[Scatter]

Today on an exam we had to assign priority and designate whether the chiral centers in Captopril (an ACE inhibitor used in the treatment of hypertension and some forms of congestive heart failure) are R or S.  I put that they are both S, and Wikipedia confirms this, but discussion with other people has lead to confusion.  Looking at the molecule (from Wikipedia), we see two chiral centers--one at the carbon atom with the methyl group attached at the top of the image, and the other directly right of the nitrogen.



I'm concerned with the one at the top.  Does the priority go in the direction of the sulfur?  It seems like it would (giving an S-designation), but a couple other O chem peeps think that the double-bonded oxygen and the nitrogen on the carbon on the right would mean priority goes that way...  It's just kind of driving me nuts, because even if did indeed get it right I want to know why it's right.

Thanks!

By the way, I'm new around here.  Hello everyone! 

[HuàXué]

I made a chart myself and it seems that it is an S-designation.
The adjacent atoms are 3 Carbons and 1 Hydrogen, so I assign the H with the lowest priority (d).  I looked at the adjacent atoms to those 3 Carbons and the Carbon that is adjacent to that single Sulfur atom takes the highest priority (a) over the other Carbons (even though one of the other Carbon is attached to 1 Oxygen and 1 Nitrogen, the Sulfur takes priority over them because of its higher Atomic Number).  The second highest priority (b) Carbon is the one that is doubled bonded to Oxygen and single bond to Nitrogen.  So that narrows down the (c) to the Methyl group.

I'm new here too, awesome.

[Scatter]

Cool.  That's what I thought.  Thanks for the validation!

[OrgoBorgo]

Hi there, I'm new here too. woo!

Okay, in regards to the chiral center next to the Sulfur, I am having trouble as to why this is a chiral center. I understand a chiral center is a carbon that has 4 substituents that when taken as a mirror image may not be superimposed on eachother. But than wouldn't that make every carbon in the molecule a chiral center. Thanks in advance for clearing this up!

OrgoBorgo

[movies]

Your definition is a little bit off.  A molecule is chiral if its mirror image is not superposable.  It is important to remember that chirality is a molecular property, not a property of a particular atom.  A "asymmetric carbon" is a carbon atom connected to four different substituents, but it is important to note that the presence of an asymmetric carbon does not mean that the molecule is chiral.

So, now look at the carbon with the sulfur bonded to it.  Is that carbon an asymmetric carbon?  Which carbons in the molecule are asymmetric?  By the definition of chirality, is the molecule chiral?

[OrgoBorgo]

Well thats the issue, based on the definition, "A "asymmetric carbon" is a carbon atom connected to four different substituents" I would say every carbon in the molecule is asymmetric. I have troubles distinguishing which carbon is asymmetric and why.

As well i would say the molecule is chiral because the CH3 group coming out of the page, when given the mirror image is not superimposable because the mirror image CH3 would be going into the page.

Wait... having a moment... did I just figure it out? The 2nd chiral center is the one right to the N because if given the mirror image the c --- c bond going into the page is not superimposable.

And therefore by definition an asymmetric carbon is one that has 4 different substituents that when given the mirror image of the MOLECULE the 4 substituents around the assymentric carbon (or at least one) will not be superimposable.

??

[Scatter]

Not every carbon in the molecule is asymmetric.  movies was right in that chirality is usually referring to the whole molecule, however, my original question was concerning the chiral centers (also termed "stereogenic centers").  Not every carbon is a chiral center (or asymmetric carbon as you would put it) because many of them either have two or three hydrogens bonded to them (not pictured) or a double bond.

When you look at a molecule, look for sp3 hybridization.  If there's four different substituents bonded to any carbon, the carbon is a chiral center.  Make sure you take the molecule as a whole into account though.  Like, if there is a phenyl group and a methyl group bonded to the carbon, it could be a chiral center because even though there are two carbons directly bonded to it, the larger structure coming off each bond is different.

[movies]

Look carefully at each carbon again.  Consider first the carbon bonded to the sulfur - it is also bonded directly to what other atoms?  List them and then determine whether that qualifies for an asymmetric carbon center.


A couple of other points, Scatter:
First, chirality is always referring to the whole molecule.  You can't have part of a molecule that is chiral and part that is not; it only makes sense in the context of the entire entity.  This is also why it is preferable to use the term "asymmetric carbon" as opposed to "chiral center."  It is possible that an asymmetric carbon is a chiral center, but this is not always the case (e.g., some meso compounds) so the two are not the same.

Second, the term "stereogenic center" is not interchangeable with center of chirality or asymmetric carbon.  It is a more general term that could refer to any stereocenter including things like the C of an alkene where there could be E or Z isomers.

[Scatter]

Look carefully at each carbon again.  Consider first the carbon bonded to the sulfur - it is also bonded directly to what other atoms?  List them and then determine whether that qualifies for an asymmetric carbon center.


A couple of other points, Scatter:
First, chirality is always referring to the whole molecule.  You can't have part of a molecule that is chiral and part that is not; it only makes sense in the context of the entire entity.  This is also why it is preferable to use the term "asymmetric carbon" as opposed to "chiral center."  It is possible that an asymmetric carbon is a chiral center, but this is not always the case (e.g., some meso compounds) so the two are not the same.

Second, the term "stereogenic center" is not interchangeable with center of chirality or asymmetric carbon.  It is a more general term that could refer to any stereocenter including things like the C of an alkene where there could be E or Z isomers.

Ok ok, always referring to the whole molecule.

Semantics semantics.  A chiral center IS a stereogenic center, but a stereogenic center is not necessarily a chiral center.  An asymmetric carbon is a stereogenic center, but also not necessarily a chiral center.  So... stereocenter is the best general term to use to describe asymmetry?

Thanks for the clarification.

[Dan]

Semantics semantics.  A chiral center IS a stereogenic center, but a stereogenic center is not necessarily a chiral center.  An asymmetric carbon is a stereogenic center, but also not necessarily a chiral center.  So... stereocenter is the best general term to use to describe asymmetry?

Stereogenic centre is a more general term which includes "chiral" or "asymmetric" centres. Chiral centre = asymmetric centre, and is one types of stereogenic centre (and there are a few different types). Asymmetric centre is a less misleading name, since the presence of asymmetric centres (or "chiral centres") does not necessarily mean the molecule is chiral.

For example, galactitol contains four asymmetric (or "chiral" centres) but is achiral. There are innumerable other examples, and these molecules are called meso compounds.

The existence of achiral molecules containing numerous "chiral" centres is a major source of confusion for students learning stereochemistry - using the term asymmetric makes things easier to understand from the outset.

[movies]

I think the point should be that chiral centers only exist if the molecule is chiral.  So in fact chiral center ≠ asymmetric center!

[OrgoBorgo]

Look carefully at each carbon again.  Consider first the carbon bonded to the sulfur - it is also bonded directly to what other atoms?  List them and then determine whether that qualifies for an asymmetric carbon center.

The carbon directly right of the sulfur is bonded to a:
Sulfur, Carbon, Carbon, Hydrogen.

Based on the definition of Substituent: a substituent is an atom or group of atoms substituted in place of a hydrogen on the parent chain. (wikipedia)
And the definition of an asymmetric carbon: carbon bonded to four different substituents.

Does that mean the carbon directly right of the sulfur is not asymmetric because it has a hydrogen?


Was my reasoning in my last post incorrect as to why the carbon attached to the methyl group and the carbon right of the N were assymetric?

[movies]

Your reasoning is right, but I think you are interpreting the drawing wrong.

The structure is like the attached picture.  Look at the carbon I labelled C(1) and tell me if that is an asymmetric carbon.  Then look at C(2); is that carbon asymmetric?

[OrgoBorgo]

I would say C1 is NOT asymmetric because if given the mirror image of the molecule, it can be superimposed on C1' (mirror image fo C1). On the other hand, I would say C2 IS asymmetric because given the mirror image of the molecule C2 cannot be superimposed on C2' due to the methyl group (i.e. the methyl group will not superimpose). This is my best answer, I really have a desire to understand this so I hope I'm right.

[OrgoBorgo]

As i reference my textbook (which is always a good idea) i see that C1 is NOT bonded to four different substituents as it connects to 2 hydrogens. However C2 IS bonded to four different substituents beacause its bonded to (H, CH3, C-SH and C=O.. continued to remainder of molecule)