An Expeditious Approach to Tetrazoles from Amides Utilizing Phosphorazidates

Abstract

A novel method was developed for the synthesis of tetrazoles from amides utilizing diphenyl phosphorazidate or bis­(p-nitrophenyl) phosphorazidate as both the activator of amide–oxygen for elimination and azide source. Various amides were converted into the corresponding tetrazoles in good yields. This synthetic method allows to prepare 1,5-disubstituted and 5-substituted 1H-tetrazoles from various amides without the use of toxic or explosive reagents.

A Click Reaction Enabled by Phosphorus‐Oxygen Bond for Synthesis of Triazoles

“…With the advent of phosphoryl azidate, which has been rarely used as an azide source in azide alkyne click chemistry in spite of its low toxicity compared with other azide reagents. [26] Phosphoryl azidate is more stable and less explosive than sodium azide, sulfonyl azide and hydrazoic acids due to its conjugation with phosphorus atom [27] The high bond strength of phosphorus and nitrogen compared to silicon and nitrogen is reflected in its high stability. In our approach, the directing nature of C=O group of the propiolate ester and the interaction of oxygen with phosphorus atom of reagent control the reaction and favours synthesis of triazoles (Figure 1c).…”

Synthesis of 1,5-Disubstituted Tetrazoles from Nitrones by Using Bis(p-nitrophenyl) Phosphorazidate in the Presence of 4-(Dimethylamino)pyridine

“…Initially, DMAP acts as a nucleophilic catalyst to activate p -NO 2 DPPA. 7e f 9 The oxygen atom of the nitrone then attacks the activated p -NO 2 DPPA to generate an iminium intermediate that undergoes elimination to produce a nitrilium ion. 10 The nitrilium ion is subjected to nucleophilic addition of an azide ion to give an intermediate that undergoes cyclization to the desired tetrazole.…”

Modular Approach to Substituted Pyridoazepinones

“…13 Thus, we prepared tetrazole 7 using the method reported recently by Matsugi and co-workers. 14 Another possible modification of pyridoazepinones relies on the functionalization of the α-position of the amide via the corresponding Vilsmeier salt. Thus, treatment with phosphorus pentachloride furnished dichlorolactam 8 in good yield.…”