Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• ). Correspondingly, [1,3]thiazolo[4,5-b]pyridine 5 remained unchanged upon application of methods that had been successfully utilized in the hydrogenation of 1,3-benzothiazoles, involving diboronic acid or hydrazine hydrate as key reagents [21] in protic solvents at an elevated temperature (Table 1, entries 3 and 4

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

• the two metallic centers in the tweezers cavity in a bridging mode. For the heterometallic Zn/Au system, luminescence quenching was observed in the closed state. The pyridine-hydrazine-pyridine unit has been extensively studied by Lehn and co-workers in coordination-responsive supramolecular polymers

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• of 3,4-dimethoxybenzaldehyde with 5-substituted 2-picoline derivatives in low to moderate yields ranging from 13% (2f) to 65% (2a) (Scheme 2). The amino-substituted derivative 2b was synthesized by reduction of the nitrostyrylpyridine 2a with Pd/C and hydrazine in 83% yield. Subsequent acylation of

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

• -membered macrocycle, 2,10-dimethyl-2,8,10,16-tetrahydrodipyrazolo[3,4-e:3',4'-l][1,2,4,8,9,11]hexaazacyclotetradecine-4,12-diamine, by the reaction with excess hydrazine under various conditions was studied in detail. The reaction proceeded through the initial formation of 4-imino-2-methyl-2,4-dihydro-5H

• -2-methyl-2,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine described by Baraldi et al. [41] using the reaction of 3-[(ethoxymethylene)amino]-1-methyl-1H-pyrazole-4-carbonitrile with excess hydrazine hydrate in EtOH under reflux. However, a pyrazole-fused 1,2,4,8,9,11-hexaazamacrocycle was unexpectedly

• the detailed studies of the hydrazine-promoted transformation of 3-[(ethoxymethylene)amino]-1-methyl-1H-pyrazole-4-carbonitrile (4) or 4-imino-2-methyl-2,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine (8) into 2,10-dimethyl-2,8,10,16-tetrahydrodipyrazolo[3,4-e:3',4'-l][1,2,4,8,9,11

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• , Perm State University, 15 Bukireva st., Perm 614990, Russia 10.3762/bjoc.19.87 Abstract It was shown that the reaction of 2-cyanothioacetamides with hydrazine involves both cyano- and thioamide groups, and 3,5-diaminopyrazoles are formed. In the reaction of 2-cyano-3-(dimethylamino)-N,N-dimethylprop-2

• -enethioamides with hydrazine and its derivatives, the interaction proceeds with the participation of cyano- and enamine groups, not affecting the thiocarbamoyl group, and leads to the formation of 4-thiocarbamoylpyrazoles. A synthesis method has been developed and a series of 1-substituted-4-thiocarbamoyl

• potential of such compounds. The most common method for obtaining 3,5-disubstituted pyrazoles is the cyclocondensation of 1,3-bielectrophilic reagents with hydrazine, which acts as a 1,2-dinucleophile [15][16]. It is worthy to note that a small number of methods for the synthesis of 3,5-diaminopyrazoles are

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• . The RCM reaction was performed in the presence of Grubbs first generation catalyst in DCM, affording 2-(4-methylphenyl)benzothiophene-fused 2-(benzyloxy)-3,4,5,6,7,10-hexahydro-1,2-oxaphosphecine 2-oxide 31 in 70% yield. After hydrazine reduction and Pd-catalyzed hydrogenolysis, it was converted into

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

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

• (129) followed by the reduction [61] of the aldehyde gave the corresponding benzyl alcohol 131 in 76% yield. Deacetylation in the presence of hydrazine [62] followed by intramolecular thioetherification led to the macrocycle 133. Finally, the oxidation of the obtained thioether to the corresponding

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• after the reaction is complete. Hydrazine hydrate can also be used as a hydrogen source instead of gaseous H2, as described by Jicsinszky and Iványi [14], although this method is not so widespread and has limited potential for a large-scale synthesis. As a special feature, the protocol published by

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• [10] synthesized a series of carbohydrazide derivatives through reaction of 2-methylbenzofuran-2-quinoline-4-carboxylate with hydrazine hydrate in refluxing ethanol (Figure 1b). All compounds showed higher activity against Staphylococcus aureus than ampicillin and the optimal MIC value was 0.064 mg/mL

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

• , treatment of adamantanes 4a and 4b with excess hydrazine (100–200 equiv) upon heating did not lead to any conversion. Also attempts to deprotect Boc-derivatives 4c, 4e, 6a, and 8a with trifluoroacetic acid or hydrochloric acid (in water or dioxane) were not successful and led to complex mixtures of products

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• 1,3-dicarbonyl compounds using a catalytic amount of hydrazine hydrate without solvent in a short reaction time (10 min) [14]. Reactions of 2-aminothiophenols with β-keto esters and β-diketones under microwave irradiation (MWI) using basic alumina as heterogeneous catalyst without solvent afforded 4H

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• hydrazine and sodium nitrite. Further derivation of 11f led to compounds 11g–l which include different substitution patterns for R2. The tetrazolo[1,5-a]quinoxaline products 11a–l were obtained in yields of 36% to 81% for all steps (see Supporting Information File 1 for the entire scheme). Starting from 11a

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• the prediction of the producer of natural products with the functional groups of interest, leading to a higher rate of hits. We recently exploited genome mining targeting hydrazine synthetase and the generation of inorganic hydrazine N2H4 in acid hydrolysate as an indicator of N–N bond-containing

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• pentachloride to generate ethyl (2-(chlorocarbonyl)phenyl)phosphonochloridate (200), which reacted with amine and hydrazine derivatives in the presence of triethylamine, affording the desired 1-ethoxy-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides 201 but the yields were not reported (Scheme 31) [56]. Two ethyl

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• starting bromoacetate at rt or on heating to 50 °C. The further substitution reactions, during peptoid elongation, were carried out in a 1:1 MeOH/H2O mixture (1.25 M) at 60 °C, using three equivalents of the Boc-protected hydrazine reagent. These distinct substitution conditions, together with standard

• substitution step, due to the close polarities of the products and starting hydrazine reagent. So we turned our attention to a fragment-based coupling approach for synthesizing the hexamer peptoid 6. Thus, several coupling methods were evaluated, initially starting from the hydrazine and acid monomers 1a and

• to the mixed anhydride activating method using isobutyl chloroformate (IBCF) in the presence of N-methylmorpholine (NMM) at 0 °C in DMF for 10 min, followed by the addition of hydrazine 1a [43][44]. The best results were obtained with two equivalents of preformed mixed anhydride, pure dimer 2d being

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• to the hydrazine derivative 4, followed by a Fischer indole synthesis with ethyl 4-oxopiperidine-1-carboxylate (5) provided tetracyclic compound 6. Its reduction with sodium cyanoborohydride in trifluoroacetic acid (TFA) to cis-indoline derivative (±)-7, followed by N-methylation [(±)-8] and

• chiral chromatography. Later, alternate syntheses of lumateperone were described, also by the researchers of the originator company [8][9][10] (Scheme 2). The reaction of (2-bromophenyl)hydrazine (12) with 4-piperidone monohydrate hydrochloride (13) gave pyrido[4,3-b]indole congener 14, which was reduced

• transformed into N-nitroso derivative 32 by treatment with sodium nitrite in aqueous acetic acid. The next two steps, reduction of the nitroso group to hydrazine derivative 33 and its coupling with piperidinone 5 in a Fischer indole synthesis, were telescoped to form tetracyclic product 34. The latter was

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

• ]. Examining a broad range of hydrazides in the condensation reaction with menadione, Bouhadir and co-workers reported the synthesis of various menadione acylhydrazone derivatives [126]. In this work, various acylhydrazides prepared by reaction of hydrazine hydrate with different esters were reacted with

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

• following treatment of acid 5 with hydrazine hydrate, followed by hydrazone formation with the corresponding aldehyde. When subjected to the reaction conditions, oxadiazoles 2k and 2l were obtained in low yield over this multi-step sequence. While unsuitable for large scale reactions, this methodology may

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• attempted starting from the known dioctyloxydinitro derivative DN (Scheme 1) [33]. Reduction of the nitro groups with hydrazine, in the presence of catalytic amounts of Pd/C (10 mol %) led to the corresponding diamino intermediate. This latter could be subsequently reacted with the desired phosphino benzoic

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• two steps by following known protocols [36]. Fischer indole reaction of this precursor with 1-benzyl-1-phenylhydrazine in acetic acid gave 1a in 55% yield (Scheme 6). The protecting group on the hydrazine moiety is necessary in this case, otherwise amide bond formation would occur after the initial

• methyl 4-(2-nitrophenyl)-3-oxobutanoate [36] and 1-benzyl-1-(4-bromophenyl)hydrazine in the presence of sodium acetate and sulfuric acid in glacial acetic acid affording 1b in 55% yield. It is of note that the treatment of 1b with hydrogen in the presence of Pd/C as catalyst led not only to reduction of

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• -ium-2-ide (7a) was synthesised at room temperature by treating methyl acrylate, hydrazine hydrate and benzaldehyde in a yield of 67%. On treating the synthesised azomethine imine 7a (1.2 mM) and 2-substituted-1H-indenes 6b and 6c (1 mM) in toluene at 70 °C affords 8a and 8b via [3 + 2] cycloaddition

• ; found, 174.0706 Synthesis of 1-benzylidene-3-oxopyrazolidin-1-ium-2-ide (7a) A methyl acrylate (0.0225 mol) solution was added drop-wise to the solution of hydrazine monohydrate (0.0205 mol) in 20 mL of ethanol. This solution was stirred at 78 °C for 4 hours; the solvent was evaporated and the residue

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• were removed with hydrazine under reflux and the free amino groups were acetylated to obtain the fully N-acetylated COS [255]. Control over the pattern of N-acetylation was for the first time achieved using two monosaccharides bearing an azido (N3) and a N-Phth moieties as precursors of the free and N