The alder ene reaction occurs between an enophile and an alkene, given that an alpha
hydrogen is available on the alkene.
In an alkene, the σ-bond of H-C can interact with the π bond in one of two ways: σ+π or σ-π. In the latter case, the phases of the orbitals corresponds favourably to those of the enophile π*
orbital, allowing for sufficient overlap and thus allowing the reaction to occur.
The reaction breaks the H-C σ bond, establishing two new σ bonds, as well as a new π bond. Due to the initial need to break the strong C-H σ bond, however, high temperatures are required for this reaction to occur.
Diels-Alder Reaction:[1,3]
Similar to the Alder-Ene reaction, Diels-Alder reactions occur between a diene and a dienophile. In the case of benzyne, the dienophile, reactions yield polycyclic species with an aromatic component;
it is mainly for this reason that the Diels-Alder reaction is of such great importance to benzyne
chemistry.
In the Diels-Alder reaction, the sp2 hybrid bond of benzyne orientates itself to interact favourable with the π orbital of the diene. The reaction then occurs via a concerted, cyclic mechanism,
breaking two π bonds and producing two σ bonds.
The orientation of attack of this reaction leads to a stereospecific reaction. This, coupled to the addition of an aromatic component, has made Diels-Alder reactions amongst the most important reactions for drug design and natural product synthesis. Below are a few reactions for production of important pharmaceuticals [3]
Some other drugs synthesised via the Diels-Alder mechanism include:
Nucleophilic Addition[3]:
Amongst the simplest reactions underwent by benzyne is a simple nucleophilic addition reaction. In these reactions, nucleophiles (or electrophiles) attach benzyne, joining at either end of the triple bond (directed by steric effects). Contrary to normal aromatic additions, the addition of this first substitutent does not play a role in directing the addition of the second
substitutent; two substituents will always be added ortho to each other on the ring.
This has substantial importance in areas such as
- synthesis of strained ring systems:
- insertion of new c-c bonds:
- Synthesis of Substituted Indoles:
- Drug synthesis: eg Dynemicin A.
Carbon Nanotubes:
Benzyne has also been found to play a substantial role in modern nanotube and grephene research.
Gilchrist, et al. (1969)[4] demonstrated the use of benzyne as a me
thod for the nucleation and growth of carbon nanotubes, making use mainly of Kobayashi prot
ocol for benzyne generation. Others, such as Hoke et al. (1992)[5] used benzyne as a method via which to attach substituent groups to fullerenes, as well as a method via which to polymerise fullerenes.
Currently, the most important function of benzyne in nanotube research is as a 'tooth', allowing a mechanism to polymerise nanotubes, creating vast networks. Such networks have been vital in modern advances in technology (such as microchip production), water filters (graphene oxide filters), as well as much more![6, 7]
[6]
References:
[1] Clayden, J, et al (2001) Organic Chemistry, 1st ed. Oxford University Press, New York, USA
[2] Organic Chemistry Portal. Accessed 6 Feb. 2012, Available from: http://www.organic-chemistry.org/namedreactions/alder-ene-reaction.shtm
[3] Tadross, P. (2006) Benzyne, The Adventures of a Reactive Intermediate. Stoltz Group Literature Presentaiton
[4] Gilchrist, T. and Rees, C. (1969) Carbenes, Nitrenes and Arynes., Nelson. London.
[5] Hoke, S., Molstad, J. Dilettato, D., Jay, M., Carlson, D., Kahr, B and Cooks, R. (1992), Jornal of Organic Chemistry, Vol 57, pp 5096.
[6] Globus, A., Bauschlicher, C., Han, J., Jaffe, R., Levit, C and Srivastave, D. (1998) Machine Phase Fullerene Nanotechnology, Nanotechnology, Vol. 9, pp 192-199.
[7]Deng, W., Xu, X., Goddard, W (2004) A Two Stage Mechanism of Bimetallic Catalyzed Growth of Single Walled Carbon Nanotubes, Nano letters Vol 4, No. 12, 2331-2335
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