Synthesis and spectroscopic characterization of cyclobutyl hydantoins (original) (raw)

Efficient Synthesis of 5,5-Disubstituted Bis-hydantoins/spirohydantoins and a Tetrakis-analogue: A Drug-like Multi-cyclic Scaffold

2017

An easy method was developed for the efficient preparation of diversely new 5,5-disubstituted N(3),N'(3)-linkaged bis-hydantoins. At first, using the same methods, some ketones and terephthalaldehyde were converted to several hydantoins and a new bis-hydantoin , respectively. Then 1,6-dibromohexane, as a mild reagent, was employed for the alkylation and incorporation of synthesized substrates to produce quantitative yields of the desired bis-hydantoins. A tetrakis-hydantoin including four effective heterocyclic rings was also surprisingly synthesized from 5,5'-(1,4-phenylene)bis(imidazolidine-2,4-dione). The aim of this study is to synthesis of bis- and tetra core-hydantoins, bis-drug-like molecules employing a practical and reliable reaction process that requires slight amount of reagents; a process that is simple, accessible producing remarkable yields from an easy procedure that is cost effective and/or environmentally friendly. The resultant hydantoins potentially have b...

Synthesis of New Imidazolidin-2,4-dione and 2-Thioxoimidazolidin-4-ones via C-Phenylglycine Derivatives

Molecules, 2009

Hydantoins and their derivatives constitute a group of pharmaceutical compounds with anticonvulsant and antiarrhythmic properties, and are also used against diabetes. N-3 and C-5 substituted imidazolidines are examples of such products. As such, we have developed a synthesis of 2,4-dione and 2-thioxo-4-one imidazolidinic derivatives by reaction of amino acids with C-phenylglycine, phenyl isocyanate and phenyl isothiocyanate. Four amino-derivatives IG(1-4) and eight imidazolidinic derivatives, IM(1-8), were obtained in yields of 70-74%. The mass, infrared, 1 H and 13 C-NMR spectra of representative products are discussed.

A Manifold Three-Step Synthetic Route to Polycyclic Annulated Hydantoins via Cyclic Imines

Helvetica Chimica Acta, 2012

Dedicated to Professor Dieter Seebach on the occasion of his 75th birthday A new three-step synthetic pathway to generate polycyclic annulated hydantoins via rarely investigated heterocyclic imines is described. This procedure includes a one-pot reaction forming imines as precursor structures (e.g., Asinger reaction), followed by an Ugi reaction to build up a bisamide structure that allows a ring-closing reaction to the targeted hydantoins via substitution. This pathway leads to a multiplicity of substances with a potential pharmacological activity.

Synthesis of 3',4'-dihydro-2H,2'H,5H-spiro [imidazolidine-4,1'-naphthalene]-2,5-dione and its derivatives

Acta chimica Slovenica, 2014

The synthesis of two novel compounds, 1-amino-3',4'-dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5dione and 1,3-bis(hydroxymethyl)-3',4'-dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, was reported. The structures of the compounds were verified by 1 H, 13 C NMR and IR spectroscopy and quantum-chemical calculations at DFT level.

Synthesis of New Imidazolidin 2 4 dione and 2 Thioxoimidazolidin

Hydantoins and their derivatives constitute a group of pharmaceutical compounds with anticonvulsant and antiarrhythmic properties, and are also used against diabetes. N-3 and C-5 substituted imidazolidines are examples of such products. As such, we have developed a synthesis of 2,4-dione and 2-thioxo-4-one imidazolidinic derivatives by reaction of amino acids with C-phenylglycine, phenyl isocyanate and phenyl isothiocyanate. Four amino-derivatives IG(1-4) and eight imidazolidinic derivatives, IM(1-8), were obtained in yields of 70-74%. The mass, infrared, 1 H and 13 C-NMR spectra of representative products are discussed.

Synthesis of series of different imidazolidine-2,4-dione derivatives and evaluation of their antimicrobial potential

Kragujevac Journal of Science

A series of twenty two different imidazolidine-2,4-dione derivatives, divided according to their structure into five groups, including alkyl, alkenyl or aryl 5,5disubstituted hydantoins, spirohydantoins, and fused bicyclic and tricyclic hydantoins, was synthesized and examined for in vitro antimicrobial activity against 15 strains of bacteria and 4 strains of yeast. The antimicrobial activity was evaluated by the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC) using the microdilution method. The assayed compounds exerted moderate antibacterial and weak antifungal activity. The antimicrobial activities were influenced by the structure and concentration of the tested compounds as well as the type of test microorganisms. The fused bicyclic hydantoin derivatives obtained by organoselenium induced intramolecular cyclization exhibited the highest inhibitory activity. The examined hydantoin derivatives seem as drug-like candidate...

A new straightforward approach to 3-(arylideneamino)hydantoins

Chemistry of Heterocyclic Compounds, 2020

Hydantoin, first described in 1861, and its derivatives are one of the most important representatives of imidazole family due to their availability 1-4 and a wide range of biological activities. 5 Among hydantoins, N-aminosubstituted structures are particularly interesting from the pharmaceutical point of view. For example, 1-aminohydantoin derivatives such as dantrolene, azimilide, and nitrofurantoin are used as important drugs (Fig. 1). 3-5 It is also known that some 3-aminohydantoin derivatives are formyl peptide receptor (FPR2) modulators 6 and TNF-α inhibitors, 7 show anticonvulsant, 8 antihypertensive, 9 antibacterial, 10 and fungicidal activities. 11 However, in contrast to 1-aminohydantoins, their 3-amino analogs are much less studied. The described syntheses of 3-aminohydantoin derivatives from acyclic precursors generally involve formation of one or two C-N bonds, e.g., N(3)-C(4), 8,12-15 C(2)-N(3), 16-18 both N(1)-C(2) and N(3)-C(4), 19-23 both N(1)-C(5) and N(3)-C(4) bonds. 24 3-Aminohydantoins were also prepared using recyclizations of certain heterocyclic compounds. 25-33 It should be noted that there are only a few reports on the synthesis of N-arylidene-3-aminohydantoins. The latter, being analogs of 1-aminohydantoin pharmaceuticals (see Fig. 1), can be considered as promising compounds for the discovery of new drugs. They have been synthesized by condensation of 5,5-disubstituted 3-aminohydantoins with aldehydes, 34,35 reaction of N-phenoxycarbonylhydrazones with N-substituted glycine esters, 19,36 and treatment of hexahydro-1,2,4-triazine-3,6-dione with 4-dimethylaminobenzaldehyde or 4-nitrobenzaldehyde in AcOH under reflux. 33 However, these methods suffer from various disadvantages including poor synthetic flexibility, the use of some toxic reagents, sometimes low yields, etc. Thus, the development of a new efficient approach to N-arylidene derivatives of 3-aminohydantoins is of great importance. Previously, we have described a general method for the synthesis of various 4-(tosylmethyl)semicarbazones 1 and demonstrated that they readily react with some H-, O-, S-, N-, P-, and C-nucleophiles to give the corresponding products of the tosyl group substitution. 37 We hypothesized