5.9 A Review of Isomerism

Types of Isomers

Isomers are molecules that share the same molecular formula but differ in structure. The two broad categories are constitutional isomers (different connectivity) and stereoisomers (same connectivity, different spatial arrangement). Keeping this classification straight is one of the most important skills in stereochemistry, because the type of isomeric relationship between two molecules determines how their physical and chemical properties compare.

Constitutional vs. Stereoisomers

Constitutional isomers have the same molecular formula but different bonding connectivity. The atoms are literally hooked together in a different order. For example, butane and 2-methylpropane both have the formula $C_4H_{10}$, but butane is a straight chain while 2-methylpropane is branched. Ethanol ($CH_3CH_2OH$) and dimethyl ether ($CH_3OCH_3$) share the formula $C_2H_6O$ yet belong to entirely different functional group classes.

Stereoisomers have the same molecular formula and the same connectivity, but the atoms are arranged differently in three-dimensional space. (R)-2-butanol and (S)-2-butanol are stereoisomers: every atom is bonded to the same neighbors, yet the two molecules are non-superimposable mirror images. Cis-2-butene and trans-2-butene are also stereoisomers, differing only in how substituents are oriented around the double bond.

Types of Constitutional Isomers

• Skeletal (chain) isomers differ in the arrangement of the carbon skeleton. Pentane and 2-methylbutane both have the formula $C_5H_{12}$, but pentane is a continuous five-carbon chain while 2-methylbutane has a branch at carbon 2.
• Functional group isomers share a molecular formula but contain different functional groups. Propanal (an aldehyde) and acetone (a ketone) are both $C_3H_6O$, yet they react very differently because the carbonyl is in a different bonding environment.
• Positional isomers have the same functional group placed at different locations on the carbon chain. 1-Propanol and 2-propanol are both alcohols with the formula $C_3H_8O$, but the $-OH$ group sits on carbon 1 versus carbon 2.

Stereoisomers

Categories of Stereoisomers

Enantiomers are non-superimposable mirror images. Every stereogenic center has the opposite configuration. (R)-2-butanol and (S)-2-butanol are enantiomers. They share identical physical properties (boiling point, melting point, solubility) except for the direction they rotate plane-polarized light: one rotates it clockwise (+), the other counterclockwise (−), by equal amounts.

Diastereomers are stereoisomers that are not mirror images. In a molecule with multiple stereocenters, diastereomers share the configuration at one or more centers but differ at others. For example, (2R,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol are diastereomers. Unlike enantiomers, diastereomers generally have different physical properties (different melting points, solubilities, etc.).

Cis-trans (geometric) isomers differ in the arrangement of substituents across a double bond or ring.

• Cis isomers have substituents on the same side.
• Trans isomers have substituents on opposite sides.
• Cis-2-butene and trans-2-butene are a classic pair. These are actually a subcategory of diastereomers, since they're stereoisomers that aren't mirror images.

Chirality and Representation

Chirality is the property of a molecule that cannot be superimposed on its mirror image. The most common source of chirality is a tetrahedral carbon bonded to four different substituents (a stereogenic center), though chirality can also arise from other structural features.

Meso compounds contain stereogenic centers yet are optically inactive. This happens because the molecule has an internal plane of symmetry that makes one half the mirror image of the other, so the rotations from each stereocenter cancel out. Meso-2,3-butanediol is a classic example: it has two stereocenters but is superimposable on its mirror image.

Fischer projections represent 3D stereochemistry in 2D. Horizontal bonds point toward you (out of the page), and vertical bonds point away. They're especially common for sugars and amino acids. The key rule: you can slide substituents along the vertical axis, but you cannot rotate the projection 90° without inverting the configuration.

Newman projections show the conformation of a molecule as viewed along a specific $C{-}C$ bond. The front carbon is a dot, the back carbon is a circle, and substituents radiate outward from each. These are most useful for analyzing steric strain and comparing eclipsed vs. staggered conformations, which matters when you're thinking about the energy and reactivity of different rotational arrangements.