Five-membered heterocycles with one

In the reactions of electrophilic substitution, isoxazole is far less active than the five-membered heterocycles with one hetero atom and pyrazole. It is closer to pyridine, but more reactive. 

Five-Membered Heterocycles with One Heteroatom 6.24.3.1 Pyrroles... 

Fig. 3.6 Five-membered heterocycles with one heteroatom obtained by solid-phase chemistry.

Pyrazoles Fused to Five-Membered Heterocycles WITH One Heteroatom... 

The chemistry of cyclopentafurazans (cyclopen-ta-1,2,5-oxadiazoles) and furazans fused to five-membered heterocycles with one to four heteroatoms has been reviewed (95JHC371). Treatment of 3-amino-4-nitro-l,2,5-oxadiazole with dinitrogen pentoxide yields dinitro-1,2,5-oxadiazole 89 (95MC102). The latter reacts normally with benzenethiol to give the sulfide 90,... 

Fig. 6.1. Plots of reactivity versus electron demand for a series of five-membered heterocycles with one heteroatom (indicated on the plots).

Section 3.1 is a brief overview Section 3.2 deals with six-membered heterocycles, including those with more than one heteroatom in the ring Section 3.3 deals with five-membered heterocycles with one heteroatom Section 3.4 deals with five-membered heterocycles with more than one heteroatom in the ring Section 3.5 covers small (three- and four-membered) and large (>six) ring heterocycles. 

Electrophilic substitution is an important type of reactions for five-membered heterocycles with one heteroatom and enables compounds with various substituents to be obtained. The present work is devoted to certain features of substrate and positional selectivities in electrophilic substitution reactions of derivatives of pyrrole, furan, thiophene and selenophene, and also the corresponding benzannulated systems, which had not been explained until recently. In a recent review (05RKZ(6)59), these problems were mainly discussed for thiophenes, while in a previous review (94H(37)2029) only monocyclic pyrrole, furan and thiophene derivatives were considered. 

To explain the noncorrespondence in the series of substrate and positional selectivities in electrophilic substitution reactions of five-membered heterocycles with one heteroatom, a hypothesis was put forward (79MI2, 80KGS1587). Namely, the formation of jS-substituted... 

Table 1 Differences in total energies ( tot) of five-membered heterocycles with one heteroatom and cationic ir-complexes formed on their protonation for ot- (d ) and /i-positions AEp), as well as values of AE p = AE —AEp (all in kcal/mol) ...

The photoreactions of five-membered heterocycles with one heteroatom give structural isomers. In some cases Dewar isomers were proposed as intermediates, but only a small number were isolated. 

II. Dewar Isomers of Five-Membered Heterocycles with One... 

DIMEDONE-ANNULATED FIVE-MEMBERED HETEROCYCLES WITH ONE HETEROATOM... 

An example of cycloaddition reactions that involve transformation of five-membered heterocycles with one heteroatom into benzo[c]-fused heterocycles through a sequence of Diels-Alder reactions is presented in Scheme 1. 

By examining bond order uniformity, it is clear that benzyne is quite a reactive species if a triple bond is involved in the reaction, but not very reactive if a double bond is involved in the reaction. The furan ring had the highest bond order deviation and, as a result, it should be the most reactive five-membered heterocycle with one heteroatom studied here. 

With this large group of heterocycles, ring strain is of little or no importance. Ring-opening reactions are, therefore, rarer than in three- and four-membered heterocycles. The crucial consideration is rather whether a compound can be regarded as a heteroarene or whether it has to be classified as a heterocycloalkane or heterocycloalkene (see p 2). Various aromaticity criteria apply to heteroarenes, and as a consequence, different opinions have been expressed on this matter [1]. As will be shown by means of examples of the various systems, the nature and number of heteroatoms are the critical factors. The parent compound of the five-membered heterocycles with one oxygen atom is furan. 

The parent compounds of the monocyclic five-membered heterocycles with one heteroatom are aromatic. When considering the three most important systems only, it appears that the aromaticity increases as follows furan < pyrrole < thiophene (< benzene). This sequence also applies to the respective benzo[Z ] condensed systems. 

The importance of five-membered heterocycles with one heteroatom, of the benzo and dibenzo condensed systems and of the partially or completely reduced compounds as natural products, pharmaceuticals, and starting materials or auxiliaries for syntheses is much greater than for three- or four-membered heterocycles, apart from oxirane. 

On the other hand, five-membered heterocycles with one nitrogen in the ring are less readily available directly from carbohydrates. Thus, the pyrrole 11 has been formed from ammonium mucate of 10 under thermal conditions [33]. The respective pyrrole analogs of 7 and 8 with the tetrahy-... 

Five- and six-membered heterocycles are of utmost importance to both life and drug discovery. The most common five-membered heterocycles with one heteroatom are pyrrole, fiiran, and thiophene. 

Pyrrole is an aromatic five-membered heterocycle, with one nitrogen atom and two double bonds (Figure 16-12). Although it may seem that pyrrole has only four pi elec-trons, the nitrogen atom has a lone pair of electrons. The pyrrole nitrogen atom is sp ... 

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