Thiophene

Last updated
Thiophene
Full displayed formula of thiophene Thiophene-2D-full.svg
Full displayed formula of thiophene
Skeletal formula showing numbering convention Thiophene-2D-numbered.svg
Skeletal formula showing numbering convention
Ball-and-stick model Thiophene-CRC-MW-3D-balls-A.png
Ball-and-stick model
Space-filling model Thiophene-CRC-MW-3D-vdW.png
Space-filling model
Names
Preferred IUPAC name
Thiophene [1]
Other names
Thiofuran
Thiacyclopentadiene
Thiole
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.392 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
RTECS number
  • XM7350000
UNII
  • InChI=1S/C4H4S/c1-2-4-5-3-1/h1-4H Yes check.svgY
    Key: YTPLMLYBLZKORZ-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C4H4S/c1-2-4-5-3-1/h1-4H
    Key: YTPLMLYBLZKORZ-UHFFFAOYAY
  • c1ccsc1
Properties
C4H4S
Molar mass 84.14 g/mol
Appearancecolorless liquid
Density 1.051 g/mL, liquid
Melting point −38 °C (−36 °F; 235 K)
Boiling point 84 °C (183 °F; 357 K)
-57.38·10−6 cm3/mol
1.5287
Viscosity 0.8712 cP at 0.2 °C
0.6432 cP at 22.4 °C
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
Toxic
GHS labelling: [2]
GHS-pictogram-flamme.svg GHS-pictogram-exclam.svg
Danger
H225, H302, H319, H412
P210, P260, P262, P273, P305+P351+P338, P403+P235
NFPA 704 (fire diamond)
NFPA 704.svgHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 3: Liquids and solids that can be ignited under almost all ambient temperature conditions. Flash point between 23 and 38 °C (73 and 100 °F). E.g. gasolineInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
3
0
Flash point −1 °C (30 °F; 272 K)
Safety data sheet (SDS) External MSDS, External MSDS
Related compounds
Related thioethers
Tetrahydrothiophene
Diethyl sulfide
Related compounds
 Furan
Selenophene
Pyrrole
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Thiophene is a heterocyclic compound with the formula C4H4S. Consisting of a planar five-membered ring, it is aromatic 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.

Contents

Isolation and occurrence

Thiophene was discovered by Viktor Meyer in 1882 as a contaminant in benzene. [3] It 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. [4]

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. In HDS, the liquid or gaseous feed is passed over a form of molybdenum disulfide catalyst 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.

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. [5] It represents an important milestone for the mission of the Mars Science Laboratory (MSL) in the long and elusive quest of organic matter on the red planet. Heating at high temperature (500° to 820 °C) of lacustrine mudstone samples by the Sample Analysis at Mars (SAM) instrument allowed gas chromatography-mass spectrometry (GC-MS) analyses of the evolved gases and the detection of aromatic and aliphatic molecules including several thiophene compounds. [6] The presence of carbon-sulfur bonds in macromolecules could have contributed to the preservation of organic matter at very long-term. It is estimated that ~ 5 % of organic molecules analysed by the SAM instrument contains organic sulfur. It remains unknown whether the origin and the mode of formation of these molecules is biotic or abiotic, [7] but their discovery put forward the puzzling question of thiophenic compounds as a possible ancient biosignature on Mars. Detailed analyses of carbon isotopes (δ13C) at trace level by a next generation of Martian rovers, such as Rosalind Franklin , [8] will be necessary to determine if such organic molecules are enriched in light carbon (12C) as living micro-organisms usually are on Earth.

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. [9]

Properties and structure

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°. [10] 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. [10]

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 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. [11] 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): [12] [13]

Oxidation of thiophene with trifluoroperacetic acid.png

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.

Desulfurization & reduction thiophene derivatives by raney nickel.svg

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. [23]

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. [24]

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. [25] Oxidation of thienyllithium gives 2,2'-dithienyl, (C4H3S)2. Thienyl lithium is employed in the preparation of higher order mixed cuprates. [26] 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. [9] The benzene ring of a biologically active compound may often be replaced by a thiophene without loss of activity. [27] This is seen in examples such as the NSAID lornoxicam, the thiophene analog of piroxicam, and sufentanil, the thiophene analog of fentanyl.

Related Research Articles

<span class="mw-page-title-main">Heterocyclic compound</span> Molecule with one or more rings composed of different elements

A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of organic heterocycles.

<span class="mw-page-title-main">Pyridine</span> Heterocyclic aromatic organic compound

Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one methine group (=CH−) replaced by a nitrogen atom (=N−). It is a highly flammable, weakly alkaline, water-miscible liquid with a distinctive, unpleasant fish-like smell. Pyridine is colorless, but older or impure samples can appear yellow, due to the formation of extended, unsaturated polymeric chains, which show significant electrical conductivity. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Historically, pyridine was produced from coal tar. As of 2016, it is synthesized on the scale of about 20,000 tons per year worldwide.

In organic chemistry, the Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or secondary alcohol is oxidized to an aldehyde or ketone using oxalyl chloride, dimethyl sulfoxide (DMSO) and an organic base, such as triethylamine. It is one of the many oxidation reactions commonly referred to as 'activated DMSO' oxidations. The reaction is known for its mild character and wide tolerance of functional groups.

Pyrrole is a heterocyclic, aromatic, organic compound, a five-membered ring with the formula C4H4NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3. Porphobilinogen, a trisubstituted pyrrole, is the biosynthetic precursor to many natural products such as heme.

<span class="mw-page-title-main">Organic sulfide</span> Organic compound with an –S– group

In organic chemistry, a sulfide or thioether is an organosulfur functional group with the connectivity R−S−R' as shown on right. Like many other sulfur-containing compounds, volatile sulfides have foul odors. A sulfide is similar to an ether except that it contains a sulfur atom in place of the oxygen. The grouping of oxygen and sulfur in the periodic table suggests that the chemical properties of ethers and sulfides are somewhat similar, though the extent to which this is true in practice varies depending on the application.

<span class="mw-page-title-main">Thioester</span> Organosulfur compounds of the form R–SC(=O)–R’

In organic chemistry, thioesters are organosulfur compounds with the molecular structure R−C(=O)−S−R’. They are analogous to carboxylate esters with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix. They are the product of esterification of a carboxylic acid with a thiol. In biochemistry, the best-known thioesters are derivatives of coenzyme A, e.g., acetyl-CoA. The R and R' represent organyl groups, or H in the case of R.

The Friedel–Crafts reactions are a set of reactions developed by Charles Friedel and James Crafts in 1877 to attach substituents to an aromatic ring. Friedel–Crafts reactions are of two main types: alkylation reactions and acylation reactions. Both proceed by electrophilic aromatic substitution.

<span class="mw-page-title-main">Alkylation</span> Transfer of an alkyl group from one molecule to another

Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene. Alkylating agents are reagents for effecting alkylation. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character. In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins. For upgrading of petroleum, alkylation produces a premium blending stock for gasoline. In medicine, alkylation of DNA is used in chemotherapy to damage the DNA of cancer cells. Alkylation is accomplished with the class of drugs called alkylating antineoplastic agents.

Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also referred to as furans.

Organosulfur chemistry is the study of the properties and synthesis of organosulfur compounds, which are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature is abound with organosulfur compounds—sulfur is vital for life. Of the 20 common amino acids, two are organosulfur compounds, and the antibiotics penicillin and sulfa drugs both contain sulfur. While sulfur-containing antibiotics save many lives, sulfur mustard is a deadly chemical warfare agent. Fossil fuels, coal, petroleum, and natural gas, which are derived from ancient organisms, necessarily contain organosulfur compounds, the removal of which is a major focus of oil refineries.

Aromatization is a chemical reaction in which an aromatic system is formed from a single nonaromatic precursor. Typically aromatization is achieved by dehydrogenation of existing cyclic compounds, illustrated by the conversion of cyclohexane into benzene. Aromatization includes the formation of heterocyclic systems.

<span class="mw-page-title-main">Sulfone</span> Organosulfur compound of the form >S(=O)2

In organic chemistry, a sulfone is a organosulfur compound containing a sulfonyl functional group attached to two carbon atoms. The central hexavalent sulfur atom is double-bonded to each of two oxygen atoms and has a single bond to each of two carbon atoms, usually in two separate hydrocarbon substituents.

The Barton–McCombie deoxygenation is an organic reaction in which a hydroxy functional group in an organic compound is replaced by a hydrogen to give an alkyl group. It is named after British chemists Sir Derek Harold Richard Barton and Stuart W. McCombie.

<span class="mw-page-title-main">Benzothiophene</span> Aromatic organic compound

Benzothiophene is an aromatic organic compound with a molecular formula C8H6S and an odor similar to naphthalene (mothballs). It occurs naturally as a constituent of petroleum-related deposits such as lignite tar. Benzothiophene has no household use. In addition to benzo[b]thiophene, a second isomer is known: benzo[c]thiophene.

<span class="mw-page-title-main">Phosphorus pentasulfide</span> Chemical compound

Phosphorus pentasulfide is the inorganic compound with the formula P2S5 (empirical) or P4S10 (molecular). This yellow solid is the one of two phosphorus sulfides of commercial value. Samples often appear greenish-gray due to impurities. It is soluble in carbon disulfide but reacts with many other solvents such as alcohols, DMSO, and DMF.

In organic chemistry, umpolung or polarity inversion is the chemical modification of a functional group with the aim of the reversal of polarity of that group. This modification allows secondary reactions of this functional group that would otherwise not be possible. The concept was introduced by D. Seebach and E.J. Corey. Polarity analysis during retrosynthetic analysis tells a chemist when umpolung tactics are required to synthesize a target molecule.

Unlike its lighter congeners, the halogen iodine forms a number of stable organic compounds, in which iodine exhibits higher formal oxidation states than -1 or coordination number exceeding 1. These are the hypervalent organoiodines, often called iodanes after the IUPAC rule used to name them.

<span class="mw-page-title-main">Liebeskind–Srogl coupling</span>

The Liebeskind–Srogl coupling reaction is an organic reaction forming a new carbon–carbon bond from a thioester and a boronic acid using a metal catalyst. It is a cross-coupling reaction. This reaction was invented by and named after Jiri Srogl from the Academy of Sciences, Czech Republic, and Lanny S. Liebeskind from Emory University, Atlanta, Georgia, USA. There are three generations of this reaction, with the first generation shown below. The original transformation used catalytic Pd(0), TFP = tris(2-furyl)phosphine as an additional ligand and stoichiometric CuTC = copper(I) thiophene-2-carboxylate as a co-metal catalyst. The overall reaction scheme is shown below.

Alcohol oxidation is a collection of oxidation reactions in organic chemistry that convert alcohols to aldehydes, ketones, carboxylic acids, and esters where the carbon carries a higher oxidation state. The reaction mainly applies to primary and secondary alcohols. Secondary alcohols form ketones, while primary alcohols form aldehydes or carboxylic acids.

<span class="mw-page-title-main">Trifluoroperacetic acid</span> Chemical compound

Trifluoroperacetic acid is an organofluorine compound, the peroxy acid analog of trifluoroacetic acid, with the condensed structural formula CF
3COOOH. It is a strong oxidizing agent for organic oxidation reactions, such as in Baeyer–Villiger oxidations of ketones. It is the most reactive of the organic peroxy acids, allowing it to successfully oxidise relatively unreactive alkenes to epoxides where other peroxy acids are ineffective. It can also oxidise the chalcogens in some functional groups, such as by transforming selenoethers to selones. It is a potentially explosive material and is not commercially available, but it can be quickly prepared as needed. Its use as a laboratory reagent was pioneered and developed by William D. Emmons.

References

  1. ↑ International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 141. doi:10.1039/9781849733069. ISBN   978-0-85404-182-4.
  2. ↑ GHS: GESTIS 010090
  3. ↑ Meyer, Viktor (1883). "Ueber den Begleiter des Benzols im Steinkohlenteer" [On a substance that accompanies benzene in coal tar]. Berichte der Deutschen Chemischen Gesellschaft . 16: 1465–1478. doi:10.1002/cber.188301601324.
  4. ↑ Ward C., Sumpter (1944). "The Chemistry of Isatin". Chemical Reviews . 34 (3): 393–434. doi:10.1021/cr60109a003.
  5. ↑ Voosen, Paul (2018). "NASA rover hits organic pay dirt on Mars". Science. doi:10.1126/science.aau3992. ISSN   0036-8075. S2CID   115442477.
  6. ↑ Eigenbrode, Jennifer L.; Summons, Roger E.; Steele, Andrew; Freissinet, Caroline; Millan, Maëva; Navarro-González, Rafael; Sutter, Brad; McAdam, Amy C.; Franz, Heather B.; Glavin, Daniel P.; Archer, Paul D.; Mahaffy, Paul R.; Conrad, Pamela G.; Hurowitz, Joel A.; Grotzinger, John P.; Gupta, Sanjeev; Ming, Doug W.; Sumner, Dawn Y.; Szopa, Cyril; Malespin, Charles; Buch, Arnaud; Coll, Patrice (2018). "Organic matter preserved in 3-billion-year-old mudstones at Gale crater, Mars" (PDF). Science. 360 (6393): 1096–1101. Bibcode:2018Sci...360.1096E. doi: 10.1126/science.aas9185 . ISSN   0036-8075. PMID   29880683. S2CID   46983230.
  7. ↑ Heinz, Jacob; Schulze-Makuch, Dirk (2020). "Thiophenes on Mars: Biotic or Abiotic Origin?". Astrobiology. 20 (4): 552–561. Bibcode:2020AsBio..20..552H. doi: 10.1089/ast.2019.2139 . PMID   32091933.
  8. ↑ "The Curiosity rover found organic molecules on Mars. This is why they're exciting". CNN. 6 March 2020.
  9. 1 2 3 Swanston, Jonathan (2006). "Thiophene". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a26_793.pub2. ISBN   3527306730..
  10. 1 2 Cambridge Structural Database
  11. ↑ Treiber, A., Dansette, P. M., Amri, H. E., Girault, J.-P., Ginderow, D., Mornon, J.-P., Mansuy, D.; Dansette; El Amri; Girault; Ginderow; Mornon; Mansuy (1997). "Chemical and Biological Oxidation of Thiophene: Preparation and Complete Characterization of Thiophene S-Oxide Dimers and Evidence for Thiophene S-Oxide as an Intermediate in Thiophene Metabolism in Vivo and in Vitro". J. Am. Chem. Soc. 119 (7): 1565–1571. doi:10.1021/ja962466g.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. 1 2 3 4 Treiber, Alexander (2002). "Mechanism of the Aromatic Hydroxylation of Thiophene by Acid-Catalyzed Peracid Oxidation". J. Org. Chem. 67 (21): 7261–7266. doi:10.1021/jo0202177. PMID   12375952.
  13. ↑ Caster, Kenneth C.; Rao, A. Somasekar; Mohan, H. Rama; McGrath, Nicholas A.; Brichacek, Matthew (2012). "Trifluoroperacetic Acid". Encyclopedia of Reagents for Organic Synthesis. e-EROS Encyclopedia of Reagents for Organic Synthesis . doi:10.1002/047084289X.rt254.pub2. ISBN   978-0471936237.
  14. ↑ Hagen, Timothy J. (2007). "Prilezhaev reaction". In Li, Jie Jack; Corey, E. J. (eds.). Name Reactions of Functional Group Transformations. John Wiley & Sons. pp. 274–281. ISBN   9780470176504.
  15. ↑ Anslyn, Eric V.; Dougherty, Dennis A. (2006). "8.8 Miscellaneous Experiments for Studying Mechanism". Modern Physical Organic Chemistry. University Science Books. pp. 471–482. ISBN   9781891389313.
  16. ↑ Mansuy, D., Valadon, P., Erdelmeier, I., López García, P., Amar, C., Girault, J. P., and Dansette, P. M. (1991). "Thiophene S-oxides as new reactive metabolites: Formation by cytochrome-P450 dependent oxidation and reaction with nucleophiles". J. Am. Chem. Soc. 113 (20): 7825–7826. doi:10.1021/ja00020a089.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ↑ Rademacher P. M., Woods C. M., Huang Q., Szklarz G. D., Nelson S. D.; Woods; Huang; Szklarz; Nelson (2012). "Differential Oxidation of Two Thiophene-Containing Regioisomers to Reactive Metabolites by Cytochrome P450 2C9". Chem. Res. Toxicol. 25 (4): 895–903. doi:10.1021/tx200519d. PMC   3339269 . PMID   22329513.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ↑ Mansuy D., Dansette P. M.; Dansette (2011). "Sulfenic acids as reactive intermediates in xenobiotic metabolism". Archives of Biochemistry and Biophysics. 507 (1): 174–185. doi:10.1016/j.abb.2010.09.015. PMID   20869346.
  19. ↑ Dansette, PM, Rosi, J, Debernardi, J, Bertho G, Mansuy D; Rosi; Debernardi; Bertho; Mansuy (2012). "Metabolic Activation of Prasugrel: Nature of the Two Competitive Pathways Resulting in the Opening of Its Thiophene Ring". Chem. Res. Toxicol. 25 (5): 1058–1065. doi:10.1021/tx3000279. PMID   22482514.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ↑ Henry Y. Lew and C. R. Noller (1963). "2-Iodolthiophene". Organic Syntheses .; Collective Volume, vol. 4, p. 545
  21. ↑ W. S. Emerson and T. M. Patrick Jr. (1963). "2-Vinylthiophene". Organic Syntheses .; Collective Volume, vol. 4, p. 980
  22. ↑ K. B. Wiberg and H. F. McShane (1955). "2-Chloromethylthiophene". Organic Syntheses .; Collective Volume, vol. 3, p. 1
  23. ↑ J. Roncali (1992). "Conjugated poly(thiophenes): synthesis, functionalization, and applications". Chem. Rev. 92 (4): 711–738. doi:10.1021/cr00012a009.
  24. ↑ Rauchfuss, T. B., "The Coordination Chemistry of Thiophenes", Progress in Inorganic Chemistry 1991, volume 39, pp. 259-311. ISBN   978-0-471-54489-0
  25. ↑ E. Jones and I. M. Moodie (1988). "2-Thiophenethiol". Organic Syntheses .; Collective Volume, vol. 6, p. 979
  26. ↑ Lipshutz, Bruce H.; Moretti, Robert; Crow, Robert (1990). "Mixed Higher-order Cyanocuprate-induced Epoxide Openings: 1-Benzyloxy-4-penten-2-ol". Org. Synth. 69: 80. doi:10.15227/orgsyn.069.0080.
  27. ↑ Daniel Lednicer (1999). The Organic Chemistry of Drug Synthesis. Vol. 6. New York: Wiley Interscience. p. 187. ISBN   0-471-24510-0.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.