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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: Rutherford on February 20, 2014, 01:30:46 PM

Title: Stereoisomers of cefalotin
Post by: Rutherford on February 20, 2014, 01:30:46 PM
How many stereoisomers of cefalotin exist?
I'd say 4: 2*2 for stereocenters.
But do the two nitrogen count as stereocenters?
Title: Re: Stereoisomers of cefalotin
Post by: discodermolide on February 20, 2014, 01:34:14 PM
4 unless I am missing something!
Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 20, 2014, 01:38:44 PM
I am not sure about the nitrogen atoms, they are tetrahedrons and have three different substitutes + one electron pair. Is the isomerization between R and S slow enough so they can be regarded as different compound, I don't know.
Title: Re: Stereoisomers of cefalotin
Post by: AlphaScent on February 20, 2014, 01:49:45 PM
Since we are discussing stereo chemistry.

How many isomers are there of this compound?  I think there are six.  3 stereo centers.  So six isomers.  Am I wrong?

Am I missing something with the epoxide?
Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 20, 2014, 01:55:05 PM
I'd go with six.
Title: Re: Stereoisomers of cefalotin
Post by: discodermolide on February 20, 2014, 01:55:21 PM
I see 6, I don't think you are missing anything.
Title: Re: Stereoisomers of cefalotin
Post by: AlphaScent on February 20, 2014, 02:02:43 PM
Ok cool.  I was doubting myself for some reason.

Also, when it comes to nitrogen being considered a stereocenter, what are the conditions for it to be one?  I know in most biological compounds only carbon is considered.  When do you consider nitrogen?
Title: Re: Stereoisomers of cefalotin
Post by: discodermolide on February 20, 2014, 02:06:45 PM
Usually the inversion of an amine is very fast. Put some really bulky groups on it and you can slow it down so that you can see the isomers in the NMR time scale. It's a bit like chairs interconverting, at low temp you see axial and equatorial protons at RT you just see one big signal in the NMR.
But yes you can have chiral nitrogen atoms.
Title: Re: Stereoisomers of cefalotin
Post by: discodermolide on February 20, 2014, 02:17:27 PM
Think about phosphines, now they can be chiral!
Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 20, 2014, 02:24:27 PM
Here, the nitrogens' environment seems very rigid, so maybe nitrogen should be considered as a stereocenter.
Title: Re: Stereoisomers of cefalotin
Post by: sjb on February 20, 2014, 02:27:55 PM
I see 6, I don't think you are missing anything.

8, surely?
Title: Re: Stereoisomers of cefalotin
Post by: discodermolide on February 20, 2014, 02:31:24 PM
Yes, getting blind in my old age. Or my screen needs cleaning:)
Title: Re: Stereoisomers of cefalotin
Post by: AlphaScent on February 20, 2014, 02:52:25 PM
I know other elements can be chiral centers.  This is a topic I am ill equipped to talk about though.  Gonna put my nose into some information.

@sjb

You think 8 for my compound??  Please explain further.
Title: Re: Stereoisomers of cefalotin
Post by: zsinger on February 20, 2014, 03:04:24 PM
When I learned it (and what I accepted as fact?!?) was that Nitrogens rapidly interconvert between R and S, therefore giving them chirality.  As was mentioned, tertiary nitrogens might have a bigger energy barrier to rotation, however I am somewhat certain that it is, in fact, always, chiral.  Unless, of course, it is a Carbon DB Nitrogen.  Then no free rotation….and no stereo center :).
                     -Zack
Title: Re: Stereoisomers of cefalotin
Post by: Dan on February 20, 2014, 03:13:55 PM
You think 8 for my compound??  Please explain further.

2n, not 2n.

Try writing them all out:

RRR
RRS
etc. etc.
Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 20, 2014, 03:17:27 PM
Is only the tertiary nitrogen a stereocenter, or both are?
Title: Re: Stereoisomers of cefalotin
Post by: AlphaScent on February 20, 2014, 03:42:36 PM
Brain fart.

I did indeed write them out a bit ago and it is 8.

Dummy.
Title: Re: Stereoisomers of cefalotin
Post by: AWK on February 21, 2014, 02:34:37 AM
Only quaternary nitrogen atom does not interconvert between R and S configurations. In the case of tertiary one only sterically hindered N atom involved in three-fold ring (oxaziridines or aziridines) shows sufficient inversion barrier. First reports ~1976.
Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 21, 2014, 07:49:08 AM
So there are 8 stereoisomers? The tertiary nitrogen can be regarded as a stereocenter.
Title: Re: Stereoisomers of cefalotin
Post by: clarkstill on February 21, 2014, 09:03:13 AM
All this talk of lone pair tunnelling is largely irrelevant; both nitrogens are amides, not amines, so are sp2 not tetrahedral.  The one in the ring is fixed, so definitely won't have any E/Z isomerism.  The open chain amide can potentially adopt E or Z stereochemistry, so overall there are 8 stereoisomers when the 2 stereogenic centres are considered.
Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 21, 2014, 09:35:14 AM
I don't think that we can strictly say that they are sp2, as they are actually something between sp2 and sp3. Now I really don't know what to say about the number of the stereoisomers.
Title: Re: Stereoisomers of cefalotin
Post by: clarkstill on February 21, 2014, 10:33:23 AM
Nope, amides are most definitely sp2.  Have a look at any protein crystal structures and you'll see hundreds of them...
Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 21, 2014, 11:19:04 AM
Okay, I read a little about it. So, there are 2 carbon stereocenters and one nitrogen atom causing E/Z isomerism.

The other nitrogen (in the rings) is still problematic for me. It can't be planar as the angle tension would be very big (30°). It has to be near sp3, and that would imply that it is a stereocenter.
Title: Re: Stereoisomers of cefalotin
Post by: clarkstill on February 21, 2014, 12:05:30 PM
Yeah I guess it's probably slightly distorted from being planar, but even so it won't add to the stereoisomer count as the ring junction could never be trans...
Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 21, 2014, 02:16:32 PM
How do you mean trans? Why wouldn't it be possible as I draw in the picture? The six membered ring could also be below the plane.
Title: Re: Stereoisomers of cefalotin
Post by: clarkstill on February 24, 2014, 11:39:01 AM
I agree both cis stereoisomers are possible, but the two trans ones arent:

Title: Re: Stereoisomers of cefalotin
Post by: Rutherford on February 24, 2014, 11:42:12 AM
Okay, so it is 8 as you said. Thank you very much.