Sulfonamides
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In
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 group with the structure . It consists of a sulfonyl 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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...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 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; 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 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 ...
, 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 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 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 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. 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 discovered. File:Sulfanilamide-skeletal.svg, Sulfanilamide, 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 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 organic synthesis.


Sulfinamides

The related sulfinamides (R(S=O)NHR) are amides of sulfinic acids (R(S=O)OH) (see sulfinyl). Chiral sulfinamides such as tert-butanesulfinamide, p-toluenesulfinamide and 2,4,6-trimethylbenzenesulfinamide are relevant to asymmetric synthesis.


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 synthesis.


See also

* Sulfonamide (medicine) * Sulfamic acid *
Sulfamide Sulfamide (IUPAC name: sulfuric diamide) is an organosulfur compound with the chemical formula and structure . Sulfamide is produced by the reaction of sulfuryl chloride with ammonia. Sulfamide was first prepared in 1838 by the French chemist ...


References

{{Functional groups Functional groups