ChemInform Abstract: Tetrazoles. Part 21. Reaction of Benzonitrile with Azides.

Titova, I. E.; Poplavskii, V. S.; Koldobskii, G. I.; Островский, В. А.; Николаев, В. Д.; Erusalimskii, G. B.

doi:10.1002/chin.198708208

Cited by 3 publications

(4 citation statements)

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“…[109] This is most likely the reason why these reactions proceeded with high regioselectivity, even in the case of unsubstituted tetrazole. [111] However, the reaction between a 5-ST with a more compact substituent at the 5-position yielded the two isomers 34 and 35 in comparable amounts, putting the major role of the above hypothesis into question. However, the influence of these associates on the reaction rates or regioselectivity is not still clearly understood, although many examples have shown that the regioselectivity is controlled in the same manner as in the case of the tetrazolate anion.…”

Section: Alkylation Of 5-stsmentioning

confidence: 99%

Synthesis and Functionalization of 5‐Substituted Tetrazoles

2012

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Tetrazoles are synthetic heterocycles with numerous applications in organic chemistry, coordination chemistry, the photographic industry, explosives, and, in particular, medicinal chemistry. In organic chemistry, 5‐substituted tetrazoles are used as advantageous intermediates in the synthesis of other heterocycles and as activators in oligonucleotide synthesis. In drug design, 5‐monosubstituted tetrazoles are the most important tetrazole derivatives because they represent non‐classical bioisosteres of carboxylic acids, with similar acidities but higher lipophilicities and metabolic resistance. In this review we focus on the preparation and further functionalization of these heterocycles. Firstly, the role of 5‐substituted tetrazoles in medicinal chemistry is described, including examples of their effects on pharmacokinetics, pharmacodynamics, and metabolism of the associated drugs. Then, the main synthetic approaches to 5‐substituted tetrazoles – consisting of methods based on acidic media/proton catalysis, Lewis acids, and organometallic or organosilicon azides – are presented, from the early procedures to the most recent ones, with special attention paid to the reaction mechanisms. Functionalization of 5‐substituted tetrazoles is a challenging task because it usually leads to the formation of two isomers, 1,5‐ and 2,5‐disubstituted tetrazoles, in various ratios. In this overview, reactions with high or unusual regioselectivities are described, with comments on the possible mechanisms. Microwave‐assisted approaches to the synthesis and functionalization of 5‐substituted tetrazoles are also included.

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Section: Alkylation Of 5-stsmentioning

confidence: 99%

Synthesis and Functionalization of 5‐Substituted Tetrazoles

2012

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“…Since the corresponding nitrile ( 1 ) was commercially available, it was proposed that the tetrazole ring should be introduced directly via azide cycloaddition. We were thus faced with the task of deciding which of the dozens of tetrazole-forming reaction conditions to employ. − Considering ease of operation, reagent cost, and waste minimization, we decided to first investigate the simple conditions reported by Finnegan, Henry, and Lofquist in 1958: NaN 3 in the presence of NH 4 Cl in DMF . While nitrile 1 was successfully transformed to 2 under these conditions, the reaction was unfortunately very sluggish, as is often the case for ortho-substituted nitriles. ,,, Full consumption of the nitrile starting material required >40 h at 120 °C with a significant excess of reagents (2.0 eq NaN 3 , 2.5 eq NH 4 Cl).…”

Section: Resultsmentioning

confidence: 99%

“…In order to avoid the use of hydrazoic acid, dozens of alternative protocols have since been developed for the conversion of an aryl nitrile to the corresponding 5-aryltetrazole . In the simplest of these procedures, hydrazoic acid is generated in situ by the reaction of sodium azide with a weak Brönsted acid, typically ammonium chloride or triethylamine hydrochloride (Scheme , eq B) . Alternatively, myriad Lewis acids have been demonstrated to mediate the reaction between an aryl nitrile and sodium azide.…”

Section: Introductionmentioning

confidence: 99%

Development and Demonstration of a Safer Protocol for the Synthesis of 5-Aryltetrazoles from Aryl Nitriles

Treitler

Leung

Lindrud

2017

Org. Process Res. Dev.

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The search for a faster, safer protocol for the direct synthesis of 5-aryltetrazoles from aryl nitriles in the presence of sodium azide and an amine hydrochloride salt led to the discovery of a buffered system comprised of BnNH 2 , BnNH 2 •HCl, and NaN 3 . After optimization of reaction conditions and a thorough investigation of reaction safety, the procedure was demonstrated for the synthesis of several hundred grams of 4-chloro-2-(2Htetrazol-5-yl)phenol. The generality of the developed reaction conditions was established by a small-scale reactivity screen using 16 additional aryl and heteroaryl nitrile substrates.

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“…In addition, these salts increase the reactivity of the azide ion. They are prepared using ammonium chloride, 22,23 alkylamine hydrochlorides, 14,15 tetramethylguanidinium chloride, 24 boron trifluoride etherate 25 and aluminium chloride. 21 Temporary protection of the double bond of acrylonitrile by addition of dimethylamine has made it possible to avoid polymerisation and resinification in the reaction of the azide ion with the nitrile group of 3-dimethylaminopropionitrile: 5-(2-dimethylaminoethyl)tetrazole (3) was prepared in high yield.…”

Section: Synthesis Of C-vinyltetrazolesmentioning

confidence: 99%