Aromatization of N-heterocyclics

Homogeneous dehydrogenation Aromatization of N-heterocyclics Cleavage of N-ylids... 

Although several methods are used to aminate heterocyclic aromatic hydroxy-N-heterocycles [36], some additional, special, amination procedures are used for nucleoside modification. When we planned to synthesize a series of N -substituted cytidines 5 starting from uridine 1 we considered known classical methods, which imply (Scheme 4.14) ... 

The amination of aromatic hydroxy-N-heterocycles is a standard reaction in medicinal and agricultural chemistry and has heen reviewed [36]. The hitherto commonly used two-step procedure for amination of hydroxy-N-heterocycles, starts with conversion into the chloro-N-heterocycles, e.g. by treatment of the hydroxy-N-heterocycle with POCI3, PCI5, or SOCI2, followed by reaction with the amine moiety. This methodology has several drawbacks however, for example ... 

Hydrazone Dyes If the diazonium salts of aromatic amines are coupled with the methylene derivatives of N heterocycles, hydrazone dyes (i.e., the monoaza derivatives of the enamine dyes) are obtained. Paper and leather can be dyed in yellow to red shades with these dyes [23], They are moderately lightfast on polyacrylonitrile. If the diazo components contain substituents in the 2-position relative to the amino group that can form a hydrogen bond (e.g., 2-nitroaniline [24] or 1-ami-noanthraquinone [25]), lightfastness is improved considerably (10). 

The most important method for preparing apocyanine dyes is the reaction of N heterocycles containing 2- or 4-carbonyl groups with secondary or tertiary aromatic amines in the presence of dehydrating agents (e.g., phosphorus oxychloride or tin tetrachloride). 

A variety of N-heterocycles can be catalytically phenylated with iodobenzene (Table 4) [11]. This reaction provides substrate scope complementary to that of existing Pd-catalyzed N-heterocycle arylation methods [17]. Both aromatic and non-aromatic heterocycles serve as suitable substrates. Dihydroquinazoline (Table 4,... 

While there are no extensive reports on the relative aromaticity of the heterocycles covered in this chapter, the general reactivity of these systems can be predicted based on first principles. By assuming that these fused systems are comprised of a five-membered rc-excessive heterocyclic system and a five-membered -deficient heterocyclic system, electrophilic agents are expected to react on the n-excessive subunit. Ab initio calculations on the thienothiazoles and furothiazoles predicted that electrophilic substitutions should occur exclusively on the furan or thiophene subunit with the regioselectivity being a function of the resonance-stabilization of the reactive intermediates <76KGS1202>. A priori, C-H deprotonation by a nonnucleophilic base should occur preferentially on the -deficient heterocyclic component. 

As structural criteria of aromaticity, indexes N= + b (where R are bond lengths, and a and b are parameters characteristic for a given pair of atoms) and Julg s parameter J = 1 — 225/ S,s(l —d Jdf (where n is the number of peripheral bonds rs, are their lengths, and d is their mean length) have been applied. The less the value SaA and closer to 1 the value J, the greater is the aromaticity of a heterocycle. Polarizability exaltations F = M — M , where M and M arc the mean dipole polarizability and the mean atomic or group polarizability, respectively. 

S-adenosyl-L-methionine (SAM)-dependent methyl-ation was briefly discussed under Thiomethylation (see Figure 14). Other functional groups that are methylated by this mechanism include aliphatic and aromatic amines, N-heterocyclics, monophenols, and polyphenols. The most important enzymes involved in these methylation reactions with xenobiotics are catechol O-methyltransferase, histamine N-methylt-ransferase, and indolethylamine N-methyltransferase - each catalyzes the transfer of a methyl group from SAM to phenolic or amine substrates (O- and N-methyltransferases, respectively). Methylation is not a quantitatively important metabolic pathway for xenobiotics, but it is an important pathway in the intermediary metabolism of both N- and O-contain-ing catechol and amine endobiotics. 

A possible rationale for different models for AN- vs. BIT-coked catalysts is as follows anthracene is relatively weakly adsorbed, and consequently requires high energy sites whereas the coke precursors in BIT adsorb strongly, and consequently can utilize weaker sites, as well as strong sites. The latter may be due to the relatively high nitrogen content of the bitumen (1.1 wt.%), mostly in the form of N-heterocyclics. The latter are known to exhibit stronger adsorption than aromatics (AN). 

Nitrenium ions and direct electrophilic aromatic amination (cyclic nitrenium ions, formation of N-heterocycles by intramolecular amination, N-aminopyridinium salts) 05ZOR487. 

Mammalian aldehyde oxidases (AOs) catalyze the oxidation of aldehydes to carboxylic acids and play important roles in the metabolism of N-heterocyclic compounds, the reduction of nitro-aromatic compounds and the... 

Sodium hydroxide Elimination of N-heterocycles via Hofmann degradation of quaternary ammonium salts with opening of O-heterocycles Aromatization by ring elimination... 

This section deals with the reactions in which the formation of N-heterocycles proceeds through the Mannich-type cyclocondensations of anionic o-adducts of nitroarenes. The reactions of o-adducts with formaldehyde and primary amines result in 1,3-annelation of the piperidine ring to the core structure of nitroarenes. Depending on nitroarene structure, there are two main routes for these reactions to take (a) the o-adduct is formed via the addition of C-nucleophile to a nitroarene bearing the hydroxy group and (b) cyclocondensation of hydride adducts of nitroarenes, where the hydride ion acts as a nucleophile. At least two wcta-positioned nitro groups in aromatic ring are necessary for these reactions to proceed. Scheme 52 demonstrates both of these options. 

Sovadinova, L Blaha, L. Janosek, J. Hilscherova, K. Giesy, J. R Jones, P. D. Holoubek, I. Cytotoxicity and aryl hydrocarbon receptor-mediated activity of N-heterocyclic polycyclic aromatic hydrocarbons structure-activity relationships. Environ. Toxicol. Chem. 2006, 25, 1291-1297. 

Conway B, Hevia E, Kennedy AR, Mulvey Structurally-defined direct C-mag-nesiation and C-zincation of N-heterocyclic aromatic compounds using alkali-metal-mediated metaUation. Chem Commun. 2007 (27) 2864-2866. 

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