Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• Abstract We confirm the previously revised stereochemistry of spiroviolene by X-ray crystallographically characterizing a hydrazone derivative of 9-oxospiroviolane, which is synthesized by hydroboration/oxidation of spiroviolene followed by oxidation of the resultant hydroxy group. An unexpected thermal

• stereochemistry by X-ray crystallography using a hydrazone derivative of 1. Results and Discussion Our work commenced with the heterologous production of spiroviolene by E. coli using a recently developed isopentenol utilization pathway for the efficient supply of two C5 precursors for terpene biosynthesis

• organoborane intermediate, which was formed by elimination of BH3 from IM-16 followed by re-addition of BH3 from the opposite β-face to the proposed C8–C9 double bond intermediate, would also be possible. To further advance the intermediate to crystalline hydrazone product (Scheme 2B), we have found that both

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• that binds to the OH groups instead of the pyrimidine nitrogen atoms. The group of Aprahamian has developed hydrazone-based molecular switches that can be controlled by photochemical or chemical stimuli such as pH [27]. They reported mesogenic tweezers-like compound 5 composed of a hydrazone switch

• substituted by two mesogenic cholesteryl groups (Figure 6) [28]. Due to strong hydrogen bonding between the pyridyl moiety and the N–H of the hydrazone, tweezers 5 predominantly exist in the closed E-form in a CD2Cl2 solution (E/Z-isomer ratio of 91:9). Upon protonation of the pyridyl group, a complete

• host–guest complexation, it can also only bind to coordinating guests (terpyridine, bipyridine) due to the proximity of the coordination sphere with the binding pocket. Tweezers 11 with NDI arms and an extended pyridine-hydrazone-pyridine-hydrazone-pyridine switchable unit have thus been developed

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• -hexafluorobut-2-ene and an oxalamide hydrazone [17]. In the present study, we investigated the reactions of commercially available butenes 1a,b with halogens, as well as subsequent transformations of the resulting compounds. Results and Discussion In 1952 Haszeldine found that the reaction of bromine with (E

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes (Scheme 1). Results and Discussion To initiate our studies, 3-ethylbenzo[d]isothiazole 1,1-dioxide (1a) and α-halogeno hydrazone 2a were selected as the model substrates. Our aim was to explore the possibility of enamine–iminium tautomerism of N-sulfonyl

• reaction of 3-ethylbenzo[d]isothiazole 1,1-dioxide (1a, 1.0 g) and α-halogeno hydrazone 2a (2.1 g) afforded 3aa (2.0 g) in 91% yield (Scheme 3) [34]. Finally, we focused on the transformation of 3aa. When 3aa was treated with KOH and H2O in methanol at 60 °C, the 3,3-disubsitituted-1,2-benzothiazin-4-one

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• the starting material. This compound was prepared according to the described regioselective method [42] based on the reaction of malononitrile with triethyl orthoformate followed by subsequent treatment of the obtained dinitrile 2 with benzaldehyde methyl hydrazone in benzene, conc. aqueous HCl in

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• studied and reported biological properties of this class [2][18][19][20]. Angelova and co-workers, for example, reported the ability of sulfonyl hydrazones and 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives to inhibit the growth of several bacterial strains by interfering with their metabolism or

• ][35][36]. Our lead compound INHHQ (or 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone) has been successfully tested in the prevention of short- and long-term memory deficits in a mice model of sporadic AD [33]. Additionally, INHHQ decreases copper-mediated production of reactive oxygen

• proved the promising anti-PD and metallophoric effect, especially towards intracellularly relevant copper(I) ions, of X1INH (1-methyl-1H-imidazole-2-carboxaldehyde isonicotinoyl hydrazone) [32]. This year, we evaluated the effects of the presence of three methoxy substituents in an N-acylhydrazone

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• of different templates [64][65][66][67][68][69]. The use of pyridyl-acyl hydrazone rotaxanes in the construction of light-responsive interlocked materials is envisioned as a promising approach to circumvent both issues, since these interlocked molecules are obtained in high yields (over 80%) and show

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• and the base the initial direct C–H activation of the ylide 12 gives the copper pyridinium ylide 15. The latter reacts with the diazo compound formed through reaction of hydrazone 13 with the base to give the copper–carbene species 16. Then, the intermediate 16 undergoes a Cu–carbene migratory

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• experimentally. In this work, we present our results on the computational study of the transannular reaction illustrated in Scheme 1 for several nonsymmetric tether combinations between the hydrazone and double bond moieties leading to a sort of condensed cyclohexanes (series a–f) and other bicyclic systems

• common reaction conditions. The reaction has been defined by Houk and Rueping as a (3+ + 2) monopolar cycloaddition [33] pointing out the protonated state of the imino nitrogen of the hydrazone in contrast to the well-known 1,3-dipolar cycloaddition of azomethine imines in which the terminal nitrogen has

• a negative charge. While both reacting C–N–N systems fulfil the requirements to give a cycloaddition with an alkene; which are (i) electron density default on the carbon atom and (ii) an electron density excess on the nitrogen atom; the overall positive charge of the hydrazone moiety forces a role

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• , the reaction of the isocoumarin 3ia with p-toluenesulfonyl hydrazide proceeded smoothly to deliver hydrazone 5 in 66% yield (Scheme 4b, right). Of note, oxime and hydrazone compounds are versatile synthetic building blocks, which have been widely applied in transition-metal-catalyzed cross-coupling

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• hydrazone groups. The use of N-TAAD derivatives as potential ligands and receptors was showcased through forming boron chelates and host–guest complexes with water and simple alcohols. Keywords: azaadamantanes; cyclotrimerization; hydrazones; inclusion complexes; molecular recognition; Introduction

• cyclization of the corresponding tris-hydrazones, as well as the assembly of unsymmetrically substituted TAADs having both amino(amido) and hydroxy groups at bridge nitrogen atoms (2N,1O-TAADs and 1N,2O-TAADs) via a hitherto unknown co-trimerization of oxime and hydrazone units [35]. Also, structural studies

• -oxime form 1). Previous experimental and computational data evidence that cyclotrimerization of hydrazone groups proceeds more readily compared to oximes [18]. Hence, hydrazones 3 were expected to cyclize to corresponding TAADs 4 with high efficiency. On the other hand, cyclization of mixed oxime

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• for the fullerenes to pass through. However, the capsule 5 is sensitive to mechanochemical stress due to the porosity, conformational rigidity, and due to the presence of hydrazone and/or disulfide moieties that act as mechanophores. Therefore, during ball milling, 5 gets partially disintegrated at

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• show the presence of the product 2a, but it showed the presence of 91% of the starting hydrazone (Table 1, entry 8). To evaluate the effect of the base, K3PO4 or Cs2CO3 was used, but the yield was lower than 60% (Table 1, entries 9 and 10). The influence of the catalyst/ligand molar ratio (Table 1

• (Scheme 1). In the 1H NMR spectrum of the crude reaction mixture, only 3% of the desired product 2a was detected, together with an undefined amount of the intermediate hydrazone 1a (Figures S5 and S6, Supporting Information File 1). Next, the most effective conditions as determined from the optimization

• signal at 8.21 ppm and the hydrazone triplet at 6.89 ppm, respectively, vs the integral value of the calibration compound singlet at 6.46 ppm (see Supporting Information File 1). HRMS spectra were acquired on a hybrid high-resolution and high-accuracy microTof (Q-TOF, Bruker Scientific) spectrometer with

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

• formation of hydrazone 28. As one equivalent of water is formed in this condensation process, which is detrimental for the subsequent Shapiro reaction, water is continuously removed by in-line separation of the reaction mixture using a PTFE-membrane separator. The organic layer is then mixed with a solution

• of n-butyllithium in hexanes to initiate the Shapiro reaction of hydrazone 28 proceeding supposedly via dilithiated intermediate 29. As the nitrogen produced in the reaction increases the volume of the reaction mixture and therefore is drastically shortening the residence time, a cooled glass column

• ) via selective hydrogenation to enone 27, condensation to hydrazone 28 and subsequent Shapiro reaction. DMPS = dimethylpolysilane-modified platinum catalyst; Ts = tosyl. Selective hydrogenation of alkyne 31 to “leaf alcohol” 32 employing a solid-supported palladium catalyst. A) Synthesis of jasmonal

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• resorcinol (74), generating the intermediate 75 which underwent intramolecular condensation, to furnish 76. In method B, menadione (10) was treated with 3-methyl-2-benzothiazolinone hydrazone (77) in alkaline medium forming diazocompounds as addition products, which spontaneously lose N2 to form product 78

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• setup. The initial setup consisted of a heated glass column (i.d. 7 mm, length 7 cm), packed with K2CO3, through which a solution of acyl hydrazone and iodine were passed. It was anticipated that the larger excess of K2CO3 present in the packed bed reactor (when compared to batch mode), in addition to

• in a slight decrease in yield, and an increase in decomposition was observed with an increase in temperature despite the short residence times (entries 6 and 7, Table 2). The lack of solubility of the hydrazone substrates limited options with regards to variation in reaction solvent, with adequate

• ]pentane (BCP) building blocks [36], we investigated their use in the oxadiazole-forming reaction. The BCP acid chloride 5 was synthesised from [1.1.1]propellane (3) via the photochemical reaction with isopropyl 2-chloro-2-oxoacetate (Scheme 4). The corresponding BCP acyl hydrazone was then obtained

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• ], disulfide- [13], thioether- [14][15][16][17][18][19][20], triazole- [21][22], oxime- [23] and hydrazone formation [24] as well as multicomponent reactions such as the Ugi- or Petasis reaction [25][26][27][28][29][30][31][32]. The content of helicity can moreover be changed by the introduction of a photo

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• alkyl radical with formaldehyde hydrazone, which resulted in hydrazide 74 that could afford formal hydromethylated compounds 75 after the extrusion of nitrogen and sulfinic acid (Scheme 28) [95]. The hydrazone was generated in situ due its instability, and a simple exchange of the solvent from THF to

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• cholesterol 44 and histamine 45. Scientific literature [97] reports a three-step continuous synthesis of [6,6]-tert-butyl phenyl-C61-butyrate 47 based on tert-butyl 4-benzoylbutyrate hydrazone in a microstructured flow reactor that eliminates the need for stage-by-stage isolation of intermediate products and

• illustrated in Scheme 20 [105]. A methanofullerene variety 69 with a pincer ligand containing a disulfidoaryl moiety was synthesized from 3,5-bis(phenylsulfidomethyl)benzaldehyde hydrazone. In the presence of [Pd(CH3CN)4](BF4)2, the latter gives the corresponding palladium complex 70 (Scheme 21) [106]. A

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• 2014 and 2017, respectively (Scheme 2B and Scheme 2C). The synthesis of (−)-crinipellin A (15) began with the treatment of hydrazone 42 with sodium hydride under reflux to produce the tetraquinane 46 in 87% yield [30] (Scheme 2B). The authors suggested that the diazo compound 43 formed undergoes an

• upon refluxing in toluene and subsequent epoxidation afforded 51 [32], which was converted to (−)-crinipelline A (15) in two steps. The synthesis of waihoensene (16) commenced with the conversion of aldehyde 52a to the corresponding hydrazone 52b, which was treated with sodium hydride under reflux to

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• ketyl radicals 113•, which, in the presence of a hydrazone, cyclises to give N-centred radical 114•. Subsequent HAT from HEH furnishes aza-pinacol product 115 in good yields and excellent enantioselectivities (14 examples, up to 98:2 er). Since this initial report, a variety of processes have been

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• the chemistry of the sumanene and its congeners, quite recently the same group has also prepared sumanene-based carbene 60 starting from monosumanenone 38 by reacting it with hydrazine hydrate to provide the corresponding hydrazone 58 which on further oxidation with MnO2 followed by irradiation using

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• ], antiprotozoal [47], antidiabetic [48], and antitubercular [49]. Relevant is the role of the hydrazone moiety as antitumor agent [50][51][52][53]. An interesting example reported by Ferreira demonstrates that the chemical derivatization of the indole alkaloids dregamine and tabernaemontanine to yield new

• hydrazone derivatives enhances the apoptosis inducing activity [54]. Another particularly useful feature of the hydrazone group is related by its high tendency to provide solid derivatives. The target of the here reported strategy is to recover as pure products the desired functionalized DHBERs to evaluate

• -bromohydrazones 1a–n (Scheme 2). All the hydrazono-DHBERs 2a–n directly precipitate as pure products in the reaction medium with yields ranging from poor to good (30–83%). Probably the low affinity of the iminium and hydrazone groups of compounds 2a–n with a medium-low polarity solvent such as DCM causes their

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• borylated, the choice of a suitable pyridine-hydrazone ligand [42] allowed to perform the borylation reactions at 55 °C, showing complete regioselectivity in the C–H borylation. This procedure afforded the dyes 16–19 in good to very good yields of 51–83% (Scheme 3). The introduction of the Bpin moiety

Ultrafast processes triggered by one- and two-photon excitation of a photochromic and luminescent hydrazone

• Alessandro Iagatti,
• Baihao Shao,
• Alberto Credi,
• Barbara Ventura,
• Ivan Aprahamian and
• Mariangela Di Donato

Beilstein J. Org. Chem. 2019, 15, 2438–2446, doi:10.3762/bjoc.15.236

• , belonging to the hydrazone family. The outstanding properties of this molecule, involving fluorescence toggling, bistability, high isomerization quantum yield and non-negligible two-photon absorption cross section, make it very promising for numerous applications. Here we show that the light induced Z/E

• absorption cross-section of the molecule. Keywords: hydrazone; molecular switch; pump-probe spectroscopy; time-resolved fluorescence; Introduction Molecular switches are systems that are able to rapidly respond to an external stimulus, which can be of chemical or physical nature, through a variation of

• issue, considering that most of the commonly used switches absorb in the UV spectral window, as well as low solubility in water. Among the variety of newly developed systems, a promising class of switches is based on the hydrazone molecular motif [27]. These systems present a variety of interesting