Thiophene

At room temperature, thiophene is a colorless liquid with a mildly pleasant odor reminiscent of benzene,^{[citation needed]} with which thiophene shares some similarities. The high reactivity of thiophene toward sulfonation is the basis for the separation of thiophene from benzene, which are difficult to separate by distillation due to their similar boiling points (4 °C difference at ambient pressure). Like benzene, thiophene forms an azeotrope with ethanol.

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°.

In the minor reaction pathway, a Prilezhaev epoxidation^[14] results in the formation of thiophene-2,3-epoxide that rapidly rearranges to the isomer thiophene-2-one.^[12] Trapping experiments^[15] 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.^[12] If the reaction mixture is not anhydrous, this minor reaction pathway is suppressed as water acts as a competing base.^[12]

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.^{[16][17][18][19]}

Alkylation

Although the sulfur atom is relatively unreactive, the flanking carbon centers, the 2- and 5-positions, are highly susceptible to attack by electrophiles. Halogens give initially 2-halo derivatives followed by 2,5-dihalothiophenes; perhalogenation is easily accomplished to give C₄X₄S (X = Cl, Br, I).^[20] 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.^[9]

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.^[21][22]

Desulfurization by Raney nickel

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

n C₄H₄S → (C₄H₂S)_n + 2n H⁺ + 2n e⁻

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.^[23]

Coordination chemistry

Thiophene exhibits little sulfide-like character, but it does serve as a pi-ligand forming

• Some Thiophenes
• 
  Thieno[3,2-b]thiophene, one of the four thienothiophenes
• 
  2,2'-Bithiophene
• 
  3,4-Ethylenedioxythiophene (EDOT), the precursor to commercial antistatic and electrochromic displays
• 
  Benzothiophene

Thienyl

Upon deprotonation, thiophene converts to the thienyl group, C₄H₃S⁻. Although the anion per se does not exist, the

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.