Ring-fused derivatives tetrazoles

A Hungarian research group observed a nonexpected formation of a tetrazolo[l,5- ]derivative <2001J(P 1) 1131 >. These authors found that treatment of the /3-lactam-substituted tetrazolylmethyl ketone 135 with lead tetraacetate results in a ring closure to pyridine ring fused to tetrazole, and product 136 was formed as a mixture of diastereomers in low yield (Scheme 33). 

Synthesis of Tetrazoles and Ring-Fused Derivatives via Nitrogenation Strategy... 

Several ring-fused tetrazole compounds have been reported. 2-Methyl-3-cyanopyridines were converted into their corresponding 2-azidomethyl derivatives, which underwent intramolecular cycloaddition reactions to give 3-(tetrazol-5-yl)pyridines 186 <04TL9127>. Fused tetrazole derivatives 187 were obtained via tandem cycloaddition and yV-allylation reactions <04JOC1346>. Expeditive synthesis of homochiral fused tetrazole piperazines 188 from 3-amino alcohols has been reported <04TL3725>. A novel Ugi-five-center-four-component reaction (U-5C-4CR) of aldehydes, primary amines, trimethylsilyl azide and 2-isocyanoethyl tosylate afforded tetrazolopiperazine type compounds <04TL6421>. 

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. 

Extension of these studies to benzologues of tetrazolo[l,5- ]pyridine, that is, for tetrazolo[l,5- ]quinoline 21 and tetrazolo[5,l- ]isoquinoline 22, led to interesting results <2003JOC1470> as shown in Scheme 7. Both of these fused tetrazoles resulted in formation of a nitrene 23 and 24, respectively, which could be interconverted via formation of the fused cyclic carbodiimide derivative 25. Isoquinolylnitrene 24, furthermore, was found to undergo subsequent reactions ring opening afforded the vinylnitrene 26, which was transformed to o-cyanophe-nylacetonitrile 27 by a 1,2-H shift and to 4-cyanoindole 28 by an intramolecular cyclization in 40% and 25% yields, respectively. 

The fused tetrazole 422 (Scheme 19) was originally assumed307" to be nitrated on the thiazole ring, but recent NMR studies have shown that a p-nitrophenyl derivative is formed.1836 Since 422 (and 424) display azide tetrazole tautomerism (Section IV,B,1), the exact structure of the reacting species is unknown, but the product exists predominantly as the azide. 

Chi the basis of the tautomeric formulas shown for 5-monosubstituted tetrazoles (where R is any substituent) there are three classes of monosub stituted and two classes of disubstituted derivatives (where the H is replaced). Also, there are fused ring tetrazoles of the 1,5-disub stituted class. In addn, there are salts and substituted derivatives which have 2,3-, 1,4- and 1,2-sub-stituents. However, compds of ordn interest are usually 1,5-, 2,5- or 1,3-substituted. Bis expl compds may be connected at the 5,5 -positions. Bis expl salts may be connected at either the 1,1 or the 5,5position with the (metallic) anion. (See in Vol 2, B157-L R and below under the pertinent compds)... 

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