Synthesis of heteroarylazulenes: transition metal free coupling strategy of azulene with heterocycles

Azulene reacts with highly electrophilic trifluoromethanesulfonates of N-containing heterocycles to give 1-dihydroheteroaryl and 1,3-bis(dihydroheteroaryl)azulene derivatives in a good yield. Treatment of the dihydroheteroarylazulene derivatives with KOH or tert-BuOK afforded 1-heteroaryl and 1,3-bis(heteroaryl)azulenes in a good yield.     

Synthesis of 1-(pyridyl, quinolyl, and isoquinolyl)azulenes by Reissert-Henze type reaction

Azulene derivatives reacted with N-oxide of several heterocycles in the presence of trifluoromethanesulfonic anhydride (Tf₂O) to afford 1-(pyridyl, quinolyl, and isoquinolyl)azulenes in good yield, respectively. In the case of the reaction with the 1-azulenyl methyl sulfide (12), 1,1′-biazulene derivative 13 was obtained under the similar reaction conditions. The first synthesis of unsymmetrical 1,3-di(pyridyl)azulene derivative was also established via our new preparation method following the electrophilic pyridinylation using the reaction with pyridine in the presence of Tf₂O.     

The first regioselective double electrophilic substitution of the C2-symmetric pseudo-meta-disubstituted [2.2]paracyclophanes

We report here the first examples of the regioselective double electrophilic substitution of chiral C₂-symmetric pseudo-meta-disubstituted [2.2]paracyclophanes. Thus, the double acylation of 4,15-dihydroxy[2.2]paracyclophane occurs ortho-regioselectively, whereas the double acylation of its respective dimethyl ether is completely para-regioselective. Double bromination of 4,15-dicarbomethoxy[2.2]paracyclophane regioselectively generates the pseudo-gem-substitution pattern. The approaches elaborated allow the synthesis of all three possible types of chiral bis-bifunctional compounds, which have two independent, although chemically and stereochemically equal, functional fragments with pseudo-meta mutual orientation of both pairs of identical substituents.     

First electrophilic substitution of 4-methoxyindole with triethyl orthoformate as an a1-synthon

Summary 4-Methoxyindole (2) reacts with triethyl orthoformate (1a) under proton catalysis to yield the functionalized indoles3a–3e in dependence on the reaction conditions. The attack of the electrophile takes place regiospecifically at the 3-position of the indole2

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Erste elektrophile Substitution von 4-Methoxyindol mit Orthoameisensäuretriethylester als a¹-Synthon (Kurze Mitt.)

Zusammenfassung In Abhängigkeit von den Reaktionsbedingungen reagiert 4-Methoxyindol (2) mit Orthoameisensäuretriethylester (1a) zu funktionalisierten Indolderivaten3a–3e. Der Angriff des Elektrophils erfolgt regiospezifisch an der 3-Position von2.

     

The Direct Synthesis of Arylxenon Trifluoromethanesulfonates via electrophilic substitution

The reaction of xenonbis(trifluoroacetate) and trifluoromethanesulfonic acid (triflic acid) gave the new, highly reactive unsymmetrical xenon-oxo species CF₃COOXeOSO₂CF₃. Benzene derivates, containing electron withdrawing substituents such as -F, -CF₃, -Cl or -NO₂ were electrophilic attacked by this intermediate to yield arylxenon trifluoromethanesulfonates. Via this one-pot synthesis trifluoromethanesulfonates with the cations [Xe(2,4,6-F₃C₆H₂)]⁺, [Xe(2-F-5-NO₂C₆H₃)]⁺, [Xe(2-F-5-CF₃C₆H₃)]⁺ and [Xe(3,5-(CF₃)₂C₆H₃)]⁺ were prepared. All compounds were characterized by their NMR, mass, and vibrational spectra. Additionally, several new arylxenon trifluoromethanesulfonates were detected by ¹²⁹Xe-NMR spectroscopy as products of the reaction of 1,3-F₂C₆H₄ and further deactivated benzenes with xenontrifluoroacetate trifluoromethane sulfonate. Fluoro substituents in ortho position to xenon significantly increase the thermal stability of the arylxenon trifluoromethanesulfonates obtained. The molecular structure of [Xe(2,6-F₂C₆H₃)][OSO₂CF₃] was determined by single crystal diffraction methods. The arylxenon unit is weakly coordinated by one oxygen atom of the CF₃SO₃ anion. The salt crystallizes in the triclinic space group P1 , a = 880.9(3) pm, b = 1093.9(5) pm, c = 1209.8(5) pm, α = 89.04(4)°, β = 74.23(3)°, γ = 86.03(3)°, Z = 4.     

Palladium-catalyzed direct 5-arylation of 1,3-dimethyluracil with aryl bromides: an electrophilic metalation-deprotonation with electrophilic arylpalladium intermediate

An efficient method of palladium-catalyzed direct 5-arylation of 1,3-dimethyluracil was developed with a various range of aryl bromides including electron-deficient aryl bromides. 5-Aryluracil derivatives were obtained in moderate to good yields regioselectively most likely via an electrophilic metalation-deprotonation process.     

An MNDO study of the electrophilic aromatic substitution on trifluorobenzenes

Summary MNDO calculations of trifluorosubstituted benzenes and their protonated intermediates [Ph-F₃]H⁺ were performed. The results are discussed with respect to changes in geometry, charge distribution and stabilities of the individual intermediates. It appears that the predominant influence which controls the protonation position is the ability of the substituent F to increase both the positive charge and polarities of the carbon bonds situated in themeta-position with respect to the substituent, thus directing protonation to theortho- andpara-positions.     

Two alternative approaches to modification of a cage complex: nucleophilic substitution and electrophilic addition for the synthesis of an iron(II) clathrochelate with an annulated imidazole fragment

A rib-functionalized iron(II) tris-dioximate clathrochelate bearing an annulated phenylimidazole fragment was prepared using nucleophilic substitution and electrophilic addition at the chelating α-dioximate fragment of the macrobicyclic framework. The resultant cage complex was identified with single crystal XRD, analytical data, ¹H, ¹³C, ¹⁹F, ¹¹B NMR spectroscopy, and examined with UV–vis spectroscopy and CVA. Two approaches to modification of the clathrochelate framework are compared.     

A new highly sterically demanding silyl (TEDAMS) group. Synthesis by multiple substitution of tris(diphenylmethyl)silane with diarylcarbenium ions

A highly efficient electrochemical method for synthesis of halosilanes bearing bulky substituents was developed. Electrophilic multiple substitution on tris(diphenylmethyl)silane with diarylcarbenium ions afforded a highly sterically demanding hydrosilane, tris(extended diarylmethyl)silane (TEDAMS-H), which was converted to the corresponding bromosilane (TEDAMS-Br).     

Regioselective upper rim substitution of calix[4]arenes

The electrophilic substitution of 25,27-dipropoxy-26,28-dinosyloxycalix[4]arene leads exclusively to the para-substitution of the alkylated phenol rings, while in the next step, the protecting nosyl group can be easily removed using a basic hydrolysis. The overall process yields dialkoxycalix[4]arenes with the substitution on the alkylated rings—the substitution pattern, which is complementary to the common dialkoxycalix[4]arenes with substituted nonalkylated phenolic units. The usefulness of this protection/deprotection procedure was documented by the synthesis of novel type of calixarene dipropoxy derivatives, and by the preparation of a novel anion receptor based on this substitution pattern.     

Synthesis of novel DOXYL labelling reagents with electrophilic groups

The oxalic acid salt of 2-aminomethyl-3-oxyl-2,4,4-trimethyl-1,3-oxazolidine has been synthesised from 1-chloroacetone. Being water soluble, the salt is a promising candidate for varied applications. It has been functionalised with electrophilic groups generating novel spin labelling reagents.     

Efficient synthesis and applications of 2-substituted azulene derivatives: towards highly functionalized carbo- and heterocyclic molecules

An efficient synthesis of 2-substituted azulene derivatives (3-6) was accomplished from ethyl 2-oxo-2H-cyclohepta[b]furan-3-carboxylate 1 and its derivative 2, which in turn were prepared from readily available tropolone. Compounds 1 and 2 were utilized to construct densely functionalized benz[a]azulene and azulene-furan frameworks (16-25, 29-34, 37, 38).     

Synthesis of activated 3-substituted indoles: an optimised one-pot procedure

3-Substituted-4,6-dimethoxyindoles can be synthesised in a one-pot procedure from 3,5-dimethoxyaniline and 2-haloketones in the presence of lithium bromide and sodium bicarbonate.     

Phase-transfer catalysis in reactions of electrophilic aromatic substitution

Electrophilic substitution in aromatic compounds under conditions of phase-transfer catalysis is considered. Catalysts of phase transfer of electrophilic reagents are used; their efficiency and the mechanism of their action in organic solvent-water systems are discussed.This review is based on materials of the report delivered at the Conference Phase-Transfer Catalysis. New Ideas and Methods (March 1994).Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1895–1900, October, 1995.     

Synthesis of 5-bromo-6-methyl imidazopyrazine, 5-bromo and 5-chloro-6-methyl imidazopyridine using electron density surface maps to guide synthetic strategy

Small heteroaromatic rings are valuable monomers in drug discovery that can enable rapid access to novel and desirable chemical space. Installation of a synthetic handle on a heteroaromatic core may be difficult if steric and electronic factors are not in alignment with the desired transformation. Described are practical routes for the construction of 5-bromo-6-methyl imidazopyrazine (1) as well as 5-bromo and 5-chloro-6-methyl imidazopyridines (2a and 2b), which were developed using electron density surface maps encoded with ionization potential to guide synthetic strategy.     

Synthesis of a new series of ditopic proligands for metal salts: differing regiochemistry of electrophilic attack at 3{5}-amino-5{3}-(pyrid-2-yl)-1H-pyrazole

An improved synthesis of 3{5}-amino-5{3}-(pyrid-2-yl)-1H-pyrazole (I) is described, which affords the compound on a multi-gram scale. Reaction of I with acid chloride and isothiocyanate electrophiles in MeCN cleanly results in attack at its amino group, yielding N-(3-{pyrid-2-yl}-1H-pyrazol-5-yl)amide and N-(3-{pyrid-2-yl}-1H-pyrazol-5-yl)thiourea products. These are good candidates as proligands for the simultaneous complexation of metal cations and anions. However, treatment of I with isocyanates under the same conditions instead yields attack at the pyrazole ring, giving 3-(pyridin-2-yl)-5-aminopyrazole-1-carboxylic acid amides as the only isolable products. The differing regiochemistries of these reactions were confirmed by ¹H NMR and X-ray crystallography.     

Reactions of methyl(pentafluorophenyl)- and methyl(pentafluorophenyl)phenylsilanes with electrophiles. A convenient preparative route to halogeno(methyl)pentafluorophenylsilanes C6F5SiMe2X and C6F5SiMeX2 (X=F, Cl and Br)

Halogeno(methyl)pentafluorophenylsilanes C₆F₅SiMe_nX_3−n (n=1, 2) (X=F, Cl, Br) were prepared in good yields from the corresponding phenylsilanes C₆F₅SiMe_nPh_3−n by reactions with the electrophiles aHF, HCl–AlCl₃, Br₂–AlBr₃ or AlX₃ (X=Cl, Br) halogenated hydrocarbons. Additionally, reactions of C₆F₅SiMe₃ and (C₆F₅)₂SiMe₂ with selected electrophiles were studied.