Tetrazoles, fused

A substantial amount of research has been carried out in the field of tetrazole-fused sugars (rhamnose, mannose, and glucose derivatives) - mostly because of the biological importance of these derivatives. In many of these cases synthesis of the fused tetrazole moieties has been perfected by intramolecular 1,3-cycloaddition reactions with participation of a cyano and azido group. Some of these results are shown in Schemes 26 and 27. 

The second possibility is illustrated by a-azidoazines which exist in equilibrium with tetrazole fused systems thus, 3-azido-l,2,4-triazines (103a) exist predominantly as the tetrazolotriazines (103b). 

Tetrazoles fused to six-membered nitrogen heterocycles wherein the two rings share a nitrogen are known to exist in equilibrium with the azido tautomer (C) (D) (73S123). 

The reaction of ketones with hydrazoic acid-boron trifluoride has been used to synthesize a further series of tetrazoles fused to ring b of the cholestane nuc-... 

Tetrazoles Fused with Five-Membered Rings.404... 

The reaction is illustrated by the intramolecular cycloaddition of the nitrilimine (374) with the alkenic double bond separated from the dipole by three methylene units. The nitrilimine (374) was generated photochemically from the corresponding tetrazole (373) and the pyrrolidino[l,2-6]pyrazoline (375) was obtained in high yield 82JOC4256). Applications of a variety of these reactions will be found in Chapter 4.36. Other aspects of intramolecular 1,3-dipolar cycloadditions leading to complex, fused systems, especially when the 1,3-dipole and the dipolarophile are substituted into a benzene ring in the ortho positions, have been described (76AG(E)123). 

Tetrazoles (744), as bis(nitrilimine) (745) generators (Section 4.04.3.1.2(ii)), afford polypyrazoles when reacted with diynes. Benzoquinone has also been condensed with bis-sydnones to incorporate a fused pyrazole nucleus (746). 

Compounds containing a fused quinoline-tetrazole ring system (90 Z = N) behave similarly to compounds containing the simple tetrazole ring and give salts of type 91 (Z =... 

Alkenyl-substituted diarylnitrilimines 325, generated by photolysis or thermolysis of corresponding tetrazoles 324, undergo a regioselective INIC reaction to yield fused 2-pyrazolines (Scheme 34) [93]. Similarly, with alkynyl derivatives... 

Fused ring tetrazoles such as 96 are obtained from the reaction of nitrous acid with heterocyclic hydrazines (95) (Eq. 19).159 160 This method is also suitable for the preparation of fused ring ditetrazoles such as... 

Chukhadzyan et al. made N-junction fused tricyclic systems such as 123 via a base-catalyzed cyclization onto the tetrazole 122 (Equation 29). The exothermic reaction proceeds at room temperature <1999CHE343>. 

Nucleophilic substitution of the chloropyridazine 166 with sodium azide in DMF is followed by cyclization to give the fused tetrazole 167 (Equation 41) <1997JHC39>. 

Major advancements in the chemistry of pyrazoles, imidazoles, triazoles, tetrazoles, and related fused heterocyclic derivatives continued in 2000. Solid-phase combinatorial chemistry of pyrazoles and benzimidazoles has been particularly active. Synthetic routes to all areas continue to be pursued vigorously with improvements and applications. Notably, metal-promoted and cross-coupling reactions of all classes seemed to be a dominant theme in 2000. Applications of pyrazole-, imidazole-, and 1,2,3-benzotriazole-containing reagents to a wide array of synthetic applications remained active. 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

The hydrolysis product 51 can alternatively be accessed directly from the reaction of the thiol derivative 48 with chloro acetamide. Other electrophiles for the reaction with the thiol derivative were also described which lead to functionalized tetrazole or 5-6 fused bicyclic ring systems. 

An alternative approach to 5-5 bicyclic fused ring systems utilizing a condensation reaction was described by Moderhack et al. <2000JPC591> (Scheme 10). The amino-substituted tetrazole derivatives 52 and 54 gave the neutral 53 as well as the mesoionic derivatives 55 in moderate to excellent yields (16-86% R = CH3 or Ph). 

Simoni et al. described <2000TL2699> that some fused tetrazoles readily participate in thermolytic ring contraction reactions which result in the formation of cyanopyrroles (Scheme 5). Thus, heating of tetrazolo[l,5- ]pyridine derivatives 14 at 150-170 °C yields the corresponding 2-cyanopyrrole 16. The process is believed to proceed via a nitrene intermediate 15. 

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