Tetrazolo pyridine

Reisinger, A. and Wentrup, C. (1996) Synthesis of 1H- and 5 H-l, 3-diazepines from azido and tetrazolo-pyridines. Chemical Communications, (7), 813-814. 

Phosphines have been used to trap sulphenes produced by dehydrochlorination of methanesulphonyl chlorides. The reaction of tetrazolo-pyridine with triphenylphosphine to give an iminophosphorane was shown, by kinetic measurements, not to involve a nitrene intermediate, but rather to involve reaction of the phosphine with the azide (12). The reaction... 

Evans, R. A. and Wentrup, C, Trifluoromethyl-substituted dehydroazepines and cyanopyrroles from azido-/tetrazolo-pyridines,/. Chem. Soc., Chem. Commun., 1062,1992. 

Pyridine A-oxides were converted to tetrazolo[l,5-a]pyridines 172 by heating in the presence sulfonyl or phosphoryl azides and pyridine in the absence of solvent <06JOC9540>. 3-R-5-Trinitromethyltetrazolo[l,5-a]-l,3,5-triazin-7-ones 173 have been prepared from the alkylation of 5-trinitromethyltetrazolo[l,5-a]-l,3,5-triazin-7-one silver salt with different alkylation agents <06CHE417>. The use of 2-fluorophenylisocyanide in the combinatorial Ugi-tetrazole reaction followed by a nucleophilic aromatic substitution afforded tricylic tetrazolo[l,5-a]quinoxaline 174 in good yields and with high diversity <06TL2041>. 

Cyclization of 776 with ortho-esters gave (83JOC1628) [l,2,4]triazolo-[4,3-fc]pyrimido[5,4-< ][ 1,2,4]triazines 777, whereas reaction with sodium nitrite afforded the corresponding tetrazolopyrimidotriazine 778.3-Azido-pyrimido[4,5-e][l, 2,4]triazine 779 exists in a cyclic form as tetrazolo derivative 780, as shown by X-ray analysis (86KGS114). In solution the position of the 779 780 equilibrium depended on temperature and solvent. Higher temperatures favored 779. Azido compound 779 predominated in water, and tetrazolo compound 780 predominated in pyridine. Addition of sodium azide to the aqueous solution shifted the equilibrium toward 780. The... 

A kinetic study of thermolysis reactions of TV-crotyl substituted 1,2,4-triazoles was performed at temperatures in the range of 260-350 CC <00JHC1135>. Thermolysis of tetrazolo[l, 5- >]pyridazines, tetrazolo[l,5-a]pyrimidines and tetrazolo[l,5-a]pyridines allowed easy ring contraction to a facile preparation of cyanopyrazole heterocycles . 

Novel calculations on the tetrazolo[l,5-tf]pyridine-2-azidopyridine equilibrium (Scheme 2, 1-7) in the case of 5-substituted derivatives using ab initio (6-31G /MP2) methods appeared recently <2000T8775>. It has been shown that these substituents sensitively influence the equilibrium as revealed by the calculated energies shown in Table 1. 

Theoretical studies on the experimentally observed selectivity of alkylation of tetrazolo[l,5-tf]pyridine 1 and its benzologues to alkyltetrazolo[l,5- ]pyridinium salts revealed that the site of the alkylation can be fairly well predicted by the help of molecular electronic potential (MEP) maps <1998JMT191>. Earlier it was shown that transformation of 1 to the three possible alkyl-substituted salts 8-10 (Scheme 3) results in a mixture containing high... 

Table 2 15N NMR shifts in DMSO and TFA solutions of some 6- and 8-substituted tetrazolo[1,5-a]pyridines...

Quite recently, the same research group compared the electrophilicity of 6-nitro-tetrazolo[l,5- ]pyridine and 6,8-dini-trotetrazolo[l,5- ]pyridine 11 with a series of electron-deficient aromatic and heteroaromatic compounds <2005JOC6242>. As reference nucleophiles, fV-methylpyrrole, indole, fV-methylindole, and some morpholino enamines were used. The reactivity of the electrophiles studied followed the linear-free energy relationship defined by Mayr et al. <2003ACR66>. 

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. 

Similar observations with tetrazolo[l,5- ]pyridines bearing a phenylurea side chain have independently been reported by a French research group <1996JHC1035>. 

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. 

A photoextrusion of a nitrogen molecule from a partially saturated tetrazolo[l,5- ]pyridine derivatives has been described by Quast et al. <1998EJ0317> (Scheme 11). The starting bicyclic compound 39 when irradiated at low temperature (at -60 °C) afforded annulated iminoaziridine 40 as a mixture of (E)- and (Z)-isomers. These two geometric isomers equilibrated at higher temperature (20 °C). Upon heating of the mixture of ( )-40 and (Z)-40, a thermal cycloreversion took place with methyl isocyanide elimination to afford the dihydropyrrole 41. 

The fact that tetrazolo[l,5- ]pyridine reacts with phosphines - via ring opening to the valence bond isomer azide -to give a phosphorane has been long recognized. Some novel applications of this transformation have been published during the recent period. The fused tetrazoles subjected to this reaction, the resulting phosphoranes, and the literature sources are summarized in Table 4. 

As mentioned already in CHEC-II(1996) <1996CHEC-II(8)411>, some tetrazolo[l,5- ]pyridines can react with their C(5)-C(6) and C(7)-C(8) double bonds as dienophiles in Diels-Alder reactions. A novel study again supported this recognition Goumont et al. described that 6,8-dinitrotetrazolo[l,5- ]pyridine 11 easily react with some 2,3-disub-stituted butadienes to give bis-cycloadducts 48 <2002T3249>. These products when treated with potassium /-butoxide undergo base catalyzed elimination of nitric acid followed by oxidation reaction to yield the fully aromatic tetracyclic compounds 49 (Scheme 14). 

Table 4 Synthesis of some phosphoranes from tetrazolo[1,5-a]pyridines and its benzologues...

A photolytic reduction of the 5-chloro-substituted tetrazolo[l,5- ]pyridine derivative 60 was observed by Dias et al. <1996JHC1035> (Scheme 17). These authors found that the photolysis of the starting compound 60 when carried out with unfiltered light followed an unusual pathway instead of a ring-enlargement reaction experienced with use of Pyrex filter in many cases, a photolytic reduction takes place in 44% yield, and the chlorine substituent is replaced by... 

As discussed in Section 11.15.4 on thermodynamic aspects, dinitrotetrazolo[l,5- ]pyridines 11 are electrophiles and can react with nucleophilic species in addition reactions as shown in Scheme 18 <1994IZV1278, 2003OBC2764>. In the presence of alcohols on addition of the alcoholate anion in position 5 of tetrazolo[l,5-tf]pyridine takes place. The primary addition product 12 formed in an equilibrium was characterized by its H NMR spectrum and can be isolated in the form of potassium salts 62 in good to high yields 53-96% <1994IZV1278>. 

Some more or less routine transformations with side chains of tetrazolo[l,5-tf]pyridine or its benzologue have also been published during the recent period, and these results are shown in Scheme 19. 

Based on earlier experiences ring opening of the pyridine moiety in methyl 4-tetrazolo[l,5- ]pyridine carboxylate 70 on reaction with allylamine was predicted by Okawa et al. <1997T16061> (Scheme 19). Instead of the expected major structural change, however, a routine aminolysis was found to yield the allylamide 71. 

Thus, the 2-hydrazinopyridone compound 89 was transformed to the corresponding fused tetrazolo[l,5- ]pyridine 90 in 61% yield <2000J(P1)3686>, and the partially saturated 1-hydrazinoisoquinoline compound 91 when reacted with nitric acid gave the appropriate tetrazole 92 in 64% yield <1994KGS511>. In the case of the acylhydrazino isoquinoline derivative 93, a deprotection of the hydrazine group was carried out first followed by treatment with... 

In contrast to the cyclization strategies where ring closure of the tetrazole part of tetrazolo[l,5- ]pyridines and benzologues has been carried out, much less attention has been paid to reaction pathways starting from appropriate... 

In studying the reactivity of iV-fluoropyridinium fluoride 127 obtained from pyridine 126 by treatment with fluorine gas in chloroform at low temperature (Scheme 30), Kiselyov studied reactions with isocyanides in the presence of trimethylsilylazide <2005TL4851>. A mixture of products was obtained in which, besides tetrazolylpyr-idine 128 and a nicotinamide derivative 129 also tetrazolo[l,5-tf]pyridine 1 was obtained in very poor yield (5-10%). 

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). 

Conversion of aromatic amines to azides was studied by Scechter et al. <2002TL8421> and these studies lead to the recognition of a new approach to tetrazolo[l,5- ]pyridine. Thus, reaction of 2-aminopyridine 142 with butyl-lithium followed by treatment with azidotris(diethylamino)phosphonium bromide gave rise to tetrazolo[l,5- ]pyr-idine 1 in 80% yield. The first intermediate is obviously the azide 7. 

Novak et al. <1998JA1643> devised a novel approach to amino-substituted tctrazolo[ 1,5-tf Jpyridine which provides a really unique pathway (Scheme 34). These authors studied the possibility of formation of nitrenium ions from the pivaloylhydroxylamine 143 and found that if azide anion is present in the main reaction route is the formation of tetrazolo[l,5-tf]pyridine 146. The authors concluded that the first intermediate is the formation of the carbonium cation 144 which captures the azide anion to yield 2-azidopyridine 145, that is, the valence bond isomer of the product 146. 

Recently a new synthetic pathway to tctrazolo[l,5-z/ pyridine has been explored by Keith <2006JOC9540>. According to this new procedure, pyridine iV-oxides can be treated by sulfonyl or phosphoryl azide to furnish tetrazolo[ 1,5-tf]pyridines in one reaction step in medium to good yields (30-100%). 

C. K. Lowe-Ma, R. A. Nissan and W. S. Wilson, Tetrazolo[l,5-a]pyridines and Eurazano[4,5-b]pyridine-l-oxides as Energetic Materials, NWC TP 6985 (1989), Naval Weapons Center, China Lake, CA. 

---