Tetrazole Analogs of Amino Acids¹

Photochemistry and Vibrational Spectra of Matrix-Isolated 5-Ethoxy-1-Phenyl-1H-Tetrazole

“…2 The free N-H bond of tetrazoles makes them acidic molecules, and not surprisingly it has been shown that both the aliphatic and aromatic heterocycles have pK a values that are similar to those of the corresponding carboxylic acids (4.5-4.9 vs 4.2-4.4, respectively), due to the ability of the tetrazole moiety to stabilize a negative charge by electron delocalization. [3][4][5][6][7] In general, tetrazolic acids are strongly influenced by the effect of substituents at the C (5) -position. 4 It has been held that 5-substituted-1H-tetrazoles (RCN 4 H) may serve as a nonclassical isostere for the carboxylic acid moiety (RCO 2 H) in biologically active molecules.…”

Facile One-Pot Multicomponent Synthesis of Biaryl Tetrazoles through In Situ Formed Secondary Amides

“…We started our investigation by employing piperonal, o-phenyl diamine with benzoyl chloride in the presence of PCl 5 and NaN 3 as model substrates. As we expected the reaction was successful and gave the desired biaryl tetrazole.…”

“…They have long been recognized as carboxylic acid isosteres 2,3 and are important heterocycles in medicinal chemistry, owing to their increased stability towards metabolic degradation pathways 4 . The acidity of the tetrazole NH group corresponds roughly to that of the carboxylic acid 5 . Interest in tetrazole chemistry over the past few years has been increasing rapidly, mainly as a result of the role played by this heterocyclic functionality in medicinal chemistry as a metabolically stable surrogate for carboxylic acid functionalities [6][7][8] .…”

Asymmetric Synthesis of 5‐(1‐Hydroxyalkyl)tetrazoles by Catalytic Enantioselective Passerini‐Type Reactions

“…[2] The acidity of the tetrazole NH group corresponds roughly to that of the carboxylic acid. [3] Consequently, chiral 5-substituted tetrazoles have been investigated as efficient organocatalysts. [4] In addition, the 1,5-disubstituted tetrazole ring has been considered as a surrogate for the cis-amide bond, making it a valuable tool in the design of conformationally constrained peptidomimetics.…”

“…In addition, the adduct 1 t can easily be converted, in 82 % yield, into bicyclic compound 9, following a standard hydrolysis/lactonization sequence (Scheme 3). When 5-isocyanobenzo[d] [1,3]dioxole 3 i was used, the corresponding adduct 1 q was isolated in 88 % yield with 97 % ee ( Table 2, entry 17).…”