ISOMERS: Same song, different dance


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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

ISOMERS: Same song, different dance.
Isomer = “one of two or more compounds, radicals, or ions that contain the same number of atoms of the same elements but differ in structural arrangement and properties.” -Websters.
You began learning about isomers in GenChem, now they are going to be integral to your understanding of organic chemistry. Below is a schematic showing the relationships between the different kinds of isomers that we are going to study…

isomers

structural (different bond pattern)

stereoisomer (same bond pattern)

enantiomer (non-superimposable
on mirror image)

diastereomer (non-mirror images, non-superimposable)

conformers (interconvertable by bond rotation)

geometric (cis/trans)

configurational R,R vs. R,S.

Various forms of this isomer tree appear in different books, but this is a good place to start. In this short section, we’ll look at the easy difference between structural isomers and all others.
Consider pentane (n-, bp = 36.1 oC; mp = -129.8 oC). It has a molecular formula of C5H12…with 3 structural isomers: n-pentane, isopentane…neopentane

2

2

1

1

2

2 1

1 3
1

1

4

1

1

1

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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

The numbers designate the primary (1o), secondary (2o), tertiary (3o), quaternary (4o) carbon…(dependent on how many other carbons are attached). There are 8 pentyl derivatives…3 n-pentyl, 4 isopentyl and 1 neopentyl, (if 1 substitution allowed)
There are 5 structural isomers of hexane, 9 heptane isomers, but 18 octane isomers…yikes. C10 – 75 isomers; C15 – 4,347 isomers; C20 - 366,319 isomers…double yikes. How do you draw them?…Just be systematic about it.
Draw the 5 hexane isomers (each with a molecular formula of C6H14)…

hexane

2-methylpentane

3-methylpentane

2,3-dimethylbutane

2,2 dimethylbutane

Again, the compounds above all have the same molecular formula (C6H14). What varies is the connectivity, or the different bond patterns (literally, what is attached to what) of the different compounds. These compounds all have unique chemistry (bp, mp, NMR spectra, etc.). They are all structural isomers of one another.

isomer
n-hexane 2-methylpentane 3-methylpentane 2,3-dimethybutane 2,2-dimethylbutane

bp (oC)
69 60.3 63.3 58 49.7

mp (oC)
-95 -153
-128.5 -99.9

density
.6603 .6532 .6645 .6616 .6485

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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

“iso, sec and tert”
Now is a good place to introduce some more nomenclature. The best way to explain the prefixes iso, sec and tert, is by example…

hexane

isohexane

butylcyclohexane

sec-butylcyclohexane

tert-butylcyclohexane

isobutylcyclohexane

isopentylcyclohexane

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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

4. STEREOCHEMISTRY: Molecules through the looking glass.

Consider methane. The simplest hydrocarbon. A gas at RT; bp = -162 oC; mp = -182.5 oC. CH4. Tetrahedral. Very boring. It’s only real reaction of practical value is combustion (reaction with O2) to give carbon dioxide and water. Oh, and it is a very important green house gas with a major source being bovine ruminations (cow farts). Boring. Now let me ask you a
question. If you start to take off the hydrogens one at a time and replace them with different
things, how many can you replace and still have the same compound? Lets replace hydrogens
one at a time with Cl, Br and I.

H

Cl

Cl

Cl

CH

H

H

CH

H

H

CH

Br

H

CH

Br

I

Now, for the first compound…methane…if I shuffle the H’s around, will I still end up with the
same compound, no matter how I shuffle the H’s? Yes. How about for choromethane? Yes.
How about bromochloromethane? Yes. How about the last one, bromochloroiodomethane? NO.
There are two different possibilities. The game of identifying different spatial arrangements of atoms in organic molecules is called stereochemistry.

4.1 Chirality…

Chirality = handedness. It is usually determined/defined by having a mirror image that is non-superimposable…usually a carbon center with 4 different substituents

Examples…

bromochloroiodomethane

Cl

Cl

CH

Br

I

C

H

Br

I

3-methylhexane

CH3

CH3

CH

H C

The above example, no matter which way I try to rotate or otherwise orient the molecules, I cannot get them to superimpose on one another. They are different isomers of the same
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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

compound. They are enantiomers…isomeric compounds that are non-superimposable mirror images of one another.

So, how do we distinguish one enantiomer from another? …assign priority to groups. …highest (1) to lowest (4), based on molecular weight. …look down the carbon – (4) bond …1 - 2 - 3 goes clockwise, then R. …1 - 2 - 3 goes counterclockwise, then S.

3

3

1

4

4

1

H

H

2

2

(S)-3-methylhexane

(R)-3-methylhexane

3 CH3

CH3CH3CH2 1

CH2CH3 2

3 CH3

CH3CH2 2

CH2CH2CH3 1

Do more examples (cyclo) in class…
Or…L and D notation.
Based on the rotation of light. Chiral molecules can rotate plane polarized light.
L = levorotory (-) = counterclockwise rotation of light. D = dextrorotory (+) = clockwise rotation of light.
Best examples of light rotation are likely shown in your book…
[α] = specific rotation, rotation induced by 1mg/mL over 10 dm (1 m). = α / (c * l) where c = concentration in mg/mL 1 = optical path length in dm
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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

α = observed rotation.
Notation [α]20D = angle measured at 20oC, using sodium D line (589 nm)
Compounds that have no chiral (stereogenic) centers do not rotate light. 50:50 mixtures of R/S or L/D do not rotate light…RACEMIC MIXTURES R/S/ notation does NOT relate to L/D (+/-)
Chirality affects the reactivity and the outcome of final products due to reaction. For example, life is “handed”…we (biology) are based on L amino acids that bind to D sugars. One way we know that amino acids found in/on meteorites is extraterrestrial is to look for an enantiomeric excess of D amino acids.
4.2 Stereogenic Centers vs. Chiral Molecules
“Molecules are chiral…atoms are not” (…or so says Maitland Jones)

OH O HO

chiral chiral center no symetry

achiral no chiral center
symmetry

achiral chiral centers
symmetry

DIASTEREOMERS …two or more chiral centers …stereoisomers that are not mirror images (not enantiomeric). …different compounds.
For every N stereogenic (chiral) centers, there are potentially 2N stereoisomers.
For example…
Br

2-bromo-3-methylpentane How many stereogenic centers? 2 (C2 and C3). # of stereoisomers? 4
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Organic Chemistry (CHEM311)

Fall 2005

Draw the 4 isomers (as Fisher projections…)

Dr. Robert F. Dias

H

H

H3C

Br

Br

CH3

H3C

Et

Et

CH3

H

H

2R, 3R

2S, 3S

Enantiomers

H

H

H3C

Br

Br

CH3

Et

CH3 H3C

Et

H

H

2R, 3S

2S, 3R

Enantiomers

Diastereomers

MESO Compounds…compounds with chiral centers, but due to a plane of symmetry, apparent enantiomers are actually identical compounds.

3,4-dimethylhexane

H

Et

Me

Me

Et

H
3R,4R

H

Me

Et

Et

Me

H
3S,4S

enantiomers

H

H

Et

Me

Me

Et

Et

Me

Me

Et

H
3R,4S

H
3S,4R

meso compounds

diastereomers

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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

EPIMERS…two compounds that differ in configuration around only one specific carbon atom. e.g., (3R,4R) and (3R,4S)- 3,4-dimethyl hexane or (3S,4S) and (3S,4R)-3,4-dimethyl hexane.
STRUCTURAL ISOMERS…Same molecular formula, different bond arrangements. I.e., 2chloropentane vs. 3-chloropentane. (as opposed to conformational isomers R-2-chloropentane vs. S-2-chloropentane.
REACTIVITY DIFFERENCES DUE TO R/S (L/D)
Life…D sugars and L amino acids. D amino acid enantiomeric excess in meteorites R and S thalidomide

O

O

N H
O

NH O

O

O

H

N

O

NH O

(R)-thalidomide (S)-thalidomide

R – antiabortive agent, used to help prevent miscarriages (late fifties, early sixties?)
S - very potent teratogen (any environmental agent, be it a drug, chemical, infection or pollutant which harms a developing embryo or fetus).
Drug was marketed in South America in racemic form…with disastrous results. Never licensed in the US, but not without a major power struggle.

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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

4.3 Alkene Stereohcemistry
Consider ethene. How many hydrogens can we replace before we have to worry about isomers? The answer is 2. Once we have the formula C2H2X2, we have to worry about which “side” of the double bond the substituents are located…for example,

H

Cl

H

Cl

H

Cl

Cl

H

Cl

Cl

H

H

1,1-dichloroethene

E-1,2-dichloroethene

Z-1,2-dichloroethene

E = entgegen…german for opposite = trans Z = zusammen…german for together = cis

So, how do we more properly name compounds that contain double bonds? First, all previous rules apply…find longest chain/ring with double bond.
Begin numbering at the first double bond with lowest possible numbering scheme. (OH is the exception and generally takes precedence…)
E or Z (trans or cis)…
1) set priorities based on molecular weight…(Cahn-Ingold-Prelog) 2) determine the two highest priority, not on the same carbon 3) assign Z or E (cis or trans)
an example…

Low priority

H

C

Hi priority

H3C

Cl Hi priority C
F Low priority

by the rules… (E)-1-chloro-1-fluropropene
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Organic Chemistry (CHEM311)

Fall 2005

Dr. Robert F. Dias

More rules… …when there is more than one carbon, i.e. an ethyl group or higher, you look at the
atomic number of what is attached to the carbons to decide…for example,
Br hi
hi

low low
(Z)-4-bromo-3-methyl-3-nonene or…

CH2Br
trans-4-cyclohexyl-5-methylbromo-3,7-dimethyl-4-nonene Double and triple bonds as substituents are treated as if they are bound to 2 and 3 carbons respectively…for example,
(E)-3-ethenyl-4-methyl-3,5-hexadieneyne (?) …but at least it is E (trans)!
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ISOMERS: Same song, different dance