Density Functional Theory Study of the Intramolecular [2 + 3] Cycloaddition of Azide to Nitriles

Abstract

Density functional theory calculations using the hybrid functional B3LYP have been performed to study tetrazole formation by intramolecular [2 + 3] dipolar cycloaddition of organic azides and nitriles. Experimental reactivity trends are explained and rationalized in terms of a number of parameters, such as strain, tether length, and solvation and entropy effects. Interestingly, no correlation was found between the overall free energies and the free energies of activation of the reactions, due to the significant difference in strain and geometry between the transition states and products.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

“…If the necessary reaction temperature is taken as a measure of the reactivity, cyanates are more reactive in zinc‐catalyzed reactions than simple nitriles. In the absence of the catalyst, however, this reactivity is reversed 272…”

Organische Azide – explodierende Vielfalt bei einer einzigartigen Substanzklasse

“…Die Bandbreite geeigneter Azidonitrile für diese intramolekulare [3+2]‐Cycloaddition ist relativ groß, und der entstehende, zweite Ring kann dabei ungesättigt sein oder Heteroatome enthalten. Nimmt man die erforderliche Reaktionstemperatur als Messlatte für die Reaktivität, so sind Cyanate bei den Zink‐katalysierten Reaktionen wohl reaktiver als einfache Nitrile; bei Abwesenheit des Katalysators verhalten sich diese Reaktivitäten allerdings umgekehrt 272…”

A Simple and Direct Method for the Palladium‐Catalyzed Oxidative Coupling of Unactivated Allylarenes with Classic Arenes

“…chapter 2). [4d, 102b, 167, 168] For the former, a DFT study showed that the electron‐withdrawing power of the substituent is not the dominant factor governing the intra molecular reactions; rather, effects such as strain, tether length, and preorganization play equally important roles 13b. Recently, outstanding results have been achieved by catalyzing the addition of sodium azide to nitriles with zinc salts in water (see also sections 1.2. and 1.3.…”