Thiophenol is an
organosulfur compound
Organosulfur compounds 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 abounds with organosulfur compounds—sulfu ...
with the formula C
6H
5SH, sometimes abbreviated as PhSH. This foul-smelling colorless liquid is the simplest
aromatic thiol. The
chemical structures of thiophenol and its
derivatives
The derivative of a function is the rate of change of the function's output relative to its input value.
Derivative may also refer to:
In mathematics and economics
* Brzozowski derivative in the theory of formal languages
* Formal derivative, an ...
are analogous to
phenols except the
oxygen atom in the
hydroxyl group
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy g ...
(-OH) bonded to the aromatic ring is replaced by a
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
atom. The prefix thio- implies a sulfur-containing compound and when used before a root word name for a compound which would normally contain an oxygen atom, in the case of 'thiol' that the alcohol oxygen atom is replaced by a sulfur atom.
Thiophenols also describes a class of compounds formally derived from thiophenol itself. All have a
sulfhydryl group (-SH)
covalently bonded to an aromatic ring. The organosulfur ligand in the medicine
thiomersal
Thiomersal (INN), or thimerosal (USAN, JAN), is an organomercury compound. It is a well-established antiseptic and antifungal agent.
The pharmaceutical corporation Eli Lilly and Company gave thiomersal the trade name Merthiolate. It has been u ...
is a thiophenol.
Synthesis
There are several methods of synthesis for thiophenol and related compounds, although thiophenol itself is usually purchased for laboratory operations.
Methods are the reduction of
benzenesulfonyl chloride with
zinc. and the action of elemental sulfur on
phenyl magnesium halide or
phenyllithium followed by acidification.
Via the
Newman–Kwart rearrangement
The Newman–Kwart rearrangement is a type of rearrangement reaction in which the aryl group of an ''O''-aryl thiocarbamate, ArOC(=S)NMe2, migrates from the oxygen atom to the sulfur atom, forming an ''S''-aryl thiocarbamate, ArSC(=O)NMe2. The re ...
, phenols (1) can be converted to the thiophenols (5) by conversion to the O-aryl dialkylthiocarbamates (3), followed by heating to give the isomeric ''S''-aryl derivative (4).
:
In the
Leuckart thiophenol reaction
The Leuckart thiophenol reaction is the decomposition of a diazoxanthate, by gentle warming in a slightly acidic cuprous medium, to its corresponding aryl xanthates which give aryl thiols on alkaline hydrolysis and aryl thioethers on further warmi ...
, the starting material is an
aniline through the
diazonium salt (ArN
2X) and the
xanthate (ArS(C=S)OR). Alternatively,
sodium sulfide
Sodium sulfide is a chemical compound with the formula Na2 S, or more commonly its hydrate Na2S·9 H2O. Both the anhydrous and the hydrated salts in pure crystalline form are colorless solids, although technical grades of sodium sulfide are gener ...
and
triazene can react in organic solutions and yield thiophenols.
Thiophenol can be manufactured from
chlorobenzene and
hydrogen sulfide
Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...
over alumina at . The
disulfide is the primary byproduct. The reaction medium is corrosive and requires ceramic or similar reactor lining. Aryl iodides and
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
in certain conditions may also produce thiophenols.
Applications
Thiophenols are used in the production of
pharmaceuticals
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
including of
sulfonamides
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
. The antifungal agents
butoconazole
Butoconazole (trade names Gynazole-1, Mycelex-3) is an imidazole antifungal used in gynecology. It is administered as a vaginal cream.Butoconazole
Synthesis
Reaction of epichlorohydrin with 4-Chlorobenzyl magnesium bromide leads to 1-chloro-4 ...
and
merthiolate are derivatives of thiophenols.
Properties and reactions
Acidity
Thiophenol has appreciably greater
acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
ity than does phenol, as is shown by their
p''K''a values (6.62 for thiophenol and 9.95 for phenol). A similar pattern is seen for
H2S versus H
2O, and all
thiols versus the corresponding
alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
s. Treatment of PhSH with strong base such as
sodium hydroxide
Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions .
Sodium hydroxide is a highly caustic base and alkali ...
(NaOH) or
sodium metal affords the salt sodium thiophenolate (PhSNa).
Alkylation
The thiophenolate is highly nucleophilic, which translates to a high rate of alkylation. Thus, treatment of C
6H
5SH with
methyl iodide
Iodomethane, also called methyl iodide, and commonly abbreviated "MeI", is the chemical compound with the formula CH3I. It is a dense, colorless, volatile liquid. In terms of chemical structure, it is related to methane by replacement of one h ...
in the presence of a base gives methyl phenyl sulfide, C
6H
5SCH
3, a
thioether often referred to as
thioanisole. Such reactions are fairly irreversible. C
6H
5SH also adds to α,β-unsaturated carbonyls via
Michael addition.
Oxidation
Thiophenols, especially in the presence of base are easily oxidized to
diphenyl disulfide:
: 4 C
6H
5SH + O
2 → 2 C
6H
5S-SC
6H
5 + 2 H
2O
The disulfide can be reduced back the thiol using
sodium borohydride followed by acidification. This redox reaction is also exploited in the use of C
6H
5SH as a source of H atoms.
Chlorination
Phenylsulfenyl chloride, a blood-red liquid (b.p. 41–42 °C, 1.5 mm Hg), can be prepared by the reaction of thiophenol with
chlorine (Cl
2).
Coordination to metals
Metal cations form thiophenolates, some of which are polymeric. One example is "C
6H
5SCu," obtained by treating
copper(I) chloride with thiophenol.
Safety
The US
National Institute for Occupational Safety and Health has established a
recommended exposure limit at a ceiling of 0.1 ppm (0.5 mg m
−3), and exposures not greater than 15 minutes.
CDC - NIOSH Pocket Guide to Chemical Hazards
/ref>
References
External links
Thiophenol
Toxicology Data Network
{{Authority control
Thiols
Phenyl compounds
Foul-smelling chemicals