Skraup reaction

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Skraup reaction
Named after Zdenko Hans Skraup
Reaction type Ring forming reaction
Identifiers
RSC ontology ID RXNO:0000062

The Skraup synthesis is a chemical reaction used to synthesize quinolines. It is named after the Czech chemist Zdenko Hans Skraup (1850-1910). In the archetypal Skraup reaction, aniline is heated with sulfuric acid, glycerol, and an oxidizing agent such as nitrobenzene to yield quinoline. [1] [2] [3] [4]

Chemical reaction process that results in the interconversion of chemical species

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 breaking of chemical bonds between atoms, with no change to the nuclei, and can often be described by a chemical equation. Nuclear chemistry is a sub-discipline of chemistry that involves the chemical reactions of unstable and radioactive elements where both electronic and nuclear changes can occur.

Quinoline chemical compound

Quinoline is a heterocyclic aromatic organic compound with the chemical formula C9H7N. It is a colorless hygroscopic liquid with a strong odor. Aged samples, especially if exposed to light, become yellow and later brown. Quinoline is only slightly soluble in cold water but dissolves readily in hot water and most organic solvents. Quinoline itself has few applications, but many of its derivatives are useful in diverse applications. A prominent example is quinine, an alkaloid found in plants. 4-Hydroxy-2-alkylquinolines (HAQs) are involved in antibiotic resistance.

Zdenko Hans Skraup Czech chemist

Zdenko Hans Skraup was a Czech-Austrian chemist who discovered the Skraup reaction, the first quinoline synthesis.

The Skraup reaction Skraup Reaktion overview V1-Seite001.svg
The Skraup reaction
The Skraup reaction with substituted aryl Skraup2.svg
The Skraup reaction with substituted aryl

In this example, nitrobenzene serves as both the solvent and the oxidizing agent. The reaction, which otherwise has a reputation for being violent, is typically conducted in the presence of ferrous sulfate. [5] Arsenic acid may be used instead of nitrobenzene and the former is better since the reaction is less violent. [6]

Nitrobenzene chemical compound

Nitrobenzene is an organic compound with the chemical formula C6H5NO2. It is a water-insoluble pale yellow oil with an almond-like odor. It freezes to give greenish-yellow crystals. It is produced on a large scale from benzene as a precursor to aniline. In the laboratory, it is occasionally used as a solvent, especially for electrophilic reagents.

Solvent substance that dissolves a solute (a chemically different liquid, solid or gas), resulting in a solution

A solvent is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. The quantity of solute that can dissolve in a specific volume of solvent varies with temperature. Common uses for organic solvents are in dry cleaning, as paint thinners, as nail polish removers and glue solvents, in spot removers, in detergents and in perfumes (ethanol). Water is a solvent for polar molecules and the most common solvent used by living things; all the ions and proteins in a cell are dissolved in water within a cell. Solvents find various applications in chemical, pharmaceutical, oil, and gas industries, including in chemical syntheses and purification processes.

Iron(II) sulfate chemical compound

Iron(II) sulfate (British English: iron(II) sulphate) or ferrous sulfate denotes a range of salts with the formula FeSO4·xH2O. These compounds exist most commonly as the heptahydrate (x = 7) but are known for several values of x. The hydrated form is used medically to treat iron deficiency, and also for industrial applications. Known since ancient times as copperas and as green vitriol (vitriol is an archaic name for sulfate), the blue-green heptahydrate (hydrate with 7 molecules of water) is the most common form of this material. All the iron(II) sulfates dissolve in water to give the same aquo complex [Fe(H2O)6]2+, which has octahedral molecular geometry and is paramagnetic. The name copperas dates from times when the copper(II) sulfate was known as blue copperas, and perhaps in analogy, iron(II) and zinc sulfate were known respectively as green and white copperas.

Skraup Reaktion glycerin V1-Seite001.svg
Skraub Reaktionsmechanismus V1-Seite001.svg
Skraup quinoline synthesis mechanism.svg

See also

Related Research Articles

Acridine chemical compound

Acridine is an organic compound and a nitrogen heterocycle with the formula C13H9N. Acridines are substituted derivatives of the parent ring. It is a planar molecule that is structurally related to anthracene with one of the central CH groups replaced by nitrogen. Like the related molecule pyridine and quinoline, acridine is mildly basic. It is an almost colorless solid. There are no commercial applications of acridines but at one time acridine dyes were popular. It crystallizes in needles.

Nitromethane is an organic compound with the chemical formula CH
3
NO
2
. It is the simplest organic nitro compound. It is a polar liquid commonly used as a solvent in a variety of industrial applications such as in extractions, as a reaction medium, and as a cleaning solvent. As an intermediate in organic synthesis, it is used widely in the manufacture of pharmaceuticals, pesticides, explosives, fibers, and coatings. Nitromethane is used as a fuel additive in various motorsports and hobbies, e.g. Top Fuel drag racing and miniature internal combustion engines in radio control, control line and free flight model aircraft.

Imine any chemical compound having the structure RN=CR′R″, thus analogue of aldehyde or ketone in which an oxygen atom is replaced by substituted or unsubstituted nitrogen atom

An imine is a functional group or chemical compound containing a carbon–nitrogen double bond. The nitrogen atom can be attached to a hydrogen (H) or an organic group (R). If this group is not a hydrogen atom, then the compound can sometimes be referred to as a Schiff base. The carbon atom has two additional single bonds. The term "imine" was coined in 1883 by the German chemist Albert Ladenburg.

Nitro compound organic compounds that contain one or more nitro functional groups

Nitro compounds are organic compounds that contain one or more nitro functional groups (−NO2). The nitro group is one of the most common explosophores (functional group that makes a compound explosive) used globally. The nitro group is also strongly electron-withdrawing. Because of this property, C−H bonds alpha (adjacent) to the nitro group can be acidic. For similar reasons, the presence of nitro groups in aromatic compounds retards electrophilic aromatic substitution but facilitates nucleophilic aromatic substitution. Nitro groups are rarely found in nature, being almost invariably produced by nitration reactions starting with nitric acid.

Pyridinium chlorochromate chemical compound

Pyridinium chlorochromate (PCC) is a yellow-orange salt with the formula [C5H5NH]+[CrO3Cl]-. It is a reagent in organic synthesis used primarily for oxidation of alcohols to form carbonyls. A variety of related compounds are known with similar reactivity. Although no longer widely used, PCC offers the advantage of the selective oxidation of alcohols to aldehydes or ketones, whereas many other reagents are less selective.

In chemistry, a dehydration reaction is a conversion that involves the loss of water from the reacting molecule or ion. Dehydration reactions are common processes, the reverse of a hydration reaction. Common dehydrating agents used in organic synthesis include sulfuric acid and alumina. Often dehydration reactions are effected with heating.

Phenanthroline chemical compound

Phenanthroline (phen) is a heterocyclic organic compound. It is a white solid that is soluble in organic solvents. It is used as a ligand in coordination chemistry, forming strong complexes with most metal ions.

Ozonolysis is an organic reaction where the unsaturated bonds of alkenes, alkynes, or azo compounds are cleaved with ozone. Alkenes and alkynes form organic compounds in which the multiple carbon–carbon bond has been replaced by a carbonyl group while azo compounds form nitrosamines. The outcome of the reaction depends on the type of multiple bond being oxidized and the work-up conditions.

Nitrosylsulfuric acid chemical compound

Nitrosylsulfuric acid is the chemical compound with the formula NOHSO4. It is a colourless solid that is used industrially in the production of caprolactam, and was formerly part of the lead chamber process for producing sulfuric acid. The compound is the mixed anhydride of sulfuric acid and nitrous acid.

1,4-Benzoquinone chemical compound

1,4-Benzoquinone, commonly known as para-quinone, is a chemical compound with the formula C6H4O2. In a pure state, it forms bright-yellow crystals with a characteristic irritating odor, resembling that of chlorine, bleach, and hot plastic or formaldehyde. This six-membered ring compound is the oxidized derivative of 1,4-hydroquinone. The molecule is multifunctional: it exhibits properties of a ketone, forming an oxime; an oxidant, forming the dihydroxy derivative; and an alkene, undergoing addition reactions, especially those typical for α,β-unsaturated ketones. 1,4-Benzoquinone is sensitive toward both strong mineral acids and alkali, which cause condensation and decomposition of the compound.

The Friedländer synthesis is a chemical reaction of 2-aminobenzaldehydes with ketones to form quinoline derivatives. It is named after German chemist Paul Friedländer (1857–1923).

Doebner–Miller reaction

The Doebner–Miller reaction is the organic reaction of an aniline with α,β-unsaturated carbonyl compounds to form quinolines.

Nitrosobenzene chemical compound

Nitrosobenzene is the organic compound with the formula C6H5NO. It is one of the prototypical organic nitroso compounds. It is a bright blue species that exists in equilibrium with its pale yellow dimer. Both monomer and dimer are diamagnetic.

Lead(IV) acetate chemical compound

Lead(IV) acetate or lead tetraacetate is a chemical compound with chemical formula Pb(C2H3O2)4. It is a colorless solid that is soluble in nonpolar organic solvents, indicative that it is not a salt. It is degraded by moisture and is typically stored with additional acetic acid. The compound is used in organic synthesis.

The Combes quinoline synthesis is a chemical reaction, which was first reported by Combes in 1888. It involves the condensation of unsubstituted anilines (1) with β-diketones (2) to form substituted quinolines (4) after an acid-catalyzed ring closure of an intermediate Schiff base (3). Further studies and reviews of the Combes quinoline synthesis and its variations have been published by Alyamkina et al., Bergstrom and Franklin, Born, and Johnson and Mathews.

Gould–Jacobs reaction

The Gould–Jacobs reaction is an organic synthesis for the preparation of quinolines and 4‐hydroxyquinoline derivatives. The Gould-Jacobs reaction is a series of reactions. The series of reactions begins with the condensation/substitution of an aniline with alkoxy methylenemalonic ester or acyl malonic ester, producing anilidomethylenemalonic ester. Then through a 6 electron cyclization process, 4-hydroxy-3-carboalkoxyquinoline is formed, which exist mostly in the 4-oxo form. Saponification results in the formation of an acid. This step is followed by decarboxylation to give 4-hydroxyquinoline. The Gould-Jacobs reaction is effective for anilines with electron‐donating groups at the meta‐position.

Pyridine-<i>N</i>-oxide chemical compound

Pyridine-N-oxide is the heterocyclic compound with the formula C5H5NO. This colourless, hygroscopic solid is the product of the oxidation of pyridine. It was originally prepared using peroxyacids as the oxidising agent. The molecule is planar. The compound is used infrequently as an oxidizing reagent in organic synthesis. It also serves as a ligand in coordination chemistry.

Trifluoroperacetic acid chemical compound

Trifluoroperacetic acid is the peroxy acid analog of trifluoroacetic acid and has the condensed structural formula CF
3
COOOH
. It is a strong oxidizing agent for organic oxidation reactions, such as in Baeyer–Villiger oxidations of ketones. It is the most reactive of the organic peroxy acids, allowing it to successfully oxidise relatively unreactive alkenes to epoxides where other peroxy acids are ineffective. It can also oxidise the chalcogens in some functional groups, such as by transforming selenoethers to selenones. It is a potentially explosive material and is not commercially available, but can be quickly prepared immediately prior to use when needed. Its use as a laboratory reagent was pioneered and developed by William D. Emmons.

References

  1. Skraup, Z. H. (1880). "Eine Synthese des Chinolins". Berichte . 13: 2086.
  2. Manske, R. H. F. (1942). "The Chemistry of Quinolines". Chem. Rev. 30: 113. doi:10.1021/cr60095a006.
  3. Manske, Richard H. F.; Kulka, Marshall (1953). "The Skraup Synthesis of Quinolines". Org. React. 7: 80–99. doi:10.1002/0471264180.or007.02.
  4. Wahren, M. (1964). "Stabilisotop markierte verbindungen—II , Untersuchung der skraupschen chinolin-synthese mit hilfe von 15N". Tetrahedron . 20 (12): 2773. doi:10.1016/S0040-4020(01)98495-9.
  5. Clarke, H. T.; Davis, A. W. (1941). "Quinoline". Organic Syntheses .; Collective Volume, 1, p. 478
  6. Finar, Ivor Lionel (1973). Organic Chemistry, Volume 1 (6th ed.). p. 857. ISBN   978-0582442214.