Constitutional isomers are molecules that share an identical molecular formula, meaning they possess the exact same count and types of atoms. They are distinct compounds because the atoms are connected differently, a characteristic known as connectivity. This difference in atomic linkage results in molecules with unique chemical and physical properties. To fully capture the complete set of possible structures for a given formula, a systematic, step-by-step approach is necessary.
Defining the Rules of Connectivity
The foundation of constitutional isomerism rests on two precise criteria that must be met to establish a pair of molecules as true structural isomers. The first rule requires that both compounds have an identical molecular formula, such as \(\text{C}_{4}\text{H}_{10}\) or \(\text{C}_{2}\text{H}_{6}\text{O}\). The second rule is that the sequence of atom-to-atom bonding must be fundamentally different between the two structures. For instance, \(\text{C}_{2}\text{H}_{6}\text{O}\) can be drawn as ethanol (an alcohol) or dimethyl ether (an ether), two compounds with distinct connectivity and properties.
It is important to understand what does not constitute a new constitutional isomer. Simply rotating a molecule around a single bond, or flipping the entire structure in space, does not change the connectivity or create a new isomer. If the atoms are connected to the same neighboring atoms, the structure remains the same molecule, regardless of how it is spatially oriented or drawn on paper.
Determining Structural Possibilities
Before any drawing begins, a calculation known as the Degree of Unsaturation (DOU), or Index of Hydrogen Deficiency (IHD), provides necessary insight into the molecule’s potential structure. The DOU value indicates the total number of rings and/or pi bonds (double or triple bonds) that must be present in the final structures. Each unit of unsaturation corresponds to either one ring or one double bond, while a triple bond counts as two degrees of unsaturation.
This calculation is performed using the molecular formula, taking into account the valency of all elements present. Carbon, hydrogen, nitrogen, and halogens are factored into the formula, while oxygen and sulfur are generally disregarded. If the result is \(\text{DOU} = 0\), the molecule is fully saturated, meaning only open-chain structures with single bonds are possible. If \(\text{DOU} = 1\), the search must include structures containing one ring or one double bond to ensure all possibilities are explored.
The Systematic Method for Generation
The most reliable approach for generating isomers involves a process of chain-shortening and substitution, ensuring all structural motifs are explored logically. The first structure to draw is always the longest possible continuous chain of carbon atoms, which represents the straight-chain isomer. For a formula like \(\text{C}_{5}\text{H}_{12}\), this would be the five-carbon chain, pentane.
The next step is to reduce the length of the main carbon chain by one atom, making it a four-carbon chain (butane, in this example). The removed carbon atom must then be reattached to the main chain as a substituent, or branch. Branches must never be placed on the end carbons of the new, shorter chain, as this action would simply revert the structure back to the original, longer chain. Placing the single methyl branch on the second carbon of the four-carbon chain yields the next isomer, 2-methylbutane.
This systematic shortening continues, reducing the main chain length further while increasing the number of substituents. For \(\text{C}_{5}\text{H}_{12}\), the chain can be reduced to three carbons (propane), requiring the use of two methyl branches. The only non-duplicate way to attach two methyl groups to a propane chain is on the central carbon, resulting in 2,2-dimethylpropane.
Identifying and Eliminating Duplicates
The final step in the process is a thorough verification of all generated structures to identify and eliminate any duplicates. Molecules that appear different because of how they are drawn—perhaps flipped or rotated—must be recognized as the same compound. The most definitive method to confirm whether two structures are identical or are genuine constitutional isomers is to assign a systematic name to each one using IUPAC nomenclature rules.
If two drawn structures result in the exact same IUPAC name, including the same locants (number positions) for substituents, they are the same molecule and one must be discarded. This process requires finding the longest continuous carbon chain in each structure and then numbering the chain to give the lowest possible set of numbers to all branches and functional groups. A structure that, when correctly named, is 2-methylbutane, is a duplicate of any other structure that also names as 2-methylbutane, regardless of its initial drawing orientation.