Temperatures thermal racemization

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. 

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. 

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. 

In each mesophase mixture, the dominant atropisomer after photo or thermal resolution experiments was S(+). The sole exception occurred during irradation of a 3% BN solution in mixture C. Since the sample solidified partially during the experiment, the mechanism by which the R(-) atropisomer arose is unclear. The thermal lability of the atropisomers toward interconversion and the possible contribution of cholesteric contaminants in recovered BN samples make an accurate assessment of atropisomeric excess a formidable task. Extreme care was taken to handle all solutions containing BN during work-up at temperatures which preclude significant thermal racemization at 25°C, the half-life for racemization is ca. 10 h in normal isotropic solvents all manipulations were conducted at 4°C or below. 

In cases of higher temperatures of racemization, the thermal stability was occasionally checked by an independent experiment in which the racemate was heated in the same solvent, or the deuterated solvent, at the same temperature and for the same period oftime as in the kinetic experiments. H-NMRspectra did not show any evidence of decomposition. 

The thermal racemization of (+)5g5-Cr(phen)3(C104)3 has been examined under a variety of medium conditions. The racemization is considered to occur via an intramolecular twist process. The effect of acid, hydroxide, and various other added ions on the rate constant has been investigated. The four diastereoisomers of Cr[( +)-acp]3 (acp = 3-acetylcamphorate) can be interconverted by photolysis or thermolysis at temperatures exceeding 373 K. ... 

Mention has already been made of the involvement of the sulfenic acid 226 in the thermal racemization of the sulfoxide 225, a reaction that occurred spontaneously at room temperature (Section VI,C,l,g). When heated for a few hours in boiling toluene, compounds of type 231 equilibrate with the racemates of the thiazoline oxides 233.98 The position of the equilibrium is dependent upon the nature of the nitrogen substituent for example, with the isopropyloxymethyl group a 3 1 mixture of derivatives 231a and 233a is produced, whereas with the acetyl moiety a 1 3 mixture of compounds... 

DHPLC filled the gap of a barrier range, which was not previously accessible before. When the barriers are too low for the collection of the enantiomer before off-line thermal racemization and too high for DNMR experiments, DHPLC is useful. The domain can be extended by running the chiral separation at very low temperatures (cryo-chromatography). 

Gibson et al. determined for 68 a barrier equal to 92.7 kJ mol ti/2 = 31 min at 20 °C) by thermal racemization after collecting enriched enantiomers from a sample which showed a slightly raised baseline between the peaks, consistent with interconversion of species on the column (02JOC9354). This is a typical example of a borderline for which the barrier might be determined either by DHPLC (at slightly higher temperature) or off-line thermal racemization after quick collection of the enantiomer. 

Helicenes are rather easily racemized [58,59]. [5]Helicene racemizes at room temperature [60], whereas total racemization of [9]helicene at 380°C takes place within 10 min [61]. Substitution of helicenes often results in higher racemization energy, leading to their greater stability during thermal racemization [62]. Heterocyclic (tiophenone-benzene) [63,64] and pyrrole [65] analogues of helicenes were obtained as optically active isomers. 

The relative ease with which aryl benzyl sulfoxides undergo homolytic dissociation (Rayner et al., 1966) as compared to aryl benzyl sulfides or sulfones is supportive of this idea that ArSO radicals are easier to form than ArS or ArS02 radicals. Another interesting set of observations is the following. Booms and Cram (1972) found that optically active arene-sulfinamides ArS(0)NRPh (R = H or CH3) racemize thermally very readily at room temperature and that this racemization is the result of a free radical chain reaction (160) that is initiated by the dissociation of some of the sulfinamide into an ArSO and a PhNR radical (159). While the length of the inhibition... 

Despite the theoretical difficulties outlined above, some small PVED between enantiomers does exist, on the order of 10 18 3 times the average thermal energy (feT) at room temperature per light-atom molecule. In a mole of a racemic mixture of amino acids, for example, this energy difference leads to an excess of approximately a million molecules of the more energetically stable enantiomer. Thus, we are led to search experimentally for how such minuscule excesses could be translated into a macroscale preference. As yet, another challenge, the measurement of the energy differences associated with the different enantiomers (PVEDs) so far eludes our detection abilities. 

However, the procedure has some drawbacks to overcome. First, it requires an elevated temperature (70 °C) for the activation of the racemization catalyst Such a high temperature is unacceptable for thermally less-stable enzymes. Second, the racemization proceeds through a mechanism including the release of ketone as a byproduct and thus the lowering of yield is inevitable. Third, PCPA used in an... 

The main interest in (212) and related dibenzo and dinaphtho compounds is in the conformational barrier to racemization of optically active derivatives, which requires deformation of the tub to the planar form. The compounds have proven to be optically stable at very high temperatures (64JCS2326). A minimum AH value of 71 kJ mol-1 has been calculated for racemization of the resolved 3,10-dicarboxylic esters of (212). Thermal decomposition sets in at 240 °C and leads to the phenanthridine (214) and benzonitrile, presumably via a diradical (213) (63JOC3007). 

Naphthalene 1,2-oxide (136), a non-K-region epoxide, shows low thermal stability. Anthracene 1,2-oxide, on the other hand, is stable at ambient temperatures for several weeks. Preparation of (+ )-(lR,2S)-anthracene 1,2-oxide (137), using the above method, constitutes the first example of preparation of an optically pure arene oxide. However, the non-K-region oxides of phenanthrene, namely, its 1,2- and 3,4-oxides (47 and 48), obtained from chiral precursors, racemize fast.66 Perturbational molecular orbital calculations indicate that epoxide-oxepin valence tautomerism is possible. However, the oxepin could not be detected by NMR. 

Photochemical experiments with BN in cholesteric and optically active isotropic phases. Photoinduced interconversions of BN atropisomers are in competition with thermally induced racemization at the temperatures of our experiments. Thus, the observed rotations reflect lower limits to the actual atropisomeric pho-... 

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