Tetrazole reactions

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>. 

We first consider the Demko and Sharpless article (2001) on the synthesis of substituted tetrazoles from nitriles in water (excerpt 5D). This excerpt is particularly useful because it illustrates several types of content that authors typically discuss in synthesis papers. The authors begin by proposing two possible mechanisms for the tetrazole reaction, a two-step mechanism and a concerted mechanism. The mechanisms are presented in a scheme (Scheme 1). In the accompanying text, the authors cite evidence for both mechanisms, highlight salient features of the mechanisms, mention the results of kinetic studies, and point out that the role of zinc metal is as yet unclear. 

Other solid supports have been reported to promote the Finnegan tetrazole reaction, like catalytic FeCl3-Si02- The procedure was shown to be general and the catalyst could be re-used. 

Tetrazoles. Aryl nitriles and alkyl nitriles are converted into the corresponding tetrazoles in the presence of dibutyltin oxide or trimethylaluminum in moderate to good yields. Amides or thioamides also react with TMSA to form tetrazoles. Reaction of a,/3-unsaturated ketones with TMSA can be catalyzed by TMSOTf in dichloromethane. A tandem strategy for fused tetra-zole formation has also been reported a [3-1-2] cycloaddition between a nitrile and TMSA in presence of dibutyltin oxide is followed by an intramolecular allylation to form a fused tetrazole in 60-82% yields. 

A combinatorial synthetic route yielding fused tetrazolo[l,5-a]quinoxalines has been described by Kalinski et al. [128] using the classical fom--component Ugi reaction (Scheme 92). The Ugi-tetrazole reaction between amine, aldehyde, carboxylic acid, and isocyanide, followed by a nucleophilic aromatic substitution (SnAc) affords the tri-cylic tetrazolo[l,5-a]quinoxaline moiety in good yields and with high diversity. Amines and carbonyls can be varied broadly, yielding tricyclic tetrazoles with three potential diversity points giving access to thousands of diverse analogs. 

A comprehensive review of reactions of isocyanates and 1,3-dipolar compounds has been previously pubhshed (51). The example shown illustrates the reaction of azides and isocyanates to yield tetrazoles (14,R = alkyl or aryl, R = aryl or sulfonyl) (52,53). 

Similar ambiguities arise in the reactions of azole anions. At least as regards alkylation reactions in the 1,2,3-triazole series (79), the product appears to depend on the reagent used. In the 1,2,4-triazole series (80) a single product is formed, whereas tetrazole (81) gives mixtures. 

Imidazoles and benzimidazoles (155) react with acid chloride and alkali to give compounds of type (157), but these are reactions of the cation (156). 1,2,4-Triazoles and tetrazoles similarly undergo ring opening. 

However, in some cases carboxylic acid-derived groups can participate in ring fission-reclosure reactions. Thus photolysis of 1,5-disubstituted tetrazole (399) gives nitrogen and appears to involve the amino-nitrene intermediate (400), which reacts further to give (401) (77AHC(21)323). 

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). 

Other amino substituted isoxazoles undergo ring-opening reactions on treatment with base. Thus the amidine derivative (249) gave the triazole (250) (64TL149), while the triazene (251) on reaction with ammonia gave the tetrazole (252) (64X461). 

Tetrazole, 5-phenoxy-l -phenyl-mass spectra, 5, 801 photolysis, 5, 811 Tetrazole, 1-phenyl-deuterium-hydrogen exchange, 5, 806 mercuration, 5, 59 NMR, 5, 798 tautomerism, 5, 804 UV spectra, 5, 798 Tetrazole, 2-phenyl-NMR, 5, 798 tautomerism, 5, 804 UV spectra, 5, 798 Tetrazole, 5-phenyl-alkylation, 5, 818 anti-inflammatory activity, 5, 835 blowing agent, 1, 410 reactions... 

Tetrazole, l-(p-substituted phenyl)-antimicrobial activity, 5, 835 Tetrazole, 5-thio-rearrangements, 5, 823 Tetrazole, 2-thioacyl-reactions, 5, 109 Tetrazole, 5-(o-tolyl)-tautomerism, 5, 804 Tetrazole, 5-(p-tolyl)-dipole moments, 5, 795 tautomerism, 5, 804 Tetrazole, 5-(trimethylsilylamino)-synthesis, 5, 832 Tefrazolecarbaldehydes reactions, 5, 820 Tetrazole-5-carbaldehydes reactions, 5, 820 Tetrazolecarbonitriles reactions, 5, 820 Tetrazole carbonyl compounds reactions, 5, 820 Tetrazolecarboxylic acid, 5-aryl-acidity, 5, 816... 

Azides have been shown to react with itniniutn salts to give addition products. The same product is obtained if the iminium salt is treated with azide ion or if the enamine is treated with hydrazoic acid 14). The yields of the products were all very high (85-95 %). The interest in this reaction centers on the fact that the azides react with isonitriles to give substituted tetrazoles (83) 44). 

The addition of isocyanides and azide to aldehyde-derived enamines has led to tetrazoles (533,536). On the other hand the vinylogous amide of acetoacetic ester and related compounds reacted with aldehydes, isocyanides and acids to give a-acylaminoamides (534). Iminopyrrolidones and imino-thiopyrrolidones were obtained from the addition of cyclohexylisocyanide and isocyanates or isothiocyanates to enamines (535). An interesting method for the formation of organophosphorus compounds is found in the reactions of imonium salts with dialkylphosphites (536). 

The disadvantage of this method is that the dichloridites and monochloridites are sensitive to water and thus could not be used readily in automated oligonucleotide synthesis. This problem was overcome by Beaucage and Caruthers, who developed the phosphoramidite approach. In this method, derivatives of the form R 0P(NR2)2 react with one equivalent of an alcohol (catalyzed by species such as l//-tetrazole) to form diesters, R OP(OR")NR2, which usually are stable, easily handled solids. These phosphoroamidites are easily converted to phosphite triesters by reaction with a second alcohol (catalyzed by l//-tetrazole). Here, again, oxidation of the phosphite triester with aqueous iodine affords the phosphate triester. Over the years, numerous protective groups and amines have been examined for use in this approach. Much of the work has been reviewed. ... 

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