THIOPHENE

Thiophene is a sulfur-containing aromatic heterocyclic compound that serves as a highly versatile building block in organic synthesis, supporting the manufacture of pharmaceuticals, agrochemicals, dyes, specialty chemicals, and performance materials.
Thiophene and its derivatives are widely incorporated into advanced polymer systems, conductive materials, organic semiconductors, coatings, and electronic applications because their aromatic structure can contribute to favorable chemical and electronic properties.
Thiophene is also an important intermediate for producing structurally diverse compounds, allowing manufacturers and researchers to introduce sulfur-containing functionality into molecules designed for industrial, material-science, and fine-chemical applications.

CAS Number: 110-02-1
EC Number: 203-729-4
Molecular Formula: C4H4S
Molecular Weight: 84.14 g/mol

Synonyms: THIOPHENE, 110-02-1, Thiofuran, Thiole, Thiophen, Thiotetrole, Thiacyclopentadiene, Thiofurfuran, Divinylene sulfide, Thiaphene, Thiofuram, Furan, thio-, Huile HSO, Thiofen, Huile H50, CP 34, USAF EK-1860, CCRIS 2935, HSDB 130, NSC 405073, DTXSID8026145, UNII-SMB37IQ40B, EINECS 203-729-4, SMB37IQ40B, BRN 0103222, AI3-15417, NSC-405073, DTXCID006145, CHEBI:30856, EC 203-729-4, Divinylene sulphide, RefChem:6305, HUILE HS0, CP34, 203-729-4, C4H4S, MFCD00005413, Hopkin's lactic acid reagent, 51325-05-4, Thiofen [Czech], Thiophenes, UN2414, monothiophene, thio-furan, thiophene-, 2-Thiophene, Thiophene, Reagent, Thiophene, polymers, MFCD26958734, Thiophene [UN2414] [Flammable liquid], Thiophene, >=99%, THIOPHENE [MI], THIOPHENE [HSDB], WLN: T5SJ, SCHEMBL1044, THIOPHENE [WHO-DD], SCHEMBL26419, SCHEMBL50930, SCHEMBL102956, SCHEMBL130803, SCHEMBL189349, SCHEMBL912836, Thiophene, analytical standard, CHEMBL278958, orb3029587, SCHEMBL1395710, SCHEMBL2166079, SCHEMBL5081748, SCHEMBL16820937, PDK0023, Tox21_200002, NSC405073, Thiacyclopentadiene;Divinylene sulfide, AKOS000120157, MSK14147-100M, UN 2414, NCGC00091806-01, NCGC00091806-02, NCGC00257556-01, CAS-110-02-1, Thiophene [UN2414] [Flammable liquid], Thiophene Solution in Methanol, 100ug/mL, DB-038045, NS00009124, EN300-19105, poly(thiophene-2,5-diyl), bromine terminated, F032744, InChI=1/C4H4S/c1-2-4-5-3-1/h1-4, Q305364, F0001-0214, 107760-19-0, 103222, [Beilstein], 110-02-1, [RN], 203-729-4, [EINECS], 5-17-01-00297, [Beilstein], Furan, thio-, Thiofen, [Czech], Thiofuran, Thiofurfuran, Thiole, Thiophen, [German], [IUPAC name – generated by ACD/Name], Thiophene, [Wiki] , [IUPAC name – generated by ACD/Name], [Index name – generated by ACD/Name], Thiophène, [French], [IUPAC name – generated by ACD/Name], Thiophene [UN2414] [Flammable liquid], Unverified, 2,5-Dideuteriothiophene, 203-729-4MFCD00005413, 2036-39-7, [RN], 2041-42-1, [RN], 99%, Dibenzothiophene, [USAN], Divinylene sulfide, EINECS 203-729-4, including dithienyl., Poly(thiophene-2,5-diyl), POLY(THIOPHENE-2,5-DIYL), BR TERMINATED, T5SJ, [WLN], Thiacyclopentadiene, Thiaphene, Thio-Furan, Thiofen, Thiofuram, Thiophene-2,5-d2, Thiophene-d4, THIOTETROLE, 噻吩, [Chinese]

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

Thiophene is a colorless liquid with a benzene-like odor.
In most of its reactions, Thiophene resembles benzene.
Compounds analogous to thiophene include furan (C4H4O), selenophene (C4H4Se) and pyrrole (C4H4NH), which each vary by the heteroatom in the ring.

Thiophene is one of the most representative five-membered sulfur-containing aromatic heterocycles.
Thiophene is both a classical scaffold in organic synthesis and a high-frequency structural unit in medicinal chemistry, functional materials, conductive polymers, and sensor research.

Thiophene was identified by Viktor Meyer in the early 1880s in coal-tar benzene-related systems; in 1883, Thiophene was isolated from coal-tar benzene and entered systematic study.
Today, thiophene has become a highly representative sulfur-containing aromatic heterocyclic scaffold in organic synthesis, medicinal chemistry, and organic electronic materials.

Thiophene is a five-membered heteroaromatic ring with the molecular formula C4H4S and can be understood as a monocyclic heteroaromatic hydrocarbon formed by replacing the oxygen in furan with sulfur.
Structurally, the thiophene ring consists of 4 carbon atoms + 1 sulfur atom.
Thiophene is not an ordinary saturated five-membered ring, but rather a planar, conjugated, aromatic ring system; this allows it to retain the stability of an aromatic system while also making it more prone than benzene to electrophilic aromatic substitution.

Thiophene appears as a colorless liquid with an unpleasant odor.
Thiophene is a monocyclic heteroarene that is furan in which the oxygen atom is replaced by a sulfur.

Thiophene has a role as a non-polar solvent.
Thiophene is a volatile organic compound, a member of thiophenes, a mancude organic heteromonocyclic parent and a monocyclic heteroarene.
Thiophene is a metabolite found in or produced by Saccharomyces cerevisiae.

Thiophene is a versatile heterocyclic compound characterized by its five-membered ring structure containing four carbon atoms and one sulfur atom.
This unique configuration imparts distinct electronic properties, making thiophene a valuable building block in organic synthesis and materials science.

Thiophene is widely recognized for its role in the production of conductive polymers, pharmaceuticals, and agrochemicals.
Researchers often utilize thiophene derivatives in the development of organic light-emitting diodes (OLEDs) and solar cells due to their excellent charge transport properties and stability.
Additionally, thiophene is employed in the synthesis of various fine chemicals and intermediates, enhancing its relevance in both industrial and academic settings.

Thiophene's ability to undergo various chemical reactions, such as electrophilic substitution and polymerization, further expands its application potential.
With its favorable properties, thiophene stands out among similar compounds, offering researchers and industry professionals a reliable option for innovative applications in electronics, materials, and chemical synthesis.

Thiophene is an aromatic heterocyclic compound with molecular formula C₄H₄S — a planar five-membered ring composed of four carbon atoms and one sulphur atom, the simplest member of its family.
Like benzene, thiophene hosts a delocalised π-electron cloud (six π electrons, Hückel's rule) with a resonance energy of roughly 20 kcal/mol, granting it full aromaticity and benzene-like reactivity.

Thiophene is an aromatic heterocyclic compound consisting of four carbon atoms and one sulfur atom in a five-membered ring.
Compounds analogous to thiophene include furan and pyrrole where the S atom is replaced by O and NH, respectively.

Thiophene was discovered by Viktor Meyer in 1883 as a contaminant in benzene.
Related to thiophene are benzothiophene and dibenzothiophene, containing the thiophene ring fused with one and two benzene rings, respectively.

Thiophene is defined as a planar five-membered heterocyclic compound with the molecular formula C4H4S, containing four carbon atoms and one sulfur atom as a heteroatom.
Thiophene appears as a colorless liquid with a benzene-like odor.

Thiophene is a five-membered aromatic heterocyclic compound containing one sulfur atom in its ring structure.
Thiophene is widely used as an intermediate in pharmaceuticals, agrochemicals, dyes, polymers, and specialty chemical synthesis.
Thiophene derivatives are valued for their aromatic stability, versatile reactivity, and important role in the production of advanced organic and electronic materials.

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.

Heterocyclic compound:
Thiophene is five-member heterocyclic compounds containing a sulfur atom and is presented at coal tar crude benzene at small amounts.
Thiophene is a kind of colorless liquid having similar order as benzene aromatic with the boiling point being 84 °C.

Thiophene is insoluble in water, and can be mixed with ethanol, ethyl ether, acetone, benzene, carbon tetrachloride, heptane, pyridine, and 1,4-dioxane.
Thiophene is flammable, and has a high heat resistance without being decomposed when being heated to 850 °C.

Thiophene is not polymerized under acidic conditions, nor does it be decomposed and be susceptible to oxidation.
Thiophene also has moderate toxicity.

The 5 atoms in thiophene ring belong to sp2 hybrid and located in the same plane.
The occupied p-orbital of a pair of non-sharing electrons in the sulfur atom is parallel and overlapped with that of occupies the 4 carbon atoms which form 5 atoms/6 electrons closing conjugated system and thus having aromaticity.

Thiophene is more prone to have electrophilic substitution reaction than benzene with electrophilic substitution mainly occurring in α-position (2-position or 5-position).
An important derivative of thiophene is biotin which can have sulfonation reaction with concentrated sulfuric acid at room temperature with producing 2-thiophene acid which can be dissolved in sulfuric acid.

Thereby, people often use this method to remove the thiophene in the crude benzene.
Thiophene can be used in the production of various kinds of dyes, perfumes, thermal shock resistant plastic, highly active solvent, stimulating hormone, insecticide, brightening agents, cosmetics and bio-activating substances and vitamins, anesthetics and antibiotics.

Thiophene can also be used as the raw materials of preparing a broad spectrum anthelmintic pyrantel as well as antibacterial drugs cephalosporin I and II.
Moreover, Thiophene can be used for further preparation of solvents such as sulfolane.
Using chemical or electrochemical method can enable the synthesis of polythiophene, and having a conductivity of 2~10.6 × 103S/m after doping, and thus is a kind of conductive polymer materials of potential application.

Benzol Refining Products:
Although thiophene is able to be chemically synthesized, the cost is too high.
Thiophene is presented inside both shale oil and coal tar.

The waste acid of crude benzol fraction resulted from the coal tar washed by concentrated sulfuric acid can be used as raw materials.
Thiophene first undergoes hydrolysis in 110~150 °C, and then separated and purified to obtain thiophene.

Thiophene is mainly presented in light benzene purified from the pre-rectification of crude benzene.
When the light benzene was refined by adding hydrogen, thiophene is destroyed.

When using light benzene acid for refining it, most of thiophene is polymerized with unsaturated compounds into tar-like substance with only a small amount of thiophene taking reaction with sulfuric acid for generating thiophene sulfonic acid which is easily extracted, thus greatly reducing the yield of thiophene.
When using light benzene acid for refining, thiophene is reacted together with sulfuric acid to generate thiophene-sulfonic acid which is dissolved in wasting sulfuric acid, clarify the sulfuric acid, remove the tarry substance, followed by hydrolysis distillation.

The distilled condensed stuff was cooled and separated to obtain the thiophene-containing and benzenoid hydrocarbons-containing distilled crude oil.
The crude distilled oil was neutralized by adding alkaline to be neutral or slightly basic with a distillation column (with theoretical plate number of 30 to 40) for distillation to obtain thiophene product (with thiophene content higher than 90%).

During the rectification process, separate out the middle distilled fraction and reflux it back into the crude oil distillate.
After distilling all the amount of thiophene, people can also distill out product of inter-xylene product (with content being higher than 95%) from the waste residue.

For this method of extraction of thiophene from waste sulfuric acid, thiophene extraction efficiency from crude benzene is low and demanding using hydrolysis distillation equipment with corrosion resistant materials.
In order to increase the extraction efficiency of thiophene, many countries are studying new ways of thiophene extraction method from crude benzene, from which the relative successful method is extraction & rectification extraction method for thiophene (ER method).

The approach is adding a suitable extraction agent to thiophene containing benzene in order to increase the relative volatility between benzene and thiophene in order to separate out the thiophene from rectification.
In many kinds of extracting agents, α-pyrrolidone and N-methylpyrrolidone (NMP) have a strong dissolving ability to although this extraction agent is only with moderate selectivity.

Uses of Thiophene:
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.
Thiophene is used as a solvent, chemical intermediate, and monomer to make copolymers.

Thiophene is used not only for the synthesis of cephalosporin drugs, but also for the production of dyes, synthetic resins, solvents, etc.
Thiophene is used for making drugs and plasticizers; thiophene is an important organic chemical raw material which has broad range of applications.

Thiophene is mainly used for dyes, medicines and resins.
Thiophene can be used for synthesis of new broad-spectrum cephalosporin antibiotic, and is an important pharmaceutical and chemical additive.

Thiophene can also be applied for the manufacture of color films and trick photography and synthesizing a complicated reagent used for the extraction and separation of uranium and other metals.
Thiophene is used as the raw material and a plasticizer of medicine, dyes, and plastics.

Thiophene is mainly used as the intermediates of pharmaceutical industry used for preparing thiophene acetic pyridine, and pyrantel.
Thiophene can also been used as a raw material for synthesizing resin and dye industry.

Thiophene is also be used as an organic solvent.
As a chemical reagent, Thiophene is used as a standard reagent for chromatography analysis.

Thiophene is used as a solvent, standard reference agent for chromatography analysis, and also for organic synthesis.
Thiophene can be used for the manufacture of dyes, pharmaceuticals and resin

Thiophene is used for the synthesis of new broad-spectrum cephalosporin antibiotics.
Thiophene is uused for the manufacture of color films and trick photography; used for the synthesis of some complex reagent.
Thiophene is an important intermediate in the synthesis of Bakelite and resins.

Thiophene itself is a good dewaxing solvents and paint cleaners.
The derivatives of thiophene have a variety of pharmacological activities.

There are a variety of thiophene-azo dyes with excellent performance.
The sulfonylurea derivatives of thiophene are new herbicides of ultra-efficient as well as low toxicity.

Other derivatives can also be used as insecticides, fungicides, and animal and plant growth-promoting agent.
In addition, some derivatives of thiophene are also the component of organic semiconductors.
In short, thiophene and its derivatives have a very important position in the pharmaceutical industry, dye industry, pesticide industry, resin industry, and chemical industry.

Thiophene is used as a building block of various organic molecules and pharmaceuticals providing functional properties.
Thiophene is an important building block in dyes, agrochemicals and pharmaceuticals synthesis.

Thiophene is involved in the chloroalkylation reactions in 2,5-positions.
Thiophene is also used to prepare butane by reduction with raney nickel, 2-vinylthiophene, dithienyl, and 2-halo thiophenes by reacting with halogens.

Thiophene is an essential precursor to synthesize a wide range of conjugated organosulfur moieties, sulfur-containing polycyclic aromatic hydrocarbons, macrocycles, and pharmaceutical compounds.
Thiophene has been widely used in the synthesis of polythiophenes and a host of active materials for organic field effect transistors (OFETs) and organic solar cells (OSCs).

Thiophenes are important heterocyclic compounds and are recurring building blocks in organic chemistry with applications in 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.

Thiophenes are used as synthetic intermediates, taking advantage of the susceptibility of the carbon atoms adjacent to S toward electrophilic reactions.
Desulfurization of the resulting ring using Raney nickel affords 1,4-disubstituted butanes.

The polymer formed by linking thiophene through its 1,5 positions is called polythiophene.
Polythiophenes become electrically conductive upon partial oxidation, i.e. they become "organic metals".

Thiophene is used as a denaturant for ethanol with which it forms an azeotrope.

Structural Features of Thiophene:

Thiophene is a “five-membered sulfur-containing aromatic heterocycle,” not an ordinary thioether ring:
The key point about thiophene is not simply that it “contains sulfur,” but that the sulfur atom is embedded in an aromatic conjugated ring.
Sulfur has two lone pairs of electrons, one of which participates in the aromatic delocalized system, giving the entire ring aromatic character.
This is also the fundamental reason why thiophene behaves so differently from tetrahydrothiophene, ordinary thioethers, and acyclic sulfides.

Thiophene is planar and conjugated, making it well suited as a charge-transport and optoelectronic scaffold:
The planarity and π conjugation of thiophene make it well suited for connection into extended conjugated systems such as bithiophenes, oligothiophenes, and polythiophenes.
For materials researchers, this means that thiophene is not merely “a ring,” but an extendable π-conjugated unit.
This is precisely why thiophene-based materials are so common in organic electronics.

Thiophene's positional reactivity follows clear patterns, making directed modification easier:
Thiophene is commonly divided into α positions (2/5 positions) and β positions (3/4 positions).
In classical electrophilic aromatic substitution, the α positions usually react more readily, so the 2- and 5-positions are often the preferred sites for modification.

In metal-catalyzed C–H functionalization, however, regioselectivity can also be affected by substituents, directing effects, and the catalytic system, so the specific route must be judged together with the reaction type.
This point is highly practical for researchers designing building blocks, because Thiophene directly determines where a new fragment can be attached, how conjugation can be extended, and which position is most likely to be functionalized.

Thiophene combines “aromatic stability” with “tunable electronic properties”:
Compared with benzene, thiophene is still an aromatic ring, but it is usually more reactive toward electrophilic substitution.
Compared with purely carbocyclic aromatic rings used in materials chemistry, the sulfur atom in thiophene also alters molecular polarizability, energy levels, and intermolecular interactions.
This combination of being both stable and tunable is exactly why thiophene is popular in both medicinal and materials chemistry.

Occurence of Thiophene:

Synthesis and occurrence:
Reflecting their high stabilities, thiophenes arise from many reactions involving sulfur sources and hydrocarbons, especially unsaturated ones, e.g. acetylenes and elemental sulfur, which was the first synthesis of thiphene by Viktor Meyer in the year of its discovery.
Thiophenes are classically prepared by the reaction of 1,4-diketones with sulfiding reagents such as Lawesson's reagent or P4S10.
Specialized thiophenes can be synthesized via the Gewald reaction, which involves the condensation of two esters in the presence of elemental sulfur.

Thiophene and its derivatives occur in petroleum, sometimes in concentrations up to 1-3%.
The thiophenic content of liquids from oil and coal is removed via the hydrodesulfurization (HDS) process.

In HDS, the liquid or gaseous feed is passed over a special form of molybdenum disulfide under a pressure of H2.
Thiophenes undergo hydrogenolysis to form hydrocarbons and hydrogen sulfide.

Thus, thiophene itself is converted to butane and H2S.
More prevalent and more problematic in petroleum are benzothiophene and dibenzothiophene.

Isolation and occurrence:
Thiophene was discovered by Viktor Meyer in 1882 as a contaminant in benzene.
Thiophene was observed that isatin (an indole) forms a blue dye if it is mixed with sulfuric acid and crude benzene.

The formation of the blue indophenin had long been believed to be a reaction of benzene itself.
Viktor Meyer was able to isolate thiophene as the actual substance responsible for this reaction.

Thiophene and especially its derivatives occur in petroleum, sometimes in concentrations up to 1–3%.
The thiophenic content of oil and coal is removed via the hydrodesulfurization (HDS) process.

On Mars:
Thiophene derivatives have been detected at nanomole levels in 3.5 billions year old Martian soil sediments (Murray Formation, Pahrump Hills) by the rover Curiosity at Gale crater (Mars) between 2012 and 2017.

Properties and Structure of Thiophene:
Thiophene is a colorless liquid at room temperature.
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°.
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.

Properties:
At room temperature, thiophene is a colorless liquid with a mildly pleasant odor reminiscent of benzene, with which thiophene shares some similarities.

Thiophene is considered aromatic, although theoretical calculations suggest that the degree of aromaticity is less than that of benzene.
The participation of the lone electron pairs on sulfur in the delocalized pi electron system is significant.

As a consequence of its aromaticity, thiophene does not exhibit the properties seen for conventional thioethers.
For example the sulfur atom is not alkylated by methyl iodide.

Although the sulfur atom is unreactive, the flanking CH centers are susceptible to attack by electrophiles.
The high reactivity of thiophene toward sulfonation is the basis for the separation of thiophene from benzene, as thiophene and benzene are difficult to separate by distillation due to the mere 4 °C difference in their boiling points at ambient pressure.
Treatment of thiophene-benzene mixtures with sulfuric acid results in preferential sulfonation of the thiophene to give water-soluble thiophene sulfonic acid.

Chemical Properties:
Thiophene is colorless, transparent liquid with an aromatic odor similar to benzene.
Thiophene is soluble in alcohol, ether and other organic solvents but insoluble in water.

Thiophene is a colourless to pale yellow liquid that has an odor similar to benzene.
Thiophene is a heterocyclic compound with a five-membered ring containing four carbon atoms and one sulfur atom.

The ring system is also known as a thienyl ring.
Thiophene occurs as an impurity in commercial benzene and is used as a solvent and in organic syntheses.

Production Methods of Thiophene:
Thiophene is presented in the shale oil and coal tar.
First use the waste acid of crude benzene washing as the raw material for hydrolysis at 110-150 °C.

The gas coming from hydrolysis is put into the overhead condenser through hydrolysis distillation column.
The condensed product has content of 15%-25% thiophene, 50%-60% xylene, and also benzene, toluene, methyl thiophene and some unknown substances.

Per ton of waste acid can be extracted out for about 10 kg distillation product.
After dehydration with solid sodium hydroxide and further refined purification by distillation, you can get thiophene product of 90%-95%.

Chemical synthesis of thiophene can use butane and sulfur as raw materials; butane first undergoes dehydrogenation and then form a ring with sulfur to form thiophene.
Laboratory prepare thiophene through the reaction between 1,4-dicarbonyl compound and phosphorus trisulfide.

Thiophene is present in coal tar and is recovered in the benzene distillation fraction (up to about 0.5% of the benzene present).
Thiophene's removal from benzene is accomplished by mixing with concentrated sulfuric acid, soluble thiophene sulfonic acid being formed.

Thiophene gives a characteristic blue coloration with isatin in concentrated sulfuric acid.
The basic nomenclature of the thiophene ring system and its derivatives is indicated by the following: the sulfur atom is number 1, positions 2 and 5 are equivalent in the parent ring, as are the 3 and 4 positions.

Synthesis and Production:
Reflecting their high stabilities, thiophenes arise from many reactions involving sulfur sources and hydrocarbons, especially unsaturated ones.
The first synthesis of thiophene by Meyer, reported the same year that he made his discovery, involves acetylene and elemental sulfur.

Thiophenes are classically prepared by the reaction of 1,4-diketones, diesters, or dicarboxylates with sulfidizing reagents such as P4S10 such as in the Paal-Knorr thiophene synthesis.
Specialized thiophenes can be synthesized similarly using Lawesson's reagent as the sulfidizing agent, or via the Gewald reaction, which involves the condensation of two esters in the presence of elemental sulfur.
Another method is the Volhard–Erdmann cyclization.

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 butanol.
These reagents are contacted with an oxide catalyst at 500–550 °C.

Reactivity of Thiophene:
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 sulfides.
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 with trifluoroperacetic acid 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).

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 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.

Oxidation may be relevant to the metabolic activation of various thiophene-containing drugs, such as tienilic acid and the investigational anticancer drug OSI-930.

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).

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.

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.

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:
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.

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.

History of Thiophene:
Thiophene was observed that isatin forms a blue dye if it is mixed with sulfuric acid and crude benzene.
The formation of the blue indophenin was long believed to be a reaction with benzene.

Victor Meyer was able to isolate the substance resposible for this reaction from benzene.
This new heterocyclic compound was thiophene.

Stability and Reactivity of Thiophene:

Chemical stability:
Thiophene is stable under recommended handling and storage conditions.

Reactivity:
Thiophene can react strongly with powerful oxidizing agents, including concentrated nitric acid.

Conditions to avoid:
Avoid heat, sparks, open flames, static discharge, and other ignition sources.

Incompatible materials:
Keep away from strong oxidizing agents and other highly reactive substances.

Handling and Storage of Thiophene:

Safe handling:
Handle in a well-ventilated area and prevent contact with the eyes, skin, and clothing.

Storage conditions:
Keep the container tightly closed in a cool, well-ventilated, fire-resistant storage area away from oxidizing materials and ignition sources.

First Aid Measures of Thiophene:

Inhalation:
Move the affected person to fresh air and obtain medical attention if necessary.

Skin contact:
Remove contaminated clothing and wash the affected skin thoroughly with water and soap.

Eye contact:
Rinse immediately with plenty of water for several minutes, remove contact lenses if easily possible, and seek medical attention.

Ingestion:
Rinse the mouth, give a small amount of water if the person is conscious, and obtain medical advice.

Firefighting Measures of Thiophene:

Suitable extinguishing media:
Use foam, carbon dioxide, dry chemical powder, or water spray as appropriate.

Protective equipment:
Firefighters should wear suitable protective clothing and self-contained breathing apparatus.

Special precautions:
Cool exposed containers with water spray and prevent vapors from reaching ignition sources.

Accidental Release Measures of Thiophene:

Personal precautions:
Eliminate ignition sources, provide adequate ventilation, and avoid direct contact with the spilled material.

Cleanup methods:
Absorb the liquid with dry sand, earth, or another non-combustible absorbent and transfer it to a suitable closed container using non-sparking tools.

Environmental precautions:
Prevent the material from entering drains, waterways, basements, or confined spaces.

Exposure Controls/Personal Protective of Thiophene:

Engineering controls:
Use adequate ventilation or local exhaust to control vapor exposure.

Eye protection:
Wear suitable safety goggles.

Hand protection:
Wear appropriate chemical-resistant protective gloves.

Skin protection:
Wear suitable protective clothing.

Respiratory protection:
Use appropriate respiratory protection when ventilation is insufficient or significant vapor exposure may occur.

Identifiers of Thiophene:
Product Number: T0223
Purity / Analysis Method: >98.0%(GC)
Molecular Formula / Molecular Weight: C4H4S = 84.14
Physical State (20 deg.C): Liquid
Storage Temperature: Room Temperature (Recommended in a cool and dark place, <15°C)
Store Under Inert Gas: Store under inert gas
Condition to Avoid: Air Sensitive
CAS RN: 110-02-1
Reaxys Registry Number: 103222
PubChem Substance ID: 87576212
SDBS (AIST Spectral DB): 479
Merck Index (14): 9353
MDL Number: MFCD00005413

Empirical Formula (Hill Notation): C4H4S
CAS Number: 110-02-1
Molecular Weight: 84.14
UNSPSC Code: 12352100
NACRES: NA.22
PubChem Substance ID: 24900115
EC Number: 203-729-4
Beilstein/REAXYS Number: 103222
MDL Number: MFCD00005413
Assay: ≥99%

CAS No.: 110-02-1
Chemical Name: Thiophene
CBNumber: CB5852798
Molecular Formula: C4H4S
Molecular Weight: 84.14
MDL Number: MFCD00005413
MOL File: 110-02-1.mol

CAS Number: 110-02-1
3D Model (JSmol): Interactive image
ChEBI: CHEBI:30856
ChEMBL: ChEMBL278958
ChemSpider: 7739
ECHA InfoCard: 100.003.392
PubChem CID: 8030
RTECS Number: XM7350000
UNII: SMB37IQ40B
CompTox Dashboard (EPA): DTXSID8026145
InChI: InChI=1S/C4H4S/c1-2-4-5-3-1/h1-4H
Key: YTPLMLYBLZKORZ-UHFFFAOYSA-N
InChI: InChI=1/C4H4S/c1-2-4-5-3-1/h1-4H
Key: YTPLMLYBLZKORZ-UHFFFAOYAY
SMILES: c1ccsc1

CAS: 110-02-1
IUPAC Name: thiophene
Molecular Formula: C4H4S
InChI Key: YTPLMLYBLZKORZ-UHFFFAOYSA-N
SMILES: S1C=CC=C1
Molecular Weight (g/mol): 84.14

Properties of Thiophene:
Chemical Formula: C4H4S
Molar Mass: 84.14 g·mol−1
Appearance: colorless liquid
Density: 1.051 g/mL, liquid
Melting Point: −38 °C (−36 °F; 235 K)
Boiling Point: 84 °C (183 °F; 357 K)
Magnetic Susceptibility (χ): −57.38·10−6 cm3/mol
Refractive Index (nD): 1.5287
Viscosity: 0.8712 cP at 0.2 °C
Viscosity: 0.6432 cP at 22.4 °C

Vapor Density: 2.9 (vs air)
Quality Segment: 200
Vapor Pressure: 40 mmHg (12.5 °C)
Assay: ≥99%
Autoignition Temp.: 743 °F
Expl. Lim.: 12.5 %
Refractive Index: n20/D 1.529 (lit.)
Boiling Point: 84 °C (lit.)
Melting Point: −38 °C (lit.)
Density: 1.051 g/mL at 25 °C (lit.)
SMILES String: c1ccsc1
InChI: 1S/C4H4S/c1-2-4-5-3-1/h1-4H
InChI Key: YTPLMLYBLZKORZ-UHFFFAOYSA-N

Melting Point: -38 °C (lit.)
Boiling Point: 84 °C (lit.)
Density: 1.051 g/mL at 25 °C (lit.)
Vapor Density: 2.9 (vs air)
Vapor Pressure: 40 mm Hg (12.5 °C)
Refractive Index: n20/D 1.529(lit.)
Flash Point: -9 °C
Storage Temperature: Store below +30°C.
Solubility: Miscible with carbon tetrachloride, heptane, pyrimidine, dioxane, toluene, and many organic solvents (quoted, Keith and Walters, 1992)
Form: powder
Color: Clear
Specific Gravity: 1.06
Odor: at 0.10 % in propylene glycol. alliaceous garlic
Odor Type: sulfurous
Biological Source: mouse
Odor Threshold: 0.00056ppm
Explosive Limit: 1.5-12.5%(V)
Water Solubility: INSOLUBLE
Thermal Conductivity: 0.141 W/(m·K) at 25 ℃
Specific Heat Capacity: Cp(liquid): 1.47 J/(g·K); Cp(gas): 0.87 J/(g·K), at 25℃
Merck: 14,9353
BRN: 103222
Henry's Law Constant: 2.33 and 2.70 in distilled water and seawater, respectively (Przyjazny et al., 1983)
Dielectric Constant: 9.3(20℃)
Stability: Stable. Highly flammable. Incompatible with strong oxidizing agents, nitrates.
InChI: 1S/C4H4S/c1-2-4-5-3-1/h1-4H
InChIKey: YTPLMLYBLZKORZ-UHFFFAOYSA-N
SMILES: c1ccsc1
LogP: 1.81-1.86 at pH10
Surface Tension: 26.13mN/m at 298.15K
CAS DataBase Reference: 110-02-1(CAS DataBase Reference)
EWG's Food Scores: 1
FDA UNII: SMB37IQ40B
NIST Chemistry Reference: Thiophene(110-02-1)
EPA Substance Registry System: Thiophene (110-02-1)
UNSPSC Code: 41116107
NACRES: NA.41

Molecular Weight: 84.14 g/mol
XLogP3: 1.8
Hydrogen Bond Donor Count: 0
Hydrogen Bond Acceptor Count: 1
Rotatable Bond Count: 0
Exact Mass: 84.00337130 Da
Monoisotopic Mass: 84.00337130 Da
Topological Polar Surface Area: 28.2 Ų
Heavy Atom Count: 5
Complexity: 22.8
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Specifications of Thiophene:
Appearance: Colorless to Almost colorless clear liquid
Purity (GC): min. 98.0 %
NMR: confirm to structure
Infrared Spectrum: Conforms
Appearance (Form): Clear liquid
Color Scale: =<50 APHA
Water: =<0.1 % (K.F.)
Refractive Index: 1.5270 to 1.5290 (20°C, 589 nm)
GC: >=99.0 %
Benzene: =<0.1 % (GC)

Related Compounds of Thiophene:
Furan
Selenophene
Pyrrole

Related thioethers:
Tetrahydrothiophene
Diethyl sulfide

Names of Thiophene:

Preferred IUPAC name:
Thiophene

Other names:
Thiofuran
Thiacyclopentadiene
Thiole