-promoted ring-opening reaction of 2,2-difluorocyclopropanecarbonyl chloride (148).
Scheme 65: Ring-opening reaction of the gem-difluorocyclopropyl ketone 106 by methanolic KOH.
Scheme 66: Hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151).
Scheme 67: Synthesis of monofluoroalkenes 157.
Scheme 68: The stereoselective Ag-catalyzed defluorinative ring-opening diarylation of 1-trimethylsiloxy-2,2-d...
Scheme 69: Synthesis of 2-fluorinated allylic compounds 162.
Scheme 70: Pd-catalyzed cross-coupling reactions of gem-difluorinated cyclopropanes 161.
Scheme 71: The (Z)-selective Pd-catalyzed ring-opening sulfonylation of 2-(2,2-difluorocyclopropyl)naphthalene...
Figure 1: Structures of zosuquidar hydrochloride and PF-06700841.
Scheme 72: Synthesis of methylene-gem-difluorocyclopropane analogs of nucleosides.
Figure 2: Anthracene-difluorocyclopropane hybrid derivatives.
Figure 3: Further examples of difluorcyclopropanes in modern drug discovery.
A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach
- Michael Andresini,
- Leonardo Degannaro and
- Renzo Luisi
Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20
- preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustainable, safe
- functionalized oxazoles using acetone as the solvent (Scheme 1c) [28]. Inspired by these recent reports, we became interested in the development of an eco-friendly strategy for the safe preparation of highly functionalized NH-aziridines from acyclic precursors. Herein, we report a sustainable mixed flow-batch
- proceed stereoselectively when organolithium compounds were added to 2,3-diphenyl-2H-azirine. This is a fast, safe, green and convenient method to access this interesting structural motif without requiring protection/deprotection steps or long synthetic pathways. Flow generation and transformation of 2H
Graphical Abstract
Scheme 1: Flow generation and transformation of 2H-azirines.
Scheme 2: Flow synthesis of 2H-azirines from vinyl azides. aThe solution of vinyl azide was re-introduced twi...
Scheme 3: Mixed flow-batch approach for the preparation of functionalized NH-aziridines from vinyl azides.
Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives
- Emese Gal,
- Luiza Gaina,
- Hermina Petkes,
- Alexandra Pop,
- Castelia Cristea,
- Gabriel Barta,
- Dan Cristian Vodnar and
- Luminiţa Silaghi-Dumitrescu
Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242
- that the C-(hetero)aryl-α-(arylamino)acetonitrile derivatives can be considered genotoxically safe and possibly antimutagenic. Keywords: Ames test; α-aminoacetonitriles; ferrocene; phenothiazine; SEM; single crystal XRD; sonochemistry; Introduction Sonochemistry can be considered as a major
- -amino-C-substituted-acetonitriles pointed out that the compounds 2c, 2i, and 2l can be considered as genotoxically safe at concentrations in the range of their solubility limit in DMSO/water media. The tested compounds also exhibited antimutagenic activity by interfering with the effect of known
Graphical Abstract
Scheme 1: Synthesis of α-amino-acetonitrile derivatives. Reaction conditions: Aldimine (1 equiv), TMSCN (1 eq...
Figure 1: Crystal structure of 2-phenothiazinyl-2-(p-tolylamino)acetonitrile 2a. a) ORTEP plot and b) crystal...
Figure 2: SEM images recorded at 200× for the raw reaction product 2b obtained through a) ultrasound-assisted...
Figure 3: SEM image recorded at 200× for the raw reaction product 2c obtained through a) ultrasound-assisted ...
One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity
- Giovanna Bosica,
- Kaylie Demanuele,
- José M. Padrón and
- Adrián Puerta
Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235
- reaction for the synthesis of substituted dihydropyridines was performed under green heterogeneous and neat conditions in the presence of 0.04 g/mmol of a 40 wt % phosphotungstic acid on alumina catalyst, which is simple, safe and environmentally benign to prepare, fully recoverable, and reusable for up to
Graphical Abstract
Scheme 1: The classical Hantzsch synthesis between benzaldehyde (1a), ethyl acetoacetate (2), and ammonium ac...
Figure 1: Optimization trials with the selected solid catalysts.
Figure 2: Graphical representation of the results obtained in the reusability test.
Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors
- Emine Kayahan,
- Mathias Jacobs,
- Leen Braeken,
- Leen C.J. Thomassen,
- Simon Kuhn,
- Tom van Gerven and
- M. Enis Leblebici
Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202
- -terpinene by utilizing singlet oxygen. The permeability of the fluoropolymer film to oxygen was utilized to supply oxygen to microcapillaries. The system was suggested to be used in combination with dangerous gases to ensure safe operational conditions. With the fluoropolymer microcapillaries, space time
- be determined in order to ensure safe operating conditions. Mass transport The mass transport phenomena can be quantified by the characteristic mixing time and the overall volumetric mass transfer coefficient. The characteristic mixing time in conventional reactors depends on many parameters, such as
Graphical Abstract
Figure 1: The momentum transport affects the mass transfer and the light field. All transport phenomena need ...
Figure 2: Common photomicroreactor designs: (a) Straight channel, (b) serpentine channel, (c) square serpenti...
Figure 3: Benchmarked photoreactors: (a) Microcapillaries in parallel, (b) microcapillaries in series, (c) fl...
Figure 4: Photochemical reactions that are detailed in Table 1.
Figure 5: Structured reactors designed for enhancing the mass transfer: (a) Packed bed photoreactor, (b) mono...
Figure 6: Comparison of the LED board designs of photomicroreactors: (a) CC array design, (b) MC array design...
Figure 7: Illustration of the light scattering phenomenon inside a photocatalytic flow reactor.
Figure 8: Efficiency of the absorption process in scattering situations with respect to pure absorption situa...
Figure 9: Different types of distributors: (a) Traditional or consecutive manifold, (b) bifurcation unit dist...
