{{Short description|Position of molecules attached to benzene rings}} '''Arene substitution patterns''' are part of organic chemistry IUPAC nomenclature and pinpoint the position of substituents other than hydrogen in relation to each other on an aromatic hydrocarbon.
== ''Ortho'', ''meta'', and ''para'' substitution == class=skin-invert-image|thumb|150px|right|Main arene substitution patterns {{See also|Electrophilic aromatic substitution}} * 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.<ref>Morrison and Boyd, ''Organic Chemistry'', Allyn and Bacon Inc, Boston, 1959. Ch.9, p. 250.</ref>
===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.<ref>Morrison and Boyd, ''Organic Chemistry'', Allyn and Bacon Inc, Boston, 1959. Ch. 10, p. 290.</ref> *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.<ref>Morrison and Boyd, ''Organic Chemistry'', Allyn and Bacon Inc, Boston, 1959. Ch. 21, pp. 573-574.</ref> {{clear}}
== ''Ipso'', ''meso'', and ''peri'' substitution == <gallery class="skin-invert-image"> Image:Ipso Substitution V.3.svg|''ipso''- substitution. Image:Meso Substitution V.1.svg|''meso''- substitution. Image:Peri Substitution V.1.svg|''peri''- substitution. </gallery> * '''''Ipso''-substitution''' describes two substituents sharing the same ring position in an intermediate compound in an electrophilic aromatic substitution. Trimethylsilyl, ''tert''-butyl, and isopropyl groups can form stable carbocations, 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.{{citation needed|date=June 2020}}
== ''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.<ref>{{GoldBookRef | title = cine-substitution | file= C01081}}</ref> * '''''Tele''-substitution''' occurs when the new position is more than one atom away on the ring.<ref>{{GoldBookRef | title = tele-substitution | file = T06256}}</ref>
== Etymology == 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.<ref>Wilhelm Körner (1867) [https://www.biodiversitylibrary.org/item/28090#page/176/mode/1up "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''-.)</ref><ref>Hermann von Fehling, ed., ''Neues Handwörterbuch der Chemie'' [New concise dictionary of chemistry] (Braunschweig, Germany: Friedrich Vieweg und Sohn, 1874), vol. 1, [https://books.google.com/books?id=X_gfAQAAMAAJ&pg=PA1142 p. 1142.]</ref> 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).<ref>Graebe (1869) [http://babel.hathitrust.org/cgi/pt?id=uva.x002457978;view=1up;seq=32 "Ueber die Constitution des Naphthalins"] (On the structure of naphthalene), ''Annalen der Chemie und Pharmacie'', '''149''' : 20-28; see especially p. 26.</ref> In 1870, the German chemist Viktor Meyer first applied Gräbe's nomenclature to benzene.<ref>Victor Meyer (1870) [http://babel.hathitrust.org/cgi/pt?id=njp.32101044011672;view=1up;seq=649 "Untersuchungen über die Constitution der zweifach-substituirten Benzole"] (Investigations into the structure of di-substituted benzenes), ''Annalen der Chemie und Pharmacie'', '''156''' : 265-301; see especially pp. 299-300.</ref> The current nomenclature was introduced by the Chemical Society in 1879.<ref>William B. Jensen (March 2006) "The origins of the ''ortho''-, ''meta''-, and ''para''- prefixes in chemical nomenclature," ''Journal of Chemical Education'', '''83''' (3) : 356.</ref> <!-- to be incorporated with the above The German version of this page provides the following details. The substitution pattern names come from the Greek prefixes ortho (from ὀρθός meaning "upright" or "even"), meta (from μετά meaning "after", "beyond") and para (from παρά meaning "beside", "despite", "against [over]"). 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."<ref>{{Citation|title=Substitutionsmuster|date=2017-09-21|url=https://de.wikipedia.org/w/index.php?title=Substitutionsmuster&oldid=169300303|work=Wikipedia|language=de|access-date=2019-10-24}}</ref> -->
==Examples== Examples of the use of this nomenclature are given for isomers of cresol, C<sub>6</sub>H<sub>4</sub>(OH)(CH<sub>3</sub>): <gallery class="skin-invert-image"> File:Ortho-cresol-2D-skeletal.png|''o''-cresol File:Meta-cresol-2D-skeletal.png|''m''-cresol File:Para-cresol-vertical-2D-skeletal.png|''p''-cresol </gallery>
There are three arene substitution isomers of dihydroxybenzene (C<sub>6</sub>H<sub>4</sub>(OH)<sub>2</sub>) – the ''ortho'' isomer catechol, the ''meta'' isomer resorcinol, and the ''para'' isomer hydroquinone: <gallery class="skin-invert-image"> File:Pyrocatechol.svg|catechol File:Resorcin.svg|resorcinol File:Hydrochinon.svg|hydroquinone </gallery>
There are three arene substitution isomers of benzenedicarboxylic acid (C<sub>6</sub>H<sub>4</sub>(COOH)<sub>2</sub>) – the ''ortho'' isomer phthalic acid, the ''meta'' isomer isophthalic acid, and the ''para'' isomer terephthalic acid:
<gallery class="skin-invert-image"> File:Phthalsäure.svg|phthalic acid File:Isophthalsäure.svg|isophthalic acid File:Terephthalsäure.svg|terephthalic acid </gallery>
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.
<gallery class="skin-invert-image"> File:Niacin structure.svg|niacin File:Nicotinamid.svg|nicotinamide File:Pralidoxime-2D-skeletal.png|pralidoxime </gallery>
== See also == * Descriptor (chemistry) * Isomer * Structural isomerism
== References == {{Reflist}} {{Navbox stereochemistry}}
Category:Aromatic compounds Category:Chemical nomenclature