Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• materials can be used in the extruder, through the use of s-Buli by Höcker et al., reagents that are potentially explosive or can be ignited when dry or exposed to friction are too hazardous to be used in an extrusion process, therefore chemistry involving azides or hydrazines for example, would need to be

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• of 2-acyl-5,6,7-trichloro-1,3-tropolones under the action of alcohols [17][32] or hydrazines [32] has been previously reported. The suggested primary step of these reactions is a nucleophilic addition to the carbonyl carbon of an acyl group. In our case (compounds 5 and 6), the reaction most probably

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• -component condensation of hydrazines, methylenemalononitriles, aldehydes and alcohols has been developed via two different reaction pathways. The structures of target products were characterized by IR spectroscopy, NMR (1H and 13C) spectroscopy and HRMS (ESI) spectrometry. The crystal structure of 4-ethoxy

• , this is a novel methodology for the synthesis of pyrazolo[3,4-d]pyrimidines by the reaction of hydrazines, methylenemalononitriles, aldehydes and alcohols. During the preparation of this manuscript, Liu et al. reported the synthesis of pyrazolo[3,4-d]pyrimidines from 5-aminopyrazole-4-carbonitrile [48

• a catalyst, but also participates in the reaction. A series of hydrazines, methylenemalononitriles, aldehydes and alcohols were investigated under the optimal reaction conditions. As shown in Figure 1, the influence of different aldehydes on the reaction was studied first. The results show that

Three-component synthesis of C₂F₅-substituted pyrazoles from C₂F₅CH₂NH₂·HCl, NaNO₂ and electron-deficient alkynes

• Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16–24, doi:10.3762/bjoc.11.3

• -dicarbonyl compounds (or their synthons) with hydrazines [39][40][41][42][43][44]. In this context, novel practical methods to C2F5-pyrazoles are needed. Last year, Ma and colleagues synthesized CF3-pyrazoles by [3 + 2] cycloaddition between in situ generated CF3CHN2 and alkynes [45]. This method, however

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• properties of the RNA's 3'-terminal cis-diol, which can be specifically oxidized with metaperiodate [26][27][28], followed by reaction of the produced dialdehyde with amines or hydrazines linked to a desired functional entity [29]. We set out to select from a random library catalytically active RNAs that

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

• –Hillman; SN2' reaction; Introduction Hydrazines and their derivatives are an important class of compounds in organic chemistry. They are widely used in the fields of pesticides, polymers, dyestuff, and pharmaceutical agents [1]. They are also versatile building blocks for accessing many important

• nitrogen-containing heterocyclic compounds, especially pyrazole derivatives [2][3][4][5][6][7]. Although various methods detailing the synthesis of hydrazines have been established [8], the development of an efficient synthesis of hydrazines with highly structural diversity from simple starting materials

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

• trifunctional electrophiles and are useful building blocks for the introduction of a three carbon fragment into the resulting molecule. Thus, the reaction of enol ethers with hydrazines produces pyrazoles, with amidines pyrimidines, with hydroxylamine isoxazoles, and with anilines quinolines/ones are formed [2

• and are mostly prepared by reacting hydrazines with suitable 1,3-dielectrophiles. The synthesis of pyrazoles and related compounds can be implemented by four different approaches: reaction of (substituted) hydrazines with β-functional compounds or their equivalents (the most frequently used method

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

• functionalized dihydropyrazoles 13 starting from aryl/alkylacetylenes, aldehydes – and also more challenging ketones – and N-Boc-N’-substituted hydrazines 14 [41] (Scheme 12). Among several gold complexes tested, best results were obtained with IPrAuCl/AgOTf (2–5 mol %) in DCE (AcOH for aromatic aldehydes) at 50

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

• investigation commenced with the preparation of 1-(6-chloropyrimidin-4-yl)hydrazines 3. The required starting 4,6-dihydroxypyrimidines 1 can be prepared following the reported procedure by condensation of dimethyl malonate either with formamide (for 1a) or the respective formamidine salts (for 1b and 1c) [15

• -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

• reactions, which are under investigation in our group. The structure of two representatives of [1,2,4]triazolopyrimidines. Synthesis of 1-(6-chloropyrimidin-4-yl)hydrazines 3. Plausible mechanism for the transformation of [1,2,4]triazolo[4,3-c]pyrimidines 5 to the [1,5-c] series 6. Synthesis of the

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• ion furnishes a new amine radical cation 152. Finally, amine radical cation 152 is reduced by Ru(I) to provide the annulation product 153 and regenerate Ru(II), thus completing the catalytic cycle. Our group also realized cleavage of N–N bonds by irradiation of aromatic hydrazines or hydrazides in the

• presence of Ru(bpz)3(PF6)2 and air (Scheme 34) [108]. A 13 W compact fluorescent light was sufficient as the light source. N,N-disubstituted hydrazines and hydrazides were suitable substrates provided that at least one of the two substituents on the nitrogen atom was an aryl group. Electron-richer

• hydrazines were found to be more reactive than hydrazides. This is consistent with our expectation that, similar to amines, hydrazines and hydrazides act as an electron donor to reductively quench the photoexcited Ru(II) complex. The photoexcited state of Ru(bpz)3 (E1/2*II/I = 1.45 V vs SCE) is more

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• . [47] have demonstrated that ethynyl ketones can be generated in flow by the palladium-catalysed acylation of terminal alkynes and further transformed in a continuous process to pyrazoles by cyclocondensation with hydrazines using a commercially available conductive heating modular flow reactor. Given

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• -pyrazolines starting from α,β-unsaturated ketones and phenylhydrazine or N-tert-butyloxycarbonylhydrazine in the presence of a chiral Brønsted acid or a phase-transfer catalyst [70][71]. Compared with monosubstituted hydrazines in organocatalytic asymmetric synthesis, disubstituted hydrazines were also

• of 2-pyrazolines using disubstituted hydrazines through an asymmetric conjugate addition followed by a deprotection–cyclization sequence [75]. Due to the importance of pyrazolidine derivatives in both organic and medicinal chemistry, we have become interested in developing an efficient

• stereoselective cascade reaction for the synthesis of the pyrazolidine compounds through organocatalysis. In this paper, we present a convenient access to racemic and enantioenriched 5-hydroxypyrazolidines through a domino aza-Michael/hemiacetal organocatalytic sequence of disubstituted hydrazines to α,β

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• reduced with Na[BH3(CN)] to the corresponding hydrazines (15a–c and 16a). B: Elongation of biotinylated LacNAc (15a) and biotinylated tetrasaccharide (15b) by β3-N-acetylglucosaminyltransferase (β3GlcNAc-transferase) leads to an internally modified trisaccharide 16a as the enzymatic elongation of the

Synthesis of oleophilic electron-rich phenylhydrazines

• Aleksandra Jankowiak and
• Piotr Kaszyński

Beilstein J. Org. Chem. 2012, 8, 275–282, doi:10.3762/bjoc.8.29

• increases its stability in the reaction medium. The hydrazines were isolated in 60–86% yields and purities >90%. The hydrazides 2 were obtained in 43–71% yields from aryl bromides 5, which were lithiated with t-BuLi and subsequently reacted with di-tert-butyl azodicarboxylate (DTBAD). Keywords

• deprotection of Boc-substituted hydrazines (Scheme 2), hydrazides 2, expecting that the reaction could be performed under fully homogenous conditions. Analysis of the reaction mechanism for the deprotection of 2 under acidic conditions shows that removal of the Boc group generates t-Bu+, which reacts with the

• be optimum; the purity of the hydrazine decreased with increasing reaction times. By using this protocol, hydrazines 1 were isolated as viscous oils in purities >90% and yields of 60–86%, according to 1H NMR analysis with 1,4-dimethoxybenzene as the internal standard (Scheme 3). Attempts at the

Derivatives of phenyl tribromomethyl sulfone as novel compounds with potential pesticidal activity

• Krzysztof M. Borys,
• Maciej D. Korzyński and
• Zbigniew Ochal

Beilstein J. Org. Chem. 2012, 8, 259–265, doi:10.3762/bjoc.8.27

• ammonia, amines, hydrazines and phenolates to give 2-nitroaniline, 2-nitrophenylhydrazine and diphenyl ether derivatives. Reduction of the nitro group of 4-tribromomethylsulfonyl-2-nitroaniline yielded the corresponding o-phenylenediamine substrate for preparation of structurally varied benzimidazoles

Efficient synthesis of 1,3-diaryl-4-halo-1H-pyrazoles from 3-arylsydnones and 2-aryl-1,1-dihalo-1-alkenes

• Yiwen Yang,
• Chunxiang Kuang,
• Hui Jin,
• Qing Yang and
• Zhongkui Zhang

Beilstein J. Org. Chem. 2011, 7, 1656–1662, doi:10.3762/bjoc.7.195

• based on the condensation of hydrazines with 1,3-dicarbonyl compounds or their equivalents. However, the 1,3-dipolar cycloaddition offers a more convenient synthetic route. Sydnones are easily accessible aromatic compounds and versatile synthetic intermediates. They can be used as unusual, alternative

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• different approach to α,β-alkynyl ketone derivatives as pyrazole precursors. They established a four-component domino process combining various organic halides, terminal alkynes, hydrazines, and carbon monoxide at room temperature. In this case, all components are mixed at the very beginning of the process

• the intermediacy of α,β-alkynyl ketones in the four-component process could not be confirmed (TLC). In addition, their reaction with hydrazines was shown to be ineffective under the present solvent system in the presence or absence of palladium catalyst. This may suggest that if α,β-alkynyl ketones

• (after removal of excess acrylic acid) with the aid of an oligomeric alkyl carbodiimide 44 (Scheme 19) [19]. Interestingly, Willis and coworkers have shown that aryl N-aminosulfonamides may be accessed by three-component coupling of aryl iodides, hydrazines, and DABCO·(SO2)2 as a convenient source of

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• -diketones and hydrazines [23]. However, the synthetic methodology for the preparation of the corresponding fluoropyrazole derivatives has not been developed to any great extent despite the potential use of such systems in life science applications. Recently, we explored direct fluorination of various

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• application of [(R)-xylyl-binap-(AuOPNB)2] 383 in gold-catalyzed hydroaminations and hydroalkoxylations of allenes with hydroxylamines and hydrazines, which gave ee values of up to 99% [178]. Whereas chiral biarylphosphinegold(I) complexes are suitable catalysts for the enantioselective addition of nitrogen

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

• Olivier Debleds,
• Eric Gayon,
• Emmanuel Vrancken and
• Jean-Marc Campagne

Beilstein J. Org. Chem. 2011, 7, 866–877, doi:10.3762/bjoc.7.99

• substitution would be followed by activation of the triple bond and addition of the remaining nucleophilic group to the alkyne (Scheme 11) [63]. Whereas no reaction occurred with bis-protected hydrazines, unexpected reactions occurred with protected (P = Cbz, PhSO2) hydroxylamines (Scheme 12). In model

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• involve the reactions of β-ketonitriles, malononitrile, alkylidenemalononitriles and their derivatives with hydrazines, as well as some novel miscellaneous methods. Keywords: alkylidenemalononitriles; 5-aminopyrazoles; hydrazines; β-ketonitriles; malononitriles; Review The 5-aminopyrazole system

• methods have recently appeared. Some of the important methods are outlined below. 1. Reaction of β-ketonitriles with hydrazines The most versatile method available for the synthesis of 5-aminopyrazoles involves the condensation of β-ketonitriles with hydrazines. β-Ketonitriles 1 react smoothly with

• hydrazines to yield 5-aminopyrazoles 3 [19][20][21][22][23][24][25][26][27][28]. The reaction apparently involves the nucleophilic attack of the terminal nitrogen of the hydrazine on the carbonyl carbon with the formation of hydrazones 2, which subsequently undergo cyclization by the attack of the other