Heterocydes aromaticity

Heterocydic aromatic amine An amine in which nitrogen is one of the atoms of an aromatic ring. 

Nucleoside (Section 28.1) A building block of nucleic acids, consisting of D-iibose or 2-deoxy-D-ribose bonded to a heterocydic aromatic amine base by a 3-N-glycosidic bond. 

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, selenophene[233,234], and cyclobutadiene iron carbonyl complexpSS] react with alkenes to give vinyl heterocydes. The ease of the reaction of styrene with sub.stituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

Other examples of addition reactions that form carbon-nitrogen bonds are the reactions of hexafluoro-2-butyne with various heterocydes [77], aromatic... 

A pyridyl bis-N-heterocydic carbene (NHC) ligand has been prepared by Steel and Teasdale based on nudeophilic aromatic substitution of dichloroisonicotinic amides with N-methylimidazole (Scheme 6.122) [250]. Microwave heating of the neat reagents at 140 °C for 10 min provided a 91% yield of the corresponding bis-... 

To date, the most popular and successful designs for PN-ligands have incorporated an achiral phosphine with a substituted non-aromatic heterocyde as the primary chiral unit, largely due to the ease by which the P and N modules may be altered, and the ready availability of enantiopure, amino add-derived starting materials.1281 Considerable variation of the predse steric and electronic environment imposed on a chelated metal centre has been achieved by the synthesis of a substantial library of... 

Sovadinova, I., Blaha, L., Janosek, J., Hilscherova, K., Giesy, J.P., Jones, P.D. and Holoubek, I. (2006) Cytotoxicity and aryl hydrocarbon receptor-mediated activity of N-heterocydic polycyclic aromatic hydrocarbons structure-activity relationships. Environmental Toxicology and Chemistry, 25, 1291-1297. 

Allenylimines 186 are not easily accessible, and the most elegant approach is the reaction of alkynylimines 185 with triethylamine to generate 186 in situ the copper ) catalyst which is also present then catalyzes the cycloisomerization to the pyrrole 187 (Scheme 15.59) [120]. The method also is applicable to the imine substructure in 2-alkynylpyridines and related substrates, thus opening up a very elegant access to condensed aromatic nitrogen heterocydes. 

As aromatic compounds have been exhausted as building blocks for life science products, A-heterocyclic structures prevail nowadays. They are found in many natural products, such as chlorophyll hemoglobin and the vitamins biotin (H), folic acid, niacin (PP), pyridoxine HCl (Be), riboflavine (B2), and thiamine (Bi). In life sciences 9 of the top 10 proprietary drugs and 5 of the top 10 agrochemicals contain A-heterocycIic moieties (see Tables 11.4 and 11.7). Even modern pigments, such as diphenylpyrazolopyrazoles, quinacri-dones, and engineering plastics, such as polybenzimidazoles, polyimides, and triazine resins, exhibit an A-heterocydic structure. 

R. Akita, Y. Ohta, A. Palladium-catalyzed cross-coupling reactions of chloropyrazines with aromatic heterocydes. Heterocycles 1992, 33, 257-272. 

With its sextet of 71 electrons, thiophene possesses the typical aromatic character of benzene and other similarly related heterocydes. Decreasing orders of aromaticity have been suggested to reflect the strength of this aromatic character benzene > thiophene > pyrrole > furan (9) and benzene > thiophene > selenophene > tellurophene > furan (10). 

Arylamines are commonplace. They are part of molecules with medicinally important properties, of molecules with structurally interesting properties, of materials with important electronic properties, and of transition metal complexes with catalytic activity. An aryl-nitrogen linkage is present in nitrogen heterocydes such as indoles [1, 2] and benzopyr-azoles, conjugated polymers such as polyanilines [3-9], and readily oxidizable triarylamines used in electronic applications [10-13]. The ability of aryl halides and triflates to form arylamines allows a single group to be used as a synthetic intermediate in aromatic carbon-... 

M-Oxides. The reagent also reacts with aromatic nitrogen-containing heterocydes to give high yields of N-oxides (90-100%). However, 2,2 -bipyridyl and o-phenanthro-line are not oxidized. 

The aromatic five-membered heterocyde imidazoie is important in many biological processes. One of its nitrogen atoms is pyridine-like in that it contributes one w electron to the aromatic sextet, and the other nitrogen is pyrrole-like in that it contributes two IT electrons. Draw an orbital picture of imidazole, and account for its aromaticity. Which atom is pyridine-like and which is pyrrole-like ... 

Weidner, J. J., Peet, N. P. Direct conversion of hydroxy aromatic compounds to heteroaryiamines via a one-pot Smiies rearrangement procedure. J. Heterocyd. Chem. 1997, 34, 1857-1860. 

The carbenes derived from six- [20-22] and seven-membered heterocydes [22-24, 70] of type 14 can be obtained both with an aliphatic or an aromatic backbone. The characteristic NMR resonances for the C2 carbon atoms in six-membered carbene heterocydes ( 236-248 ppm) [20, 21] have been recorded in the same range as the Ccarbene resonances for saturated imidazolidin-2-ylidenes of type 1. Dimerization to enetetramines occurs for some carbenes derived from a six-membered heterocycle [21] and this behavior is independent from the nature of the backbone (sartirated or unsaturated), but depends strongly on the steric bulk of the /V,/V -substiments. 

Thiophene is a usefiil template for four-carbon homologation via reduction [9], as well as a bioisostere of the benzene ring and other heterocydes in medicinal chemistry. Thiophene is a n-electron-excessive heterocycle. It favors electrophilic substitution, which, similar to metalation, takes place preferably at the a-positions due to the electronegativity of the sulfiir atom [10]. In comparison to the oxygen atom in fiiran, the sulfiir atom in thiophene has lower electronegativity, so its lone pair electtons are more effectively incorporated into the aromatic system. The aromaticity of thiophene is in between that of benzene and fiiran. As a consequence, the difference in reactivity of a-halothiophenes and 3-halothiophenes is not as pronounced as that of the corresponding halofiirans. 

Oxazoles and benzoxazoles are viable participants in the heteroaryl Heck reactions. In their important work published in 1992, Ohta and colleagues demonstrated that oxazoles and benzoxazoles, along with other rr-sufficient aromatic heterocydes such as furans, benzofurans, thiophenes, benzothiophenes, pyrroles, thiazole, and imidazoles are acceptable recipient partners for the heteroaryl Heck reactions of chloropyrazines [55]. Therefore, treatment of 2-chloro-3,6-diethylpyrazme (95) with oxazole led to regioselective addition at C(5), giving rise to oxazolylpyrazine 96. Similar results were obtained for the heteroaryl Heck reaction of iodobenzene or bromobenzene with oxazole and benzoxazole [56]. 

Regioselective Substitution in Aromatic Six-Membered Nitrogen Heterocydes, 44, 199... 

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