In
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J. ...
, the sulfonamide
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
(also spelled sulphonamide) is an
organosulfur
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—sulfur ...
group with the
structure
A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such ...
. It consists of a
sulfonyl
In organosulfur chemistry, a sulfonyl group can refer either to a functional group found primarily in sulfones, or to a substituent obtained from a sulfonic acid by the removal of the hydroxyl group, similarly to acyl groups. Sulfonyl grou ...
group () connected to an
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
group (). Relatively speaking this group is
unreactive
In chemistry, reactivity is the impulse for which a chemical substance undergoes a chemical reaction, either by itself or with other materials, with an overall release of energy.
''Reactivity'' refers to:
* the chemical reactions of a single sub ...
. Because of the rigidity of the functional group, sulfonamides are typically
crystalline
A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macr ...
; for this reason, the formation of a sulfonamide is a classic method to convert an amine into a crystalline derivative which can be identified by its
melting point
The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depe ...
. Many important drugs contain the sulfonamide group.
A sulfonamide (compound) is a
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
that contains this group. The general formula is or , where each R is some organic group; for example, "methanesulfonamide" (where R =
methane
Methane ( , ) is a chemical compound with the chemical formula (one carbon atom bonded to four hydrogen atoms). It is a group-14 hydride, the simplest alkane, and the main constituent of natural gas. The relative abundance of methane on ...
, R' = R" =
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxi ...
) is . Any sulfonamide can be considered as derived from a
sulfonic acid
In organic chemistry, sulfonic acid (or sulphonic acid) refers to a member of the class of organosulfur compounds with the general formula , where R is an organic alkyl or aryl group and the group a sulfonyl hydroxide. As a substituent, it is k ...
by replacing a
hydroxyl
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 ...
group () with an amine group.
In
medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care p ...
, the term "sulfonamide" is sometimes used as a synonym for
sulfa drug
Sulfonamide is a functional group (a part of a molecule) that is the basis of several groups of drugs, which are called sulphonamides, sulfa drugs or sulpha drugs. The original antibacterial sulfonamides are synthetic (nonantibiotic) anti ...
, a derivative or variation of sulfanilamide. The first sulfonamide was discovered in Germany in 1932.
Synthesis
Sulfonamides can be prepared in the laboratory in many ways. The classic approach entails the reaction of
sulfonyl chlorides with an
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
.
:
R^1SO2Cl + R^2R^3NH -> R^1SO2NR^2R^3 + HCl
A base such as
pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with ...
is typically added to absorb the HCl that is generated. Illustrative is the synthesis of sulfonylmethylamide. A readily available sulfonyl chloride source is
tosyl chloride
4-Toluenesulfonyl chloride (''p''-toluenesulfonyl chloride, toluene-''p''-sulfonyl chloride) is an organic compound with the formula CH3C6H4SO2Cl. This white, malodorous solid is a reagent widely used in organic synthesis. Abbreviated TsCl or To ...
. The reaction of primary and secondary amines with
benzenesulfonyl chloride is the basis of the
Hinsberg reaction, a method for detecting primary and secondary amines.
Sultams
Sultams are cyclic sulfonamides. Bioactive sultams include the antiinflammatory
ampiroxicam and the anticonvulsant
sulthiame. Sultams are prepared analogously to other sulfonamides, allowing for the fact that sulfonic acids are deprotonated by amines. They are often prepared by one-pot oxidation of disulfides or thiols linked to amines. An alternative synthesis of sultams involves initial preparation of a linear sulfonamide, followed by intramolecular C-C bond formation (i.e. cyclization), a strategy that was used in the synthesis of a sultam-based deep-blue emitter for organic electronics.
File:Saccharin.svg, Saccharin
Saccharin (''aka'' saccharine, Sodium sacchari) is an artificial sweetener with effectively no nutritional value. It is about 550 times as sweet as sucrose but has a bitter or metallic aftertaste, especially at high concentrations. Saccharin is ...
, a cyclic sulfonamide that was one of the first artificial sweeteners
A sugar substitute is a food additive that provides a sweetness like that of sugar while containing significantly less food energy than sugar-based sweeteners, making it a zero-calorie () or low-calorie sweetener. Artificial sweeteners may be d ...
discovered.
File:Sulfanilamide-skeletal.svg, Sulfanilamide
Sulfanilamide (also spelled sulphanilamide) is a sulfonamide antibacterial drug. Chemically, it is an organic compound consisting of an aniline derivatized with a sulfonamide group. Powdered sulfanilamide was used by the Allies in World War II ...
, a compound that foreshadowed the development of sulfa drugs.
File:Sulfamethoxazole-skeletal.svg, Sulfamethoxazole
Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as '' Listeria monocytogen ...
is a widely used antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
.
File:Ampiroxicam int.svg, Ampiroxicam is a sultam used as an antiinflammatory drug.
File:Hydrochlorothiazide-2D-skeletal.png, Hydrochlorothiazide
Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in tho ...
is a drug that features both acyclic and cyclic sulfonamide groups.
File:Oppolzer sultam.svg , Camphorsultam is a sultam used as a chiral auxiliary
In stereochemistry, a chiral auxiliary is a stereogenic group or unit that is temporarily incorporated into an organic compound in order to control the stereochemical outcome of the synthesis. The chirality present in the auxiliary can bias the st ...
in organic synthesis.
Sulfinamides
The related
sulfinamide
Sulfinamide is a functional group in organosulfur chemistry with the structural formula RS(O)NR'2 (where R and R' are organic substituents). This functionality is composed of a sulfur- carbon (S–C) and sulfur- nitrogen (S–N) single bonds, ...
s (R(S=O)NHR) are amides of
sulfinic acid
Sulfinic acids are oxoacids of sulfur with the structure RSO(OH). In these organosulfur compounds, sulfur is pyramidal.
Structure and properties
Sulfinic acids RSO2H are about 1000x more acidic than the corresponding carboxylic acid RCO2H. S ...
s (R(S=O)OH) (see
sulfinyl
In organic chemistry, a sulfoxide, also called a sulphoxide, is an organosulfur compound containing a sulfinyl () functional group attached to two carbon atoms. It is a polar functional group. Sulfoxides are oxidized derivatives of sulfide ...
).
Chiral
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from ...
sulfinamides such as
tert-butanesulfinamide
''tert''-Butanesulfinamide (also known as 2-methyl-2-propanesulfinamide or Ellman's sulfinamide) is an organosulfur compound and a member of the class of sulfinamides. Both enantiomeric forms are commercially available and are used in asymmetric ...
, p-toluenesulfinamide and 2,4,6-trimethylbenzenesulfinamide are relevant to
asymmetric synthesis
Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecul ...
.
Disulfonimides
Bis(trifluoromethanesulfonyl)aniline is a source of the
triflyl () group.
The disulfonimides are of the type with two sulfonyl groups flanking an amine.
As with sulfinamides, this class of compounds is used as catalysts in
enantioselective
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...
synthesis.
See also
*
Sulfonamide (medicine)
Sulfonamide is a functional group (a part of a molecule) that is the basis of several groups of drugs, which are called sulphonamides, sulfa drugs or sulpha drugs. The original antibacterial sulfonamides are synthetic (nonantibiotic) anti ...
*
Sulfamic acid
Sulfamic acid, also known as amidosulfonic acid, amidosulfuric acid, aminosulfonic acid, sulphamic acid and sulfamidic acid, is a molecular compound with the formula H3NSO3. This colourless, water-soluble compound finds many applications. Sulfami ...
*
Sulfamide
References
{{Functional groups
Functional groups