Thiophene

Thiophene

• Thiophene is a heterocyclic compound with the formula C4H4S, consisting of a flat five-membered ring.
• It is aromatic, as indicated by its extensive substitution reactions.

Properties of Thiophene

• At room temperature, thiophene is a colorless liquid with a mildly pleasant odor reminiscent of benzene.
• Its boiling point is 84°C.
• It is insoluble in water but freely soluble in ethanol, ether, and acetone.
• The high reactivity of thiophene towards sulfonation is the basis for the separation of thiophene from benzene.

Thiophene Aromaticity

• Thiophene has 4C and 1S, all of which are sp2 hybridized.
• sp² hybridization is planar, making a planar thiophene ring structure.
• Each ring atom also contains an unhybridized p orbital that is perpendicular to the plane of σ bonds (plane of ring).
• The total number of non-bonding electrons is 6 (4 from four C, 2 from one S).
• The resonance of 6 electrons follows the Hückel's rule.
• Thiophene is more aromatic than furan due to the less electronegative sulfur atom, which has a greater electron donating tendency.
• The donated electrons take part in delocalization in the ring.

Synthesis of Thiophene

• Commercial method: By reaction of sulphur with n-butane in the gas phase at 650 °C.
• From Acetylene: By passing a mixture of acetylene and hydrogen sulphide through a tube containing aluminium oxide at 600°C.
• Paal-Knorr synthesis: The condensation of 1,4-dicarbonyl compounds with sulfur sources gives thiophene.
• From sod.Succinate: Laboratory synthesis by heating a mix of sod.succinate and phosphorus trisulfide.
• Hinsberg Synthesis: Condensation between a 1,2-dicarbonyl compound and diethyl thiodiacetate in the presence of a strong base gives thiophene 2,5- diacids (-diketone).

Reactions of Thiophene

• Electrophilic substitution: Thiophene is more easily substituted than benzene but less vigorously than furan and pyrrole.
• The new substituent usually enters on the 2-position. If the 2-positions are occupied, then on the 3-position.
• Thiophene undergoes electrophilic substitution reaction at 2nd position due to two reasons: C2 attack gives more resonance contributing structures than C3, and an extra stable contributing structure generates upon C2 attack.
• Very strongly acidic conditions lead to acid-catalyzed polymerization.
• The action of hot phosphoric acid on thiophene leads to a trimer.
• Friedel-crafts acylation and Chloromethylation reactions are possible.
• Reaction with organolithium or 2- lithiumthiophene is also possible.
• Reduction: Partial reduction in acidic media, but thiophene cannot be reduced under the same conditions as in furan due to sulfur poisoning the catalyst and desulphurization occurs with ring opening.

Medical uses of Thiophene

• Sitaxsentan: Cardiovascular Agent, used in pulmonary artery hypertension.
• Tiagabine: Anticonvulsant Agent, used in the treatment of epilepsy.
• Cephalothin: New semisynthetic antibacterial agent structurally related to Pencillins, effective against penicillinase-producing staphylococci as well as other gram-positive and gram-negative organisms.