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Search for "Knoevenagel" in Full Text gives 89 result(s) in Beilstein Journal of Organic Chemistry.
Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units
- Christina Schøttler,
- Kasper Lund-Rasmussen,
- Line Broløs,
- Philip Vinterberg,
- Ema Bazikova,
- Viktor B. R. Pedersen and
- Mogens Brøndsted Nielsen
Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8
- variety of reactions; that are, phosphite- or Lawesson’s reagent-mediated olefination reactions (to introduce DTF motifs), Ramirez/Corey–Fuchs dibromo-olefinations followed by Sonogashira couplings (to introduce enediynes motifs), and Knoevenagel condensations (to introduce the vinylic diester motif). By
- as a mixture of E and Z isomers (ca. 4:1). Further functionalization of the IF-DTF ketone 11 was obtained by Ramirez/Corey–Fuchs dibromo-olefination and Knoevenagel condensation to yield vinylic dibromide 14 and diester 15, respectively, as illustrated in Scheme 2. We noted that the dibromo
- -olefinations, and Knoevenagel condensations. In particular, the acetylenic scaffolds presented in this work may be useful precursors for even more elaborate, conjugated and carbon-rich structures in future work. Experimental Anhydrous MeOH was obtained by distillation from activated Mg and stored over 3 Å
Graphical Abstract
Figure 1: Overview of structural motifs relevant for the work described herein.
Figure 2: Dione/ketones 1, 4–6 and 1,3-dithiole-2-thione compounds 2, 3, 7, and 8 are building blocks used in...
Scheme 1: Synthesis of IF-DTF ketones 9–12 and dimer 13.
Scheme 2: Further functionalization of the IF-DTF ketone 11 via Ramirez/Corey–Fuchs dibromo-olefination and K...
Scheme 3: Coupling of 1,3-dithiole-2-thione building blocks 2 and 3 with fluorenone 5 to afford fluorene-exte...
Scheme 4: Synthesis of acetylenic scaffolds based on IF-DTF. Conditions: (a) Pd(PPh3)2Cl2, CuI, THF, Et3N, rt...
Scheme 5: Synthesis of acetylenic scaffolds with IF as central core. *Not fully characterized due to poor sol...
Scheme 6: Reduction of IF dione 1 to dihydro-IF 29.
Figure 3: UV–vis absorption spectra of compounds 4, 9–12, and 15 in PhMe at 25 °C.
Figure 4: UV–vis absorption spectra of compounds 13, 16, 17, and 30 in CH2Cl2 at 25 °C.
Figure 5: UV–vis absorption spectra of compounds 22, 23, 26, and 27 in CH2Cl2 at 25 °C.
Figure 6: Cyclic voltammograms of compounds 11 (in MeCN), 13 (in CH2Cl2), 15 (in MeCN), 16 (in CH2Cl2), and 17...
Figure 7: Comparison of properties of compounds 13 and 17.
Figure 8: Cyclic voltammograms of compounds 22, 23, 26, and 27 in CH2Cl2; supporting electrolyte: 0.1 M Bu4NPF...
Figure 9: Radical anion (left), dianion (middle), and radical cation (right) of compound 23; the radical anio...
Figure 10: ORTEP plots (50% probability) and crystal packing of compounds a) 25, b) 26, and c) 29. The respect...
Figure 11: Labels of bonds within five-membered ring.
Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent
- Stéphanie Hesse
Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110
- scaffolds is the introduction of a benzylidene moiety on C5 via a Knoevenagel reaction. Here, a facile synthesis of 5-arylidenerhodanines via a Knoevenagel reaction in an ʟ-proline-based deep eutectic solvent (DES) is reported. This method is fast (1 h at 60 °C), easy, catalyst-free and sustainable as no
- compounds are the more active ones. Keywords: antioxidant; deep eutectic solvent; Knoevenagel; ʟ-proline DES; rhodanine; Introduction Rhodanines and related five-membered heterocycles with multiple heteroatoms (i.e., thiazolidinediones, thiazolidinones, hydantoins, thiohydantoins) are very interesting
- Knoevenagel condensation of rhodanine with different aldehydes [3]. The reactions were performed in ChCl/urea (1:2) at 90 °C, without needing a catalyst and the products were obtained in low to good yields (10–78%). On another hand, ʟ-proline is well known as an organocatalyst and its use in aldol and
Graphical Abstract
Figure 1: Examples of rhodanines and related five-membered heterocycles with interesting biological activitie...
Scheme 1: Synthesis of 5-benzylidenerhodanine derivatives. Conditions: areaction performed for 3 h at 60 °C. b...
Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones
- Ksenia Malkova,
- Andrey Bubyrev,
- Stanislav Kalinin and
- Dmitry Dar’in
Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60
- have developed a new convenient protocol for the synthesis of 3-sulfonyl-substituted quinolines (sulfonamides and sulfones). The approach is based on a Knoevenagel condensation/aza-Wittig reaction cascade involving o-azidobenzaldehydes and ketosulfonamides or ketosulfones as key building blocks. The
- , the method for the synthesis of 3-acyl-substituted quinolines from o-azidobenzaldehydes and 1,3-dicarbonyl compounds was reported [70][71] (Figure 2a). A combination of Knoevenagel condensation and aza-Wittig reaction allowed to build up target products in high yields. In case of [70], the procedure
- quinolines (sulfonamides and sulfones) (Figure 2b). Herein, we report the successful implementation of this approach. Results and Discussion The Knoevenagel condensation/aza-Wittig reaction cascade was used for the preparation of 3-sulfonyl-substituted quinolines. The process proceeds in a domino fashion
Graphical Abstract
Figure 1: a) Conventional drugs containing either a sulfonamide fragment or a quinoline core; b) biologically...
Figure 2: Knoevenagel condensation/aza-Wittig reaction cascade for the quinoline core formation.
Scheme 1: Key reaction steps during the synthesis of 3-sulfonyl-substituted quinolines.
Scheme 2: Synthetic routes to sulfonamides and sulfones 2 and the set of reagents for the preparation of comp...
Scheme 3: Preparation of 3-sulfonyl substituted quinolines 5a–q.
Scheme 4: 3-Sulfonyl-substituted quinolines 5r–v that failed to be synthesized.
Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities
- Jorge de Lima Neto and
- Paulo Henrique Menezes
Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31
- reaction [33]. Thus, Knoevenagel condensation using the diaryl ether 29 and malonic acid gave the corresponding α,β-unsaturated compound 30, which was submitted to a concomitant hydrogenation of the double bond and the nitro group to give compound 31. Sequential diazotization/halogenation and
Graphical Abstract
Figure 1: Structures of some members of the combretastatin D series, corniculatolides, and isocorniculatolide...
Scheme 1: Biosynthetic pathway proposed by Pettit and co-workers.
Scheme 2: Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-...
Scheme 3: Retrosynthetic approaches.
Scheme 4: Attempt of total synthesis of 2 by Boger and co-workers employing the Mitsunobu approach [27].
Scheme 5: Total synthesis of combretastatin D-2 (2) reported by Boger and co-workers employing an intramolecu...
Scheme 6: Formal synthesis of combretastatin D-2 (2) by Deshpande and co-workers using the Mitsunobu conditio...
Scheme 7: Total synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 8: Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 9: Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41].
Scheme 10: Synthesis of fragment 57 by Couladouros and co-workers [43,45].
Scheme 11: Formal synthesis of compound 2 by Couladouros and co-workers [43,45].
Scheme 12: Synthesis of fragment 66 by Couladouros and co-workers [44,45].
Scheme 13: Synthesis of fragment 70 by Couladouros and co-workers [44,45].
Scheme 14: Synthesis of fragment 77 by Couladouros and co-workers [44,45].
Scheme 15: Synthesis of combretastatins 1 and 2 by Couladouros and co-workers [44,45].
Scheme 16: Formal synthesis of compound 2 by Gangakhedkar and co-workers [48].
Scheme 17: Synthesis of fragment 14 by Cousin and co-workers [50].
Scheme 18: Synthesis of fragment 91 by Cousin and co-workers [50].
Scheme 19: Formal synthesis of compound 2 by Cousin and co-workers [50].
Scheme 20: Synthesis of 2 diolide by Cousin and co-workers [50].
Scheme 21: Synthesis of combretastatin D-4 (4) by Nishiyama and co-workers [54].
Scheme 22: Synthesis of fragment 112 by Pettit and co-workers [55].
Scheme 23: Synthesis of fragment 114 by Pettit and co-workers [55].
Scheme 24: Attempt to the synthesis of compound 2 by Pettit and co-workers [55].
Scheme 25: Synthesis of combretastatin-D2 (2) starting from isovanilin (80) by Pettit and co-workers [55].
Scheme 26: Attempted synthesis of combretastatin-D2 (2) derivatives through an SNAr approach [55].
Scheme 27: Synthesis of combretastatin D-4 (4) by Pettit and co-workers [55].
Scheme 28: Synthesis of combretastatin D-2 (2) by Harras and co-workers [57].
Scheme 29: Synthesis of combretastatin D-4 (4) by Harras and co-workers [57].
Scheme 30: Formal synthesis of combretastatin D-1 (1) by Harras and co-workers [57].
Scheme 31: Synthesis of 11-O-methylcorniculatolide A (5) by Raut and co-workers [69].
Scheme 32: Synthesis of isocorniculatolide A (7) and O-methylated isocorniculatolide A 8 by Raut and co-worker...
Scheme 33: Synthesis of isocorniculatolide B (10) and hydroxyisocorniculatolide B 175 by Kim and co-workers [71].
Scheme 34: Synthesis of compound 9, 178, and 11 by Kim and co-workers [71].
Scheme 35: Synthesis of combretastatin D-2 prodrug salts [55].
Figure 2: ED50 values of the combretastatin D family against murine P388 lymphocytic leukemia cell line (appr...
Figure 3: IC50 of compounds against α-glucosidase [19].
Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones
- Benedikt Kolb,
- Daniela Silva dos Santos,
- Sanja Krause,
- Anna Zens and
- Sabine Laschat
Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17
- from a haliclona marine sponge [4], and vertinolide (5) from Verticillium intertextum [5] (Scheme 1). As outlined in Scheme 2, a variety of methods has been reported for the synthesis of conjugated dienones, mostly via addition/elimination reactions such as Knoevenagel condensation or Claisen–Schmidt
Graphical Abstract
Scheme 1: Examples of biologically active compounds with (2Ε,4E)-unsaturated ketone units.
Scheme 2: Selected examples for the synthesis of conjugated dienones from the literature [6-21].
Scheme 3: Previous work of hydrozirconations with Schwartz's reagent and our work [54,55,57,58,61,62].
Scheme 4: Synthesis of substituted enynes 25f–o via Corey–Fuchs reaction and Hunsdiecker reaction.
Scheme 5: Synthesis of non-natural (a) and natural (b) dienone-containing terpenes: synthesis of β-ionone (3)....
First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell
- Daniele Rocco,
- Ana A. Folgueiras-Amador,
- Richard C. D. Brown and
- Marta Feroci
Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98
- as ligands in organometallic catalysts [9] and as versatile organocatalysts [10] in a very wide range of organic reactions such as classical benzoin condensation, transesterification, acylation, Knoevenagel reaction, Claisen condensation etc. The electrochemical generation of carbenes from ILs avoids
Graphical Abstract
Scheme 1: Electrochemical generation of NHC.
Scheme 2: Transformation of electrochemically generated NHC into the corresponding thione by its reaction wit...
Scheme 3: Umpolung of the aldehyde carbonyl carbon atom. Formation of the Breslow intermediate using NHCs.
Figure 1: Schematic representation of a plane-parallel plate flow electrochemical reactor.
Figure 2: C/PVDF anode before (A) and after (B) the first experiment (Table 1, entry 1).
Scheme 4: Electrogenerated NHC-catalyzed self-annulation of cinnamaldehyde.
Scheme 5: Byproduct obtained from the reaction between methanol and the Breslow intermediate.
Figure 3: Expanded view of the electrochemical cell components: (a) Aluminium end plates; (b) insulating PTFE...
Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles
- Shao-Cong Zhan,
- Ren-Jie Fang,
- Jing Sun and
- Chao-Guo Yan
Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80
- different kinds of aromatic aldehydes and 5-arylidene-1,3-dimethylbarbituric acids. 5-Arylidene-1,3-dimethylbarbituric acids could be easily generated through Knoevenagel condensation of aromatic aldehydes and 1,3-dimethylbarbituric acid under the catalysis of Lewis acid. We envisioned whether the desired
- 3-substituted indole, which undergoes dehydration to form the key intermediate indole-based ortho-quinodimethanes (o-QDMs, A). In the meantime, the cyclic 1,3-diones and aromatic aldehyde undergo Knoevenagel condensation to afford the different kinds of dienophiles. Subsequently, the Diels–Alder
Graphical Abstract
Scheme 1: Construction of diverse tetrahydrocarbazoles via Levy-type reaction.
Scheme 2: Synthesis of spiro[carbazole-3,3'-inolines]. Reaction conditions: 2-methylindole (0.5 mmol), aromat...
Scheme 3: Synthesis of spiro[carbazole-2,3'-indolines]. Reaction conditions: 2-methylindole (0.5 mmol), aroma...
Scheme 4: Synthesis of tetrahydrospiro[carbazole-3,5'-pyrimidines]. Reaction conditions: 2-methylindole (0.5 ...
Scheme 5: Synthesis of tetrahydrospiro[carbazole-3,1'-cycloalkane]-diones. Reaction conditions: 2-methylindol...
Scheme 6: Synthesis of 3,3'-(arylmethylene)bis(2-methyl-1H-indole). Reaction conditions: 2-methylindole (1.0 ...
Scheme 7: Proposed reaction mechanism for the multicomponent reaction.
Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis
- Prodip Howlader and
- Michael Schmittel
Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62
- molecules through π–π stacking with the hydrophobic aromatic wall of the host. Finally, the boat was investigated as a catalyst for the Knoevenagel condensation reaction (Figure 2) of a series of aromatic aldehydes with 1,3-dimethylbarbituric acid and Meldrum’s acid in aqueous media. One of the primary
- ]. Notably, the dissipative conditions were realized by addition of a fuel acid [113][114] that surprisingly ignited a base-catalyzed Knoevenagel addition reaction (Figure 25). As DABCO is a stronger binding ligand (log β = 7.20) [115] towards zinc porphyrin (ZnPor) than pyridine (log K = 4.45) [90] the
- 115 reclaims the proton back (Figure 25, top). As a result, State-II may be afforded under dissipative conditions. A surprising facet of this State-I/State-II interconversion (Figure 24) [112] was the finding that the protonated DABCO (60-H+) was a rather efficient base catalyst for a Knoevenagel
Graphical Abstract
Figure 1: Butterfly 1 (Figure was reprinted with permission from [45]. Copyright 2012 American Chemical Society. ...
Figure 2: Synthesis of the three-component heteroleptic molecular boat 8 and its use as a catalyst for the Kn...
Figure 3: Synthesis of the two-component triangle 14 and three-component heteroleptic prism 15 [59]. Figure was a...
Figure 4: Catalytic Michael addition reaction using the urea-decorated molecular prism 15 [59].
Figure 5: Self-assembly of two-component tetragonal prismatic architectures with different cavity size. Figur...
Figure 6: Construction of artificial LHS using rhodamine B as an acceptor and 24b as donor generating a photo...
Figure 7: Synthesis of supramolecular spheres with varying [AuCl] concentration inside the cavity. Figure was...
Figure 8: Hydroalkoxylation reaction of γ-allenol 34 in the presence of [AuCl]-encapsulated molecular spheres ...
Figure 9: Two-component heteroleptic triangles of different size containing a BINOL functionality. Figure was...
Figure 10: Asymmetric conjugate addition of chalcone 42 with trans-styrylboronic acid (43) catalyzed by BINOL-...
Figure 11: Encapsulation of monophosphoramidite-Rh(I) catalyst into a heteroleptic tetragonal prismatic cage 47...
Figure 12: (a) Representations of the basic HETPYP, HETPHEN, and HETTAP complex motifs. (b) The three-componen...
Figure 13: Two representative four-component rotors, with a (top) two-arm stator and (bottom) a four-arm stato...
Figure 14: Four-component rotors with a monohead rotator. Figure was adapted with permission from [94]. Copyright ...
Figure 15: (left) Click reaction catalyzed by rotors [Cu2(55)(60)(X)]2+. (right) Yield as a function of the ro...
Figure 16: A supramolecular AND gate. a) In truth table state (0,0) two nanoswitches serve as the receptor ens...
Figure 17: Two supramolecular double rotors (each has two rotational axes) and reference complex [Cu(78)]+ for...
Figure 18: The slider-on-deck system (82•X) (X = 83, 84, or 85). Figure is from [98] and was reprinted from the jo...
Figure 19: Catalysis of a conjugated addition reaction in the presence of the slider-on-deck system (82•X) (X ...
Figure 20: A rotating catalyst builds a catalytic machinery. For catalysis of the catalytic machinery, see Figure 21. F...
Figure 21: Catalytic machinery. Figure was adapted from [100] (“Evolution of catalytic machinery: three-component n...
Figure 22: An information system based on (re)shuffling components between supramolecular structures [99]. Figure ...
Figure 23: Switching between dimeric heteroleptic and homoleptic complex for OFF/ON catalytic formation of rot...
Figure 24: A chemically fueled catalytic system [112]. Figure was adapted from [112]. Copyright 2021 American Chemical S...
Figure 25: (Top) Operation of a fuel acid. (Bottom) Knoevenagel addition [112].
Figure 26: Development of the yield of Knoevenagel product 118 in a fueled system [112]. Figure was reprinted with ...
Figure 27: Weak-link strategy to increased catalytic activity in epoxide opening [119]. Figure was adapted from [24]. C...
Figure 28: A ON/OFF polymerization switch based on the weak-link approach [118]. Figure was reprinted with permissi...
Figure 29: A weak-link switch turning ON/OFF a Diels–Alder reaction [132]. Figure was reprinted with permission fro...
Figure 30: A catalyst duo allowing selective activation of one of two catalytic acylation reactions [133] upon subs...
Figure 31: A four-state switchable nanoswitch (redrawn from [134]).
Figure 32: Sequential catalysis as regulated by nanoswitch 138 and catalyst 139 in the presence of metal ions ...
Figure 33: Remote control of ON/OFF catalysis administrated by two nanoswitches through ion signaling (redrawn...
Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)
- Tania Xavier,
- Sylvie Condon,
- Christophe Pichon,
- Erwan Le Gall and
- Marc Presset
Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135
- usually achieved by a nucleophilic substitution of an alkyl halide by the deprotonated malonate [12][13][14][15][16][17][18][19], but other strategies could be envisioned: Cu-catalyzed arylation reactions for aryl-substituted MAHOs [20][21][22][23]; Knoevenagel/reduction sequences for benzyl-substituted
- compound 5 is commercially available or easily accessible on a relatively large scale (Scheme 3) [56]. Therefore, we first achieved an alkylation step of 5 using a Knoevenagel reaction with benzaldehyde, followed by an in situ reduction of the resulting alkylidene [57][58]. Even if the reaction worked well
Graphical Abstract
Scheme 1: Main routes to SMAHOs.
Scheme 2: Preparation of α-halo-MAHOs.
Scheme 3: Preparation of SMAHOs from Meldrum's acid.
Scheme 4: Saponification of substituted malonates.
Scheme 5: Scope of the mono-esterification of substituted malonic acids. adr = 1:1.
Icilio Guareschi and his amazing “1897 reaction”
- Gian Cesare Tron,
- Alberto Minassi,
- Giovanni Sorba,
- Mara Fausone and
- Giovanni Appendino
Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93
- to name type-I Guareschi pyridone synthesis the two-component reaction between a β-aminocarbonyl and a cyanoacetic ester, a reaction first reported in 1893 [34]. It is a classic combination of a Knoevenagel condensation and ester aminolysis typical for many heterocyclic syntheses. The type-II
Graphical Abstract
Figure 1: Icilio Guareschi (1847–1918). (Source: Annali della Reale Accademia di Agricoltura di Torino 1919, ...
Scheme 1: Vitamin B6 (pyridoxine, 1), gabapentin (2), and thymol (3).
Figure 2: Baliatico (Nursing) by Francesco Scaramuzza (275 cm × 214 cm, Parma, Complesso Museale della Pilott...
Figure 3: Schiff’s fictitious report on the foundation of the Gazzetta Chimica Italiana (Image reproduced fro...
Scheme 2: Reaction of thymol (3) with chloroform under the basic conditions of the Guareschi–Lustgarten react...
Figure 4: The chemistry building of Turin University in a historical picture. Note, that one of the “mysterio...
Scheme 3: Triacetonamine (6) and the related compounds phorone (7), α-eucaine (8), and tropinone (9).
Scheme 4: Taxonomy of the Guareschi pyridone syntheses.
Scheme 5: The catalytic cycle of the “1897 reaction”.
Scheme 6: Resonance forms of the radical 10.
Figure 5: The wet chamber used by Guareschi to restore parchments (Gorrini, G. L'incendio della R. Biblioteca...
Figure 6: The Guareschi mask. (Servizio Chimico Militare. L'opera di Icilio Guareschi precursore della masche...
Figure 7: Guareschi’s bust at the Dipartimento di Scienza e Tecnologia del Farmaco of Turin University. Permi...
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
- to fragrance chemists. This section investigates the aldol reaction as this is a vital C–C and C=C bond forming tool within this class of reactions. Other sequences such as the Knoevenagel and Darzens condensation, however, will also be considered as part of the evaluation. The condensation of
- of 1,2-aminoalcohol 110 (90% yield, anti/syn 7:3, 78% ee). At the end of the Henry reaction an in-line plug of silica gel removes the catalyst before the second reduction step to prevent issues of chelation and palladium deactivation. Knoevenagel condensations are also of considerable interest to the
- processing volumes and short reaction times make the reactions quite suitable for continuous production via a flow system. Needless to say, the first example of Knoevenagel condensations in flow comes from Venturello et al. back in 1989 [154]. The authors exploited a glass column filled with 10 grams of
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.
Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues
- Rashmi Singh,
- Tomas Horsten,
- Rashmi Prakash,
- Swapan Dey and
- Wim Dehaen
Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79
- presence of a catalytic amount of piperidine afforded pyridopsoralen 22 in 46% yield. Analogously, pyridopsoralen 23 was prepared from 16 by Knoevenagel condensation with diethyl malonate and subsequent lactonization with 62% yield (Scheme 4) [13]. To the best of our understanding, the scaffolds 21–23 are
Graphical Abstract
Figure 1: Biologically relevant 2-oxydibenzofuran-containing structures 1–6.
Figure 2: Representative bioactive structures containing benzofuro-fused pyridine analogues 7–9.
Scheme 1: Strategy for metal-free access to benzofuropyridine 13.
Scheme 2: Electrophilic aromatic substitution of 6-hydroxybenzofuro[2,3-b]pyridine (13).
Scheme 3: Synthesis of isomeric oxazole-fused derivatives.
Scheme 4: Fused derivatives from 16.
Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects
- Shivani Gulati,
- Stephy Elza John and
- Nagula Shankaraiah
Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71
- -MCRs and their mechanistic insights over the past decade and shed light on its advantage over the conventional approach. Keywords: cycloaddition; Knoevenagel condensation; Michael addition; microwave; multicomponent reactions; Introduction Recently, organic chemists are focussed to develop
- moderate to good yields under catalyst-free conditions (Scheme 1). A rationale of mechanism proposed the transformation via a Knoevenagel condensation between aldehyde and a molecule of 6 affording A. The concurrent condensation of ammonium acetate with another molecule of 6 led to the formation of an
- the involvement of an elementary formation of Knoevenagel adduct A from the reaction between the aldehyde and 11. This adduct undergoes an intermolecular Michael addition to naphthylamine resulting in the formation of B. A subsequent intramolecular nucleophilic cyclization leads C followed by
Graphical Abstract
Figure 1: Marketed drugs with acridine moiety.
Scheme 1: Synthesis of 4-arylacridinediones.
Scheme 2: Proposed mechanism for acridinedione synthesis.
Scheme 3: Synthesis of tetrahydrodibenzoacridinones.
Scheme 4: Synthesis of naphthoacridines.
Scheme 5: Plausible mechanism for naphthoacridines.
Figure 2: Benzoazepines based potent molecules.
Scheme 6: Synthesis of azepinone.
Scheme 7: Proposed mechanism for azepinone formation.
Scheme 8: Synthesis of benzoazulenen-1-one derivatives.
Scheme 9: Proposed mechanism for benzoazulene-1-one synthesis.
Figure 3: Indole-containing pharmacologically active molecules.
Scheme 10: Synthesis of functionalized indoles.
Scheme 11: Plausible mechanism for the synthesis of functionalized indoles.
Scheme 12: Synthesis of spirooxindoles.
Scheme 13: Synthesis of substituted spirooxindoles.
Scheme 14: Plausible mechanism for the synthesis of substituted spirooxindoles.
Scheme 15: Synthesis of pyrrolidinyl spirooxindoles.
Scheme 16: Proposed mechanism for pyrrolidinyl spirooxindoles.
Figure 4: Pyran-containing biologically active molecules.
Scheme 17: Synthesis of functionalized benzopyrans.
Scheme 18: Plausible mechanism for synthesis of benzopyran.
Scheme 19: Synthesis of indoline-spiro-fused pyran derivatives.
Scheme 20: Proposed mechanism for indoline-spiro-fused pyran.
Scheme 21: Synthesis of substituted naphthopyrans.
Figure 5: Marketed drugs with pyrrole ring.
Scheme 22: Synthesis of tetra-substituted pyrroles.
Scheme 23: Mechanism for silica-supported PPA-SiO2-catalyzed pyrrole synthesis.
Scheme 24: Synthesis of pyrrolo[1,10]-phenanthrolines.
Scheme 25: Proposed mechanism for pyrrolo[1,10]-phenanthrolines.
Figure 6: Marketed drugs and molecules containing pyrimidine and pyrimidinones skeletons.
Scheme 26: MWA-MCR pyrimidinone synthesis.
Scheme 27: Two proposed mechanisms for pyrimidinone synthesis.
Scheme 28: MWA multicomponent synthesis of dihydropyrimidinones.
Scheme 29: Proposed mechanism for dihydropyrimidinones.
Figure 7: Biologically active fused pyrimidines.
Scheme 30: MWA- MCR for the synthesis of pyrrolo[2,3-d]pyrimidines.
Scheme 31: Proposed mechanism for pyrrolo[2,3-d]pyrimidines.
Scheme 32: Synthesis of substituted pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 33: Probable pathway for pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 34: Synthesis of pyridopyrimidines.
Scheme 35: Plausible mechanism for the synthesis of pyridopyrimidines.
Scheme 36: Synthesis of dihydropyridopyrimidine and dihydropyrazolopyridine.
Scheme 37: Proposed mechanism for the formation of dihydropyridopyrimidine.
Scheme 38: Synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 39: Plausible mechanism for the synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 40: Synthesis of decorated imidazopyrimidines.
Scheme 41: Proposed mechanism for imidazopyrimidine synthesis.
Figure 8: Pharmacologically active molecules containing purine bases.
Scheme 42: Synthesis of aza-adenines.
Scheme 43: Synthesis of 5-aza-7-deazapurines.
Scheme 44: Proposed mechanism for deazapurines synthesis.
Figure 9: Biologically active molecules containing pyridine moiety.
Scheme 45: Synthesis of steroidal pyridines.
Scheme 46: Proposed mechanism for steroidal pyridine.
Scheme 47: Synthesis of N-alkylated 2-pyridones.
Scheme 48: Two possible mechanisms for pyridone synthesis.
Scheme 49: Synthesis of pyridone derivatives.
Scheme 50: Postulated mechanism for synthesis of pyridone.
Figure 10: Biologically active fused pyridines.
Scheme 51: Benzimidazole-imidazo[1,2-a]pyridines synthesis.
Scheme 52: Mechanism for the synthesis of benzimidazole-imidazo[1,2-a]pyridines.
Scheme 53: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives.
Scheme 54: Proposed mechanism for spiro-pyridines.
Scheme 55: Functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 56: Mechanism postulated for macrocyclane-fused pyrazolo[3,4-b]pyridine.
Scheme 57: Generation of pyrazolo[3,4-b]pyridines.
Scheme 58: Proposed mechanism for the synthesis of pyrazolo[3,4-b]pyridines.
Scheme 59: Proposed mechanism for the synthesis of azepinoindole.
Figure 11: Pharmaceutically important molecules with quinoline moiety.
Scheme 60: Povarov-mediated quinoline synthesis.
Scheme 61: Proposed mechanism for Povarov reaction.
Scheme 62: Synthesis of pyrazoloquinoline.
Scheme 63: Plausible mechanism for pyrazoloquinoline synthesis.
Figure 12: Quinazolinones as pharmacologically significant scaffolds.
Scheme 64: Four-component reaction for dihydroquinazolinone.
Scheme 65: Proposed mechanism for dihydroquinazolinones.
Scheme 66: Synthesis purine quinazolinone and PI3K-δ inhibitor.
Scheme 67: Synthesis of fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 68: Proposed mechanism for fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 69: On-water reaction for synthesis of thiazoloquinazolinone.
Scheme 70: Proposed mechanism for the thiazoloquinazolinone synthesis.
Scheme 71: β-Cyclodextrin-mediated synthesis of indoloquinazolinediones.
Scheme 72: Proposed mechanism for synthesis of indoloquinazolinediones.
Figure 13: Triazoles-containing marketted drugs and pharmacologically active molecules.
Scheme 73: Cu(I) DAPTA-catalyzed 1,2,3-triazole formation.
Scheme 74: Mechanism for Cu(I) DAPTA-catalyzed triazole formation.
Scheme 75: Synthesis of β-hydroxy-1,2,3-triazole.
Scheme 76: Proposed mechanism for synthesis of β-hydroxy-1,2,3-triazoles.
Scheme 77: Synthesis of bis-1,2,4-triazoles.
Scheme 78: Proposed mechanism for bis-1,2,4-triazoles synthesis.
Figure 14: Thiazole containing drugs.
Scheme 79: Synthesis of a substituted thiazole ring.
Scheme 80: Synthesis of pyrazolothiazoles.
Figure 15: Chromene containing drugs.
Scheme 81: Magnetic nanocatalyst-mediated aminochromene synthesis.
Scheme 82: Proposed mechanism for the synthesis of chromenes.
Using multiple self-sorting for switching functions in discrete multicomponent systems
- Amit Ghosh and
- Michael Schmittel
Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233
- activity in a Knoevenagel addition reaction. At the same time, the click reaction remained shut down (ON-1, OFF-2). In sum, the three interdependent states SelfSORT-I to III regulated two different reaction outcomes and an OFF state. In biology, motor proteins carry out essential tasks by walking along
Graphical Abstract
Figure 1: Some selected self-sorting outcomes and their qualitative and quantitative assessment.
Figure 2: Illustration of an integrative vs a non-integrative self-sorting.
Figure 3: The pH-driven four-component 2-fold completive self-sorting based on host–guest chemistry.
Figure 4: (a) The monomers 5 and 6 and their H-bonding array. (b) The hydrogen-bonded octameric and tetrameri...
Figure 5: (a) Two new Zn4L6-type cages. (b) The encapsulation of C70 induced distinct reconstitutions within ...
Figure 6: The formation of octahedral cages (a) [Co6(10')4]12+ and (b) [Co6(11')4]12+. (c) The 2-fold complet...
Figure 7: Exchange of Ag+ for Au+ ions in poly-NHC ligand-based organometallic assemblies.
Figure 8: The reversible interconversion between the three-component rectangle [Cu4(16)2(17)2]4+ and the four...
Figure 9: a) Chemical structure of the monomer 20 with its quadruple hydrogen-bonding array and a metal-affin...
Figure 10: Communication between the nanoswitch 21 and the supramolecular assemblies [Cu4(22)2(24)2]4+ or [Cu6(...
Figure 11: (a) The chemical structures and cartoon representations of the switch 25, the decks 26 and 27, and ...
Figure 12: Double self-sorting leads to a catalytic machinery in SelfSORT-II, in which the 46 kHz-nanorotor ac...
Figure 13: ON/OFF control of a networked catalytic catch–release system.
Figure 14: A multicomponent information system for the reversible reconfiguration of switchable dual catalysis....
Figure 15: a) The chemically fueled cascaded ion translocation, monitored by distinct emission colors. b) Work...
Figure 16: Cyclic metallosupramolecular transformations.
Figure 17: Fully reversible multiple-state rearrangement of metallosupramolecular architectures depending upon...
Figure 18: The selective encapsulation and sequential release of guests in a self-sorted mixture of three tetr...
Figure 19: Two catalytic reactions are alternately controlled by a toggle nanoswitch.
Figure 20: A biped walking along a tetrahedral track and unfolding its catalytic action. Adapted with permissi...
Figure 21: A three state supramolecular AND logic gate.
Figure 22: Four-component nanorotor and its catalytic activity. Adapted with permission from (Biswas, P. K.; S...
Synthesis and characterization of S,N-heterotetracenes
- Astrid Vogt,
- Florian Henne,
- Christoph Wetzel,
- Elena Mena-Osteritz and
- Peter Bäuerle
Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214
- -thienylcarbaldehyde (23), which was put to reaction with methyl 2-azidoactetate [46] and sodium methanolate in a Knoevenagel condensation to give azide 24 in 81% yield. A solution of the azide 24 was added to boiling toluene and cyclization to thienopyrrole 25 occurred via a nitrene intermediate in nearly
Graphical Abstract
Figure 1: Heteroacenes: tetrathienoacene (TTA), S,N-heteroacenes SN4, SN4', and SN4''.
Scheme 1: Synthesis of fused S,N-heterotetracene SN4 9 starting from thieno[3,2-b]thiophene (1).
Scheme 2: Synthesis of parent H-SN4 13 via the azide route.
Scheme 3: Synthesis of tetracyclic H-SN4 13 via the Cadogan route.
Scheme 4: Synthesis of tetracyclic indole derivative 19 via the Cadogan route.
Scheme 5: Synthesis of hexacyclic heteroacene SN4' 22 via the Cadogan route.
Scheme 6: Synthesis of heterotetracene SN4'' 33 via the azide and Buchwald–Hartwig amination route.
Figure 2: UV–vis absorption spectra of TTA, Hex-SN4 9, Pr-SN4'' 33 and fluorescence spectrum of 33 in THF at ...
Figure 3: Energy diagram of the frontier molecular orbitals of heterotetracenes TTA, 9, 13, 19, 22, and 33, a...
Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation
- Kumar Godugu,
- Venkata Divya Sri Yadala,
- Mohammad Khaja Mohinuddin Pinjari,
- Trivikram Reddy Gundala,
- Lakshmi Reddy Sanapareddy and
- Chinna Gangi Reddy Nallagondu
Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156
- . Further, dolomite is used as a heterogeneous green catalyst in very few organic transformations, such as Knoevenagel, Michael–Henry, and transesterification reactions [73][74]. To the best of our knowledge, there are no reports on the NDL-catalyzed synthesis of aforesaid N-heterocycles under ultrasonic
Graphical Abstract
Figure 1: The benzimidazoles I–IV, dihydropyrimidinones/-thiones V–VIII, and 2-amino-4-aryl-3,5-dicarbonitril...
Scheme 1: NDL-catalyzed synthesis of i) 1,2-disubstituted benzimidazoles 3, ii) dihydropyrimidinones/-thiones ...
Figure 2: XRD pattern of the NDL catalyst.
Figure 3: FTIR spectrum of the NDL catalyst.
Figure 4: Raman spectrum of the NDL catalyst.
Figure 5: SEM images of the NDL catalyst.
Figure 6: EDAX analysis of the NDL catalyst.
Scheme 2: Unexpected formation of the bisimine I, 3h, from o-phenylenediamine (1) and salicylaldehyde (2h).
Figure 7: 1H NMR spectrum of 2,2'-((1E,1'E)-(1,2-phenylenebis(azanylylidene))bis (methanylylidene))diphenol (...
Figure 8: XRD pattern of a) the fresh NDL catalyst; b) the recovered NDL catalyst after the 7th cycle of the ...
Heterogeneous photocatalysis in flow chemical reactors
- Christopher G. Thomson,
- Ai-Lan Lee and
- Filipe Vilela
Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125
Graphical Abstract
Figure 1: A) Bar chart of the publications per year for the topics “Photocatalysis” (49,662 instances) and “P...
Figure 2: A) Professor Giacomo Ciamician and Dr. Paolo Silber on their roof laboratory at the University of B...
Scheme 1: PRC trifluoromethylation of N-methylpyrrole (1) using hazardous gaseous CF3I safely in a flow react...
Figure 3: A) Unit cells of the three most common crystal structures of TiO2: rutile, brookite, and anatase. R...
Figure 4: Illustration of the key semiconductor photocatalysis events: 1) A photon with a frequency exceeding...
Figure 5: Photocatalytic splitting of water by oxygen vacancies on a TiO2(110) surface. Reprinted with permis...
Figure 6: Proposed adsorption modes of A) benzene, B) chlorobenzene, C) toluene, D) phenol, E) anisole, and F...
Figure 7: Structures of the sulfonate-containing organic dyes RB5 (3) and MX-5B (4) and the adsorption isothe...
Figure 8: Idealised triclinic unit cell of a g-C3N4 type polymer, displaying possible hopping transport scena...
Figure 9: Idealised structure of a perfect g-C3N4 sheet. The central unit highlighted in red represents one t...
Figure 10: Timeline of the key processes of charge transport following the photoexcitation of g-C3N4, leading ...
Scheme 2: Photocatalytic bifunctionalisation of heteroarenes using mpg-C3N4, with the selected examples 5 and ...
Figure 11: A) Structure of four linear conjugated polymer photocatalysts for hydrogen evolution, displaying th...
Figure 12: Graphical representation of the common methods used to immobilise molecular photocatalysts (PC) ont...
Figure 13: Wireless light emitter-supported TiO2 (TiO2@WLE) HPCat spheres powered by resonant inductive coupli...
Figure 14: Graphical representation of zinc–perylene diimide (Zn-PDI) supramolecular assembly photocatalysis v...
Scheme 3: Upconversion of NIR photons to the UV frequency by NaYF4:Yb,Tm nanocrystals sequentially coated wit...
Figure 15: Types of reactors employed in heterogeneous photocatalysis in flow. A) Fixed bed reactors and the s...
Figure 16: Electrochemical potential of common semiconductor, transition metal, and organic dye-based photocat...
Scheme 4: Possible mechanisms of an immobilised molecular photoredox catalyst by oxidative or reductive quenc...
Scheme 5: Scheme of the CMB-C3N4 photocatalytic decarboxylative fluorination of aryloxyacetic acids, with the...
Scheme 6: Scheme of the g-C3N4 photocatalytic desilylative coupling reaction in flow and proposed mechanism [208].
Scheme 7: Proposed mechanism of the radical cyclisation of unsaturated alkyl 2-bromo-1,3-dicarbonyl compounds...
Scheme 8: N-alkylation of benzylamine and schematic of the TiO2-coated microfluidic device [213].
Scheme 9: Proposed mechanism of the Pt@TiO2 photocatalytic deaminitive cyclisation of ʟ-lysine (23) to ʟ-pipe...
Scheme 10: A) Proposed mechanism for the photocatalytic oxidation of phenylboronic acid (24). B) Photos and SE...
Scheme 11: Proposed mechanism for the DA-CMP3 photocatalytic aza-Henry reaction performed in a continuous flow...
Scheme 12: Proposed mechanism for the formation of the cyclic product 32 by TiO2-NC HPCats in a slurry flow re...
Scheme 13: Reaction scheme for the photocatalytic synthesis of homo and hetero disulfides in flow and scope of...
Scheme 14: Reaction scheme for the MoOx/TiO2 HPCat oxidation of cyclohexane (34) to benzene. The graph shows t...
Scheme 15: Proposed mechanism of the TiO2 HPC heteroarene C–H functionalisation via aryl radicals generated fr...
Scheme 16: Scheme of the oxidative coupling of benzylamines with the HOTT-HATN HPCat and selected examples of ...
Scheme 17: Photocatalysis oxidation of benzyl alcohol (40) to benzaldehyde (41) in a microflow reactor coated ...
Figure 17: Mechanisms of Dexter and Forster energy transfer.
Scheme 18: Continuous flow process for the isomerisation of alkenes with an ionic liquid-immobilised photocata...
Scheme 19: Singlet oxygen synthetic step in the total synthesis of canataxpropellane [265].
Scheme 20: Scheme and proposed mechanism of the singlet oxygen photosensitisation by CMP_X HPCats, with the st...
Scheme 21: Structures of CMP HPCat materials applied by Vilela and co-workers for the singlet oxygen photosens...
Scheme 22: Polyvinylchloride resin-supported TDCPP photosensitisers applied for singlet oxygen photosensitisat...
Scheme 23: Structure of the ionically immobilised TPP photosensitiser on amberlyst-15 ion exchange resins (TPP...
Scheme 24: Photosensitised singlet oxygen oxidation of citronellol (46) in scCO2, with automatic phase separat...
Scheme 25: Schematic of PS-Est-BDP-Cl2 being applied for singlet oxygen photosensitisation in flow. A) Pseudo-...
Scheme 26: Reaction scheme of the singlet oxygen oxidation of furoic acid (54) using a 3D-printed microfluidic...
Figure 18: A) Photocatalytic bactericidal mechanism by ROS oxidative cleavage of membrane lipids (R = H, amino...
Figure 19: A) Suggested mechanisms for the aqueous pollutant degradation by TiO2 in a slurry flow reactor [284-287]. B)...
Figure 20: Schematic of the flow system used for the degradation of aqueous oxytetracycline (56) solutions [215]. M...
Scheme 27: Degradation of a salicylic acid (57) solution by a coupled solar photoelectro-Fenton (SPEF) process...
Figure 21: A) Schematic flow diagram using the TiO2-coated NETmix microfluidic device for an efficient mass tr...
Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole
- Carlos H. Escalante,
- Eder I. Martínez-Mora,
- Carlos Espinoza-Hicks,
- Alejandro A. Camacho-Dávila,
- Fernando R. Ramos-Morales,
- Francisco Delgado and
- Joaquín Tamariz
Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113
- with benzyl bromides 14b and 14d, respectively (Scheme 5). Pyrrole 16c was synthesized by Knoevenagel reaction of 13a with dimethyl malonate [42]. The Pd(0)-catalyzed cyclization of 8k and 8l required a temperature of 140 °C, but provided pyrrolo[2,1-a]isoindoles 18d and 18e, respectively, in good
Graphical Abstract
Figure 1: Fused aza-hetero polycyclic frames and natural pyrrolizine- and isoindole-containing alkaloids.
Scheme 1: Synthetic approaches for the preparation of pyrrolo-fused aza-hetero polycyclic frames.
Scheme 2: Preparation of 1,2-substituted pyrroles 8a–f and 8i,j.
Scheme 3: Diels–Alder cycloadditions of pyrroles 8a–j and 16a–b with maleimides 7b–c.
Figure 2: Structures of 9m (a) and 10m (b) as determined by single-crystal X-ray diffraction crystallography ...
Scheme 4: Pd(0)-catalyzed intramolecular Heck cross-coupling reaction of 2-vinylpyrroles 8c,d and 8g.
Scheme 5: Synthesis of 2-vinylpyrroles 8k,l and their Pd(0)-catalyzed intramolecular Heck cross-coupling to p...
Scheme 6: Diastereoselective Diels–Alder reaction of pyrrolo[2,1-a]isoindole 18a with 7c.
Scheme 7: Synthetic approach to the fused aza-heterocyclic pentacycle 12.
Figure 3: M06-2X/6-31+G(d,p) Optimized geometry for each of the SCs (a and d), TSs (b and e) and ADs (c and f...
Figure 4: M06-2X/6-31+G(d,p) Optimized geometry for each of the TSs of the Diels–Alder reactions of dienes 8b...
Figure 5: M06-2X/6-31+G(d,p) Optimized geometry of the endo SCs (a) and TSs (b) for the Diels–Alder reaction ...
Fluorinated phenylalanines: synthesis and pharmaceutical applications
- Laila F. Awad and
- Mohammed Salah Ayoup
Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91
- improve protein stability, natural hydrocarbon amino acids were replaced with Pff 77a. The effect of enhanced protein stability upon this replacement is referred as to ‘fluoro-stabilization effect’ [56]. 1.7. Knoevenagel condensation of methyl isocyanoacetate Three isomers of fluorinated phenylalanines
- 53a,b and 81 were synthesized by Knoevenagel condensation of methyl isocyanoacetate (79) and the corresponding fluorinated benzaldehyde derivatives 50a,b, and m-fluorobenzaldehyde (78) as electrophiles in the presence of catalytic amounts of Cu(I) and base. The cinnamate derivatives 80a–c obtained
- -borono-2-[18F]FPhe. Synthesis of protected 4-[18F]FPhe via arylstannane derivatives. Synthesis of FPhe derivatives via intermediate imine formation. Synthesis of FPhe derivatives via Knoevenagel condensation. Synthesis of FPhe derivatives 88a,b from aspartic acid derivatives. Synthesis of 2-(2
Graphical Abstract
Figure 1: Categories I–V of fluorinated phenylalanines.
Scheme 1: Synthesis of fluorinated phenylalanines via Jackson’s method.
Scheme 2: Synthesis of all-cis-tetrafluorocyclohexylphenylalanines.
Scheme 3: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine (nPt: neopentyl, TCE: trichloroethyl).
Scheme 4: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine derivatives 17.
Scheme 5: Synthesis of fluorinated Phe analogues from Cbz-protected aminomalonates.
Scheme 6: Synthesis of tetrafluorophenylalanine analogues via the 3-methyl-4-imidazolidinone auxiliary 25.
Scheme 7: Synthesis of tetrafluoro-Phe derivatives via chiral auxiliary 31.
Scheme 8: Synthesis of 2,5-difluoro-Phe and 2,4,5-trifluoro-Phe via Schöllkopf reagent 34.
Scheme 9: Synthesis of 2-fluoro- and 2,6-difluoro Fmoc-Phe derivatives starting from chiral auxiliary 39.
Scheme 10: Synthesis of 2-[18F]FPhe via chiral auxiliary 43.
Scheme 11: Synthesis of FPhe 49a via photooxidative cyanation.
Scheme 12: Synthesis of FPhe derivatives via Erlenmeyer azalactone synthesis.
Scheme 13: Synthesis of (R)- and (S)-2,5-difluoro Phe via the azalactone method.
Scheme 14: Synthesis of 3-bromo-4-fluoro-(S)-Phe (65).
Scheme 15: Synthesis of [18F]FPhe via radiofluorination of phenylalanine with [18F]F2 or [18F]AcOF.
Scheme 16: Synthesis of 4-borono-2-[18F]FPhe.
Scheme 17: Synthesis of protected 4-[18F]FPhe via arylstannane derivatives.
Scheme 18: Synthesis of FPhe derivatives via intermediate imine formation.
Scheme 19: Synthesis of FPhe derivatives via Knoevenagel condensation.
Scheme 20: Synthesis of FPhe derivatives 88a,b from aspartic acid derivatives.
Scheme 21: Synthesis of 2-(2-fluoroethyl)phenylalanine derivatives 93 and 95.
Scheme 22: Synthesis of FPhe derivatives via Zn2+ complexes.
Scheme 23: Synthesis of FPhe derivatives via Ni2+ complexes.
Scheme 24: Synthesis of 3,4,5-trifluorophenylalanine hydrochloride (109).
Scheme 25: Synthesis of FPhe derivatives via phenylalanine aminomutase (PAM).
Scheme 26: Synthesis of (R)-2,5-difluorophenylalanine 115.
Scheme 27: Synthesis of β-fluorophenylalanine via 2-amino-1,3-diol derivatives.
Scheme 28: Synthesis of β-fluorophenylalanine derivatives via the oxazolidinone chiral auxiliary 122.
Scheme 29: Synthesis of β-fluorophenylalanine from pyruvate hemiketal 130.
Scheme 30: Synthesis of β-fluorophenylalanine (136) via fluorination of β-hydroxyphenylalanine (137).
Scheme 31: Synthesis of β-fluorophenylalanine from aziridine derivatives.
Scheme 32: Synthesis of β-fluorophenylalanine 136 via direct fluorination of pyruvate esters.
Scheme 33: Synthesis of β-fluorophenylalanine via fluorination of ethyl 3-phenylpyruvate enol using DAST.
Scheme 34: Synthesis of β-fluorophenylalanine derivatives using photosensitizer TCB.
Scheme 35: Synthesis of β-fluorophenylalanine derivatives using Selectflour and dibenzosuberenone.
Scheme 36: Synthesis of protected β-fluorophenylalanine via aziridinium intermediate 150.
Scheme 37: Synthesis of β-fluorophenylalanine derivatives via fluorination of α-hydroxy-β-aminophenylalanine d...
Scheme 38: Synthesis of β-fluorophenylalanine derivatives from α- or β-hydroxy esters 152a and 155.
Scheme 39: Synthesis of a series of β-fluoro-Phe derivatives via Pd-catalyzed direct fluorination of β-methyle...
Scheme 40: Synthesis of series of β-fluorinated Phe derivatives using quinoline-based ligand 162 in the Pd-cat...
Scheme 41: Synthesis of β,β-difluorophenylalanine derivatives from 2,2-difluoroacetaldehyde derivatives 164a,b....
Scheme 42: Synthesis of β,β-difluorophenylalanine derivatives via an imine chiral auxiliary.
Scheme 43: Synthesis of α-fluorophenylalanine derivatives via direct fluorination of protected Phe 174.
Figure 2: Structures of PET radiotracers of 18FPhe derivatives.
Figure 3: Structures of melfufen (179) and melphalan (180) anticancer drugs.
Figure 4: Structure of gastrazole (JB95008, 181), a CCK2 receptor antagonist.
Figure 5: Dual CCK1/CCK2 antagonist 182.
Figure 6: Structure of sitagliptin (183), an antidiabetic drug.
Figure 7: Structure of retaglpitin (184) and antidiabetic drug.
Figure 8: Structure of evogliptin (185), an antidiabetic drug.
Figure 9: Structure of LY2497282 (186) a DPP-4 inhibitor for the treatment of type II diabetes.
Figure 10: Structure of ulimorelin (187).
Figure 11: Structure of GLP1R (188).
Figure 12: Structures of Nav1.7 blockers 189 and 190.
Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates
- Phil M. Pithan,
- Sören Steup and
- Heiko Ihmels
Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82
- Knoevenagel reaction from the readily available 5-formyl-substituted spirooxazine 1b. Due to the introduction of the electron-accepting quinolizinium(ethenyl) substituent, the spirooxazines 3a and 3b were photoinert towards the electrocyclic ring opening, thus constituting one of the rare cases of
Graphical Abstract
Scheme 1: Photo- or cation-induced ring-opening reaction of spirooxazine 1aSO; Mn+ = Pb2+, La3+, Eu3+, Tb3+ [17].
Scheme 2: Synthesis of the spirooxazine–quinolizinium conjugates 3a and 3b.
Figure 1: Colors of the solutions resulting from the addition of metal ions (c = 50 µM) to derivative 3a (c =...
Figure 2: Spectrophotometric titration of 3a (A) and 3b (B) (c = 20 µM) with Cu(BF4)2 (c = 2.44 mM) in MeCN. ...
Figure 3: Absorption (A) and fluorescence spectrum (B) of 3a in MeCN (c = 5 µM) in the absence (black) and in...
Figure 4: Emission colors of solutions resulting from the addition of metal ions (c = 50 µM) to derivative 3a...
Scheme 3: Cu2+-induced formation of the oxazole derivatives 4a and 4b.
Figure 5: 1H NMR spectra (600 MHz, 6.4–9.4 ppm) of 3a (c = 2.0 mM) in the absence (A) and in the presence (B–...
Figure 6: Spectral changes of 3a (c = 20 µM) upon the addition of Cu2+ (A) and Fe3+ (B) (cM+ = 60 µM) in MeCN...
Scheme 4: Proposed mechanism for the formation of the oxazole derivatives 4a and 4b (cf. Scheme 3); Mn+ = Cu2+, Fe3+,...
Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds
- Vuyisa Mzozoyana,
- Fanie R. van Heerden and
- Craig Grimmer
Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22
- , numerous methods for the synthesis of these compounds have been developed, examples are the Pechmann condensation [10][11], Stille coupling reaction [12], Knoevenagel condensation [13], Heck coupling reaction [14], Kostanecki reaction, Baylis–Hillman reaction [15], Michael reaction [16], Suzuki–Miyaura
Graphical Abstract
Scheme 1: Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin (6).
Figure 1: 1H NMR spectra for the “aromatic” region of coumarin 6; comparison of 1H spectrum and 1H-{19F} spec...
Figure 2: 13C NMR spectra for coumarin 5 and 6; showing the splitting of the signal corresponding to C5.
Figure 3: 19F,1H-HOESY NMR spectrum for coumarin 6 illustrating two through-space interactions.
Figure 4: Superposition of single-crystal X-ray structure (red) and DFT-optimized structure (green); RMSD 0.3...
Figure 5: DFT-optimized structure for coumarin (6).
Figure 6: Plots of relative energy (black trace, no units), interatomic distance F–H5 (red trace, Å), interat...
Figure 7: Short contacts within the single-crystal X-ray structure of coumarin 6.
Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation
- Sambasivarao Kotha,
- Gaddamedi Sreevani,
- Lilya U. Dzhemileva,
- Milyausha M. Yunusbaeva,
- Usein M. Dzhemilev and
- Vladimir A. D’yakonov
Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269
- synthesis of thiazolidinedione derivatives is refluxing chloroacetic acid (2) with thiourea (1), followed by a Knoevenagel condensation with an aldehyde (Scheme 1) [25]. Results and Discussion Limited reports are available dealing with the synthesis of spiro derivatives of thiazolidine-2,4-diones [26][27
Graphical Abstract
Scheme 1: Conventional method of synthesis of thiazolidine-2,4-dione derivatives.
Scheme 2: [2 + 2 + 2] Cyclotrimerization of N-methylthiazolidinedione.
Scheme 3: Unexpected product 5b obtained in the attempted NH-protection of thiazolidinedione with (Boc)2O.
Figure 1: Comparison of 13C NMR values of 9 and 5b.
Scheme 4: [2 + 2 + 2] Cyclotrimerization of dipropargylthiazolidinediones with propargyl halides.
Scheme 5: Formation of sultine 13 from compound 8b followed by DA reaction.
Scheme 6: Dipropargylation of 2,4-thiazolidinedione derivatives.
Scheme 7: [2 + 2 + 2] Cycloaddition in the presence of Wilkinson’s catalyst.
Scheme 8: N-Ester derivative 18 hydrolysis to N-acid derivative 22.
Scheme 9: Synthesis of triazolo derivative 24 via click reaction.
Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries
- Xiao Xie,
- Michela Zuffo,
- Marie-Paule Teulade-Fichou and
- Anton Granzhan
Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183
- Knoevenagel condensation of the corresponding heterocyclic precursors I1–5 and I7–16 with 1.5 molar equivalents (per styryl unit) of aromatic aldehydes ArCHO (Scheme 1A,B). The synthesis of precursors I3–5 and I15 is presented in Scheme 2 and detailed in Supporting Information File 1. Dyes 6a and 19a, which
- , B) General synthesis of A) distyryl and B) mono-styryl dyes via Knoevenagel condensation route. C) Synthesis of the dye 6a. D) Synthesis of the dye 19a. Synthesis of I3–5 and I15. Positions of maxima and intensity of long-wavelength absorption bands of dyes in MeOH and K-100 aqueous buffer.a Nucleic
Graphical Abstract
Figure 1: Some di- and mono-styryl dyes previously reported as fluorescent “light-up” probes for G4-DNA and R...
Figure 2: Design of a library of di- and mono-styryl dyes. Counter-ions are omitted for the sake of clarity.
Scheme 1: A, B) General synthesis of A) distyryl and B) mono-styryl dyes via Knoevenagel condensation route. ...
Scheme 2: Synthesis of I3–5 and I15.
Figure 3: Representative absorption spectra of distyryl dyes: A) 1d, B) 1ð, C) 1f, D) 1u, E) 10a and F) 12a i...
Figure 4: Representative absorption spectra of the distyryl dyes (c = 10 µM in MeOH) demonstrating the influe...
Figure 5: Heat map of the relative emission intensity enhancement (I/I0) of styryl dyes and thioflavin T (ThT...
Figure 6: Analysis of the light-up response matrix of the dyes. The average light-up factor of each dye with ...
Figure 7: PC1 vs PC2 plot obtained from the principal component analysis of the light-up data matrix for all ...
Figure 8: Dual-dye conformational analysis of an extended panel of 33 DNA oligonucleotides. This is performed...
Figure 9: Selected probes featuring high fluorimetric response towards G4 structures.
Figure 10: Photographs of solutions of A) distyryl dyes 1p and 1u; B) mono-styryl dyes 17a and 18a, in the abs...
A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes
- Joza Schmitt and
- Scott T. Handy
Beilstein J. Org. Chem. 2019, 15, 1781–1785, doi:10.3762/bjoc.15.171
- of new aurones by way of the common Knoevenagel condensation approach, mostly varying in the benzylidene portion. To explore benzofuranone variations using this method, different benzofuranone starting materials are required. Although not likely to be the most colorful, we elected for simplicity’s
Graphical Abstract
Figure 1: Aurone ring system and numbering.
Figure 2: Aurone syntheses.
Figure 3: UV–vis spectral comparisons in acetonitrile.
Figure 4: Fabric dying and photobleaching. The top two sets show dyed fabric strips with premordant, simultan...
Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells
- Quentin Huaulmé,
- Cyril Aumaitre,
- Outi Vilhelmiina Kontkanen,
- David Beljonne,
- Alexandra Sutter,
- Gilles Ulrich,
- Renaud Demadrille and
- Nicolas Leclerc
Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169
- corresponding dipyrromethenium chloride, which was then converted into its BODIPY analogue 2 through complexation by BF3·OEt2 in basic media. Regioselective introduction of distyryl substituents is achieved via Knoevenagel-type condensation in the presence of piperidine using aldehyde derivatives 3 and 4 whose
- Supporting Information File 1), whose spectra feature characteristic constant couplings of 16.2 and 16.1 Hz. It is worth mentioning that the fluorine substitution was performed on the boron center after introduction of the styryl residues, introduction prior to the Knoevenagel reaction is known to impede it
- dehalogenation side-product. Finally, a Knoevenagel condensation in the presence of cyanoacetic acid and piperidine is performed to lead to the targeted compounds BOD-TTPA-alk and BOD-TTPA. 3. Optical properties The optical properties of compounds BOD-TTPA-alk and BOD-TTPA were first evaluated in diluted (≈10−6
Graphical Abstract
Figure 1: Molecular structures of the two target compounds BOD-TTPA-alk and BOD-TTPA, and the chemical struct...
Figure 2: a) Geometrical optimization of four representative BODIPY-based materials for DSSCs application. b)...
Figure 3: Predicted absorption spectra of the four dyes.
Figure 4: Synthetic scheme of the selected materials. a) hydroxylamine hydrochloride, NaHCO3, DMSO, 60 °C the...
Figure 5: a) Absorption spectra of compounds BOD-TTPA-alk and BOD-TTPA (THF, ≈10−6 M, 25 °C). b) Absorbance s...
Figure 6: J(V) curves of the best performing DSSCs devices sensitized with compounds BOD-TTPA-alk (blue trace...
Figure 7: Photovoltaic parameters evolution with the increasing concentration of tBP in the electrolyte.
