Five-Membered Azaheterocycles

It is known that pyrazolines and pyrazoles are an important class of pharmacophores [1,2,3,4, 5,6], Heterocycles containing these fragments are important targets in synthetic and medicinal chemistry since they are key moieties in numerous biologically active compounds possessing tranquilizing, muscle relaxant, psychoanaleptic, anticonvulsant and antidepressant activities [7, 8, 9,10,11,12], This includes kinesin spindle protein [12] and monoamine oxidase [13, 14] inhibitors as well as antimycobacterial [15, 16] and anti-inflammatory [17] agents. 

On the other hand, pyrazoline and pyrazole derivatives are successfully used for material science tasks. For example, triarylpyrazolines are used in the synthesis of green electroluminescent polymers for light-emitting diodes [18], Some aromatic substituted 2-pyrazolines are effective organic luminophores [19,20], fluorophores [21] and scintillating materials [20, 22]. 

One of the practically important synthetic pathways to aryl-containing pyrazole derivatives is a reaction of oufi-unsaturatcd ketones with dipolar molecules or 1,2-binucleophiles. There are dozens of stereotypical publications on this topic and in this chapter we will not cite all existing references related to the synthesis and properties of pyrazole derivatives based on unsaturated carbonyl compounds but will cover the most general and some specific examples as well as mechanisms. 

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Starting materials containing one five-membered azaheterocyclic ring 400... 

The metabolism of most five-membered azaheterocycles such as pyrrolidines can be described by the scheme given in Fig. 5.23. Thus, nicotine (5.86, Fig. 5.24), tremorine (5.89, Fig. 5.24), a pharmacological reagent used to produce experimental parkinsonism, and the antidepressant prolintane (5.90, Fig. 5.24) are metabolized to both lactam and co-amino acid derivatives [185-187]. 

Metalation of 6-membered azaheterocycles is similar to that of their five-membered counterparts, and thus the rm-butylformamidine derivative of... 

Because of lower steric constraints, or/Ao-metalation generally occurs more readily with six-membered ring-fused azaheterocycles than with five-membered species, and thus the directed /3-metalation of 1,2,3,4-tetrahydroquinoline has been achieved in combination with a r-BOC protecting group (Scheme 148) (89TL1197). 

Seven-membered azaheterocycles such as azepines have received much less attention than their five- or six-membered counterparts, although, as with the related 2,3-pyrroline and 1,2,3,4-tetrahydropyridine compounds, the tm-butylformamidine derivative of azepine has been a-metalated with... 

SATURATED FIVE-MEMBERED RING AZAHETEROCYCLIC SPIROPYRANS... 

No major improvement of photodurability was observed on going from the five- to the six-membered ring azaheterocyclic spiropyrans.32 In the piperidine series, a methyl group at C3 diminishes photostability by a factor of, 2 (Table 12, 142 vs. 144). The introduction of electron-acceptor atoms such as sulfur and oxygen at the position 3 to the nitrogen atom of the azaheterocycle results in a decrease of the photostability of the modified spiropyran. On the other hand, the indoline series compounds are more photostable than the pyrrolidinospiropyrans. As noted previously, electron-donor groups (e.g., CH3) on the azaheterocyclic moiety increase photostability. 

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