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organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, 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.Clay ...
, 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 res ...
(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 . 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 groups c ...
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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...
group (). Relatively speaking this group is unreactive. 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, macros ...
; 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 depends ...
. 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 ele ...
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 Ear ...
, 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-toxic ...
) is . Any sulfonamide can be considered as derived from a sulfonic acid 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 hydrox ...
group () with an amine group. In
medicine Medicine is the science and Praxis (process), practice of caring for a patient, managing the diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, and Health promotion ...
, the term "sulfonamide" is sometimes used as a synonym for sulfa drug, 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 chloride In inorganic chemistry, sulfonyl halide groups occur when a sulfonyl () functional group is singly bonded to a halogen atom. They have the general formula , where X is a halogen. The stability of sulfonyl halides decreases in the order fluorid ...
s 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 su ...
. :R^1SO2Cl + R^2R^3NH -> R^1SO2NR^2R^3 + HCl A base such as
pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, 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, weakl ...
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. The reaction of primary and secondary amines with
benzenesulfonyl chloride Benzenesulfonyl chloride is an organosulfur compound with the formula C6H5SO2Cl. It is a colourless viscous oil that dissolves in organic solvents, but reacts with compounds containing reactive N-H and O-H bonds. It is mainly used to prepare sulfo ...
is the basis of the
Hinsberg reaction The Hinsberg reaction is a chemical test for the detection of primary, secondary and tertiary amines. The reaction was first described by Oscar Hinsberg in 1890. In this test, the amine is shaken well with Hinsberg reagent in the presence of aque ...
, a method for detecting primary and secondary amines.


Sultams

Sultams are cyclic sulfonamides. Bioactive sultams include the antiinflammatory
ampiroxicam Ampiroxicam ( INN) is a non-steroidal anti-inflammatory drug (NSAID). It is a prodrug of piroxicam Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class used to relieve the symptoms of painful inflammatory conditions ...
and the anticonvulsant
sulthiame Sultiame (or sulthiame) is a sulfonamide and inhibitor of the enzyme carbonic anhydrase. It is used as an anticonvulsant. History Sultiame was first synthesised in the laboratories of Bayer AG in the mid 1950s and eventually launched as Ospolot ...
. 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 ...
, 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 ...
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 to ...
, 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 monocytogenes ...
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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
. File:Ampiroxicam int.svg,
Ampiroxicam Ampiroxicam ( INN) is a non-steroidal anti-inflammatory drug (NSAID). It is a prodrug of piroxicam Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class used to relieve the symptoms of painful inflammatory conditions ...
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 th ...
is a drug that features both acyclic and cyclic sulfonamide groups. File:Oppolzer sultam.svg ,
Camphorsultam Camphorsultam, also known as bornanesultam, is a crystalline solid primarily used as a chiral auxiliary in the synthesis of other chemicals with a specific desired stereoselectivity. Camphorsultam is commercially available in both enantiomers of ...
is a sultam used as a chiral auxiliary in organic synthesis.


Sulfinamides

The related sulfinamides (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. Sul ...
s (R(S=O)OH) (see sulfinyl).
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 i ...
sulfinamides such as tert-butanesulfinamide, 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 molecu ...
.


Disulfonimides

Bis(trifluoromethanesulfonyl)aniline is a source of the
triflyl In organic chemistry, the triflyl group (systematic name: trifluoromethanesulfonyl group) is a functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chem ...
() 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 ant ...
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) antimi ...
*
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