| Reissert indole synthesis | |
|---|---|
| Named after | Arnold Reissert |
| Reaction type | Ring forming reaction |
The Reissert indole synthesis is a series of chemical reactions designed to synthesize indole or substituted-indoles (4 and 5) from ortho-nitrotoluene 1 and diethyl oxalate 2. [1] [2]
Potassium ethoxide has been shown to give better results than sodium ethoxide. [3]
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 with zinc in acetic acid gives indole-2-carboxylic acid 4. If desired, 4 can be decarboxylated with heat to give indole 5.
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. [4]
Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3. Porphobilinogen, a trisubstituted pyrrole, is the biosynthetic precursor to many natural products such as heme.
Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen. Chemical compounds containing such rings are also referred to as furans.
Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds such as barbiturates, artificial flavourings, vitamin B1, and vitamin B6.
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 Emil Fischer. Today antimigraine drugs of the triptan class are often synthesized by this method.
Oxalyl chloride is a chemical compound with the formula (COCl)2. This colourless, sharp-smelling liquid, the diacyl chloride of oxalic acid, is a useful reagent in organic synthesis. It can be prepared by treating oxalic acid with phosphorus pentachloride.
The Knoevenagel condensation reaction is an organic reaction named after Emil Knoevenagel. It is a modification of the aldol condensation.
The Pictet–Spengler reaction is a chemical reaction in which a β-arylethylamine undergoes condensation with an aldehyde or ketone followed by ring closure. The reaction was first discovered in 1911 by Amé Pictet and Theodor Spengler. Traditionally an acidic catalyst in protic solvent was employed with heating, however the reaction has been shown to work in aprotic media in superior yields and sometimes without acid catalysis. The Pictet–Spengler reaction can be considered a special case of the Mannich reaction, which follows a similar reaction pathway. The driving force for this reaction is the electrophilicity of the iminium ion generated from the condensation of the aldehyde and amine under acid conditions. This explains the need for an acid catalyst in most cases, as the imine is not electrophilic enough for ring closure but the iminium ion is capable of undergoing the reaction.
The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base, resulting in a β-keto ester or a β-diketone. It is named after Rainer Ludwig Claisen, who first published his work on the reaction in 1887.
The Leimgruber–Batcho indole synthesis is a series of organic reactions that produce indoles from o-nitrotoluenes 1. The first step is the formation of an enamine 2 using N,N-dimethylformamide dimethyl acetal and pyrrolidine. The desired indole 3 is then formed in a second step by reductive cyclisation.
The Madelung synthesis is a chemical reaction that produces indoles by the intramolecular cyclization of N-phenylamides using strong base at high temperature.The Madelung synthesis was reported in 1912 by Walter Madelung, when he observed that 2-phenylindole was synthesized using N-benzoyl-o-toluidine and two equivalents of sodium ethoxide in a heated, airless, reaction. Common reaction conditions include use of sodium or potassium alkoxide as base in hexane or tetrahydrofuran solvents, at temperatures ranging between 200–400 °C. A hydrolysis step is also required in the synthesis. The Madelung synthesis is important because it is one of few known reactions that produce indoles from a base-catalyzed thermal cyclization of N-acyl-o-toluidines. The overall reaction for the Madelung synthesis follows.
Indene is a flammable polycyclic hydrocarbon with chemical formula C9H8. It is composed of a benzene ring fused with a cyclopentene ring. This aromatic liquid is colorless although samples often are pale yellow. The principal industrial use of indene is in the production of indene/coumarone thermoplastic resins. Substituted indenes and their closely related indane derivatives are important structural motifs found in many natural products and biologically active molecules, such as sulindac.
The Reissert reaction is a series of chemical reactions that transforms quinoline to quinaldic acid. Quinolines will react with acid chlorides and potassium cyanide to give 1-acyl-2-cyano-1,2-dihydroquinolines, also known as Reissert compounds. Hydrolysis gives the desired quinaldic acid.
The Bartoli indole synthesis is the chemical reaction of ortho-substituted nitroarenes and nitrosoarenes with vinyl Grignard reagents to form substituted indoles.
The Paal–Knorr Synthesis in organic chemistry is a reaction that generates either furans, pyrroles, or thiophenes from 1,4-diketones. It is a synthetically valuable method for obtaining substituted furans and pyrroles, common structural components of many natural products. It was initially reported independently by German chemists Carl Paal and Ludwig Knorr in 1884 as a method for the preparation of furans, and has been adapted for pyrroles and thiophenes. Although the Paal–Knorr synthesis has seen widespread use, the mechanism wasn't fully understood until it was elucidated by V. Amarnath et al. in the 1990s.
Oseltamivir total synthesis concerns the total synthesis of the antiinfluenza drug oseltamivir marketed by Hoffmann-La Roche under the trade name Tamiflu. Its commercial production starts from the biomolecule shikimic acid harvested from Chinese star anise with a limited worldwide supply. Due to its limited supply, searches for alternative synthetic routes preferably not requiring shikimic acid are underway and to date several such routes have been published. Control of stereochemistry is important: the molecule has three stereocenters and the sought-after isomer is only 1 of 8 stereoisomers.
Carbazole is an aromatic heterocyclic organic compound. It has a tricyclic structure, consisting of two six-membered benzene rings fused on either side of a five-membered nitrogen-containing ring. The compound's structure is based on the indole structure, but in which a second benzene ring is fused onto the five-membered ring at the 2–3 position of indole.
The Fukuyama indole synthesis is a versatile tin mediated chemical reaction that results in the formation of 2,3-disubstituted indoles. A practical one-pot reaction that can be useful for the creation of disubstituted indoles. Most commonly tributyltin hydride is utilized as the reducing agent, with azobisisobutyronitrile (AIBN) as a radical initiator. Triethylborane can also be used as a radical initiator. The reaction can begin with either an ortho-isocyanostyrene or a 2-alkenylthioanilide derivative, both forming the indole through Radical cyclization via an α-stannoimidoyl radical. The R group can be a range of both basic and acidic sensitive functional groups such as esters, THP ethers, and β-lactams. In addition the reaction is not stereospecific, in that both the cis and trans isoform can be used to obtain the desired product.
Indole is an aromatic heterocyclic organic compound with formula C8H7N. 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 environment and can be produced by a variety of bacteria. As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence. The amino acid tryptophan is an indole derivative and the precursor of the neurotransmitter serotonin.
Diethylphosphite is the organophosphorus compound with the formula (C2H5O)2P(O)H. It is a popular reagent for generating other organophosphorus compounds, exploiting the high reactivity of the P-H bond. Diethylphosphite is a colorless liquid. The molecule is tetrahedral.