Isomer

This article is about the chemical concept. For "isomerism" of atomic nuclei, see nuclear isomer.

In chemistry, isomers (from Greek ἰσομερής, isomerès; isos = "equal", méros = "part") are compounds with the same molecular formula but different structural formulas.^[1] Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical isomers, etc. (see chart below). There are two main forms of isomerism: structural isomerism and stereoisomerism (spatial isomerism).

Forms

Structural isomers

Main article: Structural isomer

The different types of isomers, including position isomers 2-fluoropropane and 1-fluoropropane on the left

In structural isomers, sometimes referred to as constitutional isomers, the atoms and functional groups are joined together in different ways. Structural isomers have different IUPAC names and may or may not belong to the same functional group.^[2] This group includes chain isomerism whereby hydrocarbon chains have variable amounts of branching; position isomerism which deals with the position of a functional group on a chain; and functional group isomerism in which one functional group is split up into different ones.

For example, two position isomers would be 2-fluoropropane and 1-fluoropropane, illustrated on the right.

In skeletal isomers the main carbon chain is different between the two isomers. This type of isomerism is most identifiable in secondary and tertiary alcohol isomers.

Tautomers are structural isomers of the same chemical substance that spontaneously interconvert with each other, even when pure. They have different chemical properties, and consequently, distinct reactions characteristic to each form are observed. If the interconversion reaction is fast enough, tautomers cannot be isolated from each other. An example is when they differ by the position of a proton, such as in keto/enol tautomerism, where the proton is alternately on the carbon or oxygen.

Stereoisomers

Main article: Stereoisomerism

In stereoisomers the bond structure is the same, but the geometrical positioning of atoms and functional groups in space differs. This class includes enantiomers where different isomers are non-superimposable mirror-images of each other, and diastereomers when they are not.

Diastereomerism is again subdivided into "cis-trans isomers", which have restricted rotation within the molecule (typically isomers containing a double bond) and "conformational isomers" (conformers), which can rotate about one or more single bonds within the molecule.

An obsolete term for "cis-trans isomerism" is "geometric isomers". ^[3]
For compounds with more than two substituents E-Z notation is used instead of cis and trans. If possible, E and Z (written in italic type) is also preferred in compounds with two substituents. ^[4]

In octahedral coordination compounds, facial-meridional isomerism occurs. The isomers can be fac- (with facial ligands) or mer- (with meridional ligands).

Note that although conformers can be referred to as stereoisomers, they are not stable isomers, since bonds in conformers can easily rotate thus converting one conformer to another which can be either diastereomeric or enantiomeric to the original one.

While structural isomers typically have different chemical properties, stereoisomers behave identically in most chemical reactions, except in their reaction with other stereoisomers. Enzymes however can distinguish between different enantiomers of a compound, and organisms often prefer one isomer over the other. Some stereoisomers also differ in the way they rotate polarized light.

Isomerisation

Isomerisation is the process by which one molecule is transformed into another molecule which has exactly the same atoms, but the atoms are rearranged^[5]. In some molecules and under some conditions, isomerisation occurs spontaneously. Many isomers are equal or roughly equal in bond energy, and so exist in roughly equal amounts, provided that they can interconvert relatively freely, that is the energy barrier between the two isomers is not too high. When the isomerisation occurs intramolecularly it is considered a rearrangement reaction.

An example of an organometallic isomerisation is the production of decaphenylferrocene, [(η⁵-C₅Ph₅)₂Fe] from its linkage isomer.^[6][7]

Instances of Isomerization

• Isomerizations in hydrocarbon cracking. This is usually employed in organic chemistry, where fuels, such as pentane, a straight-chain isomer, are heated in the presence of a platinum catalyst. The resulting mixture of straight- and branched-chain isomers then have to be separated. An industrial process is also the isomerisation of n-butane into isobutane.

• Trans-cis isomerism. In certain compounds an interconversion of cis and trans isomers can be observed, for instance, with maleic acid and with azobenzene often by photoisomerization. Another example is the photochemical conversion of the trans isomer to the cis isomer of resveratrol ^[8]:

• Aldose-ketose isomerism in biochemistry.
• Isomerisations between conformational isomers. These take place without an actual rearrangement for instance inconversion of two cyclohexane conformations
• Fluxional molecules display rapid interconversion of isomers e.g. Bullvalene.
• valence isomerisation: the isomerisation of molecules which involve structural changes resulting only from a relocation of single and double bonds. If a dynamic equilibrium is established between the two isomers it is also referred to as valence tautomerism ^[9]

The energy difference between two isomers is called isomerisation energy. Isomerisations with low energy difference both experimental and computational (in parentheses) are endothermic trans-cis isomerisation of 2-butene with 2.6 (1.2) kcal/mol, cracking of isopentane to n-pentane with 3.6 (4.0) kcal/mol or conversion of trans-2-butene to 1-butene with 2.6 (2.4) kcal/mol.^[10]

Examples

Propanol

A simple example of isomerism is given by propanol: it has the formula C₃H₈O (or C₃H₇OH) and occurs as two isomers: propan-1-ol (n-propyl alcohol; I) and propan-2-ol (isopropyl alcohol; II)

Note that the position of the oxygen atom differs between the two: it is attached to an end carbon in the first isomer, and to the center carbon in the second.

There is, however, another isomer of C₃H₈O which has significantly different properties: methoxyethane (methyl-ethyl-ether; III). Unlike the isomers of propanol, methoxyethane has an oxygen connected to two carbons rather than to one carbon and one hydrogen. This makes it an ether, not an alcohol, as it lacks a hydroxyl group, and has chemical properties more similar to other ethers than to either of the above alcohol isomers.

Examples of isomers having different medical properties can be easily found. For example, in the placement of methyl groups. In substituted xanthines, Theobromine, found in chocolate, is a vasodilator with some effects in common with caffeine, but if one of the two methyl groups is moved to a different position on the two-ring core, the isomer is theophylline, which has a variety of effects, including bronchodilation and anti-inflammatory action. Another example of this occurs in the phenethylamine-based stimulant drugs. Phentermine is a non-chiral compound with a weaker effect than amphetamine. It is used as an appetite reducing medication and has mild or no stimulant properties. However, a different atomic arrangement gives dextromethamphetamine which is a stronger stimulant than amphetamine.

Allene and propyne are examples of isomers containing different bond types. Allene contains two double bonds, whereas propyne contains one triple bond.

Synthesis of fumaric acid

Industrial synthesis of fumaric acid proceeds via the cis-trans isomerization of maleic acid:

In medicinal chemistry and biochemistry, enantiomers are a special concern because they may possess quite different biological activity. The infamous case of thalidomide arose from the effects of the unwanted enantiomer. Many preparative procedure afford a mixture of equal amounts of both enantiomeric forms. In some cases, the enantiomers are separated by chromatography using chiral stationary phases. In other cases, enantioselective syntheses have been developed.

History

Isomerism was first noticed in 1827, when Friedrich Woehler prepared cyanic acid and noted that although its elemental composition was identical to fulminic acid (prepared by Justus von Liebig the previous year), its properties were quite different. This finding challenged the prevailing chemical understanding of the time, which held that chemical compounds could be different only when they had different elemental compositions. After additional discoveries of the same sort were made, such as Woehler's 1828 discovery that urea had the same atomic composition as the chemically distinct ammonium cyanate, Jöns Jakob Berzelius introduced the term isomerism in 1830 to describe the phenomenon.^[11]

In 1848, Louis Pasteur separated tiny crystals of tartaric acid into their two mirror-image forms.^[12][13] The individual molecules of each were the left and right optical stereoisomers, solutions of which rotate the plane of polarized light to the same degree but in opposite directions.

Other types of isomerism

Other types of isomerism exist outside this scope. Topological isomers called topoisomers are generally large molecules that wind about and form different shaped knots or loops. Molecules with topoisomers include catenanes and DNA. Topoisomerase enzymes can knot DNA and thus change its topology. There are also isotopomers or isotopic isomers that have the same numbers of each type of isotopic substitution but in chemically different positions. In nuclear physics, nuclear isomers are excited states of atomic nuclei. Spin isomers have differing distributions of spin among their constituent atoms.

See also

• Nuclear isomer
• Chirality (chemistry)
• Structural isomerism
• Cis-trans isomerism
• Cyclohexane conformation
• Electromerism

References

1. ^ The word “isomer” was coined by Swedish chemist Jöns Jacob Berzelius (1779-1848) in 1830. See: Jac. Berzelius (1830) “Om sammansättningen af vinsyra och drufsyra (John’s säure aus den Voghesen), om blyoxidens atomvigt, samt allmänna anmärkningar om sådana kroppar som hafva lika sammansättning, men skiljaktiga egenskaper” (On the composition of tartaric acid and racemic acid (John's acid of the Vosges), on the molecular weight of lead oxide, together with general observations on those bodies that have the same composition but different properties) Kongliga Svenska Vetenskaps Academiens Handling (Transactions of the Royal Swedish Science Academy), vol. 49, pages 49–80; see especially page 70. Reprinted in German in: J.J. Berzelius (1831) “Über die Zusammensetzung der Weinsäure und Traubensäure (John's säure aus den Voghesen), über das Atomengewicht des Bleioxyds, nebst allgemeinen Bemerkungen über solche Körper, die gleiche Zusammensetzung, aber ungleiche Eigenschaften besitzen," Annalen der Physik und Chemie, vol. 19, pages 305–335; see especially page 326. Reprinted in French in: J.J. Berzelius (1831) “Composition de l’acide tartarique et de l’acide racémique (traubensäure); poids atomique de l’oxide de plomb, et remarques générals sur les corps qui ont la même composition, et possèdent des proprietés différentes,” Annales de Chimie et de Physique, vol. 46, pages 113–147; see especially page 136.
2. ^ Smith, Janice Gorzynski. General, Organic and Biological Chemistry. The McGraw-Hill Companies. 1st ed 2010. pg. 450
3. ^ IUPAC definition of geometric isomerism
4. ^ IUPAC definition of cis and trans
5. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "isomerization".
6. ^ Brown, K. N.; Field, L. D.; Lay, P. A.; Lindall, C. M.; Masters, A. F. (1990). "(η⁵-Pentaphenylcyclopentadienyl){1-(η⁶-phenyl)-2,3,4,5-tetraphenylcyclopentadienyl}iron(II), [Fe(η⁵-C₅Ph₅){(η⁶-C₆H₅)C₅Ph₄}], a linkage isomer of decaphenylferrocene". J. Chem. Soc., Chem. Commun. (5): 408–410. doi:10.1039/C39900000408. 
7. ^ Field, L. D.; Hambley, T. W.; Humphrey, P. A.; Lindall, C. M.; Gainsford, G. J.; Masters, A. F.; Stpierre, T. G.; Webb, J. (1995). "Decaphenylferrocene". Aust. J. Chem. 48 (4): 851–860. doi:10.1071/CH9950851. 
8. ^ Resveratrol Photoisomerization: An Integrative Guided-Inquiry Experiment Elyse Bernard, Philip Britz-McKibbin, Nicholas Gernigon Vol. 84 No. 7 July 2007 Journal of Chemical Education 1159
9. ^ cartage.org.lb
10. ^ How to Compute Isomerization Energies of Organic Molecules with Quantum Chemical Methods Stefan Grimme, Marc Steinmetz, and Martin Korth J. Org. Chem.; 2007; 72(6) pp 2118 - 2126; (Article) doi:10.1021/jo062446p
11. ^ Esteban, Soledad. (2008). "Liebig–Wöhler Controversy and the Concept of Isomerism". J. Chem. Educ. 85 (9): 1201. doi:10.1021/ed085p1201. http://jchemed.chem.wisc.edu/Journal/Issues/2008/Sep/abs1201.html. 
12. ^ L. Pasteur (1848) "Mémoire sur la relation qui peut exister entre la forme cristalline et la composition chimique, et sur la cause de la polarisation rotatoire" (Memoir on the relationship which can exist between crystalline form and chemical composition, and on the cause of rotary polarization)," Comptes rendus de l'Académie des sciences (Paris), vol. 26, pages 535–538.
13. ^ L. Pasteur (1848) "Sur les relations qui peuvent exister entre la forme cristalline, la composition chimique et le sens de la polarisation rotatoire" (On the relations that can exist between crystalline form, and chemical composition, and the sense of rotary polarization), Annales de Chimie et de Physique, 3rd series, vol. 24, no. 6, pages 442–459.

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