Substituent Effects on EI-MS Fragmentation Patterns of 5-Allyloxy-1-aryl-tetrazoles and 4-Allyl-1-aryl-tetrazole-5-ones; Correlation with UV-Induced Fragmentation Channels

Abstract

1,4- and 1,5-disubstituted tetrazoles possess enriched structures and versatile chemistry, representing a challenge for chemists. In the present work, we unravel the fragmentation patterns of a chemically diverse range of 5-allyloxy-1-aryl-tetrazoles and 4-allyl-1-aryl-tetrazolole-5-ones when subjected to electron impact mass spectrometry (EI-MS) and investigate the correlation with the UV-induced fragmentation channels of the matrix-isolated tetrazole derivatives. Our results indicate that the fragmentation pathways of the selected tetrazoles in EI-MS are highly influenced by the electronic effects induced by substitution. Multiple pathways can be envisaged to explain the mechanisms of fragmentation, frequently awarding common final species, namely arylisocyanate, arylazide, arylnitrene, isocyanic acid and hydrogen azide radical cations, as well as allyl/aryl cations. The identified fragments are consistent with those found in previous investigations concerning the photochemical stability of the same class of molecules. This parallelism showcases a similarity in the behaviour of tetrazoles under EI-MS and UV-irradiation in the inert environment of cryogenic matrices of noble gases, providing efficient tools for reactivity predictions, whether for analytical ends or more in-depth studies. Theoretical calculations provide complementary information to articulate predictions of resulting products.

A Physical Organic Approach towards Statistical Modeling of Tetrazole and Azide Decomposition**

“…Although the feature (σ(N 2 −N 3 ) BO+σ(N 1 −N 2 ) BO)/2 correlates well with the N 2 −N 3 σ bond order , factoring in the N 1 −N 2 σ bond order allowed us to derive a general model, which accounts for charged NBO structures (Figure 1B) that feature an N 1 −N 2 single bond. The positive sign of this term suggests that tetrazoles with a lower N 2 −N 3 bond order are more prone to decomposition, consistent with a rate‐determining N 2 −N 3 bond breakage for 1,5‐ and 2,5‐ tetrazoles [59] …”

Reaction of Irbesartan with Nitrous Acid Produces Irbesartan Oxime Derivatives, rather than N-Nitrosoirbesartan

“…The MS/MS spectra (Figure ) of both protonated 22.6 and 27.0 min products ( m / z 458) and irbesartan ( m / z 429) did not show many fragment ions but exhibited three common fragment ions at m / z 180, m / z 207, and m / z 235 under the collision energy of 30 eV. These three ions are the specific fragments originating from the biphenyltetrazole moiety, and their occurrence is indicative of the presence of an unmodified tetrazole moiety . Hence, the presence of these three common fragment ions suggests that the 22.6 and 27.0 min products are very likely to have the same core structure of biphenyltetrazole as irbesartan.…”

A Physical Organic Approach towards Statistical Modeling of Tetrazole and Azide Decomposition**

“…The positive sign of this term suggests that tetrazoles with a lower N 2 À N 3 bond order are more prone to decomposition, consistent with a rate-determining N 2 À N 3 bond breakage for 1,5-and 2,5-tetrazoles. [59] In addition to traditional manual selection of an appropriate MLR model from a list of MLR equations obtained through forward stepwise selection, we also aimed to validate the proposed mechanism in an automated human-on-the-loop workflow. This was implemented through a fully automated statistical analysis of the prevalence and coefficients of features in all MLR models that meet a minimum threshold of statistical performance (here, N = 817, each with a combined training and test set R 2 � 0.65).…”