The determination of ring size can vary from simple to complex, but the process in difficult cases can be advantageously augmented by DFT calculation of NMR parameters such as the chemical shifts of ( ), ( ), and other nuclei as well as pertinent spin-spin (scalar) coupling constants, for example, those between protons ( ). Differentiation between 6- and 7-membered ring formation in the case of 3,4-dihydro-2H-3-hydroxymethyl-1,4-benzoxazine and 2,3,4,5-tetrahydro-1,5-benzoxazepine-3-ol was evaluated with a view to not only affecting 6- versus 7-membered ring differentiation generally for cases on hand, but also in the case of literature reports where the assigned structures may be in doubt. Thus, the main focus was on the usually reported NMR parameters of , , and and wherein the analysis was found to be highly successful, particularly for , and thus potentially amenable for broad application. 1. Introduction Obviously the determination of ring size in the framework of organic compounds is a crucial and basic precept in structural chemistry, whether the compounds in question arose through synthetic processes or were obtained from natural sources. The distinction between, for example, 6- and 7-membered rings can, in particular cases, be surprisingly difficult even by the application of sophisticated NMR experiments [1]. Evermore so in heterocyclic systems where the availability of suitable hydrogen atoms within or proximal to the cyclic unit for analysis may be limited—whether concerning either solely 1H nuclei or 1H nuclei in conjunction with other nuclei, for example, 13C, the problems and challenges of discerning between 5- and 6-membered rings in heterocyclic systems with a deficient number of 1H nuclei by NMR have been considered [1] previously in depth using DFT calculations based on the consideration of various NMR parameters as depicted in Figure 1. For example, the chemical shifts of nuclei such as 1H ( ), 13C ( ), and 15N ( ); various spin-spin (scalar) coupling constants between nuclei such as 1H and 1H , 1H and 13C ( ), and 1H and 15N ( ); NOEs between nuclei such as 1H and 1H ( ) and 1H and 13C ( ). The prediction of NMR parameters [2, 3] such as chemical shifts, but especially coupling constants, has come of age recently in terms of development and practical application [4–6], and especially with respect to conformational analysis [7–9]. Figure 1: Depiction of various NMR parameters considered in a previous study [ 1] for rendering distinction between 5- and 6-membered ring products, namely, 1,3-thiazolidin-4-one and 1,3-thiazin-4-one
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