1.3- Dipolar cycloaddition Tetrazole synthesis

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

Dipolar cycloaddition between azides and nitriles is also a well-established route to tetrazoles. If these two functional groups are closely located within one molecule, intramolecular cyclization can occur to yield fused tetrazoles. The present survey of the recent literature shows that this approach has also been successfully applied in some cases and led to the synthesis of novel ring systems belonging to this chapter. These results are depicted in Scheme 25. 

A subsequent report outlined the synthesis of a diastereomer of tetrazole 58 that used similar methodology <1997TL4655>. Treatment of nitrile mesylate 60 with sodium azide affords D-talonotetrazole 62, presumably by intramolecular [1,3] dipolar cycloaddition of a 4-azido-4-deoxy-D-talonitrile intermediate 61. Acid hydrolysis affords the deprotected tetrazole 63 (Scheme 5). 

The synthesis of tetrazoles by 1,3-dipolar cycloaddition Part III - Disconnections Outside the Ring... 

Direct irradiation of amino substituted azirines leads to neutral nitrile ylides which can be trapped with electron-deficient double bonds. H. Heimgartner described the synthesis of triazolines and oxazolines via trapping of a nitrile ylide with diethylazodicarboxylate and methyl trifluoroacetate, respectively. An elegant application of 1,3-dipolar cycloaddition chemistry is the photolysis of a tetrazole leading to a reactive nitrile imine which is trapped in an intramolecular fashion. 

Tetrazole synthesis from azides by dipolar cycloaddition with activated nitriles or intramolecularly with nitriles in the presence of acids (see 1st edition). 

A facial synthesis of tetrazole 62 as an intermediate for the synthesis of 1-deoxymannojirimycin (2) has been reported (Scheme 11). The azide 54, obtained from L-gulonolactone 53, " was treated with ammonia in methanol to produce 59, which was reacted with trifluoroacetic anhydride in pyridine to give the nitrile 60. When the azidonitrile 60 was heated in toluene for 3 days, an efficient 1,3-dipolar cycloaddition took place, resulting in the formation of the tetrazole 61. Removal of both the silyl and acetonide groups in... 

Synthesis of triazoles and tetrazoles by 1,3-dipolar cycloaddition ( click chemistry ) in bioconjugate chemistry 06CJ01640. 

Reactions of heterocycles ch29 How to make pyridazines and pyrazoles How to make pyrimidines from 1,3-dicarbonyl compounds and amidines How to make thiazoles How to make isoxazoles and tetrazoles by 1,3-dipolar cycloadditions The Fischer indole synthesis Making drugs Viagra, sumatriptan, ondansetron, indomethacin How to make quinolines and isoquinolines ... 

Demko, Z.P. Sharpless, K.B. A click chemistry approach to tetrazoles by huisgen 1,3-dipolar cycloaddition Synthesis of 5-sulfonyl tetrazoles from azides and sulfonyl cyanides. Angew. Chem. Int. Ed. 2002,... 

NHCs have proved to be very useful also in [3 + 2]-dipolar cycloadditions. Some recent examples have been reported by the group of Vadde et al. for the synthesis of isoxazoles, and by the group of Curran et al. for the synthesis of botyl triazoles, tetrazoles, and triazolidines. ... 

Z. N. Tisseh, M. Dabiri, M. Nobahar, H. R. Khavasi, A. Bazgir, Tetrahedron 2012, 68,1769-1773. Catalyst-free, aqueous and highly diastereoselective synthesis of new 5-substituted H-tetrazoles via a multi-component domino Knoevenagel condensation/l,3-dipolar cycloaddition reaction. 

Dabiri has developed a catalyst-free three-component synthesis of a series of stmc-turally diverse 5-substituted tetrazoles 24 and 25 in good yields under mild conditions from caiboityl compounds (including benzaldehydes, isatin and ninhydrin), malononitrile and sodium azide in water [19], This process can be assumed to proceed through a domino Knoevenagel condensation/l,3-dipolar cycloaddition sequence (Scheme 1.13). 

The tetrazole functionality has an important role in organic synthesis, medicinal chemistry, and various materials science applications. The simplest method to prepare this heterocyclic ring is the 1,3-dipolar cycloaddition of azides and nitriles. The reaction mechanism was recently revised. ... 

The synthesis of losartan has been the subject of considerable research. The various syntheses have been discussed [25] in regards to their patent position and their process friendliness or ability to scale. In an early synthesis, the tetrazole is formed by reacting the substituted benzonitrile with sodium azide in a 1,3-dipolar cycloaddition. By protecting the tetrazole as the trityl derivative, the product is soluble in toluene and unreacted azide can be removed by washing with aqueous base. The use of a bulky trityl group also alleviated concerns with exothermic decomposition of the unprotected tetrazole. Ben-zylic bromination under radical conditions with N-bromosuccinimide was followed by displacement of the bromide with the substituted imidazole. The aldehyde is reduced to the alcohol, the trityl group cleaved under acidic conditions and then treatment with KOH gives losartan. 

The synthetic procedures for the preparation of C-F derivatives of tri- and tetrazoles are more developed compared to the synthesis of the derivatives with the N-F bond. The preparation methods of C-F derivatives are known not only for 1,2,3-and 1,2,4-triazoles, but also for tetrazoles. The C-F bond is successfully formed by the replacement of hydrogen atom or various leaving groups under the action of the fluorination reagents. Along with the above methods diverse versions are applied of 1,3-dipolar cycloaddition of azides to dipolarophiles containing fluorine. Also very useful approach is oxidative cychzation of molecules with the hnear structure containing a C-F bond. 

Scheme 9.8 [2 + 3] Dipolar cycloaddition for the synthesis of 1,5-disubstituted sulfonyl tetrazoles (A) and acyl tetrazoles...

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