Stereochemistry racemic mixtures

Stereochemistry is all about configurations of stereocenters (R vs. S) and double bonds (E vs. Z). Whenever we have a reaction where we are forming a stereocenter, we need to ask whether we get a racemic mixture (equal amounts of R and S) or only one configuration. And, if so, why Also, whenever we form a double bond, we need to ask whether we get both E and Z isomers or only one of them And, if so, why ... 

For example, let s look at the stereochemistry of SnI reactions. We already saw that Sn2 reactions proceed via inversion of configuration. But SnI reactions are very different. Recall that a carbocation is sp hybridized, so its geometry is trigonal planar. When the nucleophile attacks, there is no preference as to which side it can attack, and we get both possible configurations in equal amounts. Half of the molecules would have one configuration and the other half would have the other configuration. We learned before that this is called a racemic mixture. Notice that we can explain the stereochemical outcome of this reaction by understanding the nature of the carbocation intermediate that is formed. 

In any reaction, the mechanism should explain not only the regiochemistry, but the stereochemistry as well. In this particular reaction (addition of H—X across alkenes), the stereochemistry is generally not relevant. Recall from the previous section that we need to consider stereochemistry (syn vs. anti) only in cases where the reaction generates two new stereocenters. If only one stereocenter is formed, then we expect a pair of enantiomers (racemic mixture), regardless of whether the reaction was anti or syn. You will probably not see an example where two new stereocenters are formed, because the stereochemical outcome in such a case is complex and is beyond the scope of our conversation. 

A summary of addition reactions of alkenes with 1-methylcyclopentene as the organic substrate. A bond designated means that the stereochemistry of the group is unspecified. For brevity the structure of only one enantiomer of the product is shown, even though racemic mixtures would be produced in all instances in which the product is chiral. 

The Yl/A isotherms of the racemic and enantiomeric forms of DPPC are identical within experimental error under every condition of temperature, humidity, and rate of compression that we have tested. For example, the temperature dependence of the compression/expansion curves for DPPC monolayers spread on pure water are identical for both the racemic mixture and the d- and L-isomers (Fig. 13). Furthermore, the equilibrium spreading pressures of this surfactant are independent of stereochemistry in the same broad temperature range, indicating that both enantiomeric and racemic films of DPPC are at the same energetic state when in equilibrium with their bulk crystals. 

Most optically active polysilanes owe their optical activity to induced main-chain chirality, as outlined above. However, backbone silicon atoms with two different side-chain substituents are chiral. Long-chain catenates, however, are effectively internally racemized by the random stereochemistry at silicon, and inherent main-chain chirality is not observed. For oligosilanes, however, inherent main-chain chirality has been demonstrated. A series of 2,3-disubstituted tetrasilanes, H3Si[Si(H)X]2SiH3 (where X = Ph, Cl, or Br), were obtained from octaphenylcyclote-trasilane and contain two chiral main-chain silicon atoms, 6.16 These give rise to four diastereoisomers the optically active S,S and R,R forms, the activity of which is equal but opposite, resulting in a racemic (and consequently optically inactive) mixture and the two meso-forms, S,R and R,S, which are optically inactive by internal compensation. It is reported that the diastereoisomers could be distinguished in NMR and GC/MS experiments. For the case of 2-phenyltetrasilane, a racemic mixture of (R)- and (A)-enantiomers was obtained. 

This presentation covers some aspects of stereochemistry of the drags that are marketed and administered as racemic mixtures with an emphasis on status of analytical chemistry methods for enantioseparation and control of enantiomeric purity. There is also a brief discussion on related historical knowledge. 

Most of the zwitterionic compounds studied so far are chiral, with a chiral A5S/-silicate skeleton. Most of them have been isolated as racemic mixtures and in some cases as enantiomerically pure compounds, some of the optically active compounds being configurationally stable in solution. With these experimental investigations, in combination with computational studies, a new research area concerning the stereochemistry of molecular pentacoordinate silicon compounds has been developed. 

Both U-62066 (spiradoline) (10) and PD 117302 (12) are racemic mixtures of two enantiomers. The kappa opioid activity has been shown to reside in the (—) enantiomer, and in the case of U62066 the (-h) enantiomer is a weak mu receptor agonist [49, 50]. (See above for discussion on absolute stereochemistry.)... 

Although exhaustive efforts have been made in the search for biologically acceptable catalysts, there are only a few examples of low toxicity, which mainly lead to atactic polymers of little practical use. Another route to gain control over the tacticity of PHB is the transformation of cheap building blocks to enantiomericaUy pure p-BL, which can be distilled off from the catalyst and polymerized with retention of the stereochemistry by ecofriendly initiators. This route combines many advantages. At first, even toxic metal centers can be chosen since the product can easily be separated from the catalyst and secondly, any tacticity of the polymer will be available by simply mixing enantiopure p-BL with the racemic mixture in the desired ratio. In this manner a fine-tuning of the mechanical properties becomes possible and easily performable (Fig. 36). 

Stereochemistry of the SnI reactions The SnI reaction is not stereospecific. The carbocation produced is planar and 5p -hybridized. For example, the reaction of (S)-2-bromobutane and ethanol gives a racemic mixture, (S)-2-butanol and (R)-2-butanol. 

Stereochemistry of hydride reduction Hydride converts a planar sp -hybridized carbonyl carbon to a tetrahedral p -hybridized carbon. Thus, hydride reduction of an achiral ketone with LiAlH4 or NaBH4 gives a racemic mixture of alcohol when a new stereocentre is formed. 

Later, Pasteur 15) had arrived at the general stereochemical criterion for a chiral or dissymmetric molecular structure. Thus, the specific rotations of the two sets of sodium ammonium tartrate crystals in solution, isolated from the racemic mixture by hand-picking, were equal in magnitude and opposite in sign, from which Pasteur inferred that enantiomorphism of the dextro- and laevorotatory crystals is reproduced in the microscopic stereochemistry of the (+)- and (—)-tartaric acid molecules. The term dissymmetry or chirality is used when there is no superimposability between the two enantiomers, as seen in Sect. 2.1. 

The fundamentals of structure and stereochemistry have been considered in previous chapters in some detail. There are, however, practical aspects of stereochemistry that have not yet been mentioned, particularly with regard to chiral compounds. How, for instance, can a racemic mixture be separated into its component enantiomers (resolution) what methods can be used to establish the configuration of enantiomers how can we tell if they are pure and how do we synthesize one of a pair of enantiomers preferentially (asymmetric synthesis) In this chapter, some answers to these questions will be described briefly. 

A-10. Write the final product of the following reaction sequence, clearly showing its stereochemistry. Is the product achiral, a meso compound, optically active, or a racemic mixture ... 

The only apparent difference between the two mechanisms is the stereochemistry of the product. If the reaction proceeds through an Sn2 mechanism, it gives inversion of configuration conversion of an R starting material into an S product, or vice versa. If the reaction proceeds through a carbocation intermediate via an SN1 mechanism, we get a racemic mixture. 

The resolution of the racemic mixture of modafinil acid 6 using thiazolidinethione 19 as the chiral auxiliary was achieved in 88% yield (Scheme 6) in the presence of DCC.33 Two diastereomeric intermediates 20 and 21 were easily separated by silica gel column chromatography and the absolute stereochemistry was assigned based on the single A-ray crystallographic analysis. Finally, the addition of ammonia to diastereomeric thiazolidinethione 20 yielded armodafinil 1. 

Even if the resolution of an amino acid is relatively easy, the synthesis of a racemic mixture when only one enantiomer is desired is wasteful, because half of the product cannot be used. Recently, considerable effort has been devoted to the development of methods that produce only the desired enantiomer by so-called asymmetric synthesis. As was discussed in Chapter 7, one enantiomer of a chiral product can be produced only in the presence of one enantiomer of another chiral compound. In some asymmetric syntheses a chiral reagent is employed. In others a compound called a chiral auxiliary is attached to the achiral starting material and used to induce the desired stereochemistry into the product. The chiral auxiliary is then removed and recycled. 

Racemic mixture (Section 7.4) An equal mixture of enantiomers. Also called a racemate. Racemization (Section 8.4) The stereochemical result of a reaction in which complete randomization of stereochemistry has occurred in the product (50% inversion and 50% retention). 

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