2-(2-Hydroxyphenyl)imidazolidines and their O-phosphorylated derivatives

2-(2-Hydroxyaryl)imidazolidines were synthesized by reaction of aromatic carbonyl compounds with N,N′-dialkylethylenediamines. The title compounds were also prepared using the corresponding Schiff bases instead of carbonyl compounds. Phosphorylation of 2-(2-hydroxyphenyl)imidazolidines with phosphoryl and phosphorothioyl chlorides and phosphorochloridites was accomplished. The reaction of O-phosphorylsalicylaldehyde with N,N′-dialkylethylenediamines also afforded 2-(2-hydroxyphenyl)imidazolidines.     

Condensation of <Emphasis Type="Italic">N</Emphasis>-(2-vinyloxyethyl)ethane-1,2-diamine with carbonyl compounds

Condensation of N-(2-vinyloxyethyl)ethane-1,2-diamine with aromatic aldehydes gave mixtures of 2-aryl-1-(2-vinyloxyethyl)imidazolidines and N-arylmethylidene-N′-(2-vinyloxyethyl)ethane-1,2-diamines in an overall yield of 79–84%, while analogous condensation with cyclic and acyclic ketones resulted in the formation of only the corresponding Schiff bases (yield 53–83%).     

Regiodivergent synthesis of pyrazino-indolines vs. triazocines via α-imino carbenes addition to imidazolidines

Hexahydropyrazinoindoles were prepared in a single step from N-sulfonyl triazoles and imidazolidines. Under dirhodium catalysis, α-imino carbenes were generated and formed nitrogen ylide intermediates that, after subsequent aminal opening, afforded the pyrazinoindoles predominantly via formal [1,2]-Stevens and tandem Friedel–Crafts cyclizations. Of mechanistic importance, a regiodivergent reactivity was engineered through the use of a specific unsymmetrically substituted imidazolidine that promoted the exclusive formation of 8-membered ring 1,3,6-triazocines. Based on DFT calculations, an original Curtin–Hammett-like situation was demonstrated for the mechanism. Further derivatizations led to functionalized tetrahydropyrazinoindoles in high yields.

Hexahydropyrazinoindoles are prepared in a single step from N-sulfonyl triazoles and imidazolidines. Of mechanistic importance, a regiodivergent reactivity can be engineered towards the exclusive formation of 8-membered ring 1,3,6-triazocines.     

Reactions of aromatic and heteroaromatic β-amino-β-polyfluoroalkylvinyl ketones with ethylenediamine. A new synthesis ofN,N′-unsubstituted imidazolidines

The reactions of aromatic and heteroaromatic β-amino-β-polyfluoroalkylvinyl ketones with ethylenediamine results in the formation of 2,3-dihydro-1H-1,4-diazepines,N,N′-unsubstituted imidazolidines, orN,N′-ethylenebis(aminovinyl ketones). The reaction route depends on the reaction conditions, the nature of the substituent at the carbonyl group, and the number of fluorine atoms in the polyfluoroalkyl radical.     

Diasteroselective synthesis of oxazolidines and imidazolidines via the Lewis acid catalyzed C-C cleavage of aziridines

In this work, cis-2,5-disubstitutedoxazolidines were efficiently constructed via a regioselective C-C bond cleavage of N-tosylaziridine 2,2-dicaboxylates and a subsequent [3+2] cycloaddition with aromatic aldehydes in the presence of Zn(OTf)₂. The reactions were highly diastereoselective to form oxazolidines in cis configurations. trans-2,5-Disubstituted imidazolidines were also diastereoselectively synthesized in the similar manner using imines as substrates and AgOTf as catalyst. Based on the detailed investigation of the substrate diversity for both reactions, including the electronic effects and the steric effects of the substituted groups on the aziridines, aldehydes, and imines, a stepwise mechanism was postulated for the diastereoselective formation of cis-2,5-disubstitutedoxazolidines and trans-2,5-disubstituted imidazolines.     

Vinyl-aziridines and cyclopropanes in Pd-catalyzed (3+2)-cycloaddition reactions with cyclic N-sulfonyl imines

Efficient palladium-catalyzed (3 + 2)-cycloaddition reactions of cyclic N-sulfonyl imines and vinyl-aziridines (or cyclopropanes) have been achieved. The reactions, with either vinylic substrate, proceed with excellent yields affording highly functionalized imidazolidine and pyrrolidine derivatives. The cycloadditions take place via the reaction of zwitterionic π-allyl palladium intermediates with cyclic N-sulfonyl imines through i) the formation of two NC bonds in the presence of vinylaziridines (synthesis of imidazolidines) and ii) one CC bond and one NC bond in the presence of vinylcyclopropanes (synthesis of pyrrolidines). Following on preliminary works on the diastereoselective synthesis of imidazolidines, herein we wish to give a broader view on the subject by describing derivatization reactions and attempts towards an enantioselective version. Moreover, we describe and discuss the behavior of each vinylic substrate (aziridine or cyclopropane) on the (3 + 2)-cycloaddition reactions. Mechanistic and (intriguing) selectivity outcomes are also going to be discussed.     

Reduction of substituted 1H-4,5-dihydroimidazolium salts

Reactions of several substituted 1H-4,5-dihydroimidazolium salts 1 with nucleophilic and electrophilic reducing agents acting via hydride transfer were explored. Reaction of compounds 1 with lithium aluminum hydride in THF afforded the corresponding imidazolidines 2 . When alkaline borohydrides (sodium borohydride, potassium borohydride, sodium cyanoborohydride) in ethanol at room temperature were used, partial or total over-reduction of compounds 2 leading to N,N,N'-trisubstituted ethylenediamines took place on occasion. Results may be explained taking into account that reductive cleavage of 2 proceeds via a stabilized iminium ion present in protic solvents. Treatment of compounds 1 with an excess of borane in THF afforded the corresponding imidazolidines 2 or their borane complexes, according to the substituent type.     

A novel atom-economic synthesis of functionalized imidazolidines through copper(I)-catalyzed domino three-component coupling and cyclization reactions

An interesting approach to functionalized imidazolidines is described. These compounds are obtained in a copper(I)-catalyzed domino three-component coupling and cyclization reaction involving two formaldehyde-derived imine units and a terminal alkyne. Alternatively, imidazolidines can be obtained from propargylamines and formaldehyde-derived imines. This strategy provides a straightforward and atom-economic pathway to construct imidazolidines with high yields and benefits from readily available starting materials, convenient one-pot operations.     

Preparation and thermal fragmentation of imidazolidines derived from aryl imines

Aryl imines of diethyl aminomalonate undergo facile dimerisation to imidazolidines. Heating the imidazolidines at 110° in the presence of N-phenyl maleimide or diethyl azodicarboxylate gives pyrrolidines and triazolidines respectively via a retro 1,3-dipolar cycloaddition.     

Heterocyclisations of 3-Trifluoroacetyl-lactams with Ethylenediamine and 2-Amino-ethanol

Heterocyclisations of 3-trifluoroacetyl-lactams 1a-d with ethylenediamine and 2-amino-ethanol proceeded without opening of the lactam structure to give imidazolidines 2a-d and oxazolidine 6.     

<Emphasis Type="Italic">N,N′</Emphasis>-Bis(9-anthrylmethyl)diamines as fluorescent chemosensors for transition metal cations

N,N′-Bis(9-anthryl)-substituted diamines, imidazolidines, and hexahydropyrimidines were synthesized, and their luminescence properties and complexing ability were studied. N,N′-Bis(9-anthrylmethyl)ethane-1,2-diamine and N,N′-bis(9-anthrylmethyl)butane-1,4-diamine were found to be effective and selective PET chemosensors for Zn²⁺ and H⁺, respectively. 2-[1,3-Bis(9-anthrylmethyl)hexahydropyrimidin-2-yl]-6-methoxyphenol can be used as fluorescent chemosensor for mercury(II) cations.     

The mass spectral fragmentation of 2-aryl-N,N′-dimethyl-1,3-imidazolidines and 2-aryl-1-3-dioxolanes

2-Aryl-N,N'-dimethyl-1,3-imidazolidines and 2-aryl-1,3-dioxolanes were subjected to 70 eV spectral analysis. Fragmentation pathways for both series of compounds are suggested. Aryl vs. benzylic hydrogen fragmentations were subjected to Hammett σ⁺  ρ plots. Incipient charge on the benzyl carbonium ion was stabilized by electron donating groups in both series of compounds. Dioxolanes were more sensitive to substituent effects (ρ = −0.639) than the imidazolidines (ρ = −0.251) implying that the positive charge on the fragmenting ion is more localized at the benzylic position of the imidazolidines than of the dioxolanes.     

Facile synthesis and cleavage of imidazolidines in a novel protection strategy for the preparation of peptides containing a reduced amide bioisostere

Unsymmetrical imidazolidines were obtained in 75-91% yield by treating monoalkoxycarbonyl vicinal diamines at room temperature with aqueous 37% formaldehyde in the presence of Montmorillonite KSF as a solid catalyst. The imidazolidines were shown to be useful intermediates in a novel protection strategy for the synthesis of peptide analogues containing a reduced glycine amide bioisostere. The imidazolidine intermediate was cleaved conveniently and efficiently by 50% TFA in methylene chloride.     

Solvent-free Mannich-type reaction as a strategy for synthesizing novel heterocalixarenes

Novel calix[2]imidazolidin[2]arenes were synthesized by solvent-free Mannich-type reaction, in quantitative yields, from 1,3-bis(2′-hydroxy-benzyl)imidazolidines and 1,3,6,8-tetraazatricyclo[4.4.1.1^3,8]dodecane (TATD).     

Convenient syntheses of unsymmetrical imidazolidines

Unsymmetrical imidazolidines 10-14, optically active imidazolidines 20-22, and 2,3-dihydro-1H-benzimidazoles 28 and 29 were synthesized in good to excellent yields by Mannich reactions of 1,2-ethanediamines 8a-c, 18a-c, or N-methyl-1,2-benzenediamine (26a) with benzotriazole and formaldehyde, followed by the nucleophilic substitution of the benzotriazolyl group with C-nucleophiles (Grignard reagents, sodium cyanide), an S-nucleophile (benzenethiol), and a P-nucleophile (triethyl phosphite).     

Condensation of 2- and 4-fluorobenzaldehydes with vinyl ethers derived from amino alcohols

2- and 4-Fluorobenzaldehydes reacted with amino alcohol vinyl ethers to give Schiff bases, oxazolidines, and imidazolidines containing a vinyloxy group. The products attract interest as potential biologically active compounds.     

Oxidative decarboxylative synthesis of 2-H-imidazolines from glyoxylic acid and 1,2-diamines

A novel method to prepare 2-H-imidazolines from glyoxylic acid monohydrate and 1,2-diamines is described; the key reaction of this method is the oxidative decarboxylation of the 2-carboxy imidazolidines by NBS.     

Synthesis of a new hetrocyclic system 7,8-dihydroimidazo[1,2-<Emphasis Type="Italic">c</Emphasis>][1,3]oxazolo[4,5-<Emphasis Type="Italic">e</Emphasis>]pyrimidine

2-(Acylaminocyanomethylene)imidazolidines are formed on interacting 2-acylamino-3,3-dichloro-acrylonitriles with ethylenediamine. The former are converted into new derivatives of oxazolo-[4,5-e]pyrimidine on treatment with trifluoroacetic acid, and then with triethyl orthoformate.     

Synthesis of Substituted 1H,5-Dihydroimidazolium Salts by Dehydrogenation of Imidazolidines

A study is presented on the scope of the method to obtain 1H-4,5-dihydroimidazolium salts 3 by dehydrogenation of 1,3-di and 1,2,3-trisubstituted imidazolidines 2. Of the dehydrogenating agents used, N-bromoacetamide leads to the best results, providing a simple and general method to prepare salts 3.     

The synthesis of 1‐[(substituted)pyrazol‐5‐yl]‐iminomethyl‐2‐nitroiminoimidazolidine and its derivatives

In this article 1‐[(substituted)pyrazol‐5‐yl]iminomethyl‐2‐nitroimino imidazolidines ( II ) and their derivatives were synthesized. All the compounds were verified by elemental analysis, ¹H NMR and IR. In the reaction of II with halides, two different results were observed.