Heteroaromatic ring system

In general, five-membered heteroaromatic ring systems with one heteroatom all undergo preferential a rather than /3 electrophilic substitution. This is rationalized in terms of the more effective delocalization of charge in the intermediate (36) leading to a substitution than in the intermediate (37) leading to /3 substitution. 

The most characteristic feature of the infrared spectra of all 5-mono- and -di-substituted-amino-l,2,3,4-thiatriazoles is a strong band in the 1540-1590 cm range, which without doubt is due to the C=N and N=N stretching vibrations of the heteroaromatic ring system. Various infrared bands between 889 and 1122 cm have been assigned to skeletal vibrations of the thiatriazole ring and a band... 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

Heteroaromatic ring systems are formed presumably with loss of functional groups, at elevated temperatures and probably under the catalytic influence of the aminopropyl groups on the sorbent surface. The compounds so formed are excited to fluorescence by long-wavelength UV light (X = 365 mn). 

Scheme 6.119 Nucleophilic aromatic substitution reactions involving halo-substituted N-heteroaromatic ring systems.

In addition, some Stille adducts have been further manipulated to form condensed heteroaromatic ring systems. The coupling of 4-acetylamino-5-bromopyrimidine 69 and ( )-1-ethoxy-2-(tributylstannyl)ethene resulted in ( )-4-acetylamino-5-(2-ethoxyethenyl)pyrimidine 70, which then cyclized under acidic conditions to furnish pyrrolo[2,3-d]pyrimidine 71. Pyrrolo[3,2-d]pyrimidines were also synthesized in a similar fashion by using 5-acetylamino-4-bromopyrimidine [40]. 

Another theoretical criterion applied to estimation of aromaticity of homo- and heteroaromatic ring system is aromatic stabilization energy (ASE). Based on this approach, the aromatic sequence of five-membered ring systems (ASE in kcal mol-1) is pyrrole (20.6) > thiophene (18.6) > selenophene (16.7) > phosphole (3.2) [29], According to geometric criterion HOMA, based on the harmonic oscillator model [30-33], thiophene is more aromatic than pyrrole and the decreasing order of aromaticity is thiophene (0.891) > pyrrole (0.879) > selenophene (0.877) > furan (0.298) > phosphole (0.236) [29],... 

You ll notice in the prior art definition, the aromatic and heteroaromatic ring systems are defined by only the number of atoms they contain. Typically, patents and patent applications will further clarify such definitions, including the possibility for additional optional substitutions on those ring systems, either in the claim itself or in the patent specification. Such further subdefinitions were left out to simplify the Markush example. 

Many novel polycyclic heteroaromatic ring systems have been prepared via a photochemical ring closure of the type depicted in equation 150593-604. 

When the carbocyclic aromatic core in the starting material is replaced by a heteroaromatic ring, systems such as 123 arise and Mori elimination/dimerization provides the dioxa- and dithia[6.6]cyclophanes 125 (Scheme 27) [74]. 

This group constitutes a virtually infinite class of heteroaromatic ring systems. However, relatively few of the parent compounds have yet been made, and fewer still have had their quantitative (or indeed qualitative) reactivities measured. The compounds described in this chapter are subdivided as follows Section 2, compounds with one five- and one six-membered ring Section 3, compounds with one five and two six-mem-bered rings Section 4, compounds with two five- and one six-membered rings Section 5, compounds with two five-membered rings and Section 6, compounds with three or more five-membered rings. 

The second generation are characterized by nitrogen-containing heteroaromatic ring-systems (Fig. 4.8). 

Methoxide addition has also been reported for two bicyclic heteroaromatic ring systems. 3-Methoxy-2-nitro- and 2-methoxy-3-nitrobenzothiophene add methoxide ion at C-3 and C-2, respectively, to give 183 and 184. Spectral, equilibrium, and kinetic studies of these reactions have been made.337... 

Photochemically induced ring closure may give rise to larger condensed heteroaromatic ring systems. For example, irradiation (>300nm) of imine 53 for 6-8h gave the tetracyclic product 54 in modest yield (30%) (Equation 1) <2006JOC7165>. 

One of the main drawbacks of the intermolecular reaction is that to achieve good yields and selectivity it is frequently necessary to run reactions to low conversion rates or use the heteroaromatic base in vast excess. Such a limitation does not apply when conducting reactions intramolecularly and in recent times much attention has been focussed on such variants. A number of synthetically useful orr/jo-cyclisation and j so-substitution reactions have been uncovered providing new routes condensed heteroaromatic ring systems and substituted pyridines. Reactions can be effected at neutral pH and may occur to each of the carbon centres in the pyridine ring system. As these recent advances have not been summarised previously, much of this review will be devoted to the intramolecular reaction. 

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