Conformational studies chair forms

As a result of these unfavourable interactions, i.e., opposition to bond strain i.e., between the pair of hydrogens shown at the bottom) and also due to bowsprit interaction, the potential energy of the boat form becomes high and this is why the boat conformation is not the preferred one. Hassel in 1947 established by means of electron diffraction studies that cyclohexane exists predominantly in the chair form. This has also been confirmed by electron diffraction studies and results obtained from Raman and I.R. spectra. Calculations made on the basis of entropy show that only about one molecule in a thousand will be in the boat form. 

A number of cis/trans 4,6-dialkyl-2,2-dimethyl-l,3-dioxanes were studied by C NMR spectroscopy (93JOC5251). The C NMR shifts of C -Me groups (Scheme 8) were found to be very sensitive to the 1,3-dioxane conformation [chair form Me(ax) ca. 19 ppm and Me(eq) ca. 30 ppm— pure 30.89 ppm in the twist-boat form both methyl carbons resonate at ca. 25 ppm (pure 24.70 ppm)]. With these values, AG° of the chair to twist-boat equilibrium was calculated (Table IV). For 13a (nitrile), 13b (alkyne), and 13e (methyl ester) (Scheme 8) in CH2CI2, the temperature dependence of the AG° values was determined. Depending on the substituent, small negative or positive entropy terms were found generally the enthalpy term dominates the -AG° value. In the tram isomers 13, the cyano and alkyne substituents favor the chair conformation, but CHO, ester, alkene, and alkyl substituents, respectively, clearly favor the twist-boat conforma-... 

Ab initio calculations at the MP2 level of theory of a collection of substituted 1,3-dioxanes, 1,3-oxathianes, and 1,3-dithianes have been employed to study both the position of the conformational equilibria and the validity of the Perlin effect <2005T7349>. The 7h,c coupling constant proved to be a valuable tool in conformational analysis both twist conformers, in addition to the chair and alternative chair forms, could be readily identified simply by comparing experimental Vh,c coupling constants to the corresponding calculated values in the particular forms. In addition, the Perlin and reversed-Perlin effects of the C2-H fragments, c in 1,3-dioxanes,... 

Complexity is added to the study of this system by the ready functionalization of the sulfur atom by alkylation, oxidation and imination. 5-Alkylation to produce a compound such as (9) <76T1873) affords a system in which either of two possible chair conformers possesses an axial t-butyl group, and this system therefore exists preferentially in a twist conformation (10). Where no such conflicts occur the sulfur substituent adopts the equatorial position in a chair form. Inversion of configuration at sulfur in cyclic sulfides has been investigated in the system (11) (12) and the corresponding ylides (13) (14) (77JA2337). 

Sauriol-Lord and St-Jacques (64) have studied 2,4-benzodithiepin 78 and the substituted derivatives 79-82 (Fig. 14). They found that these compounds exist in the chair form 39 (0=S) (Fig. 8), except for the derivative 82 where 13% of the twist-boat 40 (0=S) was detected. The fact that essentially only the chair form was observed in these compounds would simply be due to the long C - S bonds which attenuate the effects of steric repulsions in conformer 39 (0 =S). This is in accord with the fact that in contrast to 2-methoxy-l,3-dioxane which exists as a 7 3 mixture of equatorial conformer 83 and axial conformer 84, 2-methoxy-l,3-dithiane has been found to exist solely in the axial form 85. 

The same authors have also studied compounds 86 and 87 having a methoxy group (Fig. 15). These compounds could exist either in the chair form with an axial (88) or an equatorial methoxy group (89), or in the twist-boat 90. Conformer 88 is disfavored sterically but is favored electronically, whereas the twist boat 90 with a syn clinal methoxy group is favored electronically and does not suffer from severe steric hindrance. It was found... 

The spirobenzoxazepine 28 was studied by 2-D and nuclear Overhauser enhancement Spectroscopy (NOESY) NMR and X-ray crystallography, and in both cases the same chair conformation, 28, was formed (See Figure 5). The authors conclude that this compound 28 is a semirigid scaffold, able to present various substituents without undergoing hydrophobic collapse, and 28 behaves structurally as a privileged structure <2004TL1051>. 

The H-NMR studies of 23 and 24 indicated that their conformations were different (Fig. 1). Compound 23 adopts the usual half-chair form with the quasi-axial azido group, while the amino compound 24 exists in the boat-like form with the gwasZ-equatorial amino group. The latter form 24 might be due to the interaction such as hydrogen bonding between the C-l amino and C-2 hydroxy groups. 

Most aldohexopyranoses exist in a chair form in which the hydroxymethyl group at C(5) assumes an equatorial position. All the P-D-hexopyranoses exist predominantly in the 4Ci form since the alternative C4 conformer involves a large unfavourable xyn-diaxial interaction between the hydroxymethyl and anomeric group (Figure 1.8). Most of the a-D-hexopyranosides also adopt the 4Ci conformation preferentially. Only ot-idopyranoside and a-D-altropyranose show a tendency to exist in the C4 conformation, and they coexist with the alternative 4Ci conformations according to H-NMR (hydrogen nuclear magnetic resonance) spectroscopy studies. 

For the 1,4-dithiane skeleton, two S-alkyl-l,4-dithianium salts 72 and 73 were studied by variable temperature NMR spectroscopy in the solid state (13C CP-MAS) (99JMS93) line shape variations were attributed to the conformational motion of the six-membered ring (cf. Scheme 26). Also, the vibrational frequencies of the 1,4-dithiane derivative were analysed in detail it was corroborated that the molecule exists in the C2h configuration similar to the chair form of cyclohexane (99SA(A)121). 

Time-dependent effects The NMR signals are sometimes influenced by time-dependent phenomena such as conformational or prototropic changes, which take place at a rate faster than the line width and comparable to (or faster than) the inverse of the differences between the frequencies of the transitions of the different sites. This means that kinetic phenomena may be studied by the NMR technique, especially if the temperature of the sample can be adapted. As an example we mention the two chair forms of cyclohexane, which are energetically stable there is a fast inversion from the one into the other via the boat form. At room temperature the PNMR spectrum exhibits one sharp peak, corresponding to the mean of the two chemical shifts. At -120 °C the dynamic equilibrium is frozen and the spectrum exhibits two sharp peaks, whereas at -60 °C the inversion is slow and the spectrum exhibits one broad peak. 

As already mentioned in Section 14.05.5.2 for the 2-substituted 1,3-dioxocins 298a-g, the preferred conformations are the enantiomeric boat-chair forms BC and BC. For 298c, the dimethyl derivative, the pseudorotation of the BC conformation occurred via a boat-boat (BB) form <2001MRC657>. The kinetics of the thermal decomposition of 5,5,7,7-tetranitro-l,3-dioxocin were studied. The steric influence of the bulky dinitromethylene groups probably determined the high rate of decomposition (Scheme 70) <2006RJC499>. 

Semi-empirical and molecular mechanics calculations have been widely used in the study of eight-membered heterocycles with three heteroatoms. Theoretical studies have centered on conformations of this class of heterocines, which usually belong to four low-energy conformational families classified as boat-chair, crown, boat, and chair forms (see Section 14.08.4.2). 

Four main low-energy conformational families of eight-membered ring systems, consisting of the boat-chair, crown, boat, and chair forms, were surveyed in CHEC-II(1996). They are discussed in the foregoing sections of this chapter in conjunction with the theoretical and experimental structural studies of triheterocines (see sections 14.08.2 and 14.08.3). 

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