A conformational analysis of nine macrocyclic thioether musks has been carried out using molecular mechanics (MMFF), density functional theory (DFT) using both B3LYP and M06 functionals, as well as Hartree-Fock and post-Hartree-Fock (MP2) methods. in each of these conformations. Determine 1. Low-energy conformations of 6-thia-14-tetradecanolide (1). Values in parentheses are with diffuse basis sets (6C31+G* for B3LYP and M06, 6C311+G** for MP2). 2.2. 10-Thia-14-tetradecanolide (2) 10-Thia-14-tetradecanolide (2) also showed disagreement between the computational methods. There were 32 low-energy conformations from the MMFF calculations, of which a [13434] was the lowest-energy from the MMFF analysis, but a [23343] conformation was shown to be the B3LYP lowest-energy conformation while an alternative [23343] conformation was favored by M06 (Determine 2). The MP2 calculations indicated a fourth conformation, a [14334] conformation, to be the lowest energy form. A [13353] conformation was also low in buy 83207-58-3 energy. Although the C-S-C-C groups are gauche in each of these conformations, only in the [14334] and [13353] conformations do the sulfur atom adopt an exodentate corner position [21,22]. Similar to what was found for 1, the lowest-energy PR65A [33333] conformation is usually 1.44, 1.15, and 1.47 kcal/mol higher in energy than the respective lowest-energy conformations for MMFF, M06, and MP2, but only 0.65 kcal/mol higher than the [23342] for B3LYP. Determine 2. Low-energy conformations of 10-thia-14-tetradecanolide (2). Values in parentheses are with diffuse basis sets (6C31+G* for B3LYP and M06, 6C311+G** for MP2). 2.3. 4-Methyl-5-thia-14-tetradecananolide (3) The steric demands of the methyl group on 4-methyl-5-thia-14-tetradecananolide (3) seem to have reduced the number of low-energy conformations (MMFF) to 19. A [3444] (A) conformation was the lowest-energy conformation for MMFF, M06, and MP2 (Determine 3). In this conformation, the C-S-C-C unit is usually (and endodentate). The B3LYP method, on the other hand, predicted a [14334] conformation. Notably, an alternative [3444] (B) conformation was also low in energy, but not the lowest in any of the computational methods. The lowest-energy [33333] conformation was, by MMFF, 3.29 kcal/mol higher in energy than [3444] (A). Determine 3. Low-energy conformations of 4-methyl-5-thia-14-tetradecananolide (3). Values in parentheses are with diffuse basis sets (6C31+G* for B3LYP and M06, 6C311+G** for MP2). 2.4. 4-Thia-15-pentadecanolide (4) There is disagreement between the computational methods on the lowest energy conformation of 4-thia-15-pentadecanolide (4). Molecular mechanics (MMFF) indicate a [6343] conformation, B3LYP predict a [4444] conformation, but both M06 and MP2 show a [133432] lowest-energy conformation (Determine 4). Determine 4. Low-energy conformations of 4-thia-15-pentadecanolide (4). Values in parentheses are with diffuse basis sets (6C31+G* for B3LYP and M06, 6C311+G** for MP2). 2.5. 7-Thia-15-pentadecanolide (5) The lowest-energy conformation for cyclohexadecane has been determined to be the square [4444] conformation [23,24], and both B3LYP and MP2 calculations indicate a [4444] conformation to be the lowest energy for 7-thia-15-pentadecanolide (5) with a [113344] conformation only slightly higher in energy (Determine 5). Molecular mechanics (MMFF) calculations show the [4444] buy 83207-58-3 conformation to be 0.05 kcal/mol higher in energy than the [113344] form. The M06 method, on the other hand, calculates a [23344] conformation to be lowest energy. The placement of the sulfur atom with respect to the carbonyl group allows for a preferred arrangement about the ester functionality, as well as a preferred gauche arrangement for the C-S-C-C group with an exocyclic sulfur atom in the [4444] conformation. Determine 5. Low-energy conformations of 7-thia-15-pentadecanolide (5). Values in parentheses are with diffuse basis sets (6C31+G* for B3LYP and M06, 6C311+G** for MP2). 2.6. 11-Thia-15-pentadecanolide (6) The MMFF, B3LYP, and MP2 computational methods all predict a [4444] conformation to buy 83207-58-3 be the.