Aromaticity nitrogen heterocycles

Ruonne atoms in aromatic nitrogen heterocycles are readily replaced by oxygen nucleophiles [77] Bistnfluoromethyl hydroxylarmne anion is an mterest-ing nucleophile for the mtroduction of oxygen mto perfluoropyndine Rearrangement of the product occurs at 125 °C [18] (equation 12)... 

Zincke-type salts derived from other aromatic nitrogen heterocycles also undergo Zincke reactions. The isoquinolinium salt 6 (Scheme 8.4.16) permitted incorporation of a phenyl ethylamine chiral auxiliary, providing salt 48. In this context and others (vide infra), Marazano and co-workers found that refluxing -butanol was a superior solvent system for the Zincke process. Additionally, the stereochemical integrity of the or-chiral amino fragment was reliably maintained. 

CaveU and Chapman made the interesting observation that a difference exists between the orbital involved in the quatemization of aromatic nitrogen heterocycles and aromatic amines, which appears not to have been considered by later workers. The lone pair which exists in an sp orbital of the aniline nitrogen must conjugate, as shown by so many properties, with the aromatic ring and on protonation or quatemization sp hybridization occurs with a presumed loss of mesomerism, whereas in pyridine the nitrogen atom remains sp hybridized in the base whether it is protonated or quaternized. Similarly, in a saturated compound, the nitrogen atom is sp hybridized in the base and salt forms. 

One, two, or all three double bonds of certain aromatic nitrogen heterocycles can be reduced with metallic hydrides such as NaBH4 or LiAlH. For a review, see Keay, J.G Adv. Heterocycl. Chem., 1986, 39, 1. 

Redmore, D., Phosphonates of Full Aromatic Nitrogen Heterocycles, U.S. 

The relative basicity of an aromatic nitrogen heterocycle is dictated by the ring size, the presence of any other heteroatoms, and possible effects from substituents. It is potentially a rather more complex problem than with, say, simple amines, and should be approached logically and systematically. In practice, these examples do not present particularly difficult problems. 

In addition to these classical aromatic ring hydroxylations, many nitrogen heterocycles are substrates for molybdenum-containing enzymes, such as xanthine oxidase and aldehyde oxidase, which are present in the hepatic cytosolic fractions from various animal species. The molybdenum hydroxylases (B-75MI10902) catalyze the oxidation of electron-deficient carbons in aromatic nitrogen heterocycles. The reactions catalyzed by these enzymes are generally represented by equations (2) and (3). 

Isolated examples of oxidation at nitrogen have been reported for these systems. They do not form the N-oxides typical of aromatic nitrogen heterocycles, but behave similarly to amines. Thus the 1,2,5-oxadiazine (80) is rapidly oxidized by lead dioxide to the radical (81) (73JA1677), which is in equilibrium with the four-membered ring radical (82). 

Aromatic nitrogen heterocycles display considerable medium shifts (Section 3.1.4). Carbon-13 shifts of pyridine decrease in a but increase in [i and y position upon addition of water (Fig. 4.12). The dilution effect is explained in terms of intermolecular hydrogen bonding between pyridine and water [99]. 

Zachara, J. M., et al., Sorption of Binary Mixtures of Aromatic Nitrogen Heterocyclic Compounds on Subsurface Materials. Environ. Sci. Technol., 1987 21, 397-402. 

Zachara, J.M., Ainsworth, C.C., Cowan, C.E., Thomas, B.L. (1987) Sorption of binary mixtures of aromatic nitrogen heterocyclic compounds on subsurface materials. Environ. Sci. Technol. 21, 397 102. 

The reactions of complex metal hydrides occur by an attack of the nucleophilic hydride ion on an electrophilic center.1 Aromatic nitrogen heterocycles in which the nitrogen has contributed only one electron to the -system (1) are electrophilic as compared with benzene, and have been shown to undergo reduction by the active reducing agent, lithium aluminum hydride. The nitrogen heterocycles in which the heteroatom has contributed two electrons to the 77-system (2) are electron-rich as compared with benzene and usually do not undergo reaction by reduction with complex metal hydrides.2 A combination of these two structural features, as in oxazoles (3), usually induces sufficient electrophilicity to allow attack by the hydride ion and reduction. 

In a study of the lithium aluminum hydride reduction of a series of nitrogen aromatic heterocyclics, Bohlmann97 found that this metal hydride effected a conversion of acridine to 9,1O-dihydroacridine (91) in high yield and purity. The ultraviolet spectrum of the isolated dihydroacridine (Amax 288 mp, loge = 4.18) was confirmed by Braude et al.92 as a part of a study of the hydride donor properties of a series of aromatic nitrogen-heterocycles. These workers found that the dihydroacridine underwent a slow oxidation to acridine in air and a rapid hydrogen transfer in the presence of chloranil to form the quinol and acridine. The dihydroacridine was, however, quite stable under dry nitrogen. 

Figure 1 Six-membered monocyclic aromatic nitrogen heterocycles.

Figure 2 Six-membered bicyclic aromatic nitrogen heterocycles.

Figure 3 Six-membered tricyclic aromatic nitrogen heterocycles.

All of the common 5-membered aromatic nitrogen heterocycles are quite acidic with pKa s ranging from 16.2 in the case of indole (comparable to methanol) to 5 in the case of tetrazole (comparable to acetic acid). Indoles and pyrroles devoid of electron withdrawing substituents are also very susceptible to electrophilic attack and oxidation whilst imidazole, 1,2,4-triazole and tetr azole are also quite basic. In the case of imidazole, a pKan = 7 corresponds to 50% of the... 

Chiral 2//-azirines have been prepared by dehydrochlorination of 7V-chloroaziridines, Swem oxidation of aziridines and elimination from A -sulfinylaziridines. These reactions require the use of high enantiopure aziridine esters as starting materials <03T2345>. Chiral enriched ethyl 3-methyl-2//-azirine-2-carboxylate was found to act as an efficient alkylating agent for the preparation of a variety of five-membered aromatic nitrogen heterocycles <03TL6277>. 

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