Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• compounds are the more active ones. Keywords: antioxidant; deep eutectic solvent; Knoevenagel; ʟ-proline DES; rhodanine; Introduction Rhodanines and related five-membered heterocycles with multiple heteroatoms (i.e., thiazolidinediones, thiazolidinones, hydantoins, thiohydantoins) are very interesting

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• reactions of hydantoins [41][59]. However, also using this oxidant, we observed low conversions (31%) and the formation of significant amounts of byproducts, mainly halides and olefins (elimination byproducts). The use of liquid-assisted grinding (LAG) procedures [60][61][62] by adding small quantities of

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• (CSIR-NIIST), Thiruvananthapuram-19, India 10.3762/bjoc.14.49 Abstract A practical three-step protocol for the assembly of triazolobenzodiazepine-fused diketopiperazines and hydantoins has been developed. The synthesis of these tetracyclic ring systems was initiated by an Ugi reaction, which brought

• ) and two ring-closing steps toward triazolobenzodiazepine-fused diketopiperazines and hydantoins. Benzodiazepine derivatives [24][25] form an important class of ‘psychoactive drugs’ which is being extensively used in the treatment of anxiety, insomnia, agitation, seizures, muscle spasms, alcohol

• Ugi reaction in EtOH, after completion of which, the ring-closing steps (base induced and IAAC) were performed in succession. Unfortunately, the final products were obtained in slightly lower yields; 30% for 7a and 26% for 7b, respectively. Hydantoins belong to a unique class of heterocycles which can

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

• procedures have been successfully applied to the synthesis of O-glycosides [10], bioactive hydantoins [11], extended iptycenes [12] and organometallics [13] where problems can occur using solution-based synthesis due to limited solubility. Whilst mechanochemical one-pot procedures offer the inherent ability

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• hydantoins. The in situ basic conditions, necessary for the deprotonation of the amino acid methyl ester hydrochloride salts in order to make the amino group nucleophilic, were generated by the hydrolysis of KOCN. Following the addition reaction with KOCN starting from hydrochloride salts of L-phenylalanine

• (without isolation) and cyclized in the presence of a base to 5-substituted hydantoins in good to excellent yields. Then the ball milling methodology was applied to the synthesis of phenytoin (41), a known antiepileptic drug. In this case, KOCN had to be replaced with trimethylsilyl isocyanate (TMS-NCO

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• , 141700, Dolgoprudny, Russia Department of Philosophical, Educational and Economic Sciences, G. d’Annunzio University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti Scalo, Italy 10.3762/bjoc.13.3 Abstract The mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins was

• agents. In general, cleaner reaction profiles were observed in the presence of PEGs, compared to dry-grinding procedures. Keywords: ball-milling; 1,1’-carbonyldiimidazole (CDI); hydantoins; mechanochemistry; liquid-assisted grinding (LAG); poly(ethylene) glycols (PEGs); Introduction Poly(ethylene

• preparation of an active pharmaceutical ingredient (API), the anticonvulsant drug ethotoin 7 [9] (marketed as Peganone®, Scheme 1). We describe herein the impact of the addition of variable amounts of PEG, PEG chain length and end terminal groups, for the preparation of diverse 3,5-disubstituted hydantoins

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• hydantoins 24–26). On the other hand, acid hydrolysis of these adducts efficiently affords N-alkylamino acid derivatives, as for instance the N-methylamino amide 21. Additionally, from the common adduct 26, functionalized polycyclic hydantoins of type 27 and 28 can also be synthesized. The authors proposed

• ), particularly into hydantoins 37–43 after hydrolysis of the corresponding adducts 30–32 [55]. Oxidative elaboration of the ketol unit in these compounds provides the corresponding carboxylic acids 40/41, the aldehyde 42 and the ketone 43. Therefore this methodology facilitates a novel entry to functionalized

• 5,5-disubstituted hydantoins, a well-recognized scaffold for drug discovery. 2 Thiazol-4(5H)-ones 2 Thiazol-4(5H)-ones 2, which exhibit interesting applications in medicinal and pharmaceutical areas [74][75][76], can be easily synthesized and can act as (pro)nucleophiles in asymmetric catalytic

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• and are consistent with our experimental results. The preferred pathway for formation of 5-exo products is confirmed. Keywords: density functional theory; fused bicyclic hydantoins; intermediate; reaction mechanism; regioselectivity; selenocyclization; Introduction Hydantoins, a class of

• activities polycyclic hydantoins, especially spirohydantoins [13][14][15][16][17][18][19][20] and fused [21][22][23] bicyclic hydantoin derivatives, have recently attracted great interest in both organic and medicinal chemistry. In our previous work, we reported the experimental results on the

• synthesis of fused bicyclic hydantoins. 1H NMR spectroscopy monitoring, as well as 1H NMR chemical shifts prediction [29][30][31][32][33][34] is used as a useful tool in the search of the most probable intermediates in the reaction. The theoretical results are discussed and compared with our experimental

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• ketones affording the corresponding hydantoins (precursors of amino acids) via the Bucherer–Bergs reaction in the next step, which were finally transformed into sugar amino acids (precursors of biologicaly active iminosugars). Thus, using methylmagnesium iodide, some alanine-branched sugars were obtained

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• , i.e., 1-adamantylamine provided the highest yield. 8. The Bucherer–Bergs reaction The three-component Bucherer–Bergs reaction provides 5-mono- or 5,5-disubstituted hydantoins from the condensation of a carbonyl compound with potassium cyanide and ammonium carbonate (Scheme 42) [115]. The chemistry of

• hydantoins attracted a considerable attention because of their importance in medicine and industry [116][117]. N-Nucleoside analogs with (thio)hydatantoin scaffold as a nucleobase mimic were also extensively investigated [118]. (+)-Hydantocidin (Scheme 43), isolated from Streptomyces hygroscopicus, is a

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

• /bjoc.8.181 Abstract Dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives were prepared by successive N3- and N1-alkylation of hydantoins, followed by regioselective thionation and subsequent cyclization under mild conditions. In a final alkylation step a further substituent may be

• introduced. The synthetic strategy allows broad structural variation of this new drug-like heterobicyclic scaffold. In addition to extensive NMR and MS analyses, the structure of one derivative was confirmed by X-ray crystallography. Keywords: hydantoins; hydrazides; imidazotriazines; N-alkylation; regio

• 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