Thermal racemizations

L-Glutamic acid does not racemize in neutral solution, even at 100°C. Deviation of pH from neutral to greater than 8.5 results in thermal racemization with loss of taste characteristics. Racemization in neutral solution occurs at 190 °C after formation of the lactam, 5-oxo-L-proline, pyroglutamic acid [98-79-3]. 

The numerous examples of optically active sulfoxides reflect their configurational stability. Optically active sulfoxides resist thermal racemization by pyramidal inversion, so... 

In order to account for the unusually facile thermal racemization of optically active allyl p-tolyl sulfoxide (15 R = p-Tol) whose rate of racemization is orders of magnitude faster than that of alkyl aryl or diaryl sulfoxides as a result of a comparably drastically reduced AH (22kcalmol- ), Mislow and coworkers44 suggested a cyclic (intramolecular) mechanism in which the chiral sulfoxide is in mobile equilibrium with the corresponding achiral sulfenate (equation 10). 

The thermal racemization of optically active aryl allyl sulfoxides ArS(0)CHjCH=CH2 is orders of magnitude faster, and has a much lower activation energy, than that of aryl alkyl sulfoxides ArS(0)R (Bickart et ai, 1968). The reason is that the presence of the allyl group permits the sulfoxide to equilibrate with the isomeric, achiral sulfenate ester by a concerted, cyclic process (89) for whichis only about 20 kcal moM.The rates of racemiz-... 

Resolution of two chiral twisted push-pull ethylenes, 144 and 145, has been performed by chromatography on triacetylcellulose (209). The barriers obtained by thermal racemization in ethanol agree well with those found by NMR band-shape technique, taking the positive AS and the difference in solvent into account (Tables 17 and 22). 

Kinetic studies on the thermal racemization of the sulfonium salt 211 revealed that the process requires much lower activation energies when compared with thermal racemization of sulfoxides. Comparison of the relative rates for racemization of sulfonium salts 211, 212, and 213 was taken (151) as evidence that racemization of 211 is the result of pyramidal inversion, not of an alternative dissociation mechanism. On the other hand, Brower and Wu (249) concluded that the volume of activation for the racemization of sulfonium ion 211, AF = +6.4 ml/mol, is more compatible with a transition state in which partial dissociation has occurred. 

Oae (251,252) as well as Darwish and Datta (253) investigated the process of thermal racemization of chiral alkylarylsulfimides and diarylsulfimides. It was found to proceed at temperatures as low as 65 to 100°C with a rate constant of the order 1 to 10 X 10" sec" , which corresponds to an activation energy of about 23 to 30 kcal/mol. These data indicate that the thermal racemization of sulfimides is much faster than that of analogous sulfoxide systems. The racemization of sulfimides is a unimolecular reaction practically independent of the polarity of the solvent this property, coupled with the absence of decomposition products, supports the view that racemization of sulfimides occurs by pyramidal inversion. 

An extraordinarily easy thermal racemization was observed for aryl arenethiosulfinates (256). It occurs at a convenient rate at about 50°C. The following activation parameters were estimated for the racemization of p-tolyl p-toluenethiosulfinate 218 A// = 23 kcal/mol A5 = -4 e.u. Thus, the rate of racemization is about 10" times greater than that of diaryl sulfoxides. An internal displacement of sulfenyl sulfur rather than pyramidal inversion was proposed as the mechanism. Recent studies on the chemistry and stereochemistry... 

Although planar structures for 111 and 112 were not attained, it is still likely that these novel diazabiaryls can serve as chiral ligands with C2 symmetry. In support of this likelihood, the resolution of 112 was accomplished recently on swollen, microcrystalline triacetylcellulose by Jan Sandstrom. The free energy barrier to ring inversion of 112 was found to be about 101 kJ/mol, through a thermal racemization process using chiral 112. ... 

Perhaps the most intriguing observation of helicenes is the unexpected ease with which these compounds racemize thermally. According to Martin 1031 three pathways for the thermal racemization can be considered 1) via bond breaking 2) via an internal double Diels-Alder adduct, and 3) via a direct inversion. Martin rejected the first possibility because it is not in accordance with kinetic data for the racemization. He could exclude the second possibility in an elegant way by using appropriately substituted derivativesl03>. 

Another demonstration of the remarkable flexibility of helicenes is found with the double helicene 55. Dissolved in naphthalene it racemizes at 210 °C (more than 230 °C below its melting point) with about the same rate as hexahelicene at this temperature. From this observation it must be concluded that the racemization does not occur via the meso-form which has the terminal rings at one side of the central ring, but, due to the large number of bonds, via a high-vibrational state in which the terminal rings are at a non-hindering distance. Not only the racemizations mentioned in Table 11, but also the thermal racemization of [10] and [11] helicenes has been carried out successfully. 

Lindner 1040 used a rc-SCF-force field method to calculate the energies of racemiza-tion of penta-, hexa- and heptahelicene. Two different pathways for the thermal racemization were compared. In one of them the terminal rings are brought in an almost parallel position to reach the intermediate state, as suggested by Martin (see Scheme 21). In the other way the terminal rings are in one plane whereas the remainder of the molecule is strongly bended. 

Kinetic data on the oxepin-benzene oxide equilibration have been obtained from the temperature-dependent NMR studies. Low values were observed for the enthalpy of isomerization of oxepin (7.1 kJ mol-1) and 2-methyloxepin (1.7 kJ mol-1) to the corresponding benzene oxides (67AG(E)385). The relatively small increase in entropy associated with oxepin formation (5-11 J K 1 mol-1) is as anticipated for a boat conformation in a rapid state of ring inversion. Thermal racemization studies of chrysene 1,2- and 3,4-oxides have allowed accurate thermodynamic parameters for the oxepin-arene oxide equilibration process in the PAH series to be obtained (81CC838). The results obtained from racemization of the 1,2- (Ea 103.7 kJ mol-1, AS 3.7 JK-1 mol-1 and 3,4- (Ea 105.3 kJmoF1, AS 0.7 J K"1 mol ) arene oxides of chrysene are as anticipated for the intermediacy of the oxepins (31) and (32) respectively. 

Early examples of amine racemization are particularly inefficient and tend to be very substrate specific, with very few general methods that tolerate a wide variety of functional groups [11], Thermal racemization has been achieved on relatively stable benzylic amines. For example, the isoquinolines shown in Scheme 13.2 were heated at high temperatures under vacuum to effect rapid loss of ee. This is clearly very specific to relatively simple, thermally stable amines. 

The thermal racemization of vinyl- and phenyl-substituted allenes (91) has been studied, which suggests the involvement of a biradical intermediate (92) (Scheme 13).234 The experimentally determined racemization enthalpies are lower than the... 

F-Cyclooctene is chiral, and it was resolved into enantiomers by Cope and coworkers100 by separation of diasteromeric platinum complexes containing 20 and (+)-phenyl-2-aminopropane as ligands. Thermal racemization occurred around 150 °C with a rate... 

We have investigated various factors which contribute to solvent-induced partial resolution or race-mization of 1,1 -binaphthyl (BN). Only photochemical interconversions of BN conducted in cholesteric mesophases influenced the steady state concentration of atropisomers. Thermal equilibriun in cholesteric media or photochemical interconver-sions in chiral isotropic solvents did not alter appreciably the atropisomeric ratio of initially racemic BN. Solvent order accelerates the rate of BN thermal racemization. A discussion of the physical properties of the solvents and BN responsible for the observations is presented. 

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