Imidazole 3-oxides Research Articles

The crystal structure of 1-(2-carboxyethyl)-1H-imidazole 3-oxide

Abstract C6H8N2O3, monoclinic, P21/n (no. 14) a = 5.2014(4) Å, b = 13.4511(9) Å, c = 9.6808(6) Å, β = 97.867(3)∘, V = 670.94(8) Å3, Z = 4, R gt (F) = 0.0451, wR ref (F 2) = 0.1308, T = 170 K.

The crystal structure of 1-(carboxymethyl)-1H-imidazole 3-oxide

Abstract C5H6O3N2, monoclinic, P21/c (no. 14), a = 11.3451(10) Å, b = 4.9505(5) Å, c = 10.3200(8) Å, β = 99.220(3)°, V = 572.12(9) Å3, Z = 4, R gt (F) = 0.0429, wR ref (F 2) = 0.1031, T = 170 K.

A dynamic and electrostatic potential prediction of the prototropic tautomerism between imidazole 3-oxide and 1-hydroxyimidazole in external electric field.

In order to obtain an optimum scheme for separating the proton-transfer tautomer, a dynamic investigation into the effect of the external electric field on the proton-transfer tautomeric conversion in imidazole 3-oxide and 1-hydroxyimidazole was carried out at the M06-2X/6-311++G** and CCSD(T)/6-311++G(2d,p) level, accompanied by the analysis of the surface electrostatic potentials. The results show that, for both the forward reaction "imidazole 3-oxide → N-hydroxyimidazole free radical → 1-hydroxyimidazole" and its reverse reaction processes, the fields parallel to the N→O or N-OH bond axis affect the barrier heights and rate constants considerably more than those parallel to the other orientations. As the field strength is increased along the orientation from the O to N atom, the chemical equilibrium moves toward the direction for the formation of 1-hydroxyimidazole, while the amount of imidazole 3-oxide is increased with the increased field strength along the opposite orientation. In the fields along the orientation consistent with the dipole moment, the electrostatic potentials and their variances "abnormally" increase for the transition states with the N→O bond in comparison with those in no field (they decrease generally), which enhances the nucleophilicity of the coordination O atom and the electrophilicity of the activated H atom. The analyses of the AIM (atoms in molecules) and NICS (nucleus-independent chemical shift) were used to explain the above anomaly. Graphical Abstract Electrostatic potentials and their variances "abnormally" increase in the external electric field, which greatly affects tautomeric conversion.

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts.

Adamantyloxyamine reacts with formaldehyde to give N-(adamantyloxy)formaldimine as a room-temperature-stable compound that exists in solution in monomeric form. This product was used for reactions with α-hydroxyiminoketones leading to a new class of 2-unsubstituted imidazole 3-oxides bearing the adamantyloxy substituent at N(1). Their reactions with 2,2,4,4-tetramethylcyclobutane-1,3-dithione or with acetic acid anhydride occurred analogously to those of 1-alkylimidazole 3-oxides to give imidazol-2-thiones and imidazol-2-ones, respectively. Treatment of 1-(adamantyloxy)imidazole 3-oxides with Raney-Ni afforded the corresponding imidazole derivatives without cleavage of the N(1)–O bond. Finally, the O-alkylation reactions of the new imidazole N-oxides with 1-bromopentane or 1-bromododecane open access to diversely substituted, non-symmetric 1,3-dialkoxyimidazolium salts. Adamantyloxyamine reacts with glyoxal and formaldehyde in the presence of hydrobromic acid yielding symmetric 1,3-di(adamantyloxy)-1H-imidazolium bromide in good yield. Deprotonation of the latter with triethylamine in the presence of elemental sulfur allows the in situ generation of the corresponding imidazol-2-ylidene, which traps elemental sulfur yielding a 1,3-dihydro-2H-imidazole-2-thione as the final product.

SYNTHESIS OF 2-(3-CHROMENYL)-4-ETHOXYCARBONYL-1-(4-FLUOROBENZYL)-5-METHYLIMIDAZOLE 3-OXIDES

In addition to our search for probable HIV-1 integrase inhibitors in the series of imidazole derivatives a possibility of preparation of 2-(3-chromenyl)substituted imidazole 3-oxides containing fluorobenzyl moiety in position 1 of imidazole ring as a potential pharmacophore was demonstrated. 4-ethoxycarbonyl-1-(4-fluorobenzyl)-5-methyl-2-(4-oxo-4H-chromen-3-yl)imidazole 3-oxide 4a and 4-ethoxycarbonyl-2-(6-hydroxy-4-oxo-4H-chromen-3-yl)-1-(4-fluorobenzyl)-5-methyli-midazole 3-oxide 4b were synthesized starting with fluorobenzylamine 1, ethyl 2-(hydroxyimino)-3-oxobutanoate 2 and 4-oxo-4H-chromen-3-carbaldehyde 3a or 6-hydroxy-4-oxo-4H-chromen-3-carbaldehyde 3b, respectively. The condensation was carried out at room temperature in glacial acetic acid. Two novel imidazole N-oxides were characterized by 1H NMR and IR spectroscopy and mass-spectrometry. It should be noted that in 1H NMR spectra of the discussed imidazole N-oxides (recorded in deuterated DMSO) the singlet of the proton in the position 2 of chromenyl ring is shifted to lower field (8.70 and 8.78, respectively) as compared with the signals of other aromatic protons. Such deshielding is typical for this kind of heterocyclic system and may be explained by the influence of the electron-withdrawing of N-oxide moiety. In the IR spectrum of 4-ethoxycarbonyl-1-(4-fluorobenzyl)-5-methyl-2-(4-oxo-4H-chromen-3-yl)imidazole 3-oxide 4a the absorption bands corresponding to the carbonyl groups appear at 1641 cm-1 (for C=O in the position 4 of chromenyl ring) and 1641 cm-1 (C=O of the ester moiety). In the IR spectrum of 4-ethoxycarbonyl-2-(6-hydroxy-4-oxo-4H-chromen-3-yl)-1-(4-fluorobenzyl)-5-methylimidazole 3-oxide 4b the position of the former band remains practically unchanged (1646 cm-1), whereas the latter band is shifted to higher frequencies (1715 cm-1) due to intermolecular interactions with OH-group in the position 6 of the chromene. The absorption band for this group appears as a broad band with medium intensity and maximum absorption at 3228 cm-1. In the mass spectra of imidazole N-oxides under consideration peaks of the molecular ions (M+) and peaks (M-16) are observed. The demonstrated possibility of the synthesis of the titled compounds allows the further planning of the synthesis of a series of such structures varying the substituents in both chromenyl and imidazole rings. Forcitation:Razgulyaev V.I., Nikitina P.A., Koldaeva T.Yu., Miroshnikov V.S., Perevalov V.P. Synthesisof 2-(3-chromenyl)-4-ethoxycarbo-nyl-1-(4-fluorobenzyl)-5-methylimidazole 3-oxides. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2017. V. 60. N 2. P. 17-19.

Methods of synthesis and physicochemical properties of 1-hydroxyimidazoles, imidazole 3-oxides, and their benzoannulated analogs

We provide a systematic overview of methods suitable for the synthesis of 1-hydroxyimidazoles, imidazole 3-oxides, and their benzoannulated analogs. Generalized spectral and structural data of the considered compounds are presented. This review covers literature sources from 1964 until 2016, as well as some earlier works.

Synthesis of New Imidazole 3-Oxides; Unexpected Deoxygenation of Some Derivatives in the Reaction with 2,2,4,4-Tetramethylcyclobutane-1,3-dithione

Whereas the reaction of a series of 1,4,5-trisubstituted imidazole 3-oxides with 2,2,4,4-tetramethylcyclobutane-1,3-dithione gave the corresponding imidazole-2-thiones by a sulfur-transfer reaction via [2+3] cycloaddition, an unexpected deoxygenation occurred in the case of 4-acetyl- 1-(adamantan-1-yl)- 5-methylimidazole 3-oxide. It was shown that the presence of an electron- withdrawing substituent at C(4) and the bulky 1-adamantyl group at N(1) are necessary to enable this reaction course. A reaction mechanism via a zwitterion, followed by a 1,3-cyclization and elimination of an oxathiirane, is proposed.

First synthesis of the N(1)-bulky substituted imidazole 3-oxides and their complexation with hexafluoroacetone hydrate

Synthesis of new 2-unsubstituted imidazole 3-oxides bearing bulky substituents at the N(1) atom, based on the condensation of appropriate alkylamines, formaldehyde, and corresponding α- (hydroxyimino)ketone, is described. Treatment of imidazole 3-oxides with hexafluoroacetone hydrate (HFAH) yields crystalline 1:1 complexes in nearly quantitative yields. Heating of isolated complexes possessing phenyl ring at the C(4) atom of imidazole ring, results in their isomerization into imidazol-2-ones in fair yields. The formation of analogous complexes of HFAH with other azole N-oxides is also described.

Synthesis and selected transformations of 3-oxido-1H-imidazole-4-carboxamides

An efficient synthesis of newN-alkyl- andN-aryl-3-oxido-1H-imidazole-4-carboxamides based on exploration of inexpensive, commercially available ethyl acetoacetate, paraformaldehyde and primary amines is described. Representative compounds were tested in selected transformations, such as ‘sulfur-transfer reaction’ leading to imidazole-2-thiones and isomerization to corresponding imidazol-2-ones. Strong intramolecular hydrogen bonding via theN-oxide function results in the reduced reactivity of 3-oxido-1H-imidazole-4-carboxamides in both reactions. Moreover, the palladium catalyzed C(2)-arylation of imidazole ring as well as azide-alkyne [3+2] cycloaddition using theN-propargyl substituted 4-carboxamide derived from an imidazole 3-oxide as a dipolarophile, were also studied.

1,3-Dipolar cycloaddition reaction of 4,5-dihydro-1H-imidazole 3-oxides with alkynes

4,5-Dihydro-1H-imidazole 3-oxides bearing different substituents at positions 1 and 2 of the heterocycle were shown to react with a wide range of acceptor-substituted alkynes forming corrsponding cycloadducts - derivatives of 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole. High regioselectivity of this process stipulated by conjugation of the nitrogen atom with the nitrone group was revealed.

1,3-Dipolar cycloaddition or nucleophilic addition: Influence of solvents and nature of substituents in the reagent and substrate molecules on the reaction of 4,5-dihydro-1H-imidazole 3-oxides with alkynes

Two competitive processes - 1,3-dipolar cycloaddition and nucleophilic addition - in the reaction of 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole 3-oxides with asymmetrically substituted alkynes were shown to occur. The influence of solvents and the nature of substituents in the reagent and substrate molecules on the rate ratio of these competitive processes were studied.

First Examples of Reactions of AzoleN-Oxides with Thioketones: A Novel Type of Sulfur-Transfer Reaction

The reactions of 1,4,5-trisubstituted imidazole 3-oxides 1a - k with cyclobutanethiones 5a,b in CHCl3 at room temperature give imidazole-2(3H)-thiones 9a - k in high yield. The second product formed in this reaction is 2,2,4,4-tetramethylcyclobutane-1,3-dione (6a; Scheme 2). Similar reactions occur with 1 and adamantanethione (5c) as thiocarbonyl compound, as well as with 1,2,4-triazole-4-oxide derivative 10 and 5a (Scheme 3). A reaction mechanism by a two-step formation of the formal cycloadduct of type 7 via zwitterion 16 is proposed in Scheme 5. Spontaneous decomposition of 7 yields the products of this novel sulfur-transfer reaction. The starting imidazole 3-oxides are conveniently prepared by heating a mixture of 1,3,5-trisubstituted hexahydro-1,3,5-triazines 3 and alpha-(hydroxyimino) ketones 2 in EtOH (cf. Scheme 1). As demonstrated in the case of 9d, a 'one-pot' procedure allows the preparation of 9 without isolation of the imidazole 3-oxides 1. The reaction of 1c with thioketene 12 leads to a mixture of four products (Scheme 4). The minor products, 9c and the ketene 15, result from an analogous sulfur-transfer reaction (Path a in Scheme 5), whereas the parent imidazole 14 and thiiranone 13 are the products of an oxygen-transfer reaction (Path b in Scheme 5).

1-Hydroxyimidazole Derivatives IV. Quaternary Salts Derived from 1-Hydroxy-1H-imidazoles

General procedures for the synthesis of 3-substituted 1-alkoxy, 1-arylmethoxy, and 1-phenyloxyimidazolium salts are described. 1-3-Bis(arylmethoxy)imidazolium salts can be prepared using phase transfer conditions for the alkylation of 1-hydroxy-1H-imidazole 3-oxides. When the hydroxy group of 1-hydroxy-1H-imidazoles is protected during quaternization, 1-substituted imidazole 3-oxides are obtained.

ChemInform Abstract: PHOTOLYSIS OF 2‐UNSUBSTITUTED IMIDAZOLE 3‐OXIDES

Chemischer InformationsdienstVolume 9, Issue 6 Preparative Organic Chemistry ChemInform Abstract: PHOTOLYSIS OF 2-UNSUBSTITUTED IMIDAZOLE 3-OXIDES R. BARTNIK, R. BARTNIKSearch for more papers by this authorG. MLOSTON, G. MLOSTONSearch for more papers by this author R. BARTNIK, R. BARTNIKSearch for more papers by this authorG. MLOSTON, G. MLOSTONSearch for more papers by this author First published: February 7, 1978 https://doi.org/10.1002/chin.197806080Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume9, Issue6February 7, 1978 RelatedInformation

Studies in azole chemistry. Part I. Syntheses and reactions of some imidazole 3-oxides

The syntheses are described of 1-benzyl-5-methyl-, 1-benzyl-4,5-dimethyl-, and 1-benzyl-5-hydroxymethyl-4-methyl-imidazole 3-oxide. The first two are deoxygenated by phosphorus trichloride, deoxygenated and chlorinated at C-2 by phosphoryl chloride, and take part in 1,3-dipolar addition reactions. By quaternisation and reaction with cyanide they give 2-cyanoimidazoles.

The tautomerism of heteroaromatic compounds with five-membered rings. Part XII. The imidazole 3-oxide versus 3-hydroxy[3H]imidazole equilibrium

Spectroscopic and pKa value comparisons with model compounds indicate that benzimidazole 3-oxide exists predominantly in the NH-form in aqueous solution, but predominantly in the OH-form in non-polar solvents. For 2,4,5-triphenylimidazole 3-oxide, steric hindrance in the N-methyl model complicates matters, but this compound appears to exist as comparable amounts of OH- and NH-forms in aqueous solution and in the OH-form in non-polar solvents. The structures of these compounds in the solid state are discussed.

Conversions of 5-hydroxy-5, 6-dihydro-4H-1, 2, 5-oxadiazines

Oxidation of 5-hydroxy-5, 6-dihydro-4H-1, 2, 5-oxadiazines leads to the formation of 6H-1,2, 5-oxadiazine-5-oxides. Acid treatment of 5, 6-dihydro-4H-1, 2, 5-oxadiazines and 6H-1, 2, 5-oxadiazine-5-oxides results in heterocyclic-ring contraction with the formation of imidazole 3-oxides and 1-hydroxyimidazole 3-oxides. The structures of the products are established by their spectral properties and confirmed by independent synthesis.