Five-membered heterocycles with three

Numerous examples of the ring closure of a binucleophilic system with a 1,1 -bielectrophile leading to five-membered heterocycles with three or more heteroatoms have been described, the popularity of this route no doubt reflecting the comparative ease with which the penultimate product may be obtained. 

Five-Membered Heterocycles with Three Heteroatoms 6.24.5.1 1,2,3-Triazoles... 

Five-Membered Heterocycles with Three Heteroatoms 246... 

Among the five-membered heterocycles with three nitrogen atoms, triazoles and benzotriazoles are of significant practical importance. In the case of ben-zotriazole, the aromaticity of the benzenoid 1H-benzotriazole (90A, R = H) has been considered to be greater than that of the quinonoid 2/7-benzotria-zole (90B, R = H) (Scheme 43).134 However, the difference in aromaticity between tautomers is greatly dependent on the dielectric constant of the medium. 

Unsaturated and saturated compounds are considered in the same sections since the number of five-membered heterocycles with three and more heteroatoms (and especially their structure types) is limited and their reactivity does not differ fundamentally. 

Figure 1 Silicon-containing five-membered heterocycles with three or four heteroatoms.

No systematic studies on vibrational spectroscopy of five-membered heterocycles with three or more heteroatoms and at least one tetracoordinated silicon atom were reported. 

No systematic experimental studies on thermodynamic properties of five-membered heterocycles with three or more heteroatoms and at least one tetracoordinated silicon atom were reported. The aromaticity of the fully conjugated germadisiloleanion 21, a heavy congener of the cyclopentadienyl anion, was deduced mainly from its NMR spectroscopic and structural parameters <2005JA13143>. 

DIMEDONE-ANNULATED FIVE-MEMBERED HETEROCYCLES WITH THREE HETEROATOMS... 

Because these transition state structures are symmetric, all previously used approaches for determining relative reactivity of the heterocycles should be applicable in these cases. The cycloaddition is a HOMO dienophile and LUMO heterocycle (diene) controlled cycloaddition reaction with exceptionally low demand for orbital energy changes in reactants to achieve the electronic contribution present in the transition state structure (Table 41). There is no doubt that 1,3,4-oxadiazole is the most reactive of all five-membered heterocycles with three heteroatoms. However, the question remains as to whether this heterocycle is more reactive than, for instance, furan or even cyclopentadiene. To answer this question, the deviation of bond order uniformity in the six-membered ring being formed was computed (Table 42). The bond order uniformity selected 1,3,4-... 

Summary of the general chemistry of five-membered heterocycles with three and four heteroatoms ... 

In order to stabilize nitrogen-rich molecules, n aromatic delocahzation may be used. In this context five-membered heterocycles with three N atoms - triazoles -, four N atoms - tetrazoles -, and five N atoms - pentazoles - play an important role (Fig. 7). While triazoles often do not possess enough intrinsic energy to be suitable candidates for high explosives, pentazole derivatives are usually either far too sensitive and unstable for any application or need to be kinetically stabilized by bulky groups, which reduce the nitrogen con-... 

A series of five-membered heterocycles with two and three heteroatoms were synthesized. 4-Hydroxyisothiazoles 57 were prepared from a-amino ketones with sulfur monochloride (1968BCJ959). Polar solvents, especially N,Af-dimethylfor-mamide, were preferable (Scheme 28). In a similar reaction of 1-amino-l-phenyl-2-propanone with sulfur monochloride 5-chlorinated isothiazole 58 was obtained in high yield. 

In Section 4.24.2 the literature from 1982 to the beginning of 1994 (according to Chemical Abstracts) is considered. Earlier data concerning five-membered rings with three or more heteroatoms including at least one Ge, Sn or Pb atom are scarce and there is no information in CHEC-I on these heterocycles. Valuable data on germanium heterocycles can be found in the monograph by Lesbre et al. 424-01 > and some of these data have been included in this section. Tin and... 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

To test the effect of a heteroatom, Starokon et al. [175] studied three five-membered heterocycles with a similar molecular structure, containing the oxygen (2,5-dihy-drofuran), nitrogen (3-pyrrole) and sulfur (butadiene sulfone). Only the oxygen-containing cycle was carboxidized selectively, while the others showed a strong tendency towards side reactions resulting in a set of unidentified products. 

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. 

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. 

This alternate possibility was discounted by Huisgen, however, who showed that three-membered rings are not primary products in the 1,3-dipolar additions leading to five-membered heterocycles with nitrilium betaines. ... 

Application of Ionic Liquids in Heterocyclic Synthesis 4 1 Synthesis of Five-Membered Heterocycles 4.1.1 Synthesis of Five-Membered Heterocycles 443 443 with Two Heteroatoms 4.2.3 Synthesis of Six-Membered Heterocycles with Three Heteroatoms 4.3 Synthesis of Some Other Spiro Heterocycles 468 479 480... 

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