260-94-6

Usage

Uses

Used in Chemical Industry:
Acridine is used as a manufacturing dye and intermediate for antileishmanial agents. Some dyes derived from it are used as antiseptics, such as 9-aminoacridine, acriflavine, and proflavine.
Used in Pharmaceutical Industry:
Acridine and its derivatives, such as amsacrine, bind to DNA and RNA due to their abilities to intercalate. They have applications in the development of drugs that target nucleic acids.
Used in Research and Diagnostics:
Acridine orange (3,6-dimethylaminoacridine) is a nucleic acid-selective metachromatic stain useful for cell cycle determination and other research applications.
Used in Analytical Chemistry:
The hydrochloride salt of acridine has been used as a reagent for the detection of cobalt, iron, and zinc.
Used in Coal Tar:
Acridine is a compound occurring in coal tar and has been used in the manufacture of dyes and intermediates.
Derivatives with Antiseptic Properties:
Several dyes and drugs feature the acridine skeleton, and many acridines, such as proflavine, have antiseptic properties.

Reactions

Acridine displays the reactions expected of an unsaturated N-heterocycle. It undergoes N-alkylation with alkyl iodides to form alkyl acridinium iodides, which are readily transformed by the action of alkaline potassium ferricyanide to N-alkyl acridones. Basicity Acridine and its homologues are weakly basic. Acridine is a photobase which has a ground state pKa of 5.1, similar to that of pyridine, and an excited state pKa of 10.6. It also shares properties with quinoline. Reduction and oxidation Acridines can be reduced to the 9,10-dihydroacridines, sometimes called leuco acridines. Reaction with potassium cyanide gives the 9-cyano-9,10-dehydro derivative. On oxidation with potassium permanganate, it yields acridinic acid (C9H5N(CO2H)2) otherwise known as quinoline-1,2-dicarboxylic acid. Acridine is easily oxidized by peroxymonosulfuric acid to the acridine amine oxide. The carbon 9-position of acridine is activated for addition reactions.

World Health Organization (WHO)

Acridine derivatives with antiseptic and disinfectant activity, including acriflavine, proflavine and euflavine, were formerly used in the treatment of infected wounds and burns. Such use has largely been discontinued on the grounds that safer and more effective alternatives are now available. Following demonstration of the mutagenic activity of proflavine in 1978 it was withdrawn from dental products in Denmark. Subsequently, euflavine was similarly withdrawn.

Synthesis Reference(s)

The Journal of Organic Chemistry, 21, p. 1286, 1956 DOI: 10.1021/jo01117a019Synthesis, p. 732, 1987 DOI: 10.1055/s-1987-28066

Air & Water Reactions

Slightly soluble in hot water.

Reactivity Profile

Acridine neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides. Burns to give toxic oxides of nitrogen.

Health Hazard

Inhalation irritates respiratory system and causes sneezing, crying, and vomiting. Contact with liquid irritates eyes, skin, and mucous membranes. At high temperature and during sun exposure, damage to the cornea, skin, and mucous membranes may occur following the liberation of Acridine vapor.

Safety Profile

Poison by ingestion, subcutaneous, and intravenous routes. Mutation data reported. A skin, eye, and mucous membrane irritant. When heated to decomposition it emits toxic fumes of NO,.

Potential Exposure

Acridine and its derivatives are widely used in the production of dyestuffs, such as acriflavine, benzoflavine, and chrysaniline; and in the synthesis of pharmaceuticals; such as aurinacrine, proflavine, and rivanol. A constituent of coal tar, coal tar creosote; found in wastes from gas and tar plants and coke oven emissions. Incompatibilities: Strong acids, strong oxidizers.

Shipping

UN2713 Acridine, Hazard Class: 6.1; Labels: 6.1-Poisonous materials

Purification Methods

Acridine has been crystallised twice from *benzene/cyclohexane, or from aqueous EtOH, then sublimed, removing and discarding the first 25% of the sublimate. The remainder is again crystallised and sublimed, discarding the first 10-15% [Wolf & Anderson J Am Chem Soc 77 1608 1955]. Acridine can also be purified by crystallisation from n-heptane and then from ethanol/water after pre-treatment with activated charcoal, or by chromatography on alumina with pet ether in a darkened room. Alternatively, acridine can be precipitated as the hydrochloride from *benzene solution by adding HCl, after which the base is regenerated, dried at 110o/50mm, and recrystallised to constant melting point from pet ether [Cumper et al. J Chem Soc 4518 1962]. The regenerated free base may be recrystallised, chromatographed on basic alumina, then vacuum-sublimed and zone-refined. [Williams & Clarke, J Chem Soc, Faraday Trans 1 73 514 1977, Albert, The Acridines Arnold Press 1966.] It can exist in five crystalline forms and is steam volatile. It is a strong IRRITANT to skin and mucous membranes and can become a chronic irritant— handle it with CARE. [Beilstein 20/8 V 199.]

Incompatibilities

Acridine and its derivatives are widely used in the production of dyestuffs, such as acriflavine, benzoflavine, and chrysaniline; and in the synthesis of pharmaceuticals; such as aurinacrine, proflavine, and rivanol. A constituent of coal tar, coal tar creosote; found in wastes from gas and tar plants and coke oven emissions. Incompatibilities: Strong acids, strong oxidizers.

Waste Disposal

Incineration with nitrogen oxide removal from the effluent gas by scrubber, catalytic, or thermal device.

InChI:InChI=1/C13H9N/c1-3-7-12-10(5-1)9-11-6-2-4-8-13(11)14-12/h1-9H

Upstream product

• 3295-64-5 1,2,3,4-tetrahydroacridine 
• 92-81-9 acridine 
• 64-17-5 ethanol 
• 78-67-1 2,2'-azobis(isobutyronitrile) 
• 71-43-2 benzene 
• 779-84-0 N-phenylsalicylaldimine 
• 1207-69-8 9-Chloroacridine 
• 6540-78-9 acridine-9-thione 
• 74-88-4 methyl iodide 
• 68818-77-9 9,10-dihydro-acridine-9-carbonitrile 
• 38186-54-8 1,2,3,4-tetrahydro-9-acridinecarboxylic acid 
• 758640-21-0 N-Benzylaniline 
• 56798-21-1 3,4,5,6-tetrahydroacridine-1,8(2H,7H)-dione 
• 607-00-1 diphenylformamide 

Downstream Products

• 103036-21-1 2-(9,10-dihydro-acridin-9-yl)-1,2-diphenyl-ethanone 
• 92-81-9 acridine 
• 69035-42-3 9-(4-methoxy-phenyl)-9,10-dihydro-acridine 
• 15539-52-3 9-Phenacylacridin 
• 65674-20-6 10-benzylacridin-10-ium bromide 
• 18857-31-3 acridin-9-yl-triphenyl-silane 
• 18857-40-4 (9,10-dihydro-acridin-9-yl)-triphenyl-silane 
• 5326-19-2 acridine-9-carbonitrile 
• 10537-12-9 9-phenyl-9,10-dihydroacridine 
• 66333-77-5 4-(9,10-dihydro-acridin-9-yl)-N,N-dimethyl-aniline 
• 21923-37-5 9-(4'-aminophenyl)acridine 
• 4838-42-0 9,10,9',10'-tetrahydro-9,9'-biacridyl 
• 2978-79-2 9-(phenylmethyl)acridine 
• 53627-30-8 9,10-dibenzyl-9,10-dihydro-acridine 

Relevant academic research and scientific papers

N-H Bond Formation in a Manganese(V) Nitride Yields Ammonia by Light-Driven Proton-Coupled Electron Transfer

A method for the reduction of a manganese nitride to ammonia is reported, where light-driven proton-coupled electron transfer enables the formation of weak N - H bonds. Photoreduction of (saltBu)MnVN to ammonia and a Mn(II) complex has been accomplished using 9,10-dihydroacridine and a combination of an appropriately matched photoredox catalyst and weak Br?nsted acid. Acid-reductant pairs with effective bond dissociation free energies between 35 and 46 kcal/mol exhibited high efficiencies. This light-driven method may provide a blueprint for new approaches to catalytic homogeneous ammonia synthesis under ambient conditions.

Vanadium-Catalyzed Dehydrogenation of N-Heterocycles in Water

In this paper, the dehydrogenation of tetrahydroquinolines using oxovanadium(V) catalysts under mild conditions in water and oxygen atmosphere is described. This catalytic technology was successfully applied to a range of other structurally related N-heterocycles, and a reaction mechanism is proposed.

Simple and convenient conversion of acridones into 9-unsubstituted acridines via acridanes using borane tetrahydrofuran complex

A new method for the synthesis of 9-unsubstituted acridines from acridones using mild conditions is described. Various acridines bearing reduction-sensitive group(s) have been synthesized from the corresponding acridones using a two-step procedure that involved a commercially available borane complex reduction followed by an acridane oxidation.

Copper-catalyzed aerobic oxidative C-H and C-C functionalization of 1-[2-(Arylamino)aryl]ethanones leading to acridone derivatives

Efficient copper-catalyzed aerobic oxidative C-H and C-C functionalization of 1-[2-(arylamino)aryl]ethanones leading to acridones has been developed. The procedure involves cleavage of aromatic C-H and acetyl C-C bonds with intramolecular formation of a diarylketone bond. The protocol uses inexpensive Cu(O2CCF3)2 as catalyst, pyridine as additive, and economical and environmentally friendly oxygen as the oxidant, and the corresponding acridones with various functional groups were obtained in moderate to good yields. Acridone synthesis: Efficient copper-catalyzed aerobic oxidative C-H and C-C functionalization of 1-[2-(arylamino)aryl]ethanones leading to acridones has been developed. The procedure involves cleavage of aromatic C-H and acetyl C-C bonds with intramolecular formation of a diarylketone bond (see scheme). The protocol uses inexpensive Cu(O 2CCF3)2 as catalyst, pyridine as additive, and economical and environmentally friendly oxygen as oxidant. The corresponding acridones with various functional groups were obtained in moderate to good yields. Copyright

A novel flash vacuum pyrolysis route to acridine

The flash vacuum pyrolysis (FVP) of 5,6,11,12-tetrahydrodibenzo[b,f]azocine (6) gives a good yield (75%) of acridine (7). A mechanism for this novel reaction is presented.

Gossypol clathrates: Structure and thermal behavior of the gossypol acridine complex

The natural compound gossypol forms a stable clathrate with acridine. The composition of the clathrate is C30H30O 8·0.5C13H9N. The unit cell is monoclinic, C2/c space group, a = 11.3213(3) A, b = 30.5957(13) A, c = 17.0824(4) A, γ = 94.153(2)°, V = 5901.5(3) A3, M = 1153.24, Z = 8, dx = 1.369 g/cm3, and R = 0.0413 for 4726 reflections. The structure of the clathrate allows one to refer this compound to the ethyl acetate isomorphic host-guest group of gossypol complexes.

A Simple Route to C-Functionalised Azaxylylenes and Diazaxylylenes

o-Lithiation of t-butoxycarbonylaniline and 4-t-butoxycarbonylaminopyridine followed by reaction with aldehydes gives t-butoxycarbonylamino alcohols which are converted into azaxylylenes and diazaxylylenes on flash pyrolysis.

Oxidation of N-methyl-9-t-butylacridane by iodosylbenzene catalyzed by tetrakis(pentafluorophenyl) porphyrin iron(III). A tool to investigate the mechanism of the oxidative N-demethylation of aromatic tertiary amines

The PhIO promoted oxidation of N-methyl-9-t-butylacridane (1) catalyzed by tetrakis(pentafluorophenyl) porphyrin iron(III) leads first to 9-t- butylacridane and then to acridine. It is suggested that 1 can represent a reliable machanistic probe to detect the intervention of radical cations in the oxidation of aromatic amines.

Flash Vacuum Pyrolysis of o-Azidodiphenylmethanes. Nitrene Insertions with Temperature Variability

The decomposition of o-azidodiphenylmethanes by flash vacuum pyrolysis (f.v.p.) (350 - 700 deg C) gives acridan and acridine in contrast with the production of 10H-azepinoindole at lower temperatures in solution; similar f.v.p. treatment of 10H-azepinoindole gives some of the tautomeric 6H-azepinoindole.

Photocatalytic degradation of antiepileptic drug carbamazepine with bismuth oxychlorides (BiOCl and BiOCl/AgCl composite) in water: Efficiency evaluation and elucidation degradation pathways

The heterogeneous photocatalytic degradation of carbamazepine (CBZ) was investigated in the presence of BiOCl/AgCl composite photocatalyst under simulated sunlight irradiation in water. BiOCl/AgCl composite showed higher photocatalytic activity than pure BiOCl for CBZ degradation. The photocatalytic mechanism analysis was based on byproducts identification by LC–MS-QTof and active species trapping or inhibiting experiments. The results revealed that the first step of the transformation mainly results in an electron transfer implying positive holes and to a lesser extent in hydroxyl radical's involvement. The enhanced photocatalytic performance of BiOCl/AgCl was proved to be related to the suitable conduction and valence band interaction that extends optical response range but also improves the efficient separation of photoinduced electron-hole pairs. BiOCl/AgCl composite totally removed CBZ from natural surface water after 30?min irradiation, suggesting its potential application to wastewater treatments. Eight intermediate products were identified demonstrating that CBZ transformation occurs through two main routes from CBZ radical cation, hydroxylation of ring (aromatic or seven membered rings), followed by further oxidation, rearrangement ring and hydroxylation.