diphenylamine
   HOME

TheInfoList



OR:

Diphenylamine is an
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...
with the
formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...
(C6H5)2NH. The compound is a derivative of
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine In organic chemistry, an aromatic amine is an organic compound consisting of an aroma ...
, consisting of an
amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
bound to two
phenyl In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...
groups. The compound is a colorless solid, but commercial samples are often yellow due to oxidized impurities.P. F. Vogt, J. J. Gerulis, "Amines, Aromatic" in Ullmann’s Encyclopedia of Industrial Chemistry 2005, Wiley-VCH, Weinheim. Diphenylamine dissolves well in many common organic solvents, and is moderately soluble in water. It is used mainly for its
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
properties. Diphenylamine is widely used as an industrial
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
,
dye A dye is a colored substance that chemically bonds to the substrate to which it is being applied. This distinguishes dyes from pigments which do not chemically bind to the material they color. Dye is generally applied in an aqueous solution an ...
mordant A mordant or dye fixative is a substance used to set (i.e. bind) dyes on fabrics by forming a coordination complex with the dye, which then attaches to the fabric (or tissue). It may be used for dyeing fabrics or for intensifying stains in ...
and
reagent In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
and is also employed in agriculture as a
fungicide Fungicides are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores. A fungistatic inhibits their growth. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, ...
and
antihelmintic Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may a ...
.


Preparation and reactivity

Diphenylamine is manufactured by the thermal deamination of
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine In organic chemistry, an aromatic amine is an organic compound consisting of an aroma ...
over oxide
catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
s: : 2 C6H5NH2 → (C6H5)2NH + NH3 It is a weak base, with a ''K''b of 10−14. With strong acids, it forms salts. For example, treatment with
sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...
gives the bisulfate C6H5)2NH2sup>+ SO4sup>− as a white or yellowish powder with m.p. 123-125 °C.''The Merck Index, 10th Ed.'', (1983), p.485, Rahway: Merck & Co. Diphenylamine undergoes various cyclisation reactions. With
sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
, it gives
phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. T ...
, a precursor to pharmaceuticals. : (C6H5)2NH + 2 S → S(C6H4)2NH + H2S With iodine, it undergoes dehydrogenation to give
carbazole 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 str ...
, with release of
hydrogen iodide Hydrogen iodide () is a diatomic molecule and hydrogen halide. Aqueous solutions of HI are known as hydroiodic acid or hydriodic acid, a strong acid. Hydrogen iodide and hydroiodic acid are, however, different in that the former is a gas under sta ...
: : (C6H5)2NH + I2 → (C6H4)2NH + 2 HI
Arylation In organic chemistry, a cross-coupling reaction is a reaction where two fragments are joined together with the aid of a metal catalyst. In one important reaction type, a main group organometallic compound of the type R-M (R = organic fragment, M = ...
with
iodobenzene Iodobenzene is an organoiodine compound consisting of a benzene ring substituted with one iodine atom. It is useful as a synthetic intermediate in organic chemistry. It is a volatile colorless liquid, although aged samples appear yellowish. Prepa ...
gives
triphenylamine Triphenylamine is an organic compound with formula (C6H5)3N. In contrast to most amines, triphenylamine is nonbasic. At room temperature it appears as a colorless crystalline solid, with monoclinic structure. It is well miscible in diethyl ether a ...
. it is also used as a test reagent in the dische's test .


Applications


Apple scald inhibitor

Diphenylamine is used as a pre- or postharvest
scald The structured computer-aided logic design (SCALD) software was a computer aided design system developed for building the S-1 computer. It used the Stanford University Drawing System (SUDS), and it was developed by Thomas M. McWilliams and Lawrence ...
inhibitor for apples applied as an indoor drench treatment. Its anti-scald activity is the result of its antioxidant properties, which protect the
apple An apple is an edible fruit produced by an apple tree (''Malus domestica''). Apple fruit tree, trees are agriculture, cultivated worldwide and are the most widely grown species in the genus ''Malus''. The tree originated in Central Asia, wh ...
skin from the oxidation products of α-
farnesene The term farnesene refers to a set of six closely related chemical compounds which all are sesquiterpenes. α-Farnesene and β-farnesene are isomers, differing by the location of one double bond. α-Farnesene is 3,7,11-trimethyl-1,3,6,10-dodecat ...
during storage.
Apple scald This article is a list of diseases of apples (''Malus domestica''). Bacterial diseases Fungal diseases Nematodes, parasitic Viral diseases Viroid diseases Suspected viral- and viroid-like diseases Phytoplasmal diseases Miscell ...
is physical injury that manifests in brown spots after fruit is removed from cold storage.


Stabilizer for smokeless powder

In the manufacture of
smokeless powder Finnish smokeless powderSmokeless powder is a type of propellant used in firearms and artillery that produces less smoke and less fouling when fired compared to gunpowder ("black powder"). The combustion products are mainly gaseous, compared to a ...
, diphenylamine is commonly used as a stabilizer, such that the
gunshot residue Gunshot residue (GSR), also known as cartridge discharge residue (CDR), gunfire residue (GFR), or firearm discharge residue (FDR), consists of all of the particles that are expelled from the muzzle of a gun following the discharge of a bullet. It ...
analysis seeks to quantify traces of diphenylamine. Diphenylamine functions by binding nitrocellulose degradation products (e.g. NO, NO2, and nitric acid), preventing these degradation products from accelerating further degradation.


Antioxidant

Alkylated diphenylamines function as antioxidants in lubricants, approved for use in machines, in which contact with food is not ruled out. Alkylated diphenylamines and other derivatives are used as anti-ozonants in the manufacture of rubber products, reflecting the antioxidant nature of aniline derivatives.


Redox indicator

Many diphenylamine derivatives are used as
redox indicator A redox indicator (also called an oxidation-reduction indicator) is an indicator which undergoes a definite color change at a specific electrode potential. The requirement for fast and reversible color change means that the oxidation-reduction e ...
s that are particularly useful in alkaline redox titrations. The diphenylaminesulfonic acid is a simple prototype redox indicator, owing to its improved aqueous solubility compared with diphenylamine. Attempts have been made to explain the color changes associated with the oxidation of diphenylamine. In a related application, diphenylamine is oxidized by nitrate to give a similar blue coloration in the diphenylamine test for nitrates.


Dyes

Several
azo dye Azo dyes are organic compounds bearing the functional group R−N=N−R′, in which R and R′ are usually aryl and substituted aryl groups. They are a commercially important family of azo compounds, i.e. compounds containing the C-N=N ...
s like Metanil Yellow,
Disperse Orange 1 Disperse Orange 1, or 4-anilino-4'-nitroazobenzene, is an azo dye. Commercial samples contain approximately 25% dye by weight, with the remaining mass consisting of NaCl and other salts. This dye is useful in conducting experiments with flas ...
, and Acid orange 5 are
derivatives The derivative of a function is the rate of change of the function's output relative to its input value. Derivative may also refer to: In mathematics and economics * Brzozowski derivative in the theory of formal languages * Formal derivative, an ...
of diphenylamine.


History

Diphenylamine was discovered by A. W. Hofmann in 1864 amongst the products of
dry distillation Dry distillation is the heating of solid materials to produce gaseous products (which may condense into liquids or solids). The method may involve pyrolysis or thermolysis, or it may not (for instance, a simple mixture of ice and glass could be se ...
of aniline dyes; it was first purposefully synthesized through deamination of a mix of aniline and its salts by a group of French chemists two years later.


Toxicity

In animal experiments diphenylamine was rapidly and completely absorbed after ingestion by mouth. It underwent metabolism to sulfonyl and glucuronyl conjugates and was rapidly excreted mainly via urine. Acute oral and dermal toxicity were low. Diphenylamine can cause severe irritation to the eyes. It was not a skin irritant, and it has not been technically feasible to test acute toxicity study by inhalation. Diphenylamine targets the
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
system and can cause abnormal
erythropoiesis Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is stimulated by decrea ...
in the spleen, and thus congestion of the spleen, and haemosiderosis. Changes in liver and kidneys were found upon longer exposure. At clear toxic doses of parent animals reproductive effects were limited to reduced implantation sites in F1 females associated with reduced rat litter size, implicating a possible mutagenic or teratogenic effect. No effect on development could be attributed. The U.S. CDC's
NIOSH The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...
lists the following symptoms of poisoning: irritation eyes, skin, mucous membrane; eczema; tachycardia, hypertension; cough, sneezing; methemoglobinemia; increased blood pressure and heart rate; proteinuria, hematuria (blood in the urine), bladder injury; in animals: teratogenic effects. The short-term
NOAEL The no-observed-adverse-effect level (NOAEL) denotes the level of exposure of an organism, found by experiment or observation, at which there is no biologically or statistically significant increase in the frequency or severity of any adverse effec ...
of 9.6 – 10 mg/kg bw/day was derived from 90-day rat, 90-day dog and 1-year dog studies and the long-term NOAEL was 7.5 mg/kg bw/day. The
Acceptable Daily Intake Acceptable daily intake or ADI is a measure of the amount of a specific substance (originally applied for a food additive, later also for a residue of a veterinary drug or pesticide) in food or drinking water that can be ingested (orally) daily ove ...
of diphenylamine was 0.075 mg/kg bw/day based on the 2-year rat study, applying a safety factor of 100; the Acceptable Operator Exposure Level was 0.1 mg/kg bw/day. In a study of diphenylamine metabolism in harvested and dipped apples at different time intervals it was observed that radiolabelled residues of diphenylamine penetrate from the surface into the pulp, which after 40 weeks contained 32% of the residue. Diphenylamine was always the major residue, but 3 metabolites were found in good amounts in the apple samples, whose identification experts considered insufficient.(Kim-Kang, H. 1993. Metabolism of 14C-diphenylamine in stored apples—nature of the residue in plants. Report RPT00124. Study XBL 91071. XenoBiotic Laboratories, Inc., USA, unpublished) cited in There is a data gap on presence or formation of nitrosamines in apple metabolism or during processing. The carcinogen 4-Aminobiphenyl can accompany diphenylamine as an impurity. Diphenylamine has low acute and short-term toxicity to birds, but is very toxic to aquatic organisms. Risk to biological methods of sewage treatment was assessed as low. The impurity in commercial diphenylamine which induces
polycystic kidney disease Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney. These cy ...
in
rats Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' (pack rats), ''Bandicota'' (bandicoot ...
was identified in 1981. Laboratory studies with highly purified diphenylamine indicated that the impurity can be formed by heating diphenylamine.


Environmental fate

Diphenylamine is considered practically insoluble according to the 2014 MSDS. It exhibits very low persistence in direct water
photolysis Photodissociation, photolysis, photodecomposition, or photofragmentation is a chemical reaction in which molecules of a chemical compound are broken down by photons. It is defined as the interaction of one or more photons with one target molecule. ...
experiments in the laboratory and is moderately volatile. Indirect photooxidation in the atmosphere through reaction with hydroxyl radicals was estimated. Despite limited data, the information was sufficient for the EC to characterize the environmental risk as negligible, because the intended use of diphenylamine was indoors.


Residues in fruit and alternatives

Of 744 apples tested
USDA The United States Department of Agriculture (USDA) is the federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, and food. It aims to meet the needs of com ...
found 82.7% of them to have diphenylamine residue between 0.005 - 4.3 ppm, below the U.S. EPA's tolerance level of 10ppm. A number of alternatives to the use of diphenylamine exist for the control of scald of apples.Colin R. Little, Robert J. Holmes "Storage Technology for Apples and Pears: A Guide to Production, Postharvest Treatment and Storage of Pome Fruit in Australia" Institute for Horticultural Development Agriculture, 2000.


Regulation


Europe

The EC set maximum residue levels for diphenylamine in 2005. (Annex II and Part B of Annex III to Regulation (EC) No 396/2005). Diphenylamine was one of 84 substances of a
European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...
(EC) review program covered by a regulation from 2002 requiring the
European Food Safety Authority The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...
(EFSA) upon EC request to organize a peer review of the initial evaluation, i.e. a draft
risk assessment Broadly speaking, a risk assessment is the combined effort of: # identifying and analyzing potential (future) events that may negatively impact individuals, assets, and/or the environment (i.e. hazard analysis); and # making judgments "on the to ...
, and to provide the EC within 6 months with a conclusion. The assessment, received by the EFSA in 2007 started the peer review in October 2007 by dispatching it for consultation of the EC member states and the applicants, the two manufacturers, Cerexagri s.a., Italian subsidiary of United Phosphorus Ltd (UPL), and Pace International LLC. As a result of the peer review, mostly lacking data about risk to consumers, and particularly the levels and toxicity of unidentified metabolites of the substance, the possible formation of nitrosamines during storage of the active substance and during processing of treated apples, and the lack of data on the potential breakdown product of diphenylamine residues in processed commodities, the EC decided on 30 November 2009 to withdraw authorizations for plant protection products containing diphenylamine.(2009/859/EC) The 'European Diphenylamine Task Force' resubmitted an application to the EC with more data, and an additional report was received by the EFSA on 3 December 2010. EFSA concluded the risk assessment did not eliminate the concerns on 5 December 2011, published this opinion in 2012 and it became law in 2013.


WHO/FAO joint committee

The committee established an
acceptable daily intake Acceptable daily intake or ADI is a measure of the amount of a specific substance (originally applied for a food additive, later also for a residue of a veterinary drug or pesticide) in food or drinking water that can be ingested (orally) daily ove ...
of 0.02 mg/kg/day in a meeting on pesticide residues.


US EPA

After passage of the
Food Quality Protection Act The Food Quality Protection Act (FQPA), or H.R.1627, was passed unanimously by Congress in 1996 and was signed into law by President Bill Clinton on August 3, 1996. The FQPA standardized the way the Environmental Protection Agency (EPA) would man ...
(FQPA) of 1996, the U.S.
EPA The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...
had established a tolerance level for apples at 10 ppm, and for meat and milk at 0 ppm. The tentative LOAEL was 10 mg/kg/day In 1997 EPA approved the reregistration of diphenylamine, and determined that recommended tolerances met the safety standards under FQPA and that "adequate data indicate that tolerances for residues in milk and meat could be increased from 0.0 ppm and established as separate tolerances set at 0.01 ppm". EPA has not reviewed diphenylamine since then.


References


External links

* *{{PGCH, 0240 Anilines Fungicides Antioxidants Redox indicators Apple production