Compounds that have different structures even though they have the same molecular formula are called isomers, a central concept in organic chemistry. Let us classify them systematically to understand them.
Basic Knowledge
Major classification of isomers:
① Structural isomers(constitutional isomer): The order in which atoms are bonded is different
・Chain isomers: The carbon skeleton is different(n-butane and isobutane)
・Position isomers: The position of the functional group is different(1-propanol and 2-propanol)
・Functional-group isomers: The functional group itself is different(ethanol C2H5OH and dimethyl ether CH3OCH3)
② Stereoisomers(stereoisomer): The bonding order is the same, but the three-dimensional arrangement of atoms is different
・Cis-trans isomers(geometric isomers): Formed around C=C double bonds or in rings(maleic acid/fumaric acid)
・Enantiomers(optical isomers): Related as mirror images and have a chiral center(asymmetric carbon)
・Diastereomers: Stereoisomers that are not related as mirror images(with multiple chiral centers)
・Conformational isomers: Caused by rotation around single bonds(chair/boat forms of cyclohexane, etc.)
Chirality: The property of not being superimposable on one's own mirror image. Many naturally occurring amino acids are in the L form, while sugars are in the D form.
Structural isomers(different bonding order)
Cis-trans isomers(arrangement around a double bond, E/Z notation)
Asymmetric carbon atom(C*, a carbon bonded to four different groups)
Enantiomers(optical activity, identified by optical rotation)
Racemic mixture(an equimolar mixture, no optical rotation, and sometimes different medicinal effects)
R/S notation(notation of absolute stereochemical configuration according to the CIP rules)
Further Exploration (Principles and Applications)
The thalidomide incident(the 1960s) made the importance of stereoisomerism known worldwide. Thalidomide has R and S forms: the R form has a sedative effect, while the S form causes birth defects. It was sold as a racemic mixture, resulting tragically in limb deformities in many fetuses. Since then, asymmetric synthesis(selectively producing only one mirror-image form) has become essential in drug development. Ryoji Noyori's Nobel Prize(2001) recognized his work on asymmetric catalysis.
Cisplatin[PtCl2(NH3)2] shows anticancer activity only in the cis isomer, as described above.
The natural product D-glucose has nutritional value, but its mirror image, L-glucose, is not metabolized in the body and only tastes sweet(a theoretical candidate for an artificial sweetener). Among odor molecules, R-carvone has a spearmint scent, whereas S-carvone has a caraway scent; this is another famous example of a complete difference.
- Isomers are broadly classified into structural isomers and stereoisomers
- Structural isomers include chain, position, and functional-group isomers
- Geometric isomers(cis-trans)=C=C or a ring
- An asymmetric carbon=all four attached groups are different
- Enantiomers=rotate plane-polarized light in opposite directions(optical rotation±)
- With n asymmetric carbons, the maximum number of stereoisomers is 2n
- The thalidomide incident led to recognition of the importance of stereochemistry
Points to Note(Common Confusions and Frequent Mistakes)
① Cis-trans isomers do not form unless there are different groups on each side of the double bond(CH2=CHCl does not form them, while CHCl=CHCl does). ② An asymmetric carbon must have four completely different attached groups. If there are two -CH3 groups, it is not an asymmetric carbon. ③ Meso compounds: They have multiple asymmetric carbons, but the molecule as a whole is mirror-symmetric and shows no optical activity(the meso form of tartaric acid). ④ cis=Z, trans=E is a basic rule, but the relationship may be reversed because of substituent priorities(apply the CIP rules strictly).
Practice
- Draw and name all the structural isomers of C4H10.
- Draw the cis and trans forms of 2-butene CH3-CH=CH-CH3, and state which has the higher boiling point.
- Determine whether lactic acid CH3-CH(OH)-COOH has an asymmetric carbon, and state the number of stereoisomers.