91-22-5

Usage

Production Methods

Quinoline may be synthesized by heating aniline with glycerol and nitrobenzene in sulfuric acid (Skraup method) or by reacting aniline, acetaldehyde, and a formaldehyde hemiacetal (Windholz et al 1983). Commercial production is by isolation from coal tar with greater than 100,000 lbs being produced in 1977. Production of refined quinoline has almost ceased due to low demand (Parris et al 1983).

Synthesis Reference(s)

Tetrahedron Letters, 29, p. 953, 1988 DOI: 10.1016/S0040-4039(00)82491-0Chemical and Pharmaceutical Bulletin, 26, p. 1015, 1978 DOI: 10.1248/cpb.26.1015

Reactivity Profile

Quinoline is hygroscopic. Quinoline absorbs as much as 22% water. Quinoline is sensitive to light and moisture. Quinoline darkens on storage. Quinoline is a weak base. A potentially explosive reaction may occur with hydrogen peroxide. Quinoline reacts violently with dinitrogen tetraoxide. Quinoline also reacts violently with perchromates. Quinoline is incompatible with (linseed oil + thionyl chloride) and maleic anhydride. Quinoline is also incompatible with strong oxidizers and strong acids. Quinoline can be unpredictably violent. Quinoline dissolves sulfur, phosphorus and arsenic trioxide. Quinoline may attack some forms of plastics. Quinoline is a preparative hazard.

Health Hazard

Vapors are irritating to nose and throat and may cause headaches, dizziness, and nausea if inhaled. Ingestion causes irritation of mouth and stomach; vomiting may occur. Contact with eyes or skin causes irritation.

Health Hazard

No industrial injuries from quinoline exposure have been reported. Handling precautions similar to those taken for pyridine are recommended (EOHS 1971). Clinical signs of toxicity include lethargy, respiratory distress, and coma; cause of death is respiratory paralysis. Quinoline is a skin and eye irritant; it may cause permanent corneal injury (EOHS 1971). Routine occupational exposure to quinoline probably constitutes low risk for acute toxicity. Long-term exposure to low concentrations may increase cancer risk.

Health Hazard

There is little information in the publishedliterature on the toxic properties of quinoline.The acute toxicity is moderate in rodentsfrom oral and dermal administration. Thereported oral LD50 values in rats showinconsistent values ranging between 300 and500 mg/kg. Its irritant action was mild onrabbits’ skin and severe in the animals’ eyes.Quinoline exhibited carcinogenicity inrats and mice, causing liver cancer. There isno evidence of its carcinogenicity in humans.It tested positive to the histidine reversion–Ames test for mutagenicity.

Flammability and Explosibility

Nonflammable

Chemical Reactivity

Reactivity with Water No reaction; Reactivity with Common Materials: Attacks some forms of plastics; Stability During Transport: Stable; Neutralizing Agents for Acids and Caustics: Not pertinent; Polymerization: Not pertinent; Inhibitor of Polymerization: Not pertinent.

Safety Profile

Poison by ingestion, subcutaneous, and intraperitoneal routes. Moderately toxic by skin contact. A skin and severe eye irritant. Mutation data reported. Questionable carcinogen with experimental neoplastigenic and tumorigenic data. It can cause retinitis sdar to that caused by naphthalene but without causing opacity of the lens. Combustible when exposed to heat or flame. Its preparation has caused many industrial explosions. Potentially explosive reaction with hydrogen peroxide. Violent reaction with dmtrogen tetraoxide, perchromates. Incompatible with linseed oil + thionyl chloride, maleic anhydride, Unpredctably violent. When heated to decomposition it emits toxic fumes of NOx.

Potential Exposure

In manufacture of quinoline deriva- tives (dyes and pesticides); in synthetic fuel manufacture. Occurs in cigarette smoke.

Carcinogenicity

Liver tumors were observed in rats administered diets containing 0.05–0.25% quinoline. The incidence of hepatocellular carcinomas was 3/11 at 0.05%, 3/16 at 0.1%, and 0/19 at 0.25% versus 0/6 in controls. At 0.25%, most of the rats died within 40 weeks. The incidences of hemangioendotheliomas were 6/11, 12/16, 18/19, and 0/6, respectively. Hepatocellular carcinomas and hemangioendotheliomas were seen in livers of rats fed 500, 1000, or 2500 ppm for 16–40 weeks. Typical hyperplasias were also observed in the liver.

Environmental Fate

biodegradative processes occur under aerobic conditions. Anaerobic degradation is minimal (Mill et al 1981). Breakdown of quinoline in natural waters has been correlated with bacterial concentration (Rogers et al 1984). Adsorption was high in acidic soils (pH<6) and low in basic soils (pH>7). The presence of pyridine decreased quinoline adsorption on acidic, but not basic, soils. Sorption did not correlate with organic carbon or clay content (Felice et al 1984). Soil bacteria have been grown with quinoline as the sole carbon source (Grant and Al-Najjar 1976). Quinoline did not bioconcentrate to a significant extent in fathead minnows (Southworth et al 1980).

Shipping

UN2656 Quinoline, Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Purification Methods

Dry quinoline with Na2SO4 and distil it from zinc dust in a vacuum. It has also been dried by boiling with acetic anhydride, then fractionally distilled. Calvin and Wilmarth [J Am Chem Soc 78 1301 1956] cooled redistilled quinoline in ice and added enough HCl to form its hydrochloride. Diazotization removed aniline, the diazo compound being broken down by warming the solution to 60o. Non-basic impurities were removed by ether extraction. Quinoline was then liberated by neutralising the hydrochloride with NaOH, then dried with KOH and fractionally distilled at low pressure. Addition of cuprous acetate (7g/L of quinoline) and shaking under hydrogen for 12hours at 100o removed impurities due to the nitrous acid treatment. Finally the hydrogen was pumped off, and the quinoline was distilled. Other purification procedures depend on conversion to the phosphate (m 159o, precipitated from MeOH solution, filtered, washed with MeOH, then dried at 55o) or the picrate (m 201o) which, after recrystallisation, were reconverted to quinoline. The method using the picrate [Packer et al. J Am Chem Soc 80 905 1958] is as follows: quinoline is added to picric acid dissolved in the minimum volume of 95% EtOH, giving yellow crystals which were washed with EtOH, air-dried and crystallised from acetonitrile. These were dissolved in dimethyl sulfoxide (previously dried over 4A molecular sieves) and passed through a basic alumina column, onto which the picric acid is adsorbed. The free base in the effluent is extracted with n-pentane and distilled under vacuum. Traces of solvent can be removed by vapour-phase chromatography. [Moonaw & Anton J Phys Chem 80 2243 1976.] The ZnCl2 and dichromate complexes have also been used [Cumper et al. J Chem Soc 1176 1962]. [Beilstein 20 H 339, 20 I 134, 20 II 222, 20 III/IV 3334, 20/7 V 276.]

Toxicity evaluation

Quinoline undergoes Phase I metabolism to form an enamine oxide, a rapid transitional epoxide, which can then form DNA adducts. This epoxide is formed on the pyridine moiety of quinoline. Fluorination at position 3 completely prevents the mutagenicity of quinoline. The major metabolic enzyme is the CYP2E1 isoform with the primary end product from this reaction being 3-hydroxyquinoline. Refer to the sections on ‘Genotoxicity’ and ‘Carcinogenicity’ for more specific descriptions of quinoline toxicity. The primary and most severe, toxic outcome following quinoline exposure is genotoxicity followed by tumor formation.

Incompatibilities

Reacts, possibly violently, with strong oxidants, strong acids; perchromates, nitrogen tetroxide; and maleic anhydride. Keep away from moisture, steam, and light. Contact with hydrogen peroxide may cause explosion. Unpredictably violent, this substance has been the source of various plant accidents.

InChI:InChI=1/C9H7N/c1-2-6-9-8(4-1)5-3-7-10-9/h1-7H

Upstream product

• 110-86-1 pyridine 
• 830-60-4 2H-quinoline-1,2-dicarbonitrile 
• 64-19-7 acetic acid 
• 95-20-5 2-methyl-1H-indole 
• 5435-44-9 (E)-3-Ureido-but-2-enoic acid ethyl ester 
• 5840-15-3 1-phenylamino 2,3-propanediol 
• 67-56-1 methanol 
• 5332-25-2 6-bromoquinoline 
• 124-41-4 sodium methylate 
• 64-17-5 ethanol 
• 141-52-6 sodium ethanolate 
• 16567-18-3 8-bromoquinoline 
• 10500-57-9 5,6,7,8-tetrahydroquinoline 
• 635-46-1 1,2,3,4-tetrahydroisoquinoline 

Downstream Products

• 1613-32-7 2-n-Propylquinoline 
• 55570-23-5 2-allyl-1,2-dihydro-quinoline 
• 1745-77-3 2-benzylquinoline 
• 612-96-4 2-Phenylquinoline 
• 2142-01-0 N-benzylphthalimide 
• 34243-33-9 2-thiophen-2-yl-quinoline 
• 98-01-1 furfural 
• 80038-65-9 1-[4-(1-quinoliniumyl)butyl]quinolinium dibromide 
• 676551-01-2 2-((Z)-3-Phenyl-allylidene)-malonic acid 
• 91-63-4 2-methylquinoline 
• 491-35-0 C₆H₄NCH₂CHCCH₂ 
• 859820-94-3 3-benzhydrylidene-6-([1]naphthyl-phenyl-methylene)-cyclohexa-1,4-diene 
• 4612-76-4 1-isopropylidene-4,4-dimethyl-4,4a-dihydro-[1,3]oxazino[3,4-a]quinolin-3-one 
• 36037-35-1 chlorocarbonic acid-(4-chloro-2-methyl-phenyl ester) 

Relevant academic research and scientific papers

Microwaves under pressure for the continuous production of quinoline from glycerol

Abstract Microwave heating is an interesting technology for chemical engineering, since it can provide effective volumetric heating of the reaction medium and reduce energy costs. Many commercially available laboratory-scale microwave reactors have already been used to carry out chemical reactions on a small scale (a few milliliters), and at high temperatures and pressures. Some research has been undertaken to scale-up microwave processes and make them suitable for a larger scale production. Indeed, combining wave propagation through the walls of a reactor with resistance toward high pressure and temperature as well, is not an easy task. For these reasons, this work focuses on the development of a pilot scale microwave apparatus used for the heating of larger reaction volumes under pressure, and under controlled conditions. The specially designed microwave apparatus allows chemical reactions in batch or continuous mode. The applicator operates in single mode enabling a uniform electromagnetic field, and well controlled operating conditions. The main advantage of the setup is the quite large reactor volume that permits either relatively long residence times or relatively high mass flowrates (up to 1 kg/h). The developed microwave apparatus was then used for quinoline synthesis from glycerol via a modified Skraup reaction. The major advantage of our system is the ability to carry out continuous chemical synthesis, at a large pilot scale, and high temperatures (200-220 °C), while ensuring a better control of the pressure (max. 19 bar) through the control of the power absorbed by the reaction medium.

Reversible dehydrogenation-hydrogenation of tetrahydroquinoline-quinoline using a supported copper nanoparticle catalyst

Copper nanoparticles synthesized on a titania surface (Cu/TiO2) act as an efficient heterogeneous catalyst for the reversible dehydrogenation and hydrogenation of tetrahydroquinoline-quinoline under an atmospheric pressure of H2. The Japan Institute of Heterocyclic Chemistry.

Copper-Catalyzed Direct Oxidative α-Functionalization of Tetrahydroquinoline in Water under Mild Conditions

An efficient one-step α-functionalization of tetrahydroquinoline under mild conditions is achieved. The direct oxidative copper-catalyzed dehydrogenative cross C(sp3)?C(sp2) couplings of tetrahydroquinolines and indoles produced the products in aqueous and open air medium. The use of inexpensive copper catalyst, water solvent, easy to operate open air condition combined with the most step and atom economic features qualify the CDC reaction for a green process. (Figure presented.).

Copper(ii)/amine synergistically catalyzed enantioselective alkylation of cyclic N-acyl hemiaminals with aldehydes

The first catalytic asymmetric alkylation of N-acyl quinoliniums with aldehydes has been described. A copper/amine synergistic catalytic system has been developed, allowing the addition of functionalized aldehydes to a wide range of electronically varied N-acyl quinoliniums in good yields with excellent enantiocontrol. The synergistic catalytic system was also effective for N-acyl dihydroisoquinoliniums and β-caboliniums, demonstrating the general applicability of the protocol in the enantioselective alkylation of diverse cyclic N-acyl hemiaminals. This journal is

A Novel Gemini Sulfonic Ionic Liquid Immobilized MCM-41 as Efficient Catalyst for Doebner-Von Miller Reaction to Quinoline

A novel 2,2′-bipyridine-based gemini sulfonic ionic liquid was first synthesized and then immobilized on MCM-41 support (named IL1/MCM-41), which was further characterized using XRD, FT-IR, SEM, TEM, N2-physisorption, XPS and TG techniques. These characterization results revealed that the IL1/MCM-41 presented a whole ordered mesoporous structure, excellent thermal stability as well as the interaction between ionic liquid with MCM-41. Catalytic activity of the obtained IL1/MCM-41 was systematically evaluated for the Doebner-Von Miller reaction to generate quinoline. Compared to conventional imidazole-type single sulfonic ionic liquid supported on MCM-41 (named IL2/MCM-41), IL1/MCM-41 exhibited higher catalytic activity and better reusability, which was probably due to the synergistic catalytic effect of the dual sulfonic acid group on IL2 and the stronger interaction between dipyridine ring of ionic liquid with MCM-41 support, respectively. Meanwhile, a plausible reaction routes for the synergistic catalytic action of dual sulfonic acid to quinoline over the IL1/MCM-41 catalyst was also proposed in this paper.

Zn-promoted Hβ zeolite for gas-phase catalyzed aza-heterocyclic-aromatization of acrolein dimethyl acetal and aniline to quinolines

Catalytic activities of Zn-promoted Hβ zeolite for gas-phase aza-heterocyclic-aromatization of acrolein dimethyl acetal and aniline to quinolines were investigated. the Zn/Hβ catalyst showed better selectivity to quinoline than the parent Hβ one. Characterization results demonstrated that the Zn/Hβ catalyst prepared via deposition precipitation method existed the isolated Zn2+ cations as well as the highly dispersed ZnO clusters, which not only decreased concentration of strong acid sites but also enhanced enhance aromatization process. As a result, the decrease of strong acid sites restrained the cracking of acrolein to acetaldehyde as well as the alkylation of quinoline to ethylquinoline effectively; and the Zn species of catalyst further improved aromatization process of dihydroquinoline to quinoline. Moreover, the Zn/Hβ catalyst presented relatively enhanced ability of anti-activation and excellent regenerability, owing to decrease strong acid-induced polymerization of active intermediates to form the coking. Under the optimized operating conditions, more than 51 % yield of quinoline was achieved over Zn/Hβ catalyst; which far exceeded quinoline yield (28 %) over the pure Hβ one. Besides, a plausible reaction routes in vapor-phase acrolein diethyl acetal with aniline to quinolines were suggested in this paper.

Mesoporous HBeta zeolite obtained: Via zeolitic dissolution-recrystallization successive treatment for vapor-phase Doebner-Von Miller reaction to quinolines

A reassembled HBeta zeolite (HBeta-Ct) was obtained via zeolitic dissolution-recrystallization successive treatment, and characterized by means of XRD, FT-IR, SEM, TEM, N2 adsorption-desorption as well as NH3-TPD techniques. The characterization results manifested that the HBeta-Ct zeolite possessed more mesopores and less acid than the parent one. Catalyst activities of the parent and reassembled HBeta catalysts were investigated in detail in the vapor-phase Doebner-Von Miller reaction to quinolines. The results demonstrated that the reassembled HBeta zeolite showed enhanced catalyst stability and improved anti-alkylation ability. This is probably due to the existence of mesopores on the catalyst which strengthened the diffusion of bulky products from pore channels in the zeolite. Meanwhile, the decreased acid amount over the catalyst can also retard the alkylation process to generate alkylquinolines as well as the acid-induced polymerization reaction to form coke. Besides, the HBeta-Ct catalyst also exhibited good regenerability in the Doebner-Von Miller reaction. This journal is

Bioinspired Atomic Manganese Site Accelerates Oxo-Dehydrogenation of N-Heterocycles over a Conjugated Tri- s-Triazine Framework

Herein, taking inspirations from metalloenzymes, we constructed atomically dispersed manganese sites anchored onto conjugated tri-s-triazine units of graphitic carbon nitride as a bioinspired photocatalyst (Mn1/tri-CN) for the oxo-dehydrogenation of N-heterocycles. The primary coordination sphere of atomic Mn-N2 sites (role i: oxygen activation) as well as the π-πstacking interactions between tri-s-triazine units and substrate mimicking the secondary coordination sphere (role ii: substrate adsorption) synergistically realized high-efficiency electron transfer/utilization in photocatalytic oxidation reactions, as was demonstrated experimentally and theoretically. The Mn1/tri-CN catalyst exhibited impressive oxo-dehydrogenation activity and selectivity toward a broad scope of N-heterocycles in an air atmosphere. The current work suggests that simultaneously engineering the metal active sites of catalysts and the adaptive local environment of the matrix may open an avenue for the synthesis of fine chemicals.

A biomass-derived N-doped porous carbon catalyst for the aerobic dehydrogenation of nitrogen heterocycles

N-doped porous carbon (NC) was synthesized from sugar cane bagasse, which is a sustainable and widely available biomass waste. The preferred NC sample had a well-developed porous structure, a graphene-like surface morphology and different N species. More

Dehydrogenation of N-Heterocyclic Compounds Using H2O2 and Mediated by Polar Solvents

The oxidative dehydrogenation of N-heterocyclic compounds by using H2O2 as oxidant in combination with polar solvents such as 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) and H2O is described. Among these two solvents, the best yields for the heteroaromatic compounds were generally achieved in HFIP. However, it is remarkable, that the use of a non toxic solvent such as H2O gave such good yields. Furthermore, the procedure was implemented in larger-scale and HFIP was distilled from the reaction mixture and reused (up to 5 cycles) without a significant detriment in the reaction outcome. (Figure presented.).