CONFORMATIONAL DYNAMICS OF THE BENT 1,5,2,4,6,8-DITHIATETRAZOCINES

is(butylmethylamino)-1,5,2,4,6,8-dithiatetrazocine (3) was prepared in two steps from N-methylbutylamine in 14% overall yield. At room tempe rature the H-1 NMR spectrum of 3 shows two methyl resonances (in a rou ghly 1:1 ratio) and four resonances for the C-alpha methylene protons of the butyl groups (roughly 1:1:1:1). These data indicate that compou nd 3 displays both cis/trans isomerism and a bent heterocyclic ring in solution. Heating of compound 3 in a variable-temperature NMR experim ent results in coalescence of the two methyl and four C-alpha resonanc es to a singlet and a triplet, respectively, at temperatures correspon ding to an activation energy (Delta G(c)(double dagger)) of a of appro ximately 17 kcal/mol for the exchange process. This value is the free energy of activation for rotation of the dialkylamino groups and also represents a lower limit for the activation energy for inversion of th e bent dithiatetrazocine ring. Ab initio calculations on the 3,7-diami no-1,5,2,4,6,8-dithiatetrazocine system suggest that the activation en ergies for amine rotation and ring inversion are very similar: 17.1 an d 17.3 kcal/mol, respectively. Spectral simulations of the NMR data fo r 3 support this conclusion, with the best experimental estimates of t he free energies of activation for the two processes being 17.3 +/- 0. 1 and 17.7 +/- 0.5 kcal/mol, respectively. Notably, the calculations i ndicate that the ring inversion precedes asymmetrically-in the transit ion state one side of the ring is more highly bent than the other-and there is a nearly planar intermediate along the pathway.