Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• , copper(II) species A. The latter reacts with the hydrazone to the trifluoromethylated aminyl radical intermediate C which is stabilized by the lone pair of the adjacent nitrogen atom, and (2-iodobenzoyloxy)copper(II) chloride (B). Finally, intermediate C is oxidized by copper(II) to restore the hydrazone

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• compounds using labeling reagents having a hydrazide group. A hydrophilic fluorescence group Alexa Fluor 568 and polyethylene glycol-linked biotin were introduced using hydrazone formation reaction between the aldehyde group of the glutaryl-Glc linker and the hydrazide group of the labeling reagent. In

Is the tungsten(IV) complex (NEt₄)₂[WO(mnt)₂] a functional analogue of acetylene hydratase?

• Matthias Schreyer and
• Lukas Hintermann

Beilstein J. Org. Chem. 2017, 13, 2332–2339, doi:10.3762/bjoc.13.230

• , with no acetaldehyde hydrazone 9 present (Scheme 4a)! Retrospectively, this result could have been expected, since acetone is present as stabilizer in commercial acetylene pressure bottles [37]. The original report on 1-mediated acetylene hydration did not consider (and thus did not exclude) the

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• between two alternative directions affording derivatives of partially hydrogenated indole or benzofurane. The control of this regioselectivity is efficiently governed by steric effects at the hydrazone moiety of the ketazinone reagent. Keywords: nitrogen heterocycles; oxygen heterocycles; pyrrolediones

• spirocyclization via conversion of 1,3-diones 8 into mono-hydrazones. Indeed, while mono-imines of these ketones strongly prefer keto-enamine tautomeric form 13 over enol-imine form 14 (Scheme 4) [44][45], the corresponding hydrazones have been reported to favor enol-hydrazone tautomer 16 (Scheme 4) [46][47][48

• ]. Keeping this in mind we decided to test the reactivity of ketazinones 17 that were obtained via condensation of cyclohexanediones 8 with hydrazone of acetophenone. We anticipated the formation of spirolactones 20 in this process, resulting from intramolecular transesterification involving the enol moiety

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia

• Artem N. Semakin,
• Aleksandr O. Kokuev,
• Yulia V. Nelyubina,
• Alexey Yu. Sukhorukov,
• Petr A. Zhmurov,
• Sema L. Ioffe and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2016, 12, 2471–2477, doi:10.3762/bjoc.12.241

• -tetraazaadamantane derivative was demonstrated. Keywords: azoalkenes; α-halogen hydrazones; heterocage compounds; hydrazone ligands; Michael addition; Introduction Hydrazones are extensively used as key structural units in the design of various functional molecular and supramolecular architectures [1][2][3][4][5

• ][6][7][8][9][10][11][12][13][14][15][16][17]. The hydrazone group is a chemically stable, easily assembled motif with prospective coordination properties, which can be tuned by substitution at the carbon and nitrogen atoms. Furthermore, a reversible E/Z-isomerism of the C=N bond allows controllable

• modulation of the molecular geometry, for example through coordination with metal cations, hydrogen bond formation or irradiation. These unique structural features of the hydrazone fragment have been successfully exploited in the design of various molecular switches, fluorophores and machines. Bis- and

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• aromatic aldehyde, similarly to the synthesis of compounds 1a–c. The reaction of aromatic aldehydes with imidazotriazinethiones without phenyl substituents in acidic media results in hydrazone formation and triazine-ring contraction [45]. The reaction of compounds 1d–f with sarcosine and isatins 3a,d,f

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• properties. This expectation is supported by the biological activity of azomethine derivatives of pyrene-1-carboxaldehyde. They show antimicrobial action, e.g., 1-phenytoinylacetic acid hydrazone of pyrene-1-carboxaldehyde demonstrated a moderate antimicrobial activity towards Escherichia coli and

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• reaction of sulfonylhydrazone of acetone-d6 [34][35]. Thus condensation of trisylhydrazine with acetone-d6 (99.8% D) gave the expected hydrazone 14 in 55% yield. To our delight, upon treatment with two equivalents of n-BuLi and warming to 0 °C, the trisylhydrazone 14 afforded the vinyllithium reagent 15

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• major product, with the minor product coming from the predicted second-most preferred conformation 84. The May group also showed that the cascade reaction could be initiated from hydrazones. In the course of this work, it was discovered that NaOSiMe3 was a superior base for hydrazone to diazo conversion

• (i.e., 86 to 87, Scheme 20) [89]. Surprisingly, no reaction was observed in the absence of the Rh catalyst, suggesting that it may be involved in the transformation of the hydrazone to 87. While the intermediate alkyl carbene 88 could potentially undergo a 1,2-hydride shift to give the alkene 90 in a

• substrates with a 3-atom tether to the hydrazone and sterically large substituents allowed the isolation and characterization of mechanistic intermediates from the cascade reaction when it was conducted at 90 °C (Scheme 21). This confirmed some prior proposals of a cyclopropene intermediate [92], as the

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• would coordinate and direct the hydrazone 28 to the Re face of the esters 26 in order to afford the absolute configuration found in the final products 29 of this process (Figure 7). Another example of the bifunctional action of the indanol-based thiourea 4 was reported by Sibi’s group. There, 100 mol

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• ) precursors by forming dynamic hydrazone bonds [79] (Scheme 16). This dynamic covalent chemistry approach allowed for quick synthesis of viologen/TTF-alternating polymers. Driven by the intramolecular donor–acceptor interaction between the TTF and viologen units, the polymers folded into pleated conformations

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• Japp–Klingemann reaction was used to transform the diazonium salt in the presence of ethyl 2-methyl-3-oxobutyrate into the respective hydrazone. The indole was formed from the treatment of the hydrazone with polyphosphoric acid. The last heterocyclic ring was formed by an intramolecular reaction of the

Tetrathiafulvalene-based azine ligands for anion and metal cation coordination

• Awatef Ayadi,
• Aziz El Alamy,
• Olivier Alévêque,
• Magali Allain,
• Nabil Zouari,
• Mohammed Bouachrine and
• Abdelkrim El-Ghayoury

Beilstein J. Org. Chem. 2015, 11, 1379–1391, doi:10.3762/bjoc.11.149

• dinitrophenyl ring coplanar with the hydrazone unit and also by an intramolecular short contact S4···N1 (2.824(6) Å) that makes the TTF unit and the pyridine ring coplanar. In the solid state, the packing arrangement in L1 is characterized by the self-assembly between the TTF donor unit and the dinitrophenyl

• that occurs in ligand L2 leading to a resonance structure that involves the C=N hydrazone bond as it can be seen in (Figure S2, Supporting Information File 1). Theoretical calculations Theoretical calculations based on density functional theory (DFT) methods have been performed with the Gaussian 09

• two reversible oxidations at E1ox = +0.20 V, E2ox = +0.70 V and E1ox = +0.25 V, E2ox = +0.70 V vs Ag/Ag+, respectively) that are cathodically shifted when compared to the ones of 1 and 2 indicating that the pyridine-hydrazone group is less electron deficient than the corresponding

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• carbonyl groups can be exploited for carbohydrate functionalization [15][16] by reductive amination, oxime or hydrazone formation to yield suitably functionalized saccharides (Figure 1). Given the relevance of L-fucose in mammal oligosaccharides, α-L-(2-aminoethyl) fucoside [17] and α-O-L

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• -dioxan-5-one as a starting material and employed the SAMP-/RAMP-hydrazone methodology to obtain an overall yield of 18–21% [19][20]. Due to the formation of the opposite configuration at C-4′ and a lengthy synthetic route this strategy is not suitable for the total synthesis of trachycladine A and B

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• intermediate I (SNVin reaction). Thereby, a second equivalent of hydrazine captures hydrochloric acid. The amino group of the hydrazone then attacks the electrophilic C-2 position of the thiazolidinone. This way a threefold substituted 1H-pyrazole is formed (intermediate II) under ring opening of the

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• , and to deepen the understanding of how molecular structure influences the characteristics of self-assembly. Previous amphiphile libraries have been prepared using a thiol–yne reaction [14] and an in situ hydrazone formation between aldehyde tails and hydrazide head groups [15] in order to study gene

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• pharmacokinetic properties than the peptide amino-PEGylated or the unmodified ricin. The same technique was applied to glucose oxidase (GOx), a glycosylated dimeric protein. In this case the hydrazone was further stabilized by reduction with cyanoborohydride to afford a bioconjugate with retention of its activity

Substrate dependent reaction channels of the Wolff–Kishner reduction reaction: A theoretical study

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 259–270, doi:10.3762/bjoc.10.21

• , H2N–NH2 and OH−(H2O)7. Here, ketones are acetone and acetophenone. While routes of the ketone → hydrazone → diimine are similar, those from the diimines are different. From the isopropyl diimine, the N2 extrusion and the C–H bond formation takes place concomitantly. The concomitance leads to the

• . From hydrazone, the hydrazone anion is formed, which was first suggested by Seibert [6][7]. From the anion, there are two routes (a) and (b). In (a), the proton is [1,3]-shifted to give an isomer anion, R1(R2)HC–N=N(−). In (b), a diimine intermediate R1(R2)HC–N=N–H is generated [6][7][8]. Both routes

• lead to a carbanion R1(R2)HC−. Protonation of the carbanion affords the product alkane. It is believed that the hydrazone anion is involved in the rate-determining step of the W-K reaction [9]. W-K reactions of hydrazones in aprotic solvents were investigated. Cram et al. obtained diphenylmethane H2C

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

A simple, enaminone-based approach to some bicyclic pyridazinium tetrafluoroborates

• František Josefík,
• Markéta Svobodová,
• Valerio Bertolasi and
• Petr Šimůnek

Beilstein J. Org. Chem. 2013, 9, 1463–1471, doi:10.3762/bjoc.9.166

• the 2nd step) and could catalyze an intramolecular attack of hydrazone NH nitrogen to the carbonyl group. After a subsequent loss of water, the molecule of pyridazinium salt 5 is formed. This hypothesis is supported by the fact that the use of an excess of sodium acetate led to significantly lower

Dipolar addition to cyclic vinyl sulfones leading to dual conformation tricycles

• Steven S. Y. Wong,
• Michael G. Brant,
• Christopher Barr,
• Allen G. Oliver and
• Jeremy E. Wulff

Beilstein J. Org. Chem. 2013, 9, 1419–1425, doi:10.3762/bjoc.9.159

• hydrazone function should disfavor formation of one of the new C–C bonds in 3. However, we speculate that the increase in electron density serves to disfavor dimerization more than 1,3-dipolar addition to 1a. As a result, more dipole remains in solution to undergo the desired coupling. The effect of this

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• which the α-substituent on the carbene carbon varies (see below). The α-phenyl analogue of β-lactam 5b has previously been prepared by carbene C–H insertion. In these reports, the base-promoted decomposition of a hydrazone and subsequent thermolysis of the diazo compound in, e.g., toluene under reflux

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118