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The Reissert indole synthesis is a series of 
chemical reaction
A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and break ...
s designed to synthesize indole
Indole is an aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environme ...
or substituted-indoles (4 and 5) from ortho-nitrotoluene 1 and diethyl oxalate
In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry's nomenclature of organic chemistry for a saturated ...
2.
Potassium ethoxide
Potassium ethoxide, also known as potassium ethanolate, is an off-white or yellow powder with the chemical formula of C2H5KO. Potassium ethoxide contains an ethoxide ion, the conjugate base of ethanol, which makes this compounds strongly basic. It ...
has been shown to give better results than sodium ethoxide
Sodium ethoxide, also referred to as sodium ethylate, is the ionic, organic compound with the formula , or NaOEt (Et = ethane). It is a white solid, although impure samples appear yellow or brown. It dissolves in polar solvents such as ethanol. ...
.
Reaction mechanism
The first step of the synthesis is the condensation of o-nitrotoluene 1 with a diethyl oxalate 2 to give ethyl o-nitrophenylpyruvate 3. The reductive cyclization of 3 withzinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic t ...
in acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main componen ...
gives indole-2-carboxylic acid 4. If desired, 4 can be decarboxylated
Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is t ...
with heat to give indole 5.
Variations
Butin modification
In an intramolecular version of the Reissert reaction, a furan ring-opening provides the carbonyl necessary for cyclization to form an indole. A ketone side chain is present in the final product, allowing further modifications.{{cite journal , last1=Butin , first1=Alexander , last2=Stroganova , first2=Tatyana , last3=Lodina , first3=Irina , last4=Krapivin , first4=Gennady , date=2001 , title=Furan ring opening—indole ring closure: a new modification of the Reissert reaction for indole synthesis , journal=Tetrahedron Letters , volume=42 , issue=10 , pages=2031–3 , doi=10.1016/S0040-4039(01)00066-1
See also
* Leimgruber-Batcho indole synthesisReferences