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 matter, organic materials, i.e., matter in its various forms that contain ...

, the sulfonamide

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

(also spelled sulphonamide) is an

organosulfur 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 der ...

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 as ...

. It consists of a

sulfonyl In organosulfur chemistry, a sulfonyl group is either a functional group found primarily in sulfones, or a substituent obtained from a sulfonic acid by the removal of the hydroxyl group, similarly to acyl groups. Group Sulfonyl groups can be w ...

group () connected to an

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

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, macrosc ...

; 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 of matter, state from solid to liquid. At the melting point the solid and liquid phase (matter), phase exist in Thermodynamic equilib ...

. 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 abundance of methane on Earth makes ...

, R' = R" =

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

) 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 kn ...

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 Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...

, 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 antimicrobial agents th ...

, a derivative or variation of sulfanilamide. The first sulfonamide was discovered in Germany in 1932.

Synthesis and reactions

Sulfonamides can be prepared in the laboratory in many ways. The classic approach entails the reaction of

sulfonyl chloride In chemistry, a sulfonyl halide consists of a sulfonyl () group 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 fluorides > chlorides > bromides > ...

s with an

. : 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, weak ...

is typically added to absorb the HCl that is generated. Illustrative is the synthesis of sulfonylmethylamide. 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 the Hinsberg reagent ( benzenesulfonyl ch ...

, a method for detecting primary and secondary amines. Sulfonamides undergo a variety of acid-base reactions. The N-H bond can be deprotonated. The alkylsulfonamides can be deprotonated at carbon. Arylsulfonamides undergo ortho-lithiation.

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 l ...

and the anticonvulsant

sulthiame Sultiame (or sulthiame) is a sulfonamide and inhibitor of the enzyme carbonic anhydrase. It is used as an anticonvulsant and in recent studies showed promise in reducing sleep disordered breathing and other symptoms of obstructive sleep apnea ( ...

. 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 Organic electronics is a field of materials science concerning the design, Chemical synthesis, synthesis, characterization, and application of Organic compound, organic molecules or polymers that show desirable Electronics, electronic properties ...

. File:Saccharin.svg,

Saccharin Saccharin, also called saccharine, benzosulfimide, or E954, or used in saccharin sodium or saccharin calcium forms, is a non-nutritive artificial sweetener. Saccharin is a sultam that is about 500 times sweeter than sucrose, but has a bitter or ...

, a cyclic sulfonamide that was one of the first

artificial sweeteners A sugar substitute or artificial sweetener, 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. Arti ...

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 ...

, 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 ''Escherichia coli' ...

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 l ...

is a sultam used as an antiinflammatory drug. File:Hydrochlorothiazide-2D-skeletal.png,

Hydrochlorothiazide Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and t ...

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.

Disulfonimides

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, stereoselectivity is the property of a chemical reaction in which a single reactant forms an unequal mixture of stereoisomers during a non- stereospecific creation of a new stereocenter or during a non-stereospecific transformation o ...

synthesis. Bis(trifluoromethanesulfonyl)aniline is a source of the

triflyl In organic chemistry, the triflyl group (Preferred IUPAC name, systematic name: trifluoromethanesulfonyl group) is a functional group with the Chemical formula, formula and Chemical structure, structure . The triflyl group is often represented b ...

() group.

Synthesis and reactions

Sultams

Disulfonimides

See also

References

Further reading