Racemization, velocity

Chemical racemization of the 5-monosubstituted hydantoins proceeds via keto-enol tautomerism under alkaline conditions, as shown in Figure 12.1 [6]. The racemization velocity is highly dependent on the buUdness and electronic factors of the substituent in 5-position (see Table 12.1) and is usually a very slow process... 

System 1 was able to hydrolyze the 5-monosubstituted hydantoins faster than system 2 for the production of almost all the D-amino acids studied. System 1 was slightly slower than system 2 only for the production of the aromatic amino acids D-tyrosine and D-phenylglycine. This agrees with previously described results, finding that AtHyuAl enzyme (included in system 1) was more viable for industrial application than AtHyuA2 (included in system 2) due to its higher substrate affinity and racemization velocity [25]. 

Stilbene oxide (2,3-diphenyloxirane) is another compound of interest. It exists as two diastereoisomers, namely cA-stilbene oxide (10.7, Fig. 10.28) and the trans-(RJi)- and /ra/i.y-(5,5)-stilbene oxides (10.121, Fig. 10.28), which exhibit significant but condition-dependent substrate selectivity. Cytosolic EH purified from mouse liver metabolized racemic tram -sti I bene oxide with high affinity and high velocity, and cA-stilbene oxide with lower affinity and lower... 

Since CE is an on-column detection technique, analytes migrate with different velocities through the detection window. Thus, slower migrating compounds will have the same peak height but a larger peak area than faster migrating compounds. Therefore, it is common to work with corrected peak areas, i.e., peak area divided by migration time. The work on a racemic mixture of enantiomers demonstrates the importance of this correction. 

The constant for the decomposition of gaseous propionic aldehyde falls away steadily below about 80 mm., that for the decomposition of diethyl ether below about 150 mm., that for the decomposition of diethyl ether below about 300 mm. Several other ethers, dipropyl ether, methyl propyl ether and methyl ethyl ether behave in a similar manner. The velocity constant for the decomposition of azomethane also diminishes but not until lower pressures are reached for example at 290° C. k at 0-259 mm. has one-fourth of its value at 707-9 mm. In several reactions, such as the racemization of pinene, and the decomposition of gaseous acetone the falling off of the velocity constant has not actually been looked for. The decomposition of azoisopropane is unimolecular down to pressures of 0-25 mm. 

In both instances, the mutarotation velocity with pyrrolidine was faster than with the other amines. When iminazoline synthesis was conducted between alanyliminoether and 2-aminomethylpyrrolidine, excess pyrrolidine in the reaction media probably accelerated the epimerization reaction. Racemization is faster than crystallization of this, diastereomer, which is less soluble than the other diastereomers. In the case of isopropylpropylenediamine, the excess amine racemizes poorly, so the crystallization was faster than the racemization. 

There are very few cases where one can compare directly the same reaction taking place by the same mechanism in both gas phase and solution. If at all temperatures the reactions have equal velocities in the two phases the values of 5 and of E are the same, and it may be safely assumed that the reaction mechanisms are identical and the solvent has no effect. Undoubtedly the simplest comparison exists in the unimolecular decomposition of nitrogen pentoxide and in this reaction the solvent has little effect. The unimolecular racemization of pinene at 200° proceeds at the same rate in the gas phase, in liquid pinene and in a solution of petrolatum. 

Other scientists, among them Hearon (36), have simply taken up the fundamental ideas, especially the expressions for the reciprocal velocity of linear (open or closed) sequences and used them as they stand for their special purposes or have developed them in several directions. In this connection it may be mentioned that Hammett (37) recommends the use of such expressions. As a more recent example it may also be mentioned that Sch0nheyder (38) with the same method arrived at a rather unexpected mechanism for an enzymatic reaction, the saponification of racemic i-caprylyl glycerol, by means of a certain lipase. 

High velocities of chemical racemization have only been observed for d,l-5-phenyl- and D,L-5-p-hydroxy-phenylhydantoin, because of the resonance stabilization by the 5-subshtuent, while all other hydantoins take many hours to racemize... 

The effect of chiral discrimination at equilibrium is illustrated in Fig. 6 for the angular velocity acf of both enantiomers and racemic mixture at... 

SO K, in the supercooled liquid condition of the 2-chlorobutanes. There is little difference among the three cases, and this is buried in the statistical noise generated by the computer run. In the case of the center-of-mass velocity acf s in the same, equilibrium, condition (Fig. la) the difference between enantiomers and racemic mixture does, however, fall outside the noise, and this is an indication that the mixture of right and left stereoisomers has dynamical properties different from those of each component. 

Figure 6. (a) 2-Gilorobutane at 50 K, 6x6 site-site potential, angular velocity autocorrelation functions. Crosshatdiing indicates computer noise difference between R and S enantiomers. (—) Racemic mixture, (b) As for (a), under the influence of a strong field E, producing a torque — 63 XE in each molecule of the molecular dynamics sample. (1) (—) Racemic mixture (2) (—) R enantiomer. Ordinate Normalized correlation function abscissa time, ps. 

Figure 12. Velocity drift with applied field, (a) (o (in program units two runs) —) R enantiomer (—) racemic mixture, (fr) (v ) —) R enantiomer (—) racemic mixture, (c) (—) R enantiomer (—) racemic mixture. Abscissa time, ps.

To end this section and the review, we mention briefly the first results from the simulation on laboratory-frame cross-correlation of the type (v(f)J (0)). Here v is the molecular center-of-mass linear velocity and J is the molecular angular momentum in the usual laboratory frame of reference. For chiral molecules the center-of-mass linear velocity v seems to be correlated directly in the laboratory frame with the molecule s own angular momentum J at different points r in the time evolution of the molectilar ensemble. This is true in both the presence and absence of an external electric field. These results illustrate the first direct observation of elements of (v(r)J (0)) in the laboratory frame of reference. The racemic modification of physical and molecular dynamical properties depends, therefore, on the theorem (v(r)J (0)) 0 in both static and moving frames of reference. An external electric field enhances considerably the magnitude of the cross-correlations. 

It is well known that a chiral environment is essential for the enantiomeric resolution of racemates. In CE, this situation is provided by the chiral compounds used in the BGE and is known as the chiral selector or chiral BGE additive. Basically, the chiral recognition mechanisms in CE are similar to those in chromatography using a chiral mobile-phase additive mode, except that the resolution occurred through different migration velocities of the diastereoisomeric complexes in CE. The chiral resolution occurred through diastereomeric complex formation between the enantiomers of the pollutants and the chiral selector. The formation of diastereomeric complexes depends on the type and nature of the chiral selectors used and the nature of the pollutants. 

During enzymatic hydrolysis of 5-monosubstituted hydantoin derivatives in some cases the remaining, non-hydrolyzed enantiomer is racemizing chemically under alkaline reaction conditions. The velocity of this chemical racemization is strongly dependent on electronic factors of the substituent in the 5-position (see Table 12.4-6). High velocities of racemization are observed particularly for 5-phenyl- and 5-p-OH-phenylhydantoin. 

From reports in the early literature resting cell bioconversions of hydantoin derivatives, which do not racemize with high velocities, indicated an enzymatic racemization and the presence of a hydantoin racemase. In addition, the chemical and the enzymatic racemization proceed via the keto-enol tautomerism, which is shown in Fig. 12.4-20. Stabilizing effects on the enolate structure such as electronegative substituents are responsible for the velocity of the racemization12, 71. Increased racemization rates can be also seen at more alkaline pH-values and with increased temperatures[71. 

Carboxyl group clofibrate, ciprofibrate, etodolac, fenoprofen, ibuprofen, ketoprofen, naproxen (racemic > 5), valproic acid and formation of simvastatin and atorvastatin lactones via an intermediate acyl glucuronide Tertiary amines amitriptyline, chlorpheniramine, chlorpromazine, clozapine, cyproheptadine, diphenylamine, doxepin, imipramine, ketotifen, loxapine, promethazine, tripellenamine, trifluoperazine Aromatic heterocyclic amines croconazole, lamotrigine, nicotine (30X velocity than UGT1A3), 1-phenylimidazole, posaconazole, retigabine Primary and secondary amines ... 

There is of course ample evidence that acid-base catalysis in solvents of low dielectric constant does not necessarily involve a concerted process. Such a process cannot operate when catalysis is effected by a single acid or base present in an aprotic solvent, and there are many examples of this, including typical prototropic reactions such as the halogenation of acetone, the racemization and inversion of optically active ketones, and the mutarotation of nitrocamphor. Moreover, in the isomerization of mesityl oxide oxalic ester in chlorobenzene, which depends kinetically on the interconversion of two isomeric enols, the velocity in a solution containing both an amine and an acid is no greater than the sum of the velocities for the two catalysts separately, in contrast to the behaviour found by Swain for the mutarotation reaction. 

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