Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• yields. Overall, five different components are incorporated in the reaction sequence, whereas acid chlorides, anhydrides, hydrazine, etc., could also be employed in the post-MCR cyclization [44]. The library of steroidal heterocycles was tested against oxidative stress and neuroinflammation due to

Insertion of [1.1.1]propellane into aromatic disulfides

• Robin M. Bär,
• Gregor Heinrich,
• Martin Nieger,
• Olaf Fuhr and
• Stefan Bräse

Beilstein J. Org. Chem. 2019, 15, 1172–1180, doi:10.3762/bjoc.15.114

• opening of 1 with Grignard reagents enables the synthesis of aryl and some alkyl-substituted BCPs and a subsequent cross-coupling reaction [5][18]. To provide bicyclo[1.1.1]pentylamine as a building block in large-scale syntheses, Bunker et al. developed a synthesis of hydrazine BCP via a manganese

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• . Nevertheless, most of the known multicomponent methods for the preparation of 2-oxindoles are based on the use of N-aryl amides as the main partner of the reagent pool. Wu et al. reacted N-(2-iodoaryl)acrylamides 113, DABCO·(SO2)2 (69, also known as DABSO) as a surrogate of sulfur dioxide and hydrazine 114 in

• a photoinduced, catalyst-free three-component reaction (Scheme 32) [110]. In this way, a variety of (2-oxoindolin-3-yl)methanesulfonohydrazides 115 with diverse substituents in the aromatic ring and hydrazine nitrogen, were prepared with moderate to good yields. This transformation may be explained

• hydrazine 114 and sulfur dioxide (Scheme 33). Rearrangement of the so-obtained intermediate 119, through radical 120, would provide oxindole 115. The same acrylamide 113 (R1 = H) has been recently used in another multicomponent synthesis along with CO (23) and benzodiazepine derivative 121 under palladium

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• trifluoroethanol (TFE) were stirred at room temperature for 24 h to obtain acylhydrazino 1,5-disubstituted tetrazoles 14 in 30–100% yield. Attempts of this reaction without the use of catalyst provided the desired products in low yields. Subsequently, a hydrazinolysis reaction with hydrazine monohydrate led to the

• corresponding hydrazides 15, which were used in a second hydrazine-Ugi-azide reaction with various ketones, to obtain the acylhydrazino bis(1,5-disubstituted tetrazoles) 16 in yields ranging from 45–70%. Consecutive Ugi reactions for the synthesis of substituted α-aminomethyl tetrazoles have also been described

• hydantoinimide derivatives by consecutive Ugi reactions [17]. Synthesis of tetrazole-ketopiperazines by two consecutive Ugi reactions [19]. Synthesis of acylhydrazino bis(1,5-disubstituted tetrazoles) through two hydrazine-Ugi-azide reactions and a hydrazinolysis step [22]. Synthesis of substituted α

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• hydrogen in intermediate B, it is possible to form chromonyl-malononitrile conjugated system C and to eliminate the phenylhydrazine. Intermediate C is a highly potent Michael acceptor that may allow the addition of hydrazine to the nitrile group resulting in intermediate D that after elimination of water

• -resolution mass spectra and were recorded on Mass-ESI-POS(FT-ICR-Qe) spectrometer. General procedure for the synthesis of compounds 1a–g In a 25 mL flask containing 3 mL ethanol, 3-formylchromone derivatives (1 mmol) and hydrazine derivatives (1 mmol) were added and the mixture stirred for three hours at

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• /hexane 20%), resulting in 1.18 g (80%) of the cis-Gabriel amine. The free amine was obtained by the hydrazinolysis of the cis-Gabriel amine (0.40 mmol), in methanol (0.50 mL) with hydrazine hydrate (25%, 0.20 mL), stirred at room temperature for 24 h. To the mixture was added HCl until pH ≈ 2, forming a

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• reacted with the 2-chloroacetylacetone ester derivative 7 providing hydrazine 8 [66]. Upon reaction of the chloro-ester 8 with phenylenediamine (9) in the presence of triethylamine the quinoxaline moiety was formed [67]. Oxidation of the hydrazine derivative 10 using hydrogen peroxide under an oxygen

• substitution at a chloro-substituted purine (15a,b) or thienopyrimidine (15c), respectively, and subsequent oxidation of the hydrazine moiety afforded the corresponding azobenzene derivatives 16a–d [71]. Synthesis of azobenzene-extended thiopurine derivatives To further tune the photochromism and compare the

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• oxidative C–C coupling of 2-nitrotoluenes (75–82% yield) and a reductive ring closure to form the diazocines (56–60% yield). The cyclization of the dinitro compound to the azo compound was improved in yield and reproducibility, by over-reduction to the hydrazine and reoxidation to the azo unit. In contrast

• using oxygen and the yields are increased from 65% to 95% in the parent system [30]. In a recent work we observed that the reduction of 2,2′-dinitrodibenzyl is difficult to stop at the azo stage because further reduction to the hydrazine is faster than the preceding cyclization reaction [27]. The

• hydrazine is quite stable towards reduction to the diamine, and can easily be reoxidized to the azo compound using CuCl2/O2. The yields are higher and more reproducible using the above reduction/reoxidation scheme. Previously applied reducing agents include Ba(OH)2/Zn [27], glucose/NaOH [20], Pb/NEt3/HCOOH

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• dialdehydes in fluorometric methods with regard to the analysis of amino acids and biogenic amines [1][2][3]. It is also used as a derivatization reagent in order to quantify hydrazine by gas chromatography coupled with a mass spectrometer detector [4]. Recently, it was adopted for the analysis of γ

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• -inflammatory [5], and antidiabetic agents [6]. The numerous known methods for the preparation of these compounds are generally based on multicomponent reactions of an aromatic aldehyde, a β-keto ester, a hydrazine and malononitrile [7]. In a similar reaction using a pyridinium ylide instead of malononitrile

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• starting material. The efficient conversion of the acetyl group into the corresponding silyl enol ether moiety delivered OX18 that may be used for further transformations. Alternatively, OX7 and phenyl hydrazine afforded the corresponding hydrazone OX19 in excellent yield that was further treated with

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• reagent (Ag2CO3 on Celite) [36][37]. The bromination and glycosylation reaction steps had to be performed in separate reactions. Therefore, we also investigated glycosylations with the respective imidate glycosyl donor 5. First, the cleavage of the anomeric acetyl group with hydrazine acetate was

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• DBU. The glycosylation reaction with 2-propanol using TMSOTf as Lewis acid at 0 ºC cleanly provided the β-isopropyl glycoside 13 in 65% yield. Interestingly, no α-anomer was detected in the reaction mixture. Finally, cleavage of the levulinyl group using hydrazine monohydrate in pyridine/acetic acid

• by using hydrazine monohydrate. Glycosylation with 1 afforded α/β-hexasaccharides 21α and 21β that could be separated by silica gel chromatography and characterized by NMR and mass spectrometry. Overall, our results indicate an unexpected loss of β-selectivity in glycosylations involving 4,6-di-O

• the glycosylation outcome, we decided to prepare 2,3-di-O-pivaloyl compound 26 with the GlcA protecting group distribution used in this study. For this purpose, donor 3 was glycosylated with 4-methoxyphenol and then treated with hydrazine monohydrate in a pyridine/acetic acid/CH2Cl2 mixture to afford

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• − C8H7Cl]+•, 138.0 (47), 117.0 (38), 103.0 (39), 91.0 (42) [C7H7]+, 77.0 (39) ) [C6H5]+. 3-(4-Methylphenyl)-6-phenyl-1,2,4,5-tetrazine (8) 7 (434 mg, 1.66 mmol, 1 equiv) was dissolved in 11 mL acetonitrile and hydrazine (98 µL, 1.66 mmol, 1 equiv) was added. The mixture was refluxed for 1 h behind a blast

• shield. Then potassium carbonate (412 mg, 3.31 mmol, 2 equiv) was added and the mixture was refluxed for another 24 h. Hydrazine (587 µL, 9.93 mmol, 6 equiv) was added again and the mixture was refluxed for 1 h. When the mixture had cooled to room temperature 10 mL of dichloromethane were added. The

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• ) [8]. Attanasi and co-workers described the synthesis of 4-(phenylseleno)pyrazol-3-ones through α-(phenylseleno)hydrazone reagents under basic conditions [9]. In 2015, Yu and co-workers described one example for the condensation reaction of α-oxo ketene dithioacetal with hydrazine hydrate to produce

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• vacuum. The resulting brown solid material was named as graphene oxide (GO, 142). In continuation, a solution of 5% sodium carbonate was added to the sonicated GO (142) in deionized water so that the pH was increased up to 9–10. 64% hydrazine hydrate was added as well. Then, the reaction mixture was

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• % hydrazine in DMF (3 × 2 mL) was added to the resin beads to deprotect N10-(trifluoroacetyl) protecting group by bubbling through resin beads for 10 min each. The resin beads were washed with DMF (3 × 3 mL) followed by isopropanol (3 × 3 mL). The secondary amine group generated in the pteroate core does not

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• -activated acylimidazole derivative was then converted to a β-ketoester containing a two carbon atom-elongated side chain than that of the starting material. A Knorr cyclization of the bifunctional 1,3-dicarbonyl compound with hydrazine and its monosubstituted derivatives in AcOH under microwave heating

• core, using both conventional heating and MW irradiation. The reaction conditions were optimized in order to improve the yields of the desired products and the influences of substituents of the hydrazine reagents investigated. The in vitro antiproliferative activities of the synthesized compounds were

• reacted with hydrazine hydrate (5a) in refluxing ethanol containing a catalytic amount of AcOH (Scheme 2). TLC monitoring of the reaction indicated full conversion of 4 within 4 h reaction time to afford a fairly polar product insoluble or only slightly soluble in all commonly used NMR solvents. However

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• of acylated Lys in position 4, the side chain of it was protected either with Dde (1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl) or with ivDde ((1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)isovaleryl). The previous one can be removed easier with 2% hydrazine in DMF (2 × 15 min) while ivDde needs

• higher hydrazine concentration (4% in DMF) and longer treatment (12 × 5 min) for the complete removal of the protecting group. However, ivDde is more stable in circumstances (2% DBU, 2% piperidine in DMF) used for the Fmoc removal. To avoid the unwanted Dde removal during the synthesis ivDde was applied

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• used as an intermediate in the manufacture of hydrazine using the Raschig process [12][13]. N-Alkyl-N-chloramines are equally unstable, yet have only been prepared in batch via reaction of a primary or secondary amine with Cl2 gas, N-chlorosuccinimide, chloramine-T or hypochlorite salts [14][15

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• nitrated according to literature procedures [33][34] affording the di or tetranitro derivatives 2a,b and 6a,b in good yields. The reduction of the nitro groups to the corresponding amines was successfully performed by hydrazine hydrate [35][36]. In this case, Ni on silica/alumina was used as the catalyst

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• ) condensation b) aromatic nucleophilic substitution reaction, c) deprotection and d) formation of lactate salt. Details of the same are given below: Condensation: Condensation takes place in a first reactor TR1 between the nitrile and hydrazine at high temperature and under pressure. Here, the nitrile was

• dissolved in a THF and hydrazine was dissolved in a mixture of solvents such as methanol, acetone, and water. The nitrile was pumped using pump P1 and hydrazine was pumped through P2 into the tubular reactor TR1 maintained at a temperature of 130 °C at residence time of 60 minutes to obtain the pyrazole

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• -ketonitrile in the presence of a hydrazine [1][2][3][4][19][20][21][22][23][24][25][26][27][28][29], with Rao et al. [31] and Bagley et al. [32] reporting microwave-assisted protocols, the former requiring an acid catalyst. In order to conduct a solvent screen we chose β-ketonitrile 1a as a model substrate

• and reacted it with hydrazine, employing a constant temperature of 150 °C and a reaction time of 5 min. Results from the solvent screen can be found in Table 1, with high isolated yields of the product 5-aminopyrazole 2a in all cases. As expected, a significant improvement in reaction time was

• reaction conditions were chosen to match the already developed microwave-assisted synthesis of the 5-aminopyrazoles. A solution of the β-ketonitrile in methanol was treated with hydrazine and heated to 150 °C under microwave irradiation for 5 min. The β-ketoester and acetic acid were then simply added to

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• ” surrogate, and the products depicted in Scheme 2 may be deprotected to yield aniline derivatives. In a specific example, 1a is reacted under modified conditions to yield 2a. In this one-pot procedure, hydrazine in aqueous ethanol is added directly to the reaction mixture and aniline 3 is isolated in 63

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• ); h) daunomycin conjugation (rt, 24 h) in 0.2 M NH4OAc solution (pH 5.0); i) Fmoc-cleavage 4% hydrazine/DMF (rt, 2 h). (A) HT1080 and (B) HT-29 cells. Uptake of conjugate 1 (light green); 2 (red); 3 (light blue); 4 (pink); 5 (green); K (yellow). Empty control with purple color. List of the peptide