[gojase]

Organic chemistry has been giving me a headache this weekend! Hopefully, some of you will be able to help me.

According to my organic chemistry textbook (McMurry, 7th edition), during the mechanism of acid-catalyzed halogenation there's an elimination reaction that creates an enol intermediate.  The enol then undergoes an addition reaction with the X₂.  (For your reference, I attached a .png screenshot image of my textbook's mechanism.)

Here's where I'm confused.  I was looking at Michigan State University's chemistry website, which shows an example of cyclohexanone reacting with Cl₂ with an acid (or base) catalyst.  Right under that, is another example of (2S)-2-methyl-1-phenylbutan-1-one undergoing the same reaction.  The webpage reads, "If the alpha-carbon is a chiral center, as in the second example [(2S)-2-methyl-1-phenylbutan-1-one], the products of halogenation and isotopic exchange are racemic."

Does not Cyclohexanone example result in racemization?  Or is just one product formed, (2S)-2-chlorocyclohexanone or (2R)-2-chlorocyclohexanone?  My textbook mentions the stereochemical descriptors Re and Si in another chapter, but not much.  I'm wondering if there are maybe special considerations that need to be taken into account when considering Re face and Si face of sp2-hybridized carbon atoms on 6-carbon ring reactions?

Here's a link to Michigan State's website that I refer to:
http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/aldket2.htm

Thanks

[orgopete]

The chirality teaches you something about the mechanism. If the halogenation were some kind of replacement of a hydrogen, then arguably, it might be possible for the chirality to be maintained. If the halogenation occurred through an enol, the process of enol formation destroys an chirality. Halogenation of the enol will occur from the Si or Re face and a mixture should result. Ruesch and McMurray in this case are in agreement.

[gojase]

The chirality teaches you something about the mechanism. If the halogenation were some kind of replacement of a hydrogen, then arguably, it might be possible for the chirality to be maintained. If the halogenation occurred through an enol, the process of enol formation destroys an chirality. Halogenation of the enol will occur from the Si or Re face and a mixture should result. Ruesch and McMurray in this case are in agreement.

Thank you, Orgopete.  I'm unfamiliar with chair-boat conformation when there's a double bond involved in the ring.  Are there any factors that would create a preference towards where the reaction occurs, whether Si or Re face, or would the reaction result in racemized products?

[orgopete]

This is an example where model can be helpful. If you examine the structure of cyclohexanone, it is symmetrical without any chirality centers, therefore racemization is not applicable. The product of the bromination will be a mixture of R and S-products. Again, because of symmetry, they will form equally.

[adianadiadi]

A mixture of R and S is called a racemic mixture.

[gojase]

Orgopete: You were right, the model was helpful in my understanding.


Adianadiani: I know that complete racemization in most SN1 reactions are rare because the leaving group and substrate are still loosely associated around transition state, but it seems that these are usually treated as negligible (at least on the exams I've taken part in).  So, other than that, is what you're saying always going to be true?  Are there no other scenarios where a mixture of R and S isn't racemic?

Thank you both, Orogpete and Adianadiani, for your help.

[fledarmus]

Hello Gojase,

I think you're caught on a semantic issue. The term "racemization" is usually used to refer to a loss of chirality - going from a starting material which is either all R or all S to a product which is a mixture of R and S. It is not usually used to refer to a gain of chirality - going from a starting material which is achiral to a product which is a mixture of R and S.

In this sense, you can say that an enantiomerically pure compound (eg, all S) was either partially racemized or fully racemized during a reaction to give you varying mixtures of R and S product.

If you are starting with an achiral starting material (such as cyclohexanone), and getting a chiral product (such as alpha-chloro-cyclohexanone), you refer to a reaction's "selectivity" rather than racemization - a non-selective reaction would give you a racemic mixture (1:1 mixture of R and S), and selective or partially selective reactions would give you a mixture of R and S products which is enriched in one or the other enantiomer.

A racemic mixture is a 1:1 mixture of enantiomers - racemization is the process of going from a mixture of enantiomers which is not a 1:1 mixture, towards a mixture that is a 1:1 mixture. The term "racemization" is not used to describe the process of going from a compound which does not have enantiomers to a racemic mixture.

Hope this helps...