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

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• ester or hydrazine bonds, cathepsin-B labile spacers and oxime bonds [21][22][25]. Due to its structural properties, Dau cannot be attached to the homing device by an ester bond like Dox, because of the absence of the primary hydroxy group in position C-14. However, the C-13 carbonyl group of Dox/Dau

• decapeptide the Dde group of 4Lys was removed with 2% hydrazine in DMF (12 × 5 min) and the peptidyl-resin was washed with DMF (5 × 1 min). Afterwards, the ε-NH2 amino group was butyrylated with 3 equiv butyric anhydride and 3 equiv DIPEA in DMF (2 h). In the next step, 8Lys(Mtt) was deprotected with 2% TFA

• presence of superagonist triptorelin (125–1000 µM) by flow cytometry. Cells were treated simultaneously with K2 and triptorelin for 100 min. Syntheses of GnRH-III–[(4Lys(Bu)/4Ser, 6Aaa, 8Lys(Dau=Aoa)] bioconjugates. a) (1) 2% hydrazine

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• , the deprotection of the amine function with hydrazine caused also reduction of the C5–C6 double bond; two peaks at 189 and 191 Da were observed in the MS spectrum of crude post-reaction mixture (for 13b and 13c, respectively). We reasoned, that the all these problems may be overcome by an elongation

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• %. Wolff–Kishner reduction The Wolff–Kishner reaction is widely used by chemists to remove carbonyl moieties yielding unsubstituted alkyl chains. The reaction requires two steps: the hydrazine first reacts with the ketone forming a hydrazone; The addition of a strong base and heat then promote a

• rearrangement with the elimination of N2 yielding the desired alkyl chain (Figure 3). This reaction is applied to the synthesis of UDCA in order to remove the carbonyl group at C12. The use of hydrazine is a disadvantage in terms of safety (explosive risk) and economic costs (it should be used in excess

• relative to substrate). Several modifications of the Wolff–Kishner reaction can be found in literature: i.e., the Huang–Minlon modification, that consists of removing the unreacted hydrazine after the first step by distillation [42]. This results in higher yield and partial recovery of the unreacted

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• acetic acid (Scheme 1). In the same report the other regioisomers 6-trifluoromethylpyrazolo[3,4-b]pyridines 20 were obtained under multicomponent solvent-free conditions by the reaction of hydrazine 14, β-ketonitrile 15 and β-diketone 17 as an exclusive product. The structures of both the regioisomers

• shape of compound 93 makes it chiral in nature. It was proposed that there is in situ oxidation of ethanol to ethanal by conc. HNO3 which turned the reaction into a multi-component domino assembly of reactants hydrazine 14, β-ketonitriles 15 and acetaldehyde. Rahmati [75] carried out a reaction of 5

• (147) with 3-oxo-3-arylpropanenitrile 15 under solvent-free grinding conditions. The reaction was proposed to proceed via formation of hydrazine by C–N bond cleavage which under reaction conditions provided 7-aminopyrazolo[1,5-a]pyrimidines 148 on coupling with 3-oxo-3-arylpropanenitrile 15 (Scheme 42

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• reductive opening of the benzylidene acetal to give the acceptor monosaccharide 63. NIS/TMSOTf-promoted glycosylation of 63 with glycosyl donor 64 furnished desired β(1→6) disaccharide which was subjected to treatment with hydrazine hydrate to remove the phthalimido group. Subsequent acylation of the

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• [29]. It should be noted that both the bisdioxines [19] and the tetraoxaadamantanes [29] exhibit axial chirality as confirmed by 1H NMR spectroscopy with the Eu(hfc)3 chiral shift reagent. Bisdioxine oxime and hydrazine derivatives 26 and 27 (Scheme 8) are formed from 3 at room temperature without the

• ) derived from dipivaloylketene (2). Mechanisms of formation of bisdioxine acid derivatives from dimer 3. Recently reported synthesis of chromenobisdioxines. Formation of tetraoxaadamantanes. Decarboxylative hydrolysis and oxa-Michael-type ring closure. Oxime and hydrazine derivatives of bisdioxines and