Rate of racemization

In a classic expenment Edward Hughes (a colleague of Ingold s at University College Lon don) studied the rate of racemization of 2 lodooctane by sodium iodide in acetone and compared It with the rate of incorporation of radioactive iodine into 2 lodooctane... 

How will the rate of racemization compare with the rate of incorporation of radioactivity if... 

Molecules that are chiral as a result of barriers to conformational interconversion can be racemized if the enantiomeric conformers are interconverted. The rate of racemization will depend upon the conformational barrier. For example, -cyclooctene is chiral. E-Cycloalkenes can be racemized by a conformational process involving reorienting of the... 

Rotation about the 1,1 -bond is resisted by van der Waals interactions between the hydrogens shown in the structures. These hydrogens crowd each other when the two naphthyl groups are coplanar, and the racemization process requires tjie hydrogens to move past each other. The existence of enantiomeric substituted biphenyls also depends on steric interactions between substituents. The relationship between the rate of racemization and... 

Optical rotation data have been used in two different ways to study tautomerism. The rate of racemization at an optically active carbon atom gives an upper limit for the rate at which the other tautomeric form is produced rates of halogenation and deuteration can sometimes be used in a similar way. 

In the second method, which can be applied to compounds with an optically active center near the potentially tautomeric portion of the molecule, the effect of the isomerization on the optical activity is measured. In favorable cases both the rate of racemization and the equilibrium position can be determined. This method has been used extensively to study the isomerization of sugars and their derivatives (cf. reference 75). It has not been used much to study heteroaromatic compounds, although the very fact that certain compounds have been obtained optically active determines their tautomeric form. For example, oxazol-5-ones have thus been shown to exist in the CH form (see Volume 2, Section II,D,1, of article IV by Katritzky and Lagowski). 

One commonly used procedure for studying the steric stability of the carbanion is comparison of the rate of base-catalyzed H/D exchange reaction (kel) on the chiral carbon with the rate of racemization (fcrac). By this comparison, inversion, racemization or... 

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). 

CH2 groups are not acidic enough for this base (2) recovered 18 was racemized 20 is symmetrical and can be attacked equally well from either side (3) when the experiment was performed in deuterated solvent, the rate of deuterium uptake was equal to the rate of racemization and (4) recovered 18 contained up to three atoms of deuterium per molecule, though if 19 were the only ion, no more than two could be taken up. Ions of this type, in which a negatively charged carbon is stabilized by a carbonyl group two carbons away, are called homoenolate ions. 

What was actually measured was the rate of racemization, which is twice the rate of inversion, since each inversion creates, in effect, two racemic molecules. The significance of this result is that it shows that every act of exchange is an act of inversion. 

Exchange reactions can be sometimes investigated by the techniques of polari-metry, nuclear magnetic resonance and electron spin resonance. The optical activity method requires polarimetric measurements on the rate of racemization in mixtures of d-X (or /-X) and /-Y (or d-Y). 

Im and Busch have made a further study of this reaction. They used the optical activity method, investigating the rate of racemization of d-C6Y, in the presence of CoY which is optically unstable and catalyses the process, viz. 

D. Miscellaneous.—A study of the racemization of ( + )-methylphenyl-n-propylphosphine has shown that the rate of racemization has no dependence on solvent polarity and could not be correlated with any known solvent parameters. ... 

We have compared, the rate acceleration effect induced either by the CD and different moieties originated from CD, i.e quinuclidine and quinoline. These experiments were carried out in ethanol If the relative rate of racemic hydrogenation is equal to one the following relative rates has been measured quinoline = 2, quinuclidine = 3, cinchonidine = 40. In the presence of quinoline a short induction period was needed to observe the rate acceleration. It is suggested that during this period quinoline was partly hydrogenated. Other tertiary nitrogen bases, such as triethylamine, triethylenediamine, etc. resulted also rate acceleration with relative rate = 2-4. 

The last several years have seen an enormous growth in the number and use of chiral stationary phases in liquid chromatography [742,780-791]. Some problems with the gas chromatographic approach are that the analyte must be volatile to be analyzed and larger-scale preparative separations are frequently difficult. For entropic reasons relatively high temperatures tend to minimize the stability differences between the diastereomeric complexes and racemization of the stationary phase over time may also occur. The upper temperature limit for phases such as Chirasil-Val is about 230 C and is established by the rate of racemization of the chiral centers and not by column bleed. Liquid chromatography should be s ior in the above... 

If the environmental temperature is constant, the racemization process takes place at a uniform rate, which is determined, at any time during the process, by the relative amounts of / and d forms of the amino acid can be measured. As the racemization proceeds and the concentration of the / form amino acid decreases, the rate of racemization gradually slows down. When there is a mixture of 50% of each of the d and / forms, the racemization process stops altogether. The half-life of the racemization of aspartic acid, for example, a common amino acid in proteins, at 20°C is about 20,000 years. This half-life makes it possible to date proteins as old as about 100,000 years. So far, however, the dates obtained with the technique have proved somewhat inconsistent, probably because of the difficulty in verifying whether the temperature of the amino acids has been constant. 

G.G. Smith, R.C. Evans, The Effect of Structure and Conditions on the Rate of Racemization of Free and Bound Amino Acids, in Bio geochemistry of Amino Acids, edited by P.E. Hare, T.C. Hoering, J. King, John Wiley Sons, Ltd, New York, 257 282 (1980). 

In order to understand the rates of racemization of biphenyls and bihetero-cyclics, an accurate knowledge of their geometric structure is essential. Such knowledge makes it possible to estimate the amount of interference caused by substituents in the vicinity of the pivot bond in an assumed coplanar transition state for rotation. A study of the crystal structure of 1 (X = Se) found that the selenophene rings have a small but significant deviation from planarity and are nearly perpendicular to each other.17 The deviation from 9(T is such that the carboxyl groups are in transoid positions. 

It was also found that the degree of hydration of the complex affected the rate of racemization. Generally, the hydrated complexes reacted faster than anhydrous samples. It was also found that reducing the particle size increased the rate of racemization, but when the iodide compound was heated with water in a sealed tube, the racemization was slower than for the hydrated solid from which the water could escape. The fact that the hydrated samples racemized faster could indicate that an aquation-anation mechanism is involved, but the results obtained in the sealed tube experiments do not agree with that idea. 

There is now considerable interest in the relationship between the preservation of collagen and the rate of racemization of its constituent amino acids, and further data may be expected to clarify these problems. 

Roitman and Cram (1971) have shown that the kinetic basicity of potassium alkoxide increases on complexation with dicyclohexyl-18-crown-6 ([20] + [21]). Both the rate of isotopic exchange and the rate of racemization of (—)-4-biphenylylmethoxydeuteriomethane [163] by t-BuOK in t-BuOH were found to increase by factors between 30 and 17 000. Isotopic exchange was... 

J Kovac, GL Mayers, RH Johnson, RE Cover, UR Ghatak. Racemization of amino acid derivatives. Rate of racemization and peptide bond formation of cysteine active esters. J Org Chem 35, 1810, 1970. 

W Williams, GT Young. Amino acids and peptides. XXXV. Effect of solvent on the rates of racemization and coupling of acylamino acid p-nitrophenyl esters. Base strengths of amines in organic solvents, and related investigations. J Chem Soc Perkin Trans 1 1194, 1972. 

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