Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• -propynyltriphenylphosphonium bromide (24) involved propadienylphosphonium bromide (25) – the tautomeric form of the starting phosphonium salt. The same authors carried out a series of nucleophilic additions of amines and hydrazine derivatives to 24 to obtain products with the proposed structure of 2-aminovinylphosphonium

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• hydrazine, without disturbing the peptide bond structure, to give H-Gly-Pro-1. DPP-4 activity measurement The fluorescence spectra of 1 and H-Gly-Pro-1 were recorded to confirm their fluorescence profiles; the spectra are shown in Figure 3. As expected, H-Gly-Pro-1 was non-fluorescent because of the

• = 2.2, 6.4 Hz, 3F); MS m/z: M+ 565, 468, 285, 257, 188, 160; HRMS m/z: M+ calcd for C27H21F6N3O4, 565.1436; found, 595.1437. N-(S)-1-(2-Aminoacetyl)-N-(2,4-bis((E)-3,3,3-trifluoroprop-1-en-1-yl)phenyl)pyrrolidine-2-carboxamide (H-Gly-Pro-1): To solution of 7 (0.05 mmol) in ethanol was added hydrazine

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• , followed by a hydrazinolysis step and a second hydrazine-Ugi-azide reaction to provide the desired acylhydrazino bis(1,5-disubstituted tetrazoles). Recently we have reported the synthesis of acylhydrazino-peptomers by a similar strategy [31]. The hydrazides 2a–c were prepared by the reaction of esters 1, 4

• and 6 with hydrazine monohydrate, following a known procedure (Scheme 2) [31]. To access the acylhydrazino-tetrazoles, the hydrazides 2a–c were subjected to a multicomponent reaction comprising an aldehyde or ketone 7a–h, trimethylsilyl azide (TMSN3, 8), methyl isocyanoacetate (9) and ZnCl2 (10 mol

• chose hydrazine tetrazole 10j to continue the synthesis, as it was obtained in excellent yield, it shows distinct NMR spectra and offers the possibility of further functionalization after removal of the Boc protecting group. Therefore, compound 10j was subjected to hydrazinolysis with hydrazine

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• subjected to heterogeneous hydrogenation conditions to produce the indole product 12 through a reductive cyclisation sequence. From the corresponding ester functionalised indole 12 we anticipated that condensation with hydrazine would furnish the corresponding acyl hydrazine 13 which could be cyclised to

• looked at telescoping the final two steps of the process; substitution of the ethoxy group by hydrazine and then ring formation to the 3H-[1,3,4]oxadiazol-2-one unit [32][33]. In this procedure a 0.95 M THF solution of compound 12 was united with a solution of hydrazine (1.0 M in THF) and directed into a

• heated flow coil to be superheated at 100 °C (Scheme 6). A residence time of 40 min allowed full conversion to the corresponding acyl hydrazine 13 which was directly intercepted with a further input stream containing CDI (1.1 M in THF) and heated at 75 °C for an additional 26 min in a second flow coil

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• -amino-1,2,4-triazole 16-15N2 was synthesized by the interaction of 15N2-hydrazine sulphate (98%, 15N) with S-methyl isothiourea sulphate and consecutive cyclization with formic acid (see the Supporting Information File 1). The use of 16-15N2 in a reaction with ethyl 4,4,4-trifluoroacetoacetate (22

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• carboxylic acid (see Supporting Information File 1) in moderate yield. Finally, the pthalimide group was removed with hydrazine to give the target amino acid 6a (Scheme 4). The modest overall yield for this three-step sequence can be partially attributed to the challenge of purifying the penultimate and

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• determined by 1H and 13C NMR supported by COSY and HSQC techniques. The β linkage in 3, as well as the 4C1 conformation of the pyranose ring were confirmed by the coupling constant of the anomeric proton (J1,2 = 8.4 Hz). The deprotection of 3 was achieved by using 98% hydrazine hydrate in refluxing ethanol

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• amines, hydrazine, and carbohydrazides. In some of these reactions, the initially formed adducts, after subsequent elimination of HCN, undergo heterocyclization (see chapter Heterocyclization reactions). The reaction of E-1a with either aqueous ammonia or gaseous NH3 in acetonitrile leads to the enamines

• reactions with E-1b is hydrazine and its derivatives. The parent hydrazine used as the hydrate reacts with E-1 in ethanol at room temperature, and in the case of diisopropyl dicyanofumarate (E-1c), the crystalline enehydrazine was isolated in 82% yield [62]. In addition, the N-benzyl-protected (S)-proline

• products (tandem reactions). These reactions occur through an initial formation of the Michael-type adduct followed by a heterocyclization step upon involvement of either a cyano or an ester group as a second electrophilic center. Hydrazine is a powerful dinucleophile and reacts easily with E-1 in ethanol

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• formation of the indoline ring was unambiguously confirmed by the crystal structure of compound 21ab (CCDC 1546063, Figure 2). It seems that the nucleophilicity of the hydrazine moiety prevailed, and the formation of the thermodynamically more favorable amide bond governed the overall direction of this

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• corresponding hydrazine (pale yellow in color), a reaction which can be monitored by UV–vis spectroscopy. As the kinetics of the reaction varies from sample to sample, the stabilization time for a complete reduction of the DPPH· free radical was determined. For all samples studied, the steady-state

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• Discussion Initially, the reaction of enaminone 1a and sulfonyl hydrazine 2a was tentatively subjected to different iodine reagents or catalyst-free conditions. The results indicated that no product was observed in the reaction without catalyst (entry 1, Table 1), and different types of iodine reagents such

• (reaction 1, Scheme 3). In addition, sulfonyl hydrazine 2b gave disulfide 6 under the same conditions (reaction 2, Scheme 3), suggesting that chromone 5 and disulfide 6 might be key intermediates in the domino reactions. Moreover, the same reaction in the presence of TEMPO gave no formation of 6, indicating

• ), further confirming that a radical intermediate was generated during the reaction process. According to the results obtained in the control experiments, the mechanism for this domino reaction is proposed (Scheme 4). As one of the key steps, the reductive coupling of two sulfonyl hydrazine molecules may

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• the hydrazine is slow, meaning that the nucleophilicity is greatly retarded compared to lower acid loadings. Nonetheless, considering that the subsequent fluorination step should proceed optimally under basic conditions [17], the lowest amount of acid which also provided a good yield was thus chosen

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• hazardous hydrazine hydrate was replaced by 1,2-diaminoethane [39] and conversion to the corresponding benzylamines was quantitative within 1 h. As a proof of concept of reaction, p-methylbenzylamine was isolated in 41% yield in the form of acetamide 42. In this way, a three-step, two-pot (A and B, Scheme 5

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• hybrid LDHs were then reduced by hydrazine hydrate (N2H4·H2O) to obtain the Pd catalyst supported on MgAl-LDHs (Pd/MgAl-LDHs). The as-prepared Pd/MgAl-LDH catalyst was further applied in representative cross-coupling Heck reactions under HSBM conditions (Scheme 1) by using a planetary ball mill

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• by a copper-catalyzed cross-coupling reaction. Nucleophilic cyclization of N-alkyne-substituted methyl 1H-pyrrole-2-carboxylates with hydrazine afforded the 6-exo-dig/6-endo-dig cyclization products depending on the electronic nature of the substituents attached to the alkyne. On the other hand

• the presence of an electron-donating group at the benzene ring. However, when the reaction was carried out at the reflux temperature of toluene, the conversion increased to 35%. Next, we conducted cyclization reactions of N-alkyne substituted carboxylate derivatives 7a–d via hydrazine monohydrate

• . Methyl 1-(phenylethynyl)-1H-pyrrole-2-carboxylate (7c) was treated with hydrazine monohydrate in MeOH under N2 atmosphere at reflux temperature. Pyrrolopyrazinone 12c and pyrrolotriazinone 13c skeletons were formed in 67% and 24% yields, respectively (Scheme 2). The structures of cyclization products 12c

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• the reaction of guanidinium chloride with hydrazine [2], triaminoguanidinium chloride (TAG-Cl) offers the opportunity to serve as a C3-symmetrical platform for the synthesis of triaminoguanidines with multiple functionalization (see [3] and references cited there). In most studies reported so far

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• " for safety reasons, such as those involving diazo compounds, hydrazine, azides, phosgene, cyanides and other hazardous chemicals could be performed with relatively low risk using flow technology [72][73][74][75][76]. Several research groups investigated this aspect, as highlighted by several available

• in Scheme 16, diazo species 18 could be generated from simple carbonyls 15 and hydrazine (16). Intermediate hydrazones 17 can be converted into the corresponding diazo compounds by oxidation using a recyclable oxidant based on N-iodo-p-toluenesulfonamide potassium salt. The possibility to regenerate

• to handle hazardous components such as hydrazine and molecular oxygen, which represent alternative reagents for selective reduction of C=C double bonds. In fact, combination of hydrazine hydrate (N2H4·H2O) and O2 provide diimide (HN=NH) as reducing agent. Nevertheless, this strategy is rarely used in

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles

• Anastasia S. Kostyuchenko,
• Tatyana Yu. Zheleznova,
• Anton J. Stasyuk,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2017, 13, 313–322, doi:10.3762/bjoc.13.34

• semiconducting and photoluminescent properties. First, alkaline hydrolysis of the esters 7b–g led to the corresponding carboxylic acids 12b–g in good yields (70–87%, Scheme 3). The corresponding hydrazide derivatives 13b,c were obtained in 67–73% yields by refluxing the esters 7b,c with hydrazine monohydrate in

• synthesis of 14d–g. These intermediates were synthesized by the reaction of the acid chlorides with hydrazine dihydrochloride in the presence of pyridine. The required acid chlorides were prepared in situ through the reaction of the corresponding carboxylic acids 12b–g with oxalyl chloride. The yields of

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• C2-participating levulinyl ester protecting group ensured selective formation of the trans-glycoside upon activation of 11 by NIS/TfOH in the presence of the C5 linker to produce glucoside 12 in 70% yield [24]. Cleavage of the C2 levulinyl ester of 12 by treatment with hydrazine acetate furnished 13

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• hydrazino-Ugi reaction (or a classical Ugi reaction). The hydrazides 3a–c used in the first MCR were prepared by the reaction of glycine-derived esters 2, 5 and 7 with hydrazine monohydrate (hydrazinolysis), following a known procedure [63][64] (Scheme 2). The obtained hydrazides were then reacted with

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• conditions, but the presence of noble metal catalysts, packed into disposable cartridges, suffers from functional group compatibility and catalyst poisoning during time. In 2012 Kappe’s research group reported the microwave-assisted continuous-flow synthesis of anilines from nitroarenes using hydrazine as

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• . Only when treated with hydrazine, nucleophilic substitution was observed and after reduction with Raney nickel the desired 3-deazaadenosine was isolated. Our own attempts towards direct ammonolysis failed as well. Additionally, the limited commercial availability of hydrazine and its inconvenience in

• . c) Anhydrous hydrazine, steam bath, 1 h, not isolated. d) Raney nickel, water, reflux, 1 h. Synthesis of c3A described by Montgomery et al. in 1977 [23]. The final step, displacement of the 2-chlorine atom by a hydrogen atom, remains problematic [24][25][26]. a) 1,2,3,5-Tetraacetyl-ß-D-ribofuranose

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• -membered heterocycle containing two adjacent nitrogen atoms. Pyrazole Pyrazole is a well-studied 5-membered heterocycle that has been traditionally synthesized either via the Knorr [151] (1,3-diketone and hydrazine) or von Pechmann [152] (olefin and diazomethane followed by oxidation) strategies. Figure 7

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• of 1,4-diacetyl-2,5-piperazinedione with aldehydes in the presence of potassium tert-butoxide, followed by deacetylation with hydrazine hydrate (see the Supporting Information File 1 for further details). As shown in Scheme 2, treatment of these materials with N-bromosuccinimide and methanol in