Heterocyclic aromatic compounds nitrogen atom

Cyclic compounds that have one or more atoms other than carbon within the ring are called heterocyclic compounds. Those that have 4 + 2 ti electrons are heterocyclic aromatic compounds. Nitrogen and oxygen are the most commonly encountered heteroatoms in naturally occurring heterocyclic compounds. Sidfur-containing aromatic compounds also exist. The structures of a few commonly encountered heterocyclic aromatic compounds are shown below. 

No specific review of aromatic azapentalenes exists, though much of the work before 1960 is covered in a more general article on bicyclic heterocycles with bridgehead nitrogen atoms by Mosby6 in the Weissberger series on heterocyclic chemistry. That article makes no distinction between aromatic and saturated systems, and the present review, though not exhaustive, deals mainly with aromatic systems and covers most of the literature to the end of 1975. Nonaromatic compounds will not be treated except where they are sufficiently important. 

Structure and Nomenclature. The pyridine group consists of a six-membered, heterocyclic, aromatic compound with one nitrogen atom in the ring. The parent compound of this group is pyridine I with ring positions numbered as shown. Alternative denotations of the I. 2, and 4 positions in the ring are alpha, heta, and gamma, respectively. 

At the beginning of the chapter we mentioned the three six-membered aromatic heterocycles with two nitrogen atoms—pyridazine, pyrimidine, and pyrazine. In these compounds both nitrogen atoms must be of the pyridine sort, with lone pair electrons not delocalized round the ring. 

Draw the structure of adenine, a heterocyclic aromatic compound incorporated in the structure of DNA. Identify the nonbonding electron pairs that are not part of the aromatic system in the rings of adenine. Which nitrogen atoms in the rings would you expect to be more basic and which should be less basic ... 

Heterocyclic aromatic compounds contain C and H atoms other than carbon and hydrogen (Fig. 6). For the monocyclic molecules Hiickel s rule is applicable. For example both pyridine and pyrrole contain six ti electrons. Unlike the former the lone pair of the latter is delocalized. Armit and Robinson have shown a connection between the electronic sextet and the heteroaromaticity. Due to the electronegativity difference between carbon and nitrogen the bonds in pyridine are not of equal length and the delocalization is not perfect. Five membered heteroaromatics with oxygen and sulfur are furan and thiophene respectively. Pyrazole/imidazole, triazoles and tetrazoles are five membered heteroaromatics with two, three and four nitrogen atoms respectively. Three important aromatic six membered heterocyclic molecules are pyrimidine, pyrazine and pyridazine. Benzofused... 

Indole is classified as a 7c-excessive aromatic compound. It is isoelectronic with naphthalene, with the heterocyclic nitrogen atom donating twm of the ten 7t-electrons. 

The compounds of this article, ie, ftve-membered heterocycles containing two adjacent nitrogen atoms, can best be discussed according to the number of double bonds present. Pyrazoles contain two double bonds within the nucleus, imparting an aromatic character to these molecules. They are stable compounds and can display the isomeric forms, (1) and (2), when properly substituted. Pyrazoles are scarce ia nature when compared to the imidazoles (3), which are widespread and have a central role ia many biological processes. 

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. 

In many cases, however, the ortho isomer is the predominant product, and it is the meta para ratio which is close to the statistical value, in reactions both on benzenoid compounds and on pyri-dine. " There has been no satisfactory explanation of this feature of the reaction. One theory, which lacks verification, is that the radical first forms a complex with the aromatic compound at the position of greatest electron density that this is invariably cither the substituent or the position ortho to the substituent, depending on whether the substituent is electron-attracting or -releasing and that when the preliminary complex collapses to the tr-complex, the new bond is most likely to be formed at the ortho position.For heterocyclic compounds such as pyridine it is possible that the phenyl radical complexes with the nitrogen atom and that a simple electronic reorganization forms the tj-complex at the 2-position. 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

The reaction of A-acyliminium ions with nucleophilic carbon atoms (also called cationic x-amidoalkylation) is a highly useful method for the synthesis of both nitrogen heterocycles and open-chain nitrogen compounds. A variety of carbon nucleophiles can be used, such as aromatic compounds, alkcncs, alkyncs, carbcnoids, and carbanions derived from active methylene compounds and organometallics. 

In the scientific sector, the understanding of the generally higher reactivity of heteroaromatic diazo components relative to that of aromatic diazonium salts has increased. The number of heterocyclic nitrogen atoms in azolediazonium ions has a marked influence on the N-H acidity of these ions. The pvalues of a series of such ions in aqueous solution at 0 °C (Scheme 12-4) indicate that the electrophilicity of the diazonio group in these compounds increases with the number of nitrogen atoms in the ring. ... 

The most common methods suitable for the synthesis of different azolium compounds will be discussed here. Two routes are particularly useful for the preparation of the imidazolium salts (1) substitution reactions at the nitrogen atoms of imidazole [25] and (2) multicomponent reactions for the generation of an Af,Af -substituted heterocycle which are particularly useful for the synthesis of imidazolium salts bearing aromatic, very bulky, or particularly reactive N,N -sub-stituents (Fig. 3a,b) [26]. Both methods offer the opportunity to produce unsym-metrically substituted imidazolium salts of type 1 either by stepwise alkylation of imidazole or by the synthesis of an W-arylated imidazole derivative followed by 77 -alkylation [27]. Nevertheless, the method of choice for the preparation of the imidazolium salts 1 is the 77,77 -substitution of imidazole. Several other methods for the preparation of imidazolium salts with previously unattainable substitution patterns have also been described [28, 29]. 

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