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 (corresponding to R and meta in the diagram).
In para-substitution, the substituents occupy the opposite ends (positions 1 and 4, corresponding to R and para in the diagram).
The
toluidines serve as an example for these three types of substitution.
Synthesis
Electron donating groups, for example
amino,
hydroxyl,
alkyl, and
phenyl groups tend to be ortho/para-directors, and electron withdrawing groups such as
nitro,
nitrile, and
ketone groups, tend to be meta-directors.
Properties
Although the specifics vary depending on the compound, in simple disubstituted arenes, the three isomers tend to have rather similar boiling points. However, the para isomer usually has the highest melting point, and the lowest solubility in a given solvent, of the three isomers.[1]
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
cocrystallisation of the ortho isomer.[2]
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.[3]
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.[4]
Tele-substitution occurs when the new position is more than one atom away on the ring.[5]
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 names
orthophosphoric acid and trimetaphosphoric acid have nothing to do with aromatics at all. Likewise, the description para was reserved for just closely related compounds. Thus
Jöns Jakob Berzelius originally called the
racemic form of
tartaric acid "paratartaric acid" (another obsolete term:
racemic acid) in 1830. The use of the prefixes ortho, meta and para to distinguish isomers of disubstituted aromatic rings starts with
Wilhelm Körner in 1867, although he applied the ortho prefix to a 1,4-isomer and the meta prefix to a 1,2-isomer.[6][7] It was the German chemist
Karl Gräbe who, in 1869, first used the prefixes ortho-, meta-, para- to denote specific relative locations of the substituents on a disubstituted aromatic ring (namely
naphthalene).[8] In 1870, the German chemist
Viktor Meyer first applied Gräbe's nomenclature to
benzene.[9] The current nomenclature was introduced by the
Chemical Society in 1879.[10]
Examples
Examples of the use of this nomenclature are given for
isomers of
cresol, C6H4(OH)(CH3):
These terms can also be used in six-membered
heterocyclic aromatic systems such as
pyridine, where the
nitrogen atom is considered 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.
^Wilhelm Körner (1867)
"Faits pour servir à la détermination du lieu chimique dans la série aromatique" (Facts to be used in determining chemical location in the aromatic series), Bulletins de l'Académie royale des sciences, des lettres et des beaux-arts de Belgique, 2nd series, 24 : 166-185; see especially p. 169. From p. 169: "On distingue facilement ces trois séries, dans lesquelles les dérivés bihydroxyliques ont leurs terms correspondants, par les préfixes ortho-, para- et mêta-." (One easily distinguishes these three series – in which the dihydroxy derivatives have their corresponding terms – by the prefixes ortho-, para- and meta-.)
^Hermann von Fehling, ed., Neues Handwörterbuch der Chemie [New concise dictionary of chemistry] (Braunschweig, Germany: Friedrich Vieweg und Sohn, 1874), vol. 1,
p. 1142.
^William B. Jensen (March 2006) "The origins of the ortho-, meta-, and para- prefixes in chemical nomenclature," Journal of Chemical Education, 83 (3) : 356.