In ortho-substitution, two substituents occupy positions next to each other, which may be numbered 1 and 2. In the diagram, these positions are marked R and ortho.
In meta-substitution the substituents occupy positions 1 and 3.
In para-substitution, the substituents occupy the opposite ends.
The toluidines serve as an example for these three types of substitution.
Although the specifics vary depending on the compound, in simple disubstituted arenes, the three isomers tend to have rather similar boiling points. However, the paraisomer usually has the highest melting point, and the lowest solubility in a given solvent, of the three isomers.
Separation of ''ortho'' and ''para'' isomers
Because electron donating groups are both ortho and para directors, separation of these isomers is a common problem in synthetic chemistry. Several methods exist in order to separate these isomers:
Column chromatography will often separate these isomers, as the ortho is more polar than the para in general.
Fractional crystallisation can be used to obtain pure para product, relying on the principle that it is less soluble than the ortho and thus will crystallise first. Care must be taken to avoid co-crystallisation of the ortho isomer.
Many nitro compounds'ortho and para isomers have quite different boiling points. These isomers can often be separated by distillation. These separated isomers can be converted to diazonium salts and used to prepare other pure ortho or para compounds.
''Ipso'', ''meso'', and ''peri'' substitution
Ipso-substitution describes two substituents sharing the same ring position in an intermediate compound in an electrophilic aromatic substitution. MeSi, t-Bu, and iPr groups can form stable carbocation, hence are ipso directing groups.
Meso-substitution refers to the substituents occupying a benzylic position. It is observed in compounds such as calixarenes and acridines.
Peri-substitution occurs in naphthalenes for substituents at the 1 and 8 positions.
''Cine'' and ''tele'' substitution
In cine-substitution, the entering group takes up a position adjacent to that occupied by the leaving group. For example, cine-substitution is observed in aryne chemistry.
Tele-substitution occurs when the new position is more than one atom away on the ring.
Origins
The prefixes ortho, meta, and para are all derived from Greek, meaning correct, following, and beside, respectively. The relationship to the current meaning is perhaps not obvious. The ortho description was historically used to designate the original compound, and an isomer was often called the meta compound. For instance, the trivial namesorthophosphoric acid and trimetaphosphoric acid have nothing to do with aromatics at all. Likewise, the description para was reserved for just closely related compounds. Thus Berzelius originally called the racemic form of aspartic acidparaaspartic acid in 1830. The use of the prefixes ortho, meta and para to distinguish isomers of di-substituted aromatic rings starts with Wilhelm Körner in 1867, although he applied ortho prefix to a 1,4 isomer and the meta prefix to a 1,2-isomer. It was the German chemistKarl Gräbe who, in 1869, first used the prefixes ortho-, meta-, para- to denote specific relative locations of the substituents on a di-substituted aromatic ring. In 1870, the German chemist Viktor Meyer first applied Gräbe's nomenclature to benzene. The current nomenclature was introduced by the Chemical Society in 1879. The German version of this page provides the following details. The substitution pattern names come from the Greek prefixes ortho, meta and para. Vicinal stems from the Latin 'vicinus' meaning "neighbor." Ipso is also latin meaning "self" while meso and peri are from the Greek Μέσος meaning "center" or "middle" and περί meaning "about," respectively. Additionally, cine comes from the Greek κινέ which means "to move" and tele comes from the Greek τῆλε which means "at a distance."
Examples
Examples of the use of this nomenclature are given for isomers of cresol, C6H4: There are three arene substitution isomers of dihydroxybenzene - the ortho isomer catechol, the meta isomer resorcinol, and the para isomer hydroquinone: There are three arene substitution isomers of benzenedicarboxylic acid - the ortho isomer phthalic acid, the meta isomer isophthalic acid, and the para isomer terephthalic acid: These terms can also be used in six-membered heterocyclic aromatic systems such as pyridine, where the nitrogen atom is considered as one of the substituents. For example, nicotinamide and niacin, shown meta substitutions on a pyridine ring, while the cation of pralidoxime is an ortho isomer.
