Condensations 177-tetrazole

The most well-known tautomeric systems of this type involve a-azidoazoles. Unlike their azine counterparts normally existing as condensed tetrazoles (Sec. 2.2.5.4), they exist as a rule in an open-chain structure, e.g. (255). However, in alkaline media N-anion (256) has a strong tendency to cyclize into tetrazole (257) which often becomes predominant in an equilibrium mixture. 

Sodium azide Diazonium salt reactions N-Condensed tetrazole ring Thiazolo[3,2-d]tetrazoles... 

Sodium nitrite acetic acid N-Condensed tetrazoles... 

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). 

Conversion of m-bromobenzonitrile to the tetrazole and addition of the elements of acrylic acid gives 7S, starting material for the patented synthesis of the antiinflammatory agent, bropera-mole (76). The synthesis concludes by activation with thionyl chloride and a Schotten-Baumann condensation with piperidine. 

A number of studies have been reported concerning azide-isocyanide condensations to give tetrazoles. Early work by Beck and co-workers 18, 19) describes the addition of various isocyanides to metal azido species [Au(N3)4]", [Au(N3)2]", Au(PPh3)N3, and M(PPh3)2(N3)2, M = Pd, Pt, Hg. The products are carbon-bonded tetrazolato-metal complexes. It is not known whether metal isocyanide complexes are intermediates in these reactions. More recently inverse reactions with azide ion addition to metal isocyanide complexes were carried out, with similar results. From... 

Although SiCh 57 has been employed, e.g., in the presence of sodium azide to convert ketones into tetrazoles (Section 5.3), to condense cyclopentanone in high yields into 1.2.3.4.5.6-tris(trimethylene)benzene (Section 9.2), or used for the condensation of amino acids to polyamides (Chapter 14) with formation of Si02, enol-trimethylsilyl ethers 107 a of ketones such as cyclohexanone are cleanly converted by SiCh 57 in the presence of Hg(OAc)2 into the trichlorosilylenol ether 116, which adds benzaldehyde in the presence of the asymmetric catalyst 117 to give... 

The ditetrazolide of methylphosphite plays a role in the solid phase synthesis of polynucleotides. The ditetrazolide, which is stable for weeks when stored at —20 °C, is prepared in a simple condensation reaction between methylphosphordichloridite and two equivalents of tetrazole in anhydrous tetrahydrofuran in the presence of 2,4,6-tri-methylpyridine.t28]... 

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). 

Although addition of activated phosphoramidite to hemiacetals of manno-pyranoses under thermodynamic control has been reported to deliver exclusively a-phosphates in some cases,43 anomeric mixtures with preponderance of a-anomer have been reported in other examples.10,44 Since formation of phosphorotetrazolidite is a rate-limiting step of the process, initial activation of phosphoramidite followed by addition of nucleophilic hemiacetal should accelerate condensation and favour the formation of the thermodynamic a-product. Indeed, reaction of hemiacetal 101 with dibenzyl phosphorotetrazolidite assured exclusive a-selectivity of the resulting glycosyl phosphate 102.43 The accumulation in the reaction mixture of mildly acidic 1H-tetrazole, which is liberated upon reaction of tetrazolidite with hydroxylic component, could also favour predominant formation of the a-phosphate (Scheme 18, A). Conventional hydrogenolysis afforded the a-mannosyl phosphate 103. 

The mononucleoside was condensed with 3-chlorophenol in the presence of tetrazole (step a). The aryloxyphosphite obtained was separated into... 

Similarly, 5-picrylamino-l,2,3,4-tetrazole (PAT) (116) " " and 5,5 -styphnylamino-1,2,3,4-tetrazole (SAT) (117) " have been synthesized by condensing picryl chloride and styphnyl chloride with 5-amino-l,2,3,4-tetrazole in methanol respectively. A comparison of thermal and explosive properties of newly synthesized PAT (calculated VOD 8126 m/s) and SAT (calculated VOD 8602 m/s) reveals that PAT is more thermally stable than SAT but more sensitive to impact and friction. " ... 

Bienaym H, Bouzid K (1998) Synthesis of rigid hydrophobic tetrazoles using an Ugi multi-component heterocyclic condensation. Tetrahedron Lett 39(18) 2735-2738... 

Cefpiramide (64) is a third generation cephalosporin with a l-methyl-[lH]-tetrazol-5-ylthio-methyl moiety at C-3 and an acylated p-hydroxyphenylglycine moiety at C-7. It includes in its activity spectrum reasonable potency in vitro against many strains of Pseudomonas. It can be synthesized in a variety of ways including condensation of cephalosporin antibiotic 63 with 6-methyl-4-(l-H)-pyridone-3-carboxylic acid in the form of its active N-hydroxysuccinimide ester (62) to produce cefpiramide (64) [20,21]. 

The presence of the propionamide fragment in the stmcture of the anti-inflammatory agent broperamole (125-1) is reminiscent of the heterocycle-based NSAID propionic acids. The activity of this agent may trace back to the acid that would result on hydrolysis of the amide. Tetrazoles are virtually always prepared by reaction of a nitrile with hydrazoic acid or, more commonly, sodium azide in the presence of acid in a reaction very analogous to a 1,3-dipolar cycloaddition. A more recent (and safer) version of the reaction noted later (see losartan, 77-4) uses tributyltin azide. In the case at hand, reaction of the anion of mefa-bromobenzonitrile (125-1) with sodium azide and an acid affords the tetrazole (125-2). Condensation of the anion from that intermediate with ethyl acrylate leads to the product from Michael addition saponiflcation gives the corresponding carboxylic acid (125-3). This is then converted to the acid chloride reaction with piperidine affords broperamole (125-4) [136]. 

Aldol Condensation Product of 5-Ami no -tetrazole. See under Ami no tetr azole... 

Synthesis from tetrazole precursors was reported [60LA159 79JCS(P1)3085], according to which 5-aminotetrazole (388) was cyclo-condensed with 2-hydroxymethylenecyclohexanone to give tetrazolo [l,5-a]quinazoline (389) instead of the expected tetrazolo[5,l-fc] quinazoline (390). 

Finally the tetrazole derivative i is condensed with the propionamide ii by means of Na2C03 and Kl in refluxing 4-methyl-2-pentanon. 

The multicomponent Ugi-type condensation of aldehydes, secondary amines, azide, and polystyrene-bound isonitriles has been reported to yield tetrazoles in acceptable yields (Entry 9, Table 15.20). Tetrazoles have also been prepared from... 

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