Tetrazoles ring synthesis

The thermolysis of l-([l,3,4]thiadiazol-2-yl)tetrazoles 133 gives rise to the loss of dinitrogen from the tetrazole ring and the formation of 2,6-diaryl[l,2,4]triazolo[5,l+][l,3,4]thiadiazoles 71 (Equation 39) <1985IJB908, 1990FA953>. (For another synthesis of compounds 71, see Section 11.07.8.1.5.)... 

Ring synthesis involving formation of the tetrazole ring via azide-tetrazole equilibrium 656... 

Ring synthesis including formation of the tetrazole ring by intramolecular 1,3-dipolar... 

The high nitrogen content and the endothermic nature of the tetrazole ring lends itself to the synthesis of energetic materials. Compounds such as -H tetrazole and 5-aminotetrazole can be used as nucleophiles to incorporate the tetrazole ring into other molecules. 5-Aminotetrazole is synthesized from the reaction of dicyandiamide with sodium azide in hydrochloric acid. 

Cefonicid Cefonicid, 7-D-mandelamido-3-[[(l-sulfomethyl]-l/f-tetrazol-5-yl]thio] methyl]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.26), is structurally similar to cefamandole and differs in the presence of a sulfonic acid group in the methyl substituent of the tetrazol ring. It is synthesized by a method analogous to that of the synthesis of cefamandole [120-123],... 

Growing attention is directed to intramolecular reactions involving alkyls attached to position 5 of the tetrazole ring. The synthesis of 4,5-dihydrotetrazolo[l,5- ]quinoxalines 347 from 5-substituted tetrazoles 346 via the intramolecular. KNAr substitution of the halogen in the ortho-position of the iV1-aryl substituent is an example of such a reaction (Equation 64) <2006TL2041>. 

Esters of tetrazole-5-carboxylic acids are attractive substrates for aminolysis with various amines. These reactions are frequently involved in the synthesis of complex biologically active substances containing a tetrazole ring (cf. Section 6.07.12.1). Reactions of ethyl tetrazole-5-carboxylate 369 with anilines may be cited as an example that results in products of type 370 (Equation 68) <2003BML369>. 

In 1991, Duncia et al. reported on the synthesis of 1,5-disubstituted tetrazoles from secondary amides and azidotrimethylsilane under the conditions of the Mitsunobu reaction <1996CHEC-II(4)621>. The Mitsunobu protocol was successfully applied to the conversion of AT(cyanoethyl)amide into tetrazole 510. The tetrazole ring in this event forms by the cyclization of an imidoyl azide (not shown in the scheme) whose precursor is the phosphonium imidate 509 (Scheme 67) <2000JME488>. 

Currently a great number of procedures for the synthesis of 1//-unsubstituted tetrazoles from nitriles differing in the nature of azidation agents, activators of the reaction, and solvents are well known. Most of them were discussed by Butler in CHEC(1984) <1984CHEC(4)791> and in CHEC-II(1996) <1996CHEC-II(4)621>. Recently, concurrent with the development of the traditional procedures, new effective syntheses of the tetrazole ring have appeared <2004SOS(19)403>. 

Thymidine dimers in which the natural phosphodiester linkage has been replaced by a 2,5-disubstituted tetrazole ring have been synthesized and have been incorporated into oligodeoxynucleotides <02HCA2847>. The synthesis of mono- and bis-3-substituted thymidine derivatives with a polycyclic tetrazole linker (l,5-bis(tetrazol-5-yl)-3-oxapentane) has been reported <02TL1901>. a-Methylene tetrazole-based peptidomimetics were synthesized for inhibition studies of HIV protease <02JCS(P1)172>. A catalytic amount of tetrazole was found to be useful in the syntheses of symmetrical P,P -dialkyl partial esters of methylenebisphosphonic acid from the corresponding acid chloride via a facile two-step, one-... 

A neurokinin inhibitor whose strueture differs markedly from aprepitant (200) incorporates a substituted tetrazole ring. The synthesis of the tetrazole-containing moiety of vofopitant (241) start by acylation of substituted aniline 231 with trifluoroaeetyl ehloride to afford the amide (232). Reaction of that under Mitsonobu eonditions leads to the enol chloride (233). Treatment of 233 with sodium azide probablty starts with addition-elimination of azide ion this undergoes internal 1,3-cycloaddition to form the tetrazole ring. Catalytie hydrogenation then removes the benzyl... 

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