Design and synthesis of a photoswitchable guanidine catalyst

• Philipp Viehmann and
• Stefan Hecht

Beilstein J. Org. Chem. 2012, 8, 1825–1830, doi:10.3762/bjoc.8.209

• employed conditions reduction of the azobenzene function of compound 9 was observed, yet the formed hydrazine analogue reoxidized in situ upon being stirred under atmospheric conditions (air). The free amine 10 finally reacts with the in situ prepared Vilsmeyer salt 5 to provide the desired target compound

Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• with a 3% solution of hydrazine in DMF for 12 × 10 min. Subsequently, the peptide was elongated to its final length by automated SPPS. N-terminal coupling of Cym2 or 5(6)-carboxyfluorescein was carried out by using 2 equiv of the substance to be coupled and activation with 2 equiv of HATU/DIPEA in DMF

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

• good results (up to 86% yield, >10/1 regioselectivity, >20:1 dr, 99% ee) in the presence of (S)-diphenylprolinol trimethylsilyl ether catalyst. Keywords: aza-Michael; domino; hydrazine; organocatalysis; pyrazolidine; Introduction Pyrazolidines are privileged and valuable heterocyclic compounds, which

• investigated in the presence of several common secondary amines 1a–f as organocatalysts in chloroform. Pyrrolidine (1c) turned out to be an effective catalyst and di-tert-butyl hydrazine-1,2-dicarboxylate (2c) was a potent donor (see Table S1 in the Supporting Information File 1). When di-tert-butyl hydrazine

• -1,2-dicarboxylate (2c) was used as the donor and 20 mol % pyrrolidine (1c) as the catalyst, 5-hydroxypyrazolidine 4a could be obtained in 68% yield with over 20:1 dr after five days (Table 1, entry 1). Thus, the tandem aza-Michael/hemiacetal reaction between di-tert-butyl hydrazine-1,2-dicarboxylate

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• assembly of the glycopeptides the acetate protecting groups of the carbohydrates were cleaved with 5% hydrazine in DMF followed by the cleavage of the peptide from the resin with 2% aqueous TFA. Subsequently, the peptides were precipitated with cold diethyl ether and the solid residues were purified by

• mol) in the presence of DIPEA (0.13 mol) in DMF (10 mL). The acetate groups protecting the carbohydrate hydroxy groups in the glycopeptides were removed manually using 5% hydrazine in DMF (v/v, 5 mL) for 6–15 h. The peptides were cleaved from the resin by treatment with TFA in methylene chloride (2

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• (OAc)2 and catalytic amounts of BF3·Et2O [23] and gave disaccharides 12 and 13, respectively after acetylation (Scheme 1). Removal of the anomeric acetate mediated by hydrazine acetate provided the hemiacetals, which was followed by introduction of the anomeric N-phenyl trifluoroacetimidate to furnish

• Fmoc removal from the C4 hydroxy group and a second glycosylation was performed with building block 4 under the conditions optimized in the context of the synthesis of trisaccharide 20. Removal of the levulinoyl ester from C3 by treatment with hydrazine hydrate and acetic acid exposed the second

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• compounds. Route B would proceed in four steps yielding product VIII starting from V, which may be obtained from the corresponding malonyl dichloride and hydrazine derivatives. In the present study we focussed on synthetic route A starting from the commercially available hydantoins I, which would allow very

• broad structural diversity by introducing a variety of substituents and functionalities at different stages of the synthesis. As a first step ethyl (2,5-dioxoimidazolidin-1-yl)acetate derivative II is formed from hydantoins I. The condensation reaction of II with hydrazine, followed by a regioselective

• main challenge in the synthesis of 23–25 was the construction of the 1,2,4-triazine ring. Direct reaction of 13–15 with hydrazine hydrate failed, and only the corresponding hydrazides were formed. Therefore, the C5 carbonyl group of 13–15 was regioselectively thionated with phosphorus pentasulfide in

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• NDI 18 of initiator 2, designed to initiate and template for SOSIP, was accessible from NDA 13 as well. The synthesis of NDI 19 by microwave-assisted imidation with Boc-protected lysine 20 has been reported before in the literature [15]. Reaction with Cbz-hydrazine gave the Cbz-protected NDI hydrazide

Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• -mercaptoethyl auxiliary peptide 4 [6]. During the reaction courses employing Cys-peptide 3 and the 4,5,6-trimethoxy-2-mercaptobenzyl auxiliary peptide 5, only reduction of the 4,4'-AMPB thioester 2b to the corresponding hydrazine compound Red-2b was observed, in 2–4% yield (Table 1). When using the Nα-2

• gave peptide 14/peptide Red14 in an 18:82 ratio (Table 1, entry 5). However, reoxidation of the hydrazine ligation peptides Red-10, Red-13 and Red-14 to the azobenzene ligation peptides 10, 13 and 14 was observed after purification by preparative RP-HPLC, and is obviously initiated by oxygen from the

• air. Finally, the pure ligated azobenzene peptides 10, 13 and 14 were isolated in yields of 62%, 44% and 43%, respectively. When 3,4'-AMPB thioester 1b and the Nα-2-mercaptoethyl auxiliary peptide 4 were used, the desired peptide 11 and its hydrazine analogue Red-11 were detected in a ratio of 97:3 by

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

• -aldo product. Further modification of the aldehyde containing glycans, either by chemical conversion or enzymatic elongation, was established. Base-catalysed β-elimination, coupling of biotin–hydrazide with subsequent reduction to the corresponding hydrazine linkage, and coupling by reductive amination

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Armin de Meijere and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2012, 8, 621–628, doi:10.3762/bjoc.8.69

• nitropolychlorobutadienes 3 and 4 with the 3-azabicyclo[3.1.0]hexane building blocks 1 and 2. Upon treatment with N,N-dibenzyl-3-azabicyclo[3.1.0]hexan-6-amine (1) in methanol the (tetrachloroallylidene)hydrazine 5 [4][7] derived from 3 reacted in a formal nucleophilic substitution at the imidoyl chloride unit to give the

• derivative 6 in 80% isolated yield (Scheme 1). The interest in such compounds derives from the fact that a number of similar hydrazones, e.g., phenyl(phenylchloromethylidene)hydrazine, exhibit fungicidal, antibacterial, and fungistatic activity [17][18]. In view of the insecticidal properties of some

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• anomeric acetyl group of compound 2 with hydrazine acetate [29] yielding derivative 7, followed by nucleophilic fluorination with DAST [30][31] generating the diasteriomeric mixture 8. The α-anomer was isolated by HPLC and subsequent Zemplén saponification of the remaining acetate protecting groups yielded

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

• alkyl, alkoxy or alkylsulfanyl groups were successfully prepared by acid-induced removal of the Boc group in hydrazides 2. The reaction is carried out with 5 equivalents of TfOH in CF3CH2OH/CH2Cl2 at −40 °C for 1.5 min. Under these conditions, the deprotected hydrazine 1 is fully protonated, which

• hydrazide 3a was practically insoluble, and the reaction mixture was triphasic. Under these conditions no formation of hydrazine 1a was observed. Changing MeOH to EtOH and increasing its volume by two-fold gave homogenous solutions within which the desired hydrazine 1a was formed along with significant

• solvent, or alternatively it can alkylate the benzene ring of arylhydrazine (Scheme 2). For less reactive arylhydrazines the former process is faster, k1 << k2, and deprotection with HCl in iPrOH is effective [16]. For dialkoxyphenylhydrazines apparently k1 >> k2 and the desired hydrazine is not obtained

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

• various N- and O-nucleophiles was carried out (Scheme 4). First, aniline derivative 7a (by treatment of 6 with aqueous ammonia) and phenylhydrazine derivative 7b (by treatment of 6 with hydrazine hydrate and triethylamine as a coproduced HCl acceptor) were prepared. Sulfone 6 was also reacted with

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

• pyrazoles in a consecutive fashion from terminal alkynes, acid chlorides, and hydrazine derivatives. Classical approaches to these valuable compounds are notably based on the cyclocondensation of hydrazine derivatives with 1,3-disubstituted three-carbon units, including α,β-unsaturated ketones, and

• presence of Et3N and catalytic amounts of PdCl2(PPh3)2 and CuI. The resulting ynones 27 were then treated in situ with diversely substituted hydrazine derivatives to produce, upon microwave heating, a series of pyrazoles 28–30 (Scheme 15). As previously established for this type of cycloaddition, one of

• the two possible regioisomers was obtained preferentially depending on the hydrazine derivatives used, N-alkyl- and N-arylhydrazines giving opposite regioselectivities [15]. The carbonylative coupling of terminal alkynes with aryl (and heteroaryl) halides was proposed by Mori and coworkers as a

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

• uptake of oxygen helps to control the selective oxidation process. Reactions performed under air were faster but led to intractable mixtures. Analogous hydrazones prepared from pyruvic acid and benzoylformic acid with hydrazine derivatives were tested in this Ugi/oxidative cyclization sequence under

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• . Quenching with benzoyl chloride furnishes the expected unsaturated ketone, which by treatment with hydrazine (NH2-NH2·H2O, THF, 25 °C, 10 min) leads to the pyrazolopyrimidine 115 in 56% overall yield (Scheme 18) [46]. A similar approach has been used to prepare the p38 kinase inhibitor 119 in 72% overall

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• in moderate yields (Scheme 6) (for experimental details, see Supporting Information File 1). Attempts to employ phenylhydrazine, N-Boc-hydrazine, and hydrazine hydrate under standard conditions were met with failure. Based upon previous syntheses of N-methylpyrazoles from ynones and methylhydrazine

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

• Research & Development, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK 10.3762/bjoc.7.120 Abstract 4-Fluoropyrazole systems may be prepared by a single, sequential telescoped two-step continuous gas/liquid–liquid/liquid flow process from diketone, fluorine gas and hydrazine starting materials. Keywords

• of fluoropyrazole systems and, in this paper, we demonstrate that fluorination of diketones to corresponding fluorodiketones, followed by sequential cyclization to the appropriate fluoropyrazoles upon reaction with a hydrazine derivative, can be accomplished in a single, two-step, telescoped, gas

• /liquid–liquid/liquid synthesis of fluoropyrazoles from fluorine, hydrazine and diketone starting materials was constructed from nickel metal and narrow bore PTFE tubing as described previously [28][29] (Figure 1). Briefly, fluorine gas, diluted to 10% v/v solution in nitrogen was added via a mass flow

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• indole synthesis a hydrazine, which is most commonly derived from the corresponding diazonium salt, is reacted with a suitable carbonyl compound. Alternatively, the Japp–Klingemann reaction can be used to directly couple the diazonium salt with a β-ketoester to obtain a hydrazone which can then undergo

• the most obvious approach, the direct Fischer indole synthesis, to prepare the core of eletriptan as shown in Scheme 22 is not successful [30]. This is believed to be due to the instability of the phenyl hydrazine species 98 under the relatively harsh reaction conditions required to promote the

• cyclisation. However, this problem could be avoided by using an acid-labile oxalate protected hydrazine 104 as depicted in Scheme 23. The yield of this step can be further improved up to 84% if the corresponding calcium oxalate is used. The Bischler–Möhlau reaction is an alternative indole synthesis employing

Tribenzotriquinacenes bearing three peripheral or bridgehead urea groups stretched into the 3-D space

• Jörg Tellenbröker and
• Dietmar Kuck

Beilstein J. Org. Chem. 2011, 7, 329–337, doi:10.3762/bjoc.7.43

• that, accordingly, the 1:3 mixture of the trinitro compounds 8 and 9 is also reflected by three 13C NMR lines at δ 25.54, 25.46 and 25.40 in the intensity ratio of ca. 3:6:3. Reduction of the mixture of the trinitro compounds 8 and 9 was in the first instance achieved by use of hydrazine with iron(III

• reflux for 15 min and then hydrazine hydrate (97%, 120 mg) added. After heating for 4 h further FeCl3•6H2O (10 mg) and 120 mg N2H4•H2O (120 mg) were added. The mixture was heated under reflux for a total of 24 h, allowed to cool and filtered through silica with ethyl acetate. Removal of the solvent gave

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

• 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

• -ketonitriles 16 with a substituted hydrazine in the presence of Et3N in ethanol under reflux conditions. The intermediate 16 was obtained from β-ketoester 15 on treatment with TFA, which in turn was synthesized by condensing 4-(phenylsulfonamidomethyl)cyclohexane carboxylic acid or benzoic acid 13

• or 34) on Merrifield resin in the first step. Reaction of the resin-bound sulfonyl intermediate 31 with hydrazine, followed by release from the resin and intramolecular cyclization, afforded 4-arylsulfonyl-3,5-diamino-1H-pyrazoles 32. Reaction of the resin-bound carbonyl intermediate 35 with

A new and facile synthetic approach to substituted 2-thioxoquinazolin-4-ones by the annulation of a pyrimidine derivative

• Nimalini D. Moirangthem and
• Warjeet S. Laitonjam

Beilstein J. Org. Chem. 2010, 6, 1056–1060, doi:10.3762/bjoc.6.120

• of various fused heterocyclic compounds. In recent years, we have reported one-pot cyclizations of DTBA with hydrazine [23][24], hydroxylamine [25], guanidine [26], etc. In addition, one-pot cyclizations of DTBA-derived arylidenes have also been reported. Recently, we reported the synthesis of fused

Recognition properties of receptors consisting of imidazole and indole recognition units towards carbohydrates

• Monika Mazik and
• André Hartmann

Beilstein J. Org. Chem. 2010, 6, No. 9, doi:10.3762/bjoc.6.9

• equiv of 2-amino-4,6-dimethylpyridine, CH3CN/THF, K2CO3, r. t., 3 d (20%); d) potassium phthalimide, dimethyl sulfoxide, 95 °C, 8 h, (57%); e) hydrazine hydrate, ethanol/toluene, reflux, 19.5 h, KOH (43%) [27]; f) 4 equiv of 4(5)-imidazole-carbaldehyde (18), CH3OH, 3 d; g) 4 equiv of 3-indole

An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

• Rajeshwar Reddy Sagyam,
• Ravinder Buchikonda,
• Jaya Prakash Pitta,
• Himabindu Vurimidi,
• Pratap Reddy Padi and
• Mahesh Reddy Ghanta

Beilstein J. Org. Chem. 2009, 5, No. 66, doi:10.3762/bjoc.5.66

• condensation reactions, such as the condensation of oxazolo[3,2-b]pyridazinium perchlorates with malononitrile, ethyl cyanoacetate and ethyl malonate in the presence of sodium ethoxide [15]; the condensation of 1,4,7-triketones with hydrazine followed by dehydrogenation [16]; the condensation of cyanoacetic

Pd/C-mediated synthesis of α-pyrone fused with a five-membered nitrogen heteroaryl ring: A new route to pyrano[4,3-c]pyrazol-4(1H)-ones

• Dhilli Rao Gorja,
• Venkateswara Rao Batchu,
• Ashok Ettam and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 64, doi:10.3762/bjoc.5.64

• category. It involves the reaction of methyl 2-cyano-3,3-dimethylthioacrylate with 1-tetralone and subsequently with hydrazine [8]. Though a number of methods are known for the synthesis of isocoumarins by constructing the pyrone ring [9][10][11][12][13][14][15][16][17] (the second strategy) none has been