Product Code Database
Thiophene is a heterocyclic compound with the formula C4H4S. Consisting of a planar five-membered ring, it is aromaticity as indicated by its extensive substitution reactions. It is a colorless liquid with a benzene-like odor. In most of its reactions, it resembles benzene. Compounds analogous to thiophene include furan (C4H4O), selenophene (C4H4Se) and pyrrole (C4H4NH), which each vary by the heteroatom in the ring.
Thiophene and especially its derivatives occur in petroleum, sometimes in concentrations up to 1–3%. The thiophenic content of Petroleum and coal is removed via the hydrodesulfurization (HDS) process.
Thiophene is produced on a modest scale of around 2,000 metric tons per year worldwide. Production involves the vapor phase reaction of a sulfur source, typically carbon disulfide, and a C-4 source, typically n-Butanol. These reagents are contacted with an oxide catalyst at 500–550 °C..
The molecule is flat; the bond angle at the sulfur is around 93°, the C–C–S angle is around 109°, and the other two carbons have a bond angle around 114°.Cambridge Structural Database The C–C bonds to the carbons adjacent to the sulfur are about 1.34 Å, the C–S bond length is around 1.70 Å, and the other C–C bond is about 1.41 Å.
In the minor reaction pathway, a Prilezhaev epoxidation results in the formation of thiophene-2,3-epoxide that rapidly rearranges to the isomer thiophene-2-one. Trapping experiments
Oxidation of thiophenes may be relevant to the metabolic activation of various thiophene-containing drugs, such as tienilic acid and the investigational anticancer drug OSI-930.
Chloromethylation and chloroethylation occur readily at the 2,5-positions. Reduction of the chloromethyl product gives 2-methylthiophene. Hydrolysis followed by dehydration of the chloroethyl species gives 2-vinylthiophene.
Polythiophene itself has poor processing properties and so is little studied. More useful are polymers derived from thiophenes substituted at the 3- and 3- and 4- positions, such as EDOT (ethylenedioxythiophene). Polythiophenes become electrically conductive upon partial oxidation, i.e. they obtain some of the characteristics typically observed in metals.
Reactivity
Thiophene is considered to be aromatic, although theoretical calculations suggest that the degree of aromaticity is less than that of benzene. The "electron pairs" on sulfur are significantly delocalized in the pi electron system. As a consequence of its aromaticity, thiophene does not exhibit the properties seen for conventional thioether. For example, the sulfur atom resists alkylation and oxidation.
Oxidation
Oxidation can occur both at sulfur, giving a thiophene S-oxide, as well as at the 2,3-double bond, giving the thiophene 2,3-epoxide, followed by subsequent NIH shift rearrangement. Oxidation of thiophene by trifluoroperacetic acid also demonstrates both reaction pathways. The major pathway forms the S-oxide as an intermediate, which undergoes subsequent Diels-Alder-type dimerisation and further oxidation, forming a mixture of sulfoxide and sulfone products with a combined yield of 83% (based on NMR evidence):
(2025). 9781891389313, University Science Books. ISBN 9781891389313 demonstrate that this pathway is not a side reaction from the S-oxide intermediate, while isotopic labeling with deuterium confirm that a 1,2-hydride shift occurs and thus that a cationic intermediate is involved. If the reaction mixture is not anhydrous, this minor reaction pathway is suppressed as water acts as a competing base.
Alkylation
Although the sulfur atom is relatively unreactive, the flanking carbon centers, the 2- and 5-positions, are highly susceptible to attack by . Halogens give initially 2-halo derivatives followed by 2,5-dihalothiophenes; perhalogenation is easily accomplished to give C4X4S (X = Cl, Br, I). Thiophene brominates 107 times faster than does benzene. Acetylation occurs readily to give 2-acetylthiophene, precursor to thiophene-2-carboxylic acid and thiophene-2-acetic acid.
Desulfurization
Desulfurization of thiophene with Raney nickel affords butane. When coupled with the easy 2,5-difunctionalization of thiophene, desulfurization provides a route to 1,4-disubstituted butanes.
Polymerization
The polymer formed by linking thiophene through its 2,5 positions is called polythiophene. Polymerization is conducted by oxidation using electrochemical methods (electropolymerization) or electron-transfer reagents. An idealized equation is shown:
Coordination chemistry
Thiophene exhibits little sulfide-like character, but it does serve as a pi-ligand forming piano stool complexes such as Cr( η5-C4H4S)(CO)3.Rauchfuss, T. B., "The Coordination Chemistry of Thiophenes", Progress in Inorganic Chemistry 1991, volume 39, pp. 259-311.
Thiophene derivatives
Thienyl
Upon deprotonation, thiophene converts to the thienyl group, C4H3S−. Although the anion per se does not exist, the organolithium derivatives do. Thus reaction of thiophene with butyl lithium gives 2-lithiothiophene, also called 2-thienyllithium. This reagent reacts with electrophiles to give thienyl derivatives, such as the thiol. Oxidation of thienyllithium gives 2,2'-dithienyl, (C4H3S)2. Thienyl lithium is employed in the preparation of higher order mixed cuprates. Coupling of thienyl anion equivalents gives dithienyl, an analogue of biphenyl.
Ring-fused thiophenes
Fusion of thiophene with a benzene ring gives benzothiophene. Fusion with two benzene rings gives either dibenzothiophene (DBT) or naphthothiophene. Fusion of a pair of thiophene rings gives isomers of thienothiophene.
Uses
Thiophenes are important heterocyclic compounds that are widely used as building blocks in many agrochemicals and pharmaceuticals. The benzene ring of a biologically active compound may often be replaced by a thiophene without loss of activity. This is seen in examples such as the NSAID lornoxicam, the thiophene analog of piroxicam, and sufentanil, the thiophene analog of fentanyl.
External links
|
|
