Reactions of methyl 3-hydroxythiophene-2-carboxylate. Part 4. Synthesis of methyl 5-azolyl-3-hydroxythiophene-2-carboxylates

The indirect introduction of an azolyl group in position 5 of compound 1 by an easy two-step procedure taking place at room temperature is described. A similar procedure yields the 4-chloro derivatives of these 5-azolyl compounds. The same method is applied for the introduction of a 5-azido group and from the 5-azido compounds, 5-v-triazolyl derivatives are obtained by a known method.     

Synthesis of 4-aminomethyl-tetrahydrofuran-2-carboxylates with 2,4-cis and 2,4-trans relationships

Templated tetrahydrofuran-based γ-azido esters were prepared with the C-2 and C-4 functionalities in cis and trans relative configurations. This was achieved by ring contraction of the suitably protected 2-O-triflates of pentono-1,5-lactones (d-ribose and l-arabinose) with subsequent introduction of the azide via the 4-O-triflate. Access to a corresponding β-azido ester was achieved in good yield. Little elimination product was observed by introduction of the azide via the 3-O-triflate. These azido esters are scaffolds, which may be predisposed to adopt secondary structural motifs, for example, for use as peptidomimetics; they may also be utilised for the preparation of stereodiverse compound libraries.     

Heterocycles. LXXXII. Some investigations on 1,2,3-benzotriazines

Various 4-substituted 1,2,3-benzotriazines ( 2, 6, 7 ) have been prepared and of particular interest was the 4-azido derivative ( 11 ) as a potential azidotetrazolo tautomerism exhibiting compound. However, no such interconversion could be established and this compound exists exclusively in the azido form. 2,5-bis-(Arylamino)-1,3,4-thiadiazoles (9) have been found to result from the reaction between 4-hydrazino-1,2,3-benzotriazine and aryl isothiocyanates. In addition, a ring opening reaction between 4-hydrazino-1,2,3-benzotriazine gave 2-(tetrazol-5″-yl)-2′,4′-dihy-droxyazobenzene ( 10 ) and photochemical conversion of the 4-azido derivative gave s-tetrazino-[2,3-b:5,6-b′]diindazole(12).     

Alternate pathway for the click reaction of 2-(2-azidophenyl)-4,5-diaryloxazoles

The CuSO₄/ascorbate-mediated ‘click’ reaction of 2-(2-azidophenyl)-4,5-diaryloxazoles and arylacetylenes proceeded through an alternate pathway whereby reduction of the azide predominated over formation of the 1,2,3-triazole-forming cycloaddition. The unimolecular product, 2-(2-aminophenyl)-4,5-diphenyloxazole, was isolated which appears to be a formal reduction of the arylazide to the corresponding arylamine. A series of oxazoles which possessed various substituents (F, Cl, Br, OCH₃) on the 4,5-diaryl rings and having the 2-azido group on the 2-oxazolylphenyl position were submitted to the same ‘click’ conditions and gave the corresponding arylamine products (73–99%). The reaction appears to be specific toward the ortho-azido substitution of the polycyclic system, as the corresponding azidomethyl-substituted phenyl oxazoles do not give the ‘reduction’ products but gave the expected click products with the acetylenic co-reactants.     

Synthesis and Structural Characterization of [Mn(ethyl isonicotinate)(2)(N(3))(2)](n)(), a Two-Dimensional Alternating Ferromagnetic-Antiferromagnetic Compound. Magnetostructural Correlations for the End-to-End Pseudohalide-Manganese System

Three compounds with formula [Mn(L)(2)(N(3))(2)](n)(), in which L is 4-acpy = 4-acetylpyridine (1), Etinc = ethyl isonicotinate (2), and py = pyridine (3), have been studied from the magnetic point of view. The new compound [Mn(L)(2)(N(3))(2)](n)() (2) crystallizes in the monoclinic system, space group P2(1)/a (No. 14), formula [C(16)H(18)MnN(8)O(4)], with a = 15.176(5) ?, b = 9.060(3) ?, c = 15.760(6) ?, beta = 111.62(3) degrees, and Z = 4. Compounds 1 and 2 are two-dimensional systems, whereas 3 is a 3-D compound. Compound 2 shows ferromagnetic Mn(2)(N(3))(2) dimeric entities linked antiferromagnetically to the four neighboring dimeric entities by four end-to-end azido bridges, leading to an alternate ferromagnetic-antiferromagnetic two-dimensional compound. MO calculations have been performed to study the superexchange pathway for the manganese 1,3-azido system.     

Synthesis of a Chiral Hexane-1,6-Dinitrile from D-Glucose

Abstract

Using well-established methodology, D-glucose was transformed into a tribenzoyloxy cyclohexanone oxime derivative. Sodium azide treatment permitted the regiospecific exchange of the benzoyloxy group at a α-position relative to ketone oxime. Under standard Beckmann conditions the α-azido was oxime cleaved to provide an ω-dicyano compound.     

A novel tetranuclear copper(II) complex with alternating mu 1,1-azido and phenoxo bridges: synthesis,structure, and magnetic properties of [Cu4(mu-salen)2(mu 1,1-N3)2(N3)2

A novel tetranuclear copper(II) complex containing alternating mu(1,1)-azido and monophenoxo bridges has been synthesized and characterized by spectroscopic methods, X-ray single-crystal analysis, and variable-temperature magnetic measurements. The magnetic behavior, investigated in the temperature range 2-300 K, indicates that the interactions between copper ions are antiferromagnetic in nature for both azido and phenoxo bridges. The temperature dependence of the magnetic susceptibility was fitted with J(1) = -12.8 cm(-1), J(2) = -10 cm(-1), g = 2.171, 2.1% paramagnetic component, and negligible temperature-independent paramagnetism (5 x 10(-8)). At variance with the earlier reports of these types of complexes containing a mu(1,1)-azido group, the end-on double-azido-bridged copper(II) center in this complex shows an antiferromagnetic interaction.     

Reactions of 2,3,5-trichloro-4,4-ethylenedioxy-2-cyclopentenone with some ambident nucleophiles. Sterically loaded functionalized 6-azabicyclo[3.1.0]hex-5-enes

2,3,5-Trichloro-4,4-ethylenedioxy-2-cyclopentenone reacted with sodium azide in tetrahydrofuran to give the expected 3-azido derivative which was converted into 1,3-dichloro-4,4-ethylenedioxy-6-azabicyclo-[3.1.0]hex-5-en-2-one and 3-amino-2,5-dichloro-4,4-ethylenedioxy-2-cyclopentenone on heating in chloroform. The reaction of 2,3,5-trichloro-4,4-ethylenedioxy-2-cyclopentenone with potassium thiocyanate, depending on the conditions, afforded the corresponding 3-thiocyanato derivative or symmetric sulfide. Treatment of the title compound with hydroxylamine resulted in opening of the dioxolane ring with simultaneous formation of oxime via replacement of chlorine at the neighboring sp ²-carbon atom.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 10, 2004, pp. 1569–1573.Original Russian Text Copyright © 2004 by Shavaleeva, Ivanova, Usmanova, Akhmetvaleev, Miftakhov.     

A directed chiral synthesis of amino acids from boronic esters

Conversion of (s)-pinanediol (1S)-1-haloalkylboronates to (1R)-1-azido boronates, homologation with (dichloromethyl)lithium to 1-chloro-2-azido boronates, oxidation with sodium chlorite to the α-azido acids, and catalytic hydrogenation yielded L-amino acids, 92-96% enantiomeric excess.     

The mild cleavage of 2-amino-2-deoxy-D-glucoside methoxycarbonyl derivatives

The conversion of methyl carbamate to the corresponding free amine is described for a series of 2-amino-2-deoxy-D-glucosamine derivatives. Cleavage of methoxycarbonyl moiety with MeSiCl(3) and triethylamine in dry THF at 60 degrees C and subsequent aqueous hydrolysis yields the free amine in 54 to 93% yields. The selective cleavage of methyl carbamates with MeSiCl(3) in the presence of a 2,2,2-trichloroethoxycarbonyl group or 2-azido glycosides affords selectively, orthogonal N-deprotected carbohydrates.     

Alcaloides stéroïdiques—CLXVI : Synthese d'azides tertiaires en serie alicyclique-II. Mechanisme de formation et isomerisation des azido-5α et 5β pregnanes

Treatment of 6β-hydroxy 5α -prégnane by N₃H/BF₃-etherate/benzene gave 5α and 5β-azido prégnanes with C₅→C₆ hydride transfer. The kinetic product was 5α-azido pregnane which epimerized into a thermodynamic mixture 5α-azido rlarr2; 5β-azido. N₃H Assistance was necessary for epimerization. Chemical degradation and ¹³C NMR study supported these structural assignments.     

A novel synthesis, including asymmetric synthesis, of α-quaternary α-amino acid methyl esters from ketones via sulfinyloxiranes

Sulfinyloxiranes were synthesized from ketones and chloromethyl p-tolyl sulfoxide in two steps in almost quantitative yields. The sulfinyloxiranes were treated with NaN₃ in the presence of NH₄Cl to afford α-azido aldehydes, which were oxidized with iodine in the presence of KOH in methanol to give α-azido methyl esters in good overall yields. Catalytic hydrogenation of the α-azido esters afforded α-quaternary α-amino acid methyl esters in quantitative yields. Starting from β-tetralone and optically pure (R)-chloromethyl p-tolyl sulfoxide, an asymmetric synthesis of optically pure (R)-(+)-methyl 2-aminotetraline-2-carboxylate was realized in good overall yields.     

Synthesis of natural products via tertiary azides. II. 2-alkyl and 2-aryl indoles.

A new route to indoles: the acid-catalysed breakdown of 1-azido 1,2-dihydrobenzocyclobutenes.     

One-pot azidochlorination of glycals

A simple one-pot azidochlorination for the preparation of nitrogen-containing Koenigs-Knorr glycosyl donors proceeds upon reaction of protected glycals with sodium azide, ferric chloride, and hydrogen peroxide. Different mono- and disaccharide galactals and glucals are converted in a highly α-selective manner to the 2-azido glycosyl chlorides. Starting from disaccharide galactals, building blocks for the synthesis of the T-antigen are obtained in a straightforward manner. The simplicity of the reaction conditions allows for an efficient and scalable α-selective synthesis of 2-azido substituted glycosyl chlorides.     

Syntheses and Reactions of 1′,2′-Unsaturated 2′,3′-Seconucleoside Analogues

The 1′,2′-unsaturated 2′,3′-secoadenosine and 2′,3′-secouridine analogues were synthesized by the regioselective elimination of the corresponding 2′,3′-ditosylates, 2 and 18 , respectively, under basic conditions. The observed regioselectivity may be explained by the higher acidity and, hence, preferential elimination of the anomeric H–C(1′) in comparison to H? C(4′). The retained (tol-4-yl)sulfonyloxy group at C(3′) of 3 allowed the preparation of the 3′-azido, 3′-chloro, and 3′-hydroxy derivatives 5–7 by nucleophilic substitution. ZnBr₂ in dry CH₂Cl₂ was found to be successful in the removal (85%) of the trityl group without any cleavage of the acid-sensitive, ketene-derived N,O-ketal function. In the uridine series, base-promoted regioselective elimination (→ 19 ), nucleophilic displacement of the tosyl group by azide (→ 20 ), and debenzylation of the protected N(3)-imide function gave 1′,2′-unsaturated 5′-O-trityl-3′-azido-secouridine derivative 21 . The same compound was also obtained by the elimination performed on 2,2′-anhydro-3′-azido-3′-azido-3′-deoxy-5′-O-2′,3′-secouridine ( 22 ) that reacted with KO(t-Bu) under opening of the oxazole ring and double-bond formation at C(1′).     

Enzymatic and chiral HPLC resolution of α-azido acids and amides

For the first time, enzymatic resolution of α-azido acid amides has been successfully demonstrated with high yields and enantiomeric excess. In one case dynamic kinetic resolution was achieved leading to more than 50% yield of the enantiomerically pure azido acid. Chiral HPLC was also used to separate racemic α-azido acids and the separation process was automated. Two routes to enantiopure α-azido acid building blocks for solid-phase peptide synthesis have, therefore, been established.     

Nucleophilic substitution at C2 of hexopyranoses

Conclusions The 2-O-mesyl derivatives of hexopyranoses react with NaN₃ to give the 1-azido derivatives, in which connection the reaction of the D-mannose derivative proceeds with complete inversion of the configuration at C², while the reaction of the D-galactose derivative proceeds with a partial retention of the configuration at C².Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1638–1641, July, 1981.     

Crystal structure of dinuclear azide-bridged copper(II) complex [Cu2((3,4-MeO-Ba)2En)2(μ1,1-N3)2(N3)2]{(3,4-MeO-Ba)2En=N,N′-Bis(3,4-dimethoxybenzylidene)-1,2-ethanediamine}

New dinuclear copper(II)-azido complex [Cu₂((3,4-MeO-Ba)₂En)₂(μ_1,1-N₃)₂(N₃)₂] (I) ((3,4-MeO-Ba)₂En = N,N′-bis(3,4-dimethoxybenzylidene)-1,2-diaminoethane) has been synthesized and characterized by elemental analyses, FT-IR spectroscopy, and X-ray single-crystal diffraction. Complex I consists of a dinuclear unit that represents a new example of a copper(II)-azido compound and the Cu²⁺ ions are bridged by two azido ions in a double end-on fashion, consisting of two terminally bonded azido ligands. The Schiff base ligand (3,4-MeO-Ba)₂En is chelated by two imino nitrogen atoms.     

Catalyst-free preparation of 1,2,4,5-tetrasubstituted imidazoles from a novel unexpected domino reaction of 2-azido acrylates and nitrones

A highly efficient and convenient method for the synthesis of 1,2,4,5-tetrasubstituted imidazoles from readily accessible 2-azido acrylates and nitrones has been developed. This reaction proceeded under mild conditions without the assistance of any metal, acid, or base.     

Generation of new fluorophore by Click chemistry: synthesis and properties of β-cyclodextrin substituted by 2-pyridyl triazole

2-Pyridyl triazole substituted β-cyclodextrins, formed by a Huisgen [2+3] cycloaddition reaction between per-(6-azido)-β-cyclodextrins and 2-ethynylpyridine, exhibited interesting solvent-polarity dependent fluorescence properties and acted as Zn²⁺-sensitive fluorogenic chelating agents with a significant fluorescence enhancement and a large red-shift in emissions. No fluorescent emission was observed with phenyl or hydroxymethyl triazole conjugated sugar derivatives.