Mar 15, 2011 shortly after he prepared quinoline by heating the condensation product of aniline and acrolein, thus anticipating the classical skraup synthesis. Quinoline is the simplest member of the quinoline class of compounds, comprising a benzene ring ortho fused to c2 and c3 of a pyridine ring. Vapour phase synthesis of quinoline from aniline and. The skraup synthesis is very energy intensive, and many modifications have been introduced batista et al. Find, read and cite all the research you need on researchgate. Reaction mechanism of the skraup quinoline synthesis. Jun 25, 2009 quinoline from aniline, glycerol, sulfuric acid and oxidizing agent e. It is named after the czech chemist zdenko hans skraup 18501910. The vapour phase synthesis of quinoline from aniline and glycerol 1. His other works were in the fields of natural products like the structure of alkaloids, synthesis of isoquinolines etc. A green route for the vaporphase synthesis of quinoline from glycerol and aniline was developed in this work, employing nimesoporous beta zeolite denoted as nih. Synthesis of quinolines from anilines, acetophenones and. Sulfuric acid,glycerol and mild oxidising agent are heated together 16.
Quinoline is a heterocyclic aromatic organic compound with the chemical formula c 9 h 7 n. Synthesis of quinoline derivatives by a doebnervon miller. Pdf mesoporous tungstic acid functionalized kit6 has been synthesized through a condensation of 3chloropropyl triethoxysilane and. Its derivatives represent the major class of heterocycles and a number of preparations have been known for a. These include antiinflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic lightemitting diodes. Synthesis of quinolines from glycerol over tungstic acid. The synthesis of a series of indole and carbazole derivatives from 2fluorophenyl imines is reported. A number of other processes exist, which require specifically substituted anilines or related compounds. The skraup synthesis26 in this extraordinary reaction, quinoline is produced when aniline, concentrated sulphuric acid, glycerol and mild oxidizing agent are heated together. Quinoline is readily obtained by the skraup synthesis in which a mixture of aniline, glycerol and concentrated. Us6103904a skraup reaction process for synthesizing. Over the past few years, various methods have been established for the synthesis of quinolines, which has greatly enriched the development of quinoline chemistry. The classical methods for the synthesis of this heterocyclic skeleton require. Highefficiency catalytic performance over mesoporous ni.
Quinoline from aniline, glycerol, sulfuric acid and oxidizing agent e. Glycerol 11 is dehydrated with sulfuric acid to acrolein 12, which then reacts with aniline by conjugate addition scheme 1. Among these catalysts investigated, the cuoznoal 2 o 3 combination effectively performed this. The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. Functionalized catalysts, skraup synthesis, wkit6, quinoline, glycerol glycerol is produced as a major byproduct of biodiesel manufacturing process. For an alternative mechanism, see that of the doebnervon miller reaction. Synthesis from solketal continuous niobium phosphate.
Synthesis of 7nitrobenzohquinoline has been achieved by heating. Nov 09, 2012 quinoline is a heterocyclic aromatic organic compound with the chemical formula c9h7n. The skraup synthesis 10 in this extraordinary reaction, quinoline is produced when aniline, concentrated sulfuric acid, glycerol and a mild oxidising agent are heated together. An effective reductive alkylation of electrondeficient ochloroarylamines was developed.
In this work, we reported a green and economic route for vaporphase synthesis of quinoline from glycerol and aniline, for the rst time, using modi ed mesoporous beta zeolite as catalyst. Quinolines have antiseptic, antipyretic, and antiperiodic properties and are used as antimalarials and for preparing other antimalarial drugs. Part i studies on compounds consisting quinoline and 2. When glycerol is used as an in situ source of acrolein, quinolines carrying no substituents on the heterocyclic ring are produced. Novel aniline trimers are prepared using glycerol, and substituted anilines under pressure, in acidic medium and water.
Quinoline is only slightly soluble in cold water but dissolvesreadily in hot water and most organic solvents. Pdf synthesis of quinolines from glycerol over tungstic acid. In the original procedure the oxidant was nitrobenzene, but since this often leads to a violent reaction, arsenic pentoxide or iodine is preferred. Quinoline appears as a colorless liquid with a peculiar odor. In 1880, czech chemist zdenko hans skraup heated aniline and glycerol with an oxidant in concentrated sulfuric acid, a method that is still. As water is the most beneficial solvent it will be of interest to study the effect of water in glycerol on the formation of nps.
Highefficiency catalytic performance over mesoporous nibeta zeolite for the synthesis of quinoline from glycerol and aniline. Quinoline can be prepared by heating a mixture of aniline, glycerol, and sulfuric acid 1 alone or with an oxidizing agent like nitrobenzene, 2 arsenic acid, 3 ferric oxide, 4 and vanadic acid. In this work, quinoline derivatives were synthesized from reaction of aniline, benzylaldehyde and dimethylacetylene dicarboxylate dmad in sequent steps to provide quinoline derivative dimethyl 2r, 3s, 4r2phenyl4phenylamino1, 3, 4trihydroquinoline2,3dicarboxylate 12. In the archetypal skraup reaction, aniline is heated with sulfuric acid, glycerol, and an oxidizing agent such as nitrobenzene to yield quinoline. Grace and pandian reported the synthesis of spherical and prism shaped au nps in gly cerol at both reflux and microwave conditions 16. Novel aniline trimers are prepared using glycerol, and substituted anilines under. Quinoline and its derivatives are important heterocyclic systems which have great significance as a biologically active compounds as well as being useful synthon for synthesis of many heterocyclic compounds. Syntheses of symmetrically 4,6bissubstituted amino, oxo and thiopyrido3,2g quinoline derivatives were previously reported 4,5 and their mdr reversal activity 6 was demonstrated. Quinoline is a heterocyclic aromatic organic compound with the chemical formula c9h7n. Request pdf skraup quinoline synthesis quinoline from aniline, glycerol, sulfuric acid and oxidizing agent e. Influence of reaction parameters on the catalytic performance. The quinoline scaffold is present in a vast number of natural compounds and pharmacologically active substances, comprising a significant segment of the pharmaceutical market. A practicable quinoline synthesis from aniline and two amino acids provides a wide range of quinolines with high efficiency and diversity including pharmaceutical derivatives, photochemical active compounds, and challenging scaffolds.
Itis a colorless hygroscopic liquid with a strong odor. Skraup synthesis article about skraup synthesis by the. Shortly after he prepared quinoline by heating the condensation product of aniline and acrolein, thus anticipating the classical skraup synthesis. However, many of the existing methods utilise expensive transition metals, pre. Catalysts, mesoporous catalysts, functionalized catalysts, skraup synthesis, wkit6, quinoline, glycerol glycerol is produced as a major byproduct of biodiesel manufacturing process. Aged samples, if exposed to light,become yellow and later brown. Sulfuric acid, glycerol and mild oxidising agent are heated together 16. Syntheses of symmetrically 4,6bissubstituted amino, oxo and thiopyrido3,2gquinoline derivatives were previously reported 4,5 and their mdr reversal activity 6. It is the best reaction for synthesis of quinoline17 nh2 h o. Method for the preparation of quinoline and aniline. The quinoline substructure is an important heterocyclic motif which is found in many natural products, pharmaceuticals and functional materials. Microwaveassisted synthesis of phenothiazine and quinoline. The present invention relates to an improved skraup reaction process wherein pressure is applied during the reaction and the number of equivalents of sulfuric acid utilized is reduced.
Simple reaction procedures, inexpensive catalysts, and single product formation make this an attractive protocol over the existing procedures. Quinolines were first synthesized in 1879, and since then a multitude of. New quinoline2one derivatives were synthesized by reaction of 4,7dimethyl coumarin i with nitric acid in the presence of concentrated sulfuric acid to afford 4,7dimethyl6nitrocoumarin ii and 4,7dimethyl8nitrocoumarin iii. Proficient procedure for preparation of quinoline derivatives.
Vapour phase synthesis of quinoline from aniline and glycerol. Quinoline reagent grade, 98% 2,3benzopyridine sigmaaldrich. Us6103904a us08896,556 us89655697a us6103904a us 6103904 a us6103904 a us 6103904a us 89655697 a us89655697 a us 89655697a us 6103904 a us6103904 a us 6103904a authority us united states prior art keywords temperature reaction quinolones skraup substituted prior art date 19970717 legal status the legal status is an assumption and is not a legal conclusion. Pdf vapour phase synthesis of quinoline from aniline and.
Quinoline and aniline compounds have been synthesized from aromatic nitro compounds and ethylenically unsaturated hydrocarbons in the presence of complexes of group viii metals used as catalysts. Camps quinoline synthesis using an oacylaminoacetophenone and hydroxide. This work describes the synthesis of new heterocyclic compounds from quinoline derivatives and amines. Skraup synthesis using ferrous sulfate, glycerol, aniline, nitrobenzene, and sulfuric acid. Skraup synthesis involves heating aniline derivatives with glycerol, sulfuric acid and oxidizing agents.
Nov 03, 2012 this reaction was first studied in 1880 by zdenko hans skraup 18501910, a czech scientist born in prague city of czech republic. Pdf vapour phase synthesis of quinoline from aniline and glycerol. The compound ii was treated with hydrazine hydrate 80% in pyridine to give n amino4,7dimethy 6nitroquinoline2one iv. This synthesis involves a series of reactions brought about by heating a primary aromatic amine, in which at least one position ortho to the amino group is unsubstituted, with glycerol, sulfuric acid. Green synthesis of gold nanoparticles using glycerol as a. Vapour phase synthesis of quinoline from aniline and glycerol over mixed oxide catalysts. The resulting intermediate is cyclised, oxidized and dehydrated to give quinoline 16. Important green metrics were analyzed and will allow the choice of the best sustainable approaches toward quinoline synthesis. The productivity of quinoline in terms of weight time yield. Table 1 skraup reaction of glycerol with substituted aniline over. Quinoline is readily obtained by the skraup synthesis in which a mixture of aniline, glycerol and concentrated sulphuric acid is heated with a suitable oxidising agent. Quinoline reagent grade, 98% 2,3benzopyridine sigma. Activity relationship of 4substituted 22acetyloxyethyl8morpholine 4sulfonylpyrrolo3,4cquinoline 1,3diones as potent caspase3 inhibitors dmitri v.
Methylindole from glycerol cyclization with aniline over cucral 2 o 3 catalysts modified by alkali earth oxides, heteroatom chemistry on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Synthesis of quinolines from aniline and propanol over. Skraups synthesis is a chemical reaction used to synthesize quinolines by the condensation of glycerine. Us4157445a method for the preparation of quinoline and. In the archetypal skraup reaction, aniline is heated with sulfuric acid, glycerol. Quinoline and aniline compounds have been synthesized from aromatic nitro compounds and ethylenically unsaturated hydrocarbons in the presence of complexes of. The reaction proceeds via dehydration of glycerol to acrolein. Glycerol was employed as a catalyst and a green solvent in the synthesis of novel pyridazines ac. Theliteraturehowever,givesthenameoftheproduct derivedfrom the above reaction as anhydroformaldehydeaniline andrepresents it by the follovin structures. Synthesis of derivatives of 2 phenyl quinoline 4 carboxylic acid. One of the most well known methods for the preparation of quinoline is the skraup synthesis which consists of heating a primary aromatic amine, such as, aniline with glycerol, concentrated sulphuric acid and an oxidizing agent such as nitrobenzene, ferric chloride or arsenic acid. Quinoline 1azanaphthalene or benzobpyridine is a stable base. Doebnermiller synthesis the doebnermiller reaction is the organic reaction of an aniline with. Studies on potential antimicrobial agents page 59 brief introduction to quinoline.
Skraup synthesis article about skraup synthesis by the free. Skraup synthesis the synthesis of quinoline and quinoline analogues and derivatives by the. Quinoline derivatives are prevalent in a variety of pharmacologically active synthetic and natural compounds. This reaction was first studied in 1880 by zdenko hans skraup 18501910, a czech scientist born in prague city of czech republic. General description quinoline is a heterocyclic aromatic organic compound with the chemical formula c 9 h 7 n. The same idea works well in probably the most famous quinoline synthesis, the skraup reaction. Supporting information quinoline from glycerol and aniline. Approximately 10% in weight of crude glycerol is created for every 1 kg of biodiesel production. It is a mancude organic heterobicyclic parent, a member of quinolines, an azaarene and an orthofused heteroarene. Recent advances in metalfree quinoline synthesis ncbi. In conclusion, efficient synthesis of quinoline derivatives has been achieved by a onepot coupling reaction of carbonyl compounds and aminobenzophenone using catalytic amounts of nbcl 5 in glycerol. Synthesis and biological activity investigation of some. Ill the reaction has been shown to proceed via dehydration of the glycerol to acrolein, to which aniline then adds in a conjugate fashion.
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