Solution conformation, equilibrium

Theoretical work by the groups directed by Sustmann and, very recently, Mattay attributes the preference for the formation of endo cycloadduct in solution to the polarity of the solvent Their calculations indicate that in the gas phase the exo transition state has a lower energy than the endo counterpart and it is only upon introduction of the solvent that this situation reverses, due to the difference in polarity of both transition states (Figure 1.2). Mattay" stresses the importance of the dienophile transoid-dsoid conformational equilibrium in determining the endo-exo selectivity. The transoid conformation is favoured in solution and is shown to lead to endo product, whereas the cisoid conformation, that is favoured in the gas phase, produces the exo adduct This view is in conflict with ab initio calculations by Houk, indicating an enhanced secondary orbital interaction in the cisoid endo transition state . 

Quantum chemistry methods allow the prediction of the ultraviolet transitions in good agreement with the experimental values in the case of thiazole and its three methyl derivatives (Table 1-18). A very weak absorption has been indicated at 269.5 nm that could correspond to an n- TT transition given by calculation at 281.5 nm (133). Ultraviolet absorption spectroscopy has been investigated in connection with steric interactions in the A-4-thiazoline-2-thione (74) series (181). It was earlier demonstrated by NMR technique that 4-alkyl-3 isopropyl-A-4-thiazoline-2-thiones exist in solution as equilibrium mixtures of two conformers (75 and 76), the relative populations of which vary with the size of R4 (182) for R4 = rBu the population of rotamer A is 100%, whereas for R4 = Me it is only 28%. Starting from the observed absorption wavelength for... 

Reactive intermediates in solution and in the gas phase tend to be indiscriminant and ineffective for synthetic applications, which require highly selective processes. As reaction rates are often limited by bimolecular diffusion and conformational motion, it is not surprising that most strategies to control and exploit their reactivity are based on structural modihcations that influence their conformational equilibrium, or by taking advantage of the microenvironment where their formation and reactions take place, including molecular crystals. ... 

We note that the calculation of At/ will depend primarily on local information about solute-solvent interactions i.c., the magnitude of A U is of molecular order. An accurate determination of this partition function is therefore possible based on the molecular details of the solution in the vicinity of the solute. The success of the test-particle method can be attributed to this property. A second feature of these relations, apparent in Eq. (4), is the evaluation of solute conformational stability in solution by separately calculating the equilibrium distribution of solute conformations for an isolated molecule and the solvent response to this distribution. This evaluation will likewise depend on primarily local interactions between the solute and solvent. For macromolecular solutes, simple physical approximations involving only partially hydrated solutes might be sufficient. 

Diazaphosphorinanes exist as a mixture of three conformers in solution [Eq. (51)], although all heteroatoms in the ring have substituents. Conformational equilibrium is due to the low inversion barrier of nitrogen studied by H NMR and the dipole moment method (83MI1 84MI1) [Eq. (51)]. The results are presented in Table III. 

Dioxathiolane 2,2-dioxide (21) adopts a puckered conformation in the solid state, as shown by x-ray diffraction (Section 4.15.3.1). In solution, the H NMR spectrum of (21) indicates that the compound undergoes a rapid pseudorotation between twist-envelope forms (Section 4.15.3.3.1) the O NMR spectra of simple derivatives also indicate a rapid conformational equilibrium by pscudorotation, although substitution may act as a barrier to complete ring inversion (Section 4.15.3.3.3). The solution-phase dipole moment of 1,3,2-dioxathiolane 2,2-dioxide is consistent with a nonplanar conformation (Section 4.15.3.8). 

However, a quantitative evaluation, i.e, an exact determination of the r/0-parameter pairs for each nucleus in the solute, is not easy252. It should be determined only by the use of statistical methods to obtain reliable structural assignments, as shown for the four diastereomeric 1-cyano-2-ethylidene-3-methylcyclopropanes253. Quantitative evaluation is even more complicated if the solute is conformationally mobile, because a careful conformational analysis is the basis of any sound interpretation of LSR experiments. Moreover, the conformational equilibrium of the solute may change in the presence of LSR. 

Carbene fluorescence in solution is usually red shifted by 25-30 nm with respect to the band position observed in matrix at 77 K. This shift is attributed to emission from nonequilibrated conformations at low temperature. In matrices, the carbene is produced in a locked conformation similar to that for the precursor diazo compound but, in solution, it approaches the thermodynamically favored configuration. This difference has been demonstrated by variable temperature EPR studies of sterically congested carbenes (see Section 3.1.1.3). So, in solution, the equilibrium conformation is reached rapidly and only fluorescence from the relaxed state is observed. In support of this suggestion, the shift for dimesitylcarbene is smaller than for other carbenes, indicating that shifts are smaller when the carbene structure is such that it restricts conformational change. 

Diphenyl-1,3-butadiene. The excited-state behavior of this diene differs significantly from stilbene and is the subject of a review. Unlike tS in which the lowest vertical excited singlet state is the 1 B state and S2 is the 2 Ag state in solution, these two excited states lie very close to each other in all-trans-1,4-diphenyl-1,3-butadiene (DPB). The additional carbon-carbon double bond introduces a new conformational equilibrium involving the s-trans and s-cis rota-mers. Most spectroscopic studies in solution have concluded that the l B state is S. The DPB compound has a low quantum yield for photoisomerization, so the use of DPB in time-resolved spectroscopic studies on photoisomerization, especially those that monitor only fluorescence decay, needs to be considered cautiously and critically. 

The conformation of cyclodipeptides containing two nonidentical l-aromatic amino acid residues has been addressed recently [90JCS(P2)127]. In such cases, it may be possible to assess the relative strength of the attractive interaction between the piperazinedione ring and the different aromatic groups by NMR studies. On the basis of detailed analyses, the author has concluded that in the case of cyclo[L-5(MeO)Trp-L-Tyr(Me)], a fast conformational equilibrium exists between the two folded-extended conformers (Scheme 10) above room temperature in DMSO and N,N-dimethyl formamide (DMF) solutions. 

On the basis of NMR data, the conformational equilibrium of (166a) (166b) in solution... 

Apart from being a receptor for aromatic molecules, 9a also binds silver (I), as was demonstrated by a change in the conformational equilibrium upon addition of silver perchlorate to a solution of this clip. 

A value of AG° for the quinolizidine equilibrium was obtained by IR spectroscopic techniques. Dilute solution measurements (0.006 M CC14) in 10-cm cells on trans-(l-H,9a-H)-l-hydroxyquinolizidine (99 100 101) showed a small band at 3250 cm-1 corresponding to the H-bonded ds-fused con-former 101. The epimeric cis-(l-H,9a-H) compound was taken as a 100% H-bonded model, and the concentration of the cis-fused conformer 101 was then deduced. A correction must be made for the presence of 100, which was estimated by studies on the conformational equilibrium in l-methyl-3-... 

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