Search

Tri-o-thymotide (TOT) forms a cage-type clathrate with the thiophene guest molecule in a host:guest ratio of 2∶1. This clathrate crystallizes in the trigonal system (space groupP3121). The unit cell, of dimensionsa=b=13.585(4),c=29.914(12)A, contains 6 TOT and one thiophene molecule. The crystal structure, established by direct methods (R=0.053), indicates that the host cavity has an oblate-ellipsoid shape with a crystallographic twofold axis parallel to the largest dimension of the cage. The guest molecule within the cavity is disordered. Molecular dynamics simulations have been performed and indicate that the guest molecules have hindered molecular freedom around the shortest ellipsoid axis of the cavity, and may produce a dynamic disorder in the cage of the TOT clathrate.

The interconverting stereoisomers of tri-o-thymotide have been separated by HPLC on chiral stationary phases and the temperature dependence of the dynamic chromatographic patterns has been interpreted in terms of exchange between enantiomeric propeller and helical conformations. Computed low energy structures and CD spectra were used in absolute configuration assignment.

In order to improve the relatively low yield (ca. 35%) previously observed in the synthesis of tri-o-thymotide (TOT, 1) from o-thymotic acid (2)d, the cyclodehydration was studied using a variety of conditions. The low yield is due to the formation of di-o-thymotide (DOT, 3), previously reported, and at least three other products (4-6), which apparently result from the acid-catalyzed decarboxylation of 2 and subsequent condensation with thymol (7). Using pyridine as a solvent, side-product formation is inhibited. Under appropriate conditions, namely, neat POCl 3 at 50°C, the yield of 1 is 93%. Other salicylic acid derivatives also give high yields of the corresponding «trimers» under these conditions, thus providing a general, improved preparation of a family of potential clathrate host substances

Halogenated trisalicylide derivatives 1-6, representing three-fold symmetric C3 “home trimmers” as well as dissymmetric C1 “mixed trimers” have been synthesized. Clathration studies indicate that these halogenated TOT analogs do not form clathrates. Reductive removal of the halogen was demonstrated for analog 2, providing a new entry to TOT-based host molecules.

Mono-, di-, tri-, tetra-, and pentabrominated tri-o-thymotide (TOT) analogues (3-7) and mono-, di-, tri-, and tetrabrominated tri-o-carvacrotide (TOC) analogues (9-12) were synthesized by direct bromination of TOT and TOC. Total yields of about 60% were realized from TOT or TOC. The degree of bromination of the methyl group dependent upon the reaction temperature and ration of TOT (TOC):NBS. Tribromo-TOT (5) was generated in the greastest yield using a 1:18 ration of TOT:NBS

Halogenated trisalicylide derivatives 1-6, representing three-fold symmetric C3 “home trimmers” as well as dissymmetric C1 “mixed trimers” have been synthesized. Clathration studies indicate that these halogenated TOT analogs do not form clathrates. Reductive removal of the halogen was demonstrated for analog 2, providing a new entry to TOT-based host molecules.

2 Structure of TOT Inclusion Compounds . . . . . . . . . . . . . . . . . 73 2.1 Crys ta l lographic Invest igat ions . . . . . . . . . . . . . . . . . . 74 2.1.1 Crysta l D a t a . . . . . . . . . . . . . . . . . . . . . . . . 74 2.1.2 Abso lu te Conf igura t ions o f T O T . . . . . . . . . . . . . . . 74 2.1.3 C o n f o r m a t i o n a l Changes o f T O T . . . . . . . . . . . . . . . 76 2.1.4 Shape o f the Cavi ty and Gues t Or ien ta t ion . . . . . . . . . . 77 2.1.5 Gues t St ructura l D i so rde r . . . . . . . . . . . . . . . . . . 82 2.2 Phys ico-chemica l Character is t ics . . . . . . . . . . . . . . . . . . 84 2.2.1 N M R Propert ies . . . . . . . . . . . . . . . . . . . . . . 84 2.2.2 Mass Spectral Character is t ics o f T O T . . . . . . . . . . . . . 85

Variable temperature 2H NMR studies are reported for the cyclohexane/tri-o-thymotide inclusion compound in a range between 100 K and 370 K. From a quantitative analysis of the available NMR data, comprising spin-lattice and lineshape experiments, the motional and structural features of the cyclohexane guests are evaluated.

The absolute configuration of tri- o -thymotide (TOT) has been determined by X-ray crystal structure determinations of two cage-type clathrate inclusion compounds (+)-TOTS·S-(+)-2-bromobutane and (−)-TOT·RR-(+)-2,3-dimethylthiirane; (+)-TOT has a P propeller-like configuration

Application des concepts empruntes a la geometrie differentielle, des surfaces minimales et de la transformation de Bonnet a la reorganisation moleculaire. Interpretation de la racemisation et de l'isomerisation E/Z des doubles liaisons en termes de transformation de surface

The absolute configuration of tri-o-thymotide was obtained from the crystal structure of the solvate with (R)-2-butanol in association with optical measurements.

Enantiomorphous tri-o-thymotide clathrates of prochiral oxiranes were submitted to the action of gaseous hydrogen halides. Ring-opening reactions ensued that differ from those reported in homogeneous phase, showing a considerable modification of the chemical reactivity of the external reagent in the host lattice. Chirality transfer from the host receptors to the guest products was also observed, but with a poor efficiency.

1,7,13-Trimethyl-4,10,16-tris(1-methylethyl)-6H,12H,18H-tribenzo[b,f, j][1,5,9 ]trioxacyclododecin-6,12,18-trione-3-buten-2-ol (2/1), C₃₃H₃₆0₆.½C₄H₈O, Mr = 564.70, trigonal, P3₁21, a = 13.444(3), c = 30.217(9)Å, V = 4730(1)ų, Z = 6, Dx = 1.190 g cm⁻³, λ(Mo Kα) = 0.71069 Å, μ = 0.875 cm⁻¹, F(000) = 1812, T = 153 K, R = 0.068 for 1657 observed reflections at the |Fo| > 3σ(Fo) level. The host structure was refined starting from previously determined coordinates in an isomorphous tri-o-thymotide (TOT) clathrate. A strained conformation of the guest, derived from a calculated two-dimensional energy map, was favourably used as rigid component in the X-ray model. Evidence for low chiral discrimination of the guest was quantitatively demonstrated. Correlation of configuration between TOT in a single crystal and the major included enantiomer was shown to obey previously established structural rules. Lattice- energy calculations corroborate the experimental observations.

2 Structure of TOT Inclusion Compounds . . . . . . . . . . . . . . . . . 73 2.1 Crys ta l lographic Invest igat ions . . . . . . . . . . . . . . . . . . 74 2.1.1 Crysta l D a t a . . . . . . . . . . . . . . . . . . . . . . . . 74 2.1.2 Abso lu te Conf igura t ions o f T O T . . . . . . . . . . . . . . . 74 2.1.3 C o n f o r m a t i o n a l Changes o f T O T . . . . . . . . . . . . . . . 76 2.1.4 Shape o f the Cavi ty and Gues t Or ien ta t ion . . . . . . . . . . 77 2.1.5 Gues t St ructura l D i so rde r . . . . . . . . . . . . . . . . . . 82 2.2 Phys ico-chemica l Character is t ics . . . . . . . . . . . . . . . . . . 84 2.2.1 N M R Propert ies . . . . . . . . . . . . . . . . . . . . . . 84 2.2.2 Mass Spectral Character is t ics o f T O T . . . . . . . . . . . . . 85

Etude d'un nouveau cas d'induction dans lequel les cavites dissymetriques a l'interieur de cristaux de tri-o-thy-motide communique l'asymetrie a la reaction d'une substance euclathratee les methoxy-2 butenes-2 cis et trans