The Fischer indole synthesis is a chemical reaction that produces the aromatic heterocycle indole from a (substituted) phenylhydrazine and an aldehyde or ketone under acidic conditions. The reaction was discovered in 1883 by Hermann Emil Fischer. Today antimigraine drugs of the triptan class are often synthesized by this method. A chemical reaction is a process that results in the interconversion of Chemical substances . ... In chemistry, an aromatic molecule is one in which electrons are free to cycle around circular arrangements of atoms, which are alternately singly and doubly bonded to one another. ... Pyridine a simple heterocyclic compound Heterocyclic compounds are organic compounds which contain a ring structure containing atoms in addition to carbon, such as sulfur, oxygen or nitrogen, as part of the ring. ... Indole is an aromatic heterocyclic organic compound. ... An aldehyde is either a functional group consisting of a terminal carbonyl group or a compound containing a terminal carbonyl group. ... A ketone is either the functional group characterized by a carbonyl group linked to two other carbon atoms or a compound that contains this functional group. ... An acid (from Arabic Azait meaning oil, often represented by the generic formula AH) is typically a water-soluble, sour-tasting chemical compound. ... 1883 was a common year starting on Monday (see link for calendar). ... Hermann Emil Fischer (October 9, 1852 - July 15, 1919) was a German chemist and recipient of the Nobel Prize for Chemistry in 1902. ... Migraine is a form of headache, usually very intense and disabling. ... Triptans are a family of tryptamine drugs used in the treatment of migraine and cluster headaches. ...

The choice of acid catalyst is very important. Bronsted acids such as HCl, H₂SO₄, and polyphosphoric acid have been used successfully. Lewis acids such as boron trifluoride, zinc chloride, iron chloride, and aluminium chloride are also useful catalysts. Image File history File links Download high resolution version (1199x302, 4 KB) Description: Summary of the Fischer indole synthesis. ... A Brønsted acid is an acid that donates a hydrogen ion to another compound. ... HCL or HCl can stand for: Hardware Compatibility List Chemical symbol for hydrochloric acid, written HCl Higher Chinese Language, an academic subject in Singapore An Indian software company (previously Hindustan Computers Ltd. ... Sulfuric acid (British English: sulphuric acid), H2SO4, is a strong mineral acid. ... In chemistry, a Lewis acid can accept a pair of electrons and form a coordinate covalent bond, after the American chemist Gilbert Lewis. ... Boron trifluoride (BF3, trifluoroborane) is a pungent colourless toxic gas. ... Zinc chloride (ZnCl2) is a colorless or white compound of zinc and chlorine that is extremely hygroscopic. ... Aluminium chloride (AlCl3) is a compound of aluminium and chlorine. ...

Reaction mechanism

On reaction of a (substituted) phenylhydrazine with an aldehyde or ketone a phenylhydrazone forms and isomerizes into the respective enamine (or 'ene-hydrazine'). After protonation a cyclic rearrangement occurs, involving a nucleophilic aromatic S_NAr attack of the phenyl ring. The resulting aniline/imine forms a cyclic aminoacetal (or aminal) under acid catalysis that splits off NH₃, resulting in the energetically favorable aromatic indole system. Image File history File links Fischer-indole-synthesis. ... Hydrazine is a chemical compound with formula N2H4 used as a rocket fuel. ... In chemistry, isomerization is the transformation of a molecule into a different isomer. ... An enamine is an unsaturated compound derived by the reaction of an aldehyde or ketone with a secondary amine followed by loss of H2O. Form Categories: Functional groups | Stub ... Protonation is the addition of a proton (H+) to an atom, molecule, or ion. ... An electrocyclic reaction is a type of pericyclic rearrangement reaction where the net result is one pi bond being converted into one sigma bond. ... In chemistry, a nucleophile (literally nucleus lover) is a reagent which is attracted to centres of positive charge. ... In chemistry, an aromatic molecule is one in which electrons are free to cycle around circular arrangements of atoms, which are alternately singly and doubly bonded to one another. ... A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide on an aromatic ring. ... In chemistry, the phenyl group or phenyl ring (often abbreviated as -Ph) is the functional group with the formula -C6H5 Picture where the six carbon atoms are arranged in a cyclic manner. ... This article needs to be cleaned up to conform to a higher standard of quality. ... An imine is a functional group or chemical compound containing a carbon-nitrogen double bond. ... A hemiaminal is a functional group or type of chemical compound that has a hydroxyl group and a amine attached to the same carbon atom: -C(OH)(NR2)-. R can be hydrogen or an alkyl group. ... A catalyst (Greek: καταλύτης, catalytÄ“s) is a substance that accelerates the rate (speed) of a chemical reaction (see also catalysis). ... Ammonia is a compound of nitrogen and hydrogen with the formula NH3. ...

The reaction is catalyzed by acids such as sulfuric acid, hydrochloric acid, phosphoric acid, or polyphosphoric acid. Sulfuric acid (British English: sulphuric acid), H2SO4, is a strong mineral acid. ... The chemical substance hydrochloric acid is the aqueous (water-based) solution of hydrogen chloride (HCl) gas. ... R-phrases S-phrases , , Supplementary data page Structure and properties n, εr, etc. ...

Buchwald modification

Using palladium chemistry developed at MIT by Stephen Buchwald, the Fischer indole synthesis can be completed using aryl bromides as starting materials. General Name, Symbol, Number palladium, Pd, 46 Chemical series transition metals Group, Period, Block 10, 5, d Appearance silvery white metallic Atomic mass 106. ... The Massachusetts Institute of Technology, or MIT, is a research and educational institution located in the city of Cambridge, Massachusetts, USA. MIT is a world leader in science and technology, as well as in many other fields, including management, economics, linguistics, political science, and philosophy. ...

• Buchwald, S. L. et al. J. Am. Chem. Soc. 1998, 120, 6621.

Image File history File links Download high resolution version (2055x343, 7 KB) Description: Buchwald modification of the Fischer indole synthesis. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ...

References

• Fischer, E.; Jourdan, F. Ber. 1883, 16, 2241.
• Fischer, E.; Hess, O. Ber. 1884, 17, 559.
• Robinson, B. Chem. Rev. 1963, 63, 373.
• Robinson, B. Chem. Rev. 1969, 69, 227.
• Ishii, H. Accts. Chem. Res. 1981, 14, 233-247.

Hermann Emil Fischer (October 9, 1852 - July 15, 1919) was a German chemist and recipient of the Nobel Prize for Chemistry in 1902. ... Chemische Berichte (usually abbreviated as or ) is a German-language scientific journal featuring chemistry of all disciplines. ... Hermann Emil Fischer (October 9, 1852 - July 15, 1919) was a German chemist and recipient of the Nobel Prize for Chemistry in 1902. ... Chemische Berichte (usually abbreviated as or ) is a German-language scientific journal featuring chemistry of all disciplines. ... Chemical Reviews (usually abbreviated as ), is a peer-reviewed scientific journal, published since 1900 by the American Chemical Society. ... Chemical Reviews (usually abbreviated as ), is a peer-reviewed scientific journal, published since 1900 by the American Chemical Society. ... Accounts of Chemical Research (usually abbreviated as ) is a peer-reviewed scientific journal, published since 1968 by the American Chemical Society. ...

See also

• Japp-Klingemann indole synthesis
• Indole