Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• (90%), and this product was subsequently used to prepare polymers. Other nitrogen-based nucleophiles were also engaged in AT reactions. Hydrazine is a substrate which produces phosphoramidate in high yield. The first example, reported by Prokof’eva et al. [44], used arylhydrazine as a substrate. The

• reaction proceeded in CCl4 in the presence of triethylamine and produced phosphoramidates in 60–82% yield. Unsubstituted hydrazine can also be used as a nucleophile in the AT reaction [45][46][47]. The best synthetic conditions employed phase-transfer catalysis [48]. Accordingly, CCl4 was used as a solvent

• or co-solvent, triethylbenzylammonium chloride acts as a phase-transfer agent, and K2CO3 was used as a base. Hydrazine hydrate was the source of hydrazine. The expected diethoxyphosphinylhydrazine was isolated in almost quantitative yield (99%) after a purification step by liquid/liquid extraction

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• triphenylphosphine is developed, which provides an easy access to α-alkylidene-β-hydrazino acid derivatives in high yields and good stereoselectivity. This reaction represents the first direct transformation of MBH alcohols into hydrazines. Keywords: azodicarboxylate; hydrazine; Mitsunobu reaction; Morita–Baylis

• [13][14], ethers [15][16], amines [17][18], thioethers [19], phosphonates [20][21], alkyl groups [22][23], and so on. In this context, however, reports on the conversion of MBH alcohols into hydrazine derivatives are scanty. In 2009, Nair and co-workers [24] reported an interesting reaction of MBH

• (2b) and triphenylphosphine under very mild conditions (Scheme 2). To our delight, the reaction was completed in 30 minutes providing the anticipated trisubstituted hydrazine 3b in 90% isolated yield with excellent E-selectivity (E/Z > 20:1). To the best of our knowledge, this reaction represents the

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• University, Althanstrasse 14, A-1090 Vienna, Austria 10.3762/bjoc.10.70 Abstract Activated enol ethers derived from esters or the dinitrile of malonic acid, or from pentane-2,4-dione were treated with hydrazine hydrate. The structures of the obtained products – pyrazoles 5 – were studied with a focus on

• ), 1,3-dipolar cycloaddition with diazo compounds as a source of N–N linkage, degradation of fused pyrazoles or rearrangement of other monocyclic heterocycles under chemical, thermal or photochemical conditions [4]. Upon reaction of hydrazine with symmetrical enol ethers, only a single product is formed

• groups R1 only a single product is formed (Scheme 2) [7]. Results and Discussion In this work we have studied reactions of symmetric enol ethers with hydrazine hydrate according to Scheme 2. The enol ethers ethoxymethylidenemalononitrile (EMMN, 3a), dimethyl methoxymethylidenemalonate (MMMM, 3b), diethyl

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• ). Therefore, an intramolecular Paal–Knorr condensation of 104, derived from an Ugi reaction of bifunctional hydrazine 103 (Scheme 33), under basic conditions was considered. Surprisingly, use of a base did not cleave the trifluoroacetyl group but instead deprotonation of the methylene group was found

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• -catalyzed MCRs involving imines in cycloisomerization reactions follow the main reaction pathway shown in Scheme 18. Starting from a γ-ketoalkyne [51] encompassed in a (hetero)aromatic framework, a condensation step with a suitable G–NH2 group (amine or hydrazine) provides the imine intermediate, which

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• in 75% yield (Table 1, entry 9). The addition of NaHCO3 [20][33] as a base to the reaction mixture failed to give 2a, whereas it was successful for the preparation of fluorinated pyrazole, via the gold(I)-catalyzed tandem aminofluorination of 1-phenyl-2-(4-phenylbut-3-yn-2-ylidene)hydrazine. Other

Convergent synthesis of a tetrasaccharide repeating unit of the O-specific polysaccharide from the cell wall lipopolysaccharide of Azospirillum brasilense strain Sp7

• Pintu Kumar Mandal,
• Debashis Dhara and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2014, 10, 293–299, doi:10.3762/bjoc.10.26

• hydrazine hydrate (4 mL) and the mixture was allowed to stir at 80 °C for 8 h. The solvents were removed under reduced pressure, and a solution of the crude mass in pyridine (5 mL) and acetic anhydride (5 mL) was kept at room temperature for 1 h. The solvents were evaporated and co-evaporated with toluene

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

• calculations for the first time. B3LYP/6-311+G(d,p) SCRF=(PCM, solvent = 1,2-ethanediol) optimizations were carried out. To investigate the role of the base catalyst, the base-free reaction was examined by the use of acetone, hydrazine (H2N–NH2) and (H2O)8. A ready reaction channel of acetone → acetone

• hydrazine (Me2C=N–NH2) was obtained. The channel involves two likely proton-transfer routes. However, it was found that the base-free reaction was unlikely at the N2 extrusion step from the isopropyl diimine intermediate (Me2C(H)–N=N–H). Two base-catalyzed reactions were investigated by models of the ketone

• reaction to convert an aldehyde or ketone to an alkane by the use of hydrazine (H2N–NH2) and a base (OH− or alkoxide RO−) [1][2]. The reaction is illustrated in Scheme 1. It is described as a "homogeneous" reaction [3] because the platinum catalyst used initially is not included. The formal change of the W

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• proved to give the best yields, probably due to the higher reactivity of the corresponding hydrazones. Furthermore, the double bond of 29 was selectively hydrogenated under palladium on charcoal, while hydrogenolysis of the hydrazine moiety occurred in the presence of Raney nickel (Scheme 22). Following

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• diversification: (i) various aryl and heteroaryl fused indole derivatives can be assembled by choosing an appropriate hydrazine derivative, (ii) during the alkylation of diketone 2 [43] various unsaturated alkenyl fragments may be incorporated either in a symmetrical or in an unsymmetrical manner, (iii) various

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• -diaminoquinoline [7]. Another approach is based on the amination of 7-nitroquinoline in position 8 with hydroxylamine under basic conditions. The resulting 8-amino-7-nitroquinoline was reduced with SnCl2·2H2O [8] or hydrazine hydrate on Raney nickel as a catalyst [9] to obtain 7,8-diaminoquinoline. In the last

• the Skraup reaction of 4-nitroaniline produces 6-nitroquinoline as a sole product in moderate yield (47%). The latter, on treatment with hydroxylamine hydrochloride in the presence of KOH [11] followed by the reduction with hydrazine hydrate on Raney nickel, provided 5,6-diaminoquinoline in almost

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• -yl)hydrazines 3 were then obtained in 90–95% yield through the reaction of compounds 2 with two equivalents of 50% hydrazine in ethanol at 45 °C for 2 h (Scheme 1). We next examined the synthesis of the corresponding hydrazones of various aldehydes. After screening a set of conditions, optimal

• conditions could be determined. Thus, 1-(6-chloropyrimidin-4-yl)hydrazine (3a) was condensed with 20% excess benzaldehyde to give 85% yield of the chloropyrimidinylhydrazone 4a in absolute ethanol at room temperature in about 1 h. As shown in Table 1, the reaction proceeded readily for most of the employed

• synthesis of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives by iodobenzenediacetate (IBD)-mediated oxidative cyclization of suitable N-benzylidene-N′-pyrimidin-2-yl hydrazine precursors, followed by a Dimroth rearrangement [20]. We envisioned that our aldehyde chloropyrimidinylhydrazones 4 would undergo

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

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• ; then hydrazine monohydrate) [38][39][62]. Unfortunately, fluoride-mediated desilylation of allene 6c caused complete epimerization of the allenic chirality axis. Therefore, the silylallene was not used in further studies. The results of the gold-catalyzed cycloisomerization of the allenes 7 and 8 to

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

• Willmen Youngsaye,
• Cathy L. Hartland,
• Barbara J. Morgan,
• Amal Ting,
• Partha P. Nag,
• Benjamin Vincent,
• Carrie A. Mosher,
• Joshua A. Bittker,
• Sivaraman Dandapani,
• Michelle Palmer,
• Luke Whitesell,
• Susan Lindquist,
• Stuart L. Schreiber and
• Benito Munoz

Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171

• hydrazine hydrate were then reacted under microwave conditions to assemble the indazole ring 10. The ester side chain of 11 was installed under the same conditions described above for the alkylation of 3-arylindazoles. In vitro activity and SAR All of the compounds prepared above were evaluated for their

• bromoacetate, K2CO3, acetone, 60 °C; (d) alkylmagnesium bromide, Et2O, 0 °C; (e) Dess–Martin periodinane, CH2Cl2; (f) hydrazine hydrate, 175 °C. Activity of substituted indazole cores.a Investigation of 3-substituted indazoles.a Substituent effects associated with the 3-phenyl ring.a Supporting Information

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• azodicarboxylate reagent [73]. The proposed mechanism (Scheme 27) suggests a double function of the dialkyl azodicarboxylate, which acts both as an oxidant, promoting the oxidation of NHPI to PINO by ET process, and as acceptor of carbon radicals generated via HAT by PINO, leading to the formation of hydrazine

• derivatives. The scope of the reaction was investigated and its applicability was extended to different C–H bonds, including benzylic, propargylic, and aliphatic ones. Furthermore, the hydrazine compounds were readily converted to the corresponding carbamates and amines. Conclusion Metal-free oxidation

• from N-alkoxyphthalimides. Visible-light/g-C3N4 induced metal-free oxidation of allylic substrates. NHPI/o-phenanthroline-mediated organocatalytic system. NHPI/DMG-mediated organocatalytic system. NHPI catalyzed oxidative cleavage of C=C bonds. Synthesis of hydrazine derivatives. Acknowledgements We

Simple and rapid hydrogenation of p-nitrophenol with aqueous formic acid in catalytic flow reactors

• Rahat Javaid,
• Shin-ichiro Kawasaki,
• Akira Suzuki and
• Toshishige M. Suzuki

Beilstein J. Org. Chem. 2013, 9, 1156–1163, doi:10.3762/bjoc.9.129

• demonstrates the robustness of the present catalytic reactors. Experimental Materials and reagents Reagent-grade formic acid (HCO2H, 98%), p-nitrophenol, palladium acetate [Pd(CH3COO)2], silver nitrate (AgNO3), disodium ethylenediamine tetraacetate (EDTA–Na2), ammonia (NH3, 28%), hydrazine monohydrate, nitric

• containing 9 mM Pd(CH3COO)2, 1 mM AgNO3, 0.15 M EDTA–Na2, 4 M NH3, and 10 mM hydrazine monohydrate through the reactor tube at 60 °C. After 3 h plating, 67.7 mg of Pd (87%) and 10.1 mg of Ag (13%) were deposited inside the tubular reactor. After plating, washing with water was conducted to remove the

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

• of this device was for the preparation of a series of hydrazones. A continuous aqueous extraction to remove the excess hydrazine enabled the product to be collected in high purity (Figure 29). Other applications reported in this work include alkene epoxidation and dithiane preparation. Dispersion of

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• method of Tiecco [32]. Pyrazole 3g was then synthesized by the reaction with hydrazine hydrate. AZg was obtained by the Diels–Alder [4 + 2]-cycloaddition with cyclopentadiene and hydrogenation using PtO2 as a catalyst. The endo-configured structure of azoalkanes AZc–g was determined by X-ray

• (Ar = 3,5-dimethoxyphenyl) is as follows: In a 50 mL round-bottom flask, benzonitrile (3.7 g, 22.7 mmol) was dissolved in 10 mL of absolute ethanol. Hydrazine (3.6 mL, 90 mmol) and sulfur (0.43 g, 13.5 mmol) were quickly added, and the solution was stirred at room temperature for 1 h and then heated

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• hydroxylamine and hydrazine substituents in order to construct unusual heterocycles [33][34]. One typical illustration is presented in Scheme 14, where unmasking of the hydroxylamine in adduct 70 gives rise to cyclic nitrone 71, which can then be intercepted by a dipolarophile placed in the medium, as shown by

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors

• El Sayed H. El Ashry,
• El Sayed H. El Tamany,
• Mohy El Din Abdel Fattah,
• Mohamed R. E. Aly,
• Ahmed T. A. Boraei and
• Axel Duerkop

Beilstein J. Org. Chem. 2013, 9, 135–146, doi:10.3762/bjoc.9.16

• , because formerly, only conversions of 1,3,4-oxadiazolethione (by reaction of hydrazine hydrate) to 4-amino-1,2,4-triazolinethiones were reported [38][39][40]. The products of the new reactions are verified by the X-ray single-crystal analysis of the galactosyl-1,2,4-triazoline-3-thione, and a

Removal of benzylidene acetal and benzyl ether in carbohydrate derivatives using triethylsilane and Pd/C

• Abhishek Santra,
• Tamashree Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 74–78, doi:10.3762/bjoc.9.9

• reported for the removal of benzylidene acetals by using strong protic and Lewis acids [10][11][15] as well as some heterogeneous acidic catalysts [16][17]. Removal of benzylidene acetal under nonacidic conditions includes hydrogenolysis using hydrogen gas over Pd/C [18], or treatment with hydrazine [19

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• NaOH, hydrazine acetate, pyridine and benzylamine failed to cleave the linker. Even the strongly basic and weakly nucleophilic t-BuOK was not sufficient to induce premature cleavage. Thus, it is the nucleophilic action of sodium methoxide that is strong enough to induce cleavage of the safety-catch

Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

• Abhijit Sau and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2012, 8, 2053–2059, doi:10.3762/bjoc.8.230

• 101.6 (C-1B), 101.5 (PhCH), 100.8 (C-1C), 100.2 (C-1A), 97.3 (C-1D) in the 13C NMR spectrum]. Compound 10 was subjected to a sequence of reactions involving (a) removal of N-phthalimido group by using hydrazine hydrate [25]; (b) N-acetylation by using acetic anhydride and pyridine; (c) removal of