Differentiation between 6- and 7-Membered Rings Based on Theoretical Calculation of NMR Parameters

Table 1

The low-energy conformations, their Gibbs’ free energies, and other structural information found for compounds 1 and 2.

Compound, conformer^a	Group orientations; and configurations^a		Hydrogen bonding of OH: → atom, 𝑟 (Å)	gauche interactions of O-4 with:	Δ𝐺 (kcal mol^−1)	Boltzmann; population (%)
	O group^b	NH
Compound 1
1, ^2H3	equatorial, 𝛽	equatorial, 𝛼	N, 2.25	N	0.00^c	64.7
2, ^2H3	axial, 𝛼	isoclinal, 𝛽	N, 2.26	N	0.93	13.5
3, ^2H3	axial, 𝛼	equatorial, 𝛼	NH → OH, 2.43	N	1.06	10.8
4, ^2H3	axial, 𝛼	equatorial, 𝛼	NH → OH, 2.53	N	1.66	3.9
5, ^2H3	axial, 𝛼	equatorial, 𝛼	none	none	1.71	3.6
6, ^2H3	axial, 𝛼	equatorial, 𝛼	O, 2.10	N	1.73	3.5
Compound 2
1, ^3C=	axial, 𝛽	equatorial, 𝛼	N, 2.38; O, 2.48	N, O	0.00^c	90.1
2, ^2TB4	isoclinal, 𝛽	equatorial, 𝛼	N, 2.45	N	1.61	5.9
3, ^2TB4	isoclinal, 𝛼	equatorial, 𝛼	O, 2.54	O	1.85	4.0

^aDue to symmetry, the change in configuration at C-3 effected in the constructs of 1 and 2 during conformational searching is only enantiomeric and not diastereomeric and no further consideration needs to be accounted for. Structures, however, are described as presented with no reference to the actual enantiomer calculated (thus, mixed enantiomers are present). Diastereotopic proton designations, though, are corrected for this to enable correct comparison of the same nuclei in Tables 2–5. ^b–CH₂OH in the case of 1; OH in the case of 2. ^cThe global minimum of 1 was 1.82 kcal mol⁻¹ lower in energy in comparison to the global minimum of 2.