Diphenylamine
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| Names | |
|---|---|
| Preferred IUPAC name
N-Phenylaniline[1] | |
| Other names
(Diphenyl)amine
Diphenylamine (deprecated[1]) Diphenylazane N-Phenylbenzenamine Anilinobenzene (Phenylamino)benzene N,N-Diphenylamine C.I. 10355 Phenylbenzenamine | |
| Identifiers | |
3D model (JSmol)
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| Abbreviations | DPA |
| 508755 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.004.128 |
| EC Number |
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| 67833 | |
| KEGG | |
PubChem CID
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| RTECS number |
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| UNII | |
| UN number | 2811 3077 |
CompTox Dashboard (EPA)
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| Properties | |
| C12H11N | |
| Molar mass | 169.23 g/mol |
| Appearance | White, off-white[2] |
| Odor | Floral[3] |
| Density | 1.2 g/cm3 |
| Melting point | 53 °C (127 °F; 326 K) |
| Boiling point | 302 °C (576 °F; 575 K) |
| 0.03%[3] | |
| Vapor pressure | 1 mmHg (108°C)[3] |
| Acidity (pKa) | 0.79[4] |
| -109.7·10−6 cm3/mol | |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards
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Toxic. Possible mutagen. Possible teratogen. Harmful in contact with skin, and if swallowed or inhaled. Irritant. |
| GHS labelling: | |
   
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| Danger | |
| H301, H311, H319, H331, H373, H410 | |
| P260, P261, P264, P270, P271, P273, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P311, P312, P314, P321, P322, P330, P337+P313, P361, P363, P391, P403+P233, P405, P501 | |
| NFPA 704 (fire diamond) | |
| Flash point | 152 °C (306 °F; 425 K) |
| NIOSH (US health exposure limits): | |
PEL (Permissible)
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none[3] |
REL (Recommended)
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TWA 10 mg/m3[3] |
IDLH (Immediate danger)
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N.D.[3] |
| Related compounds | |
Related Amine
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Aniline |
| Supplementary data page | |
| Diphenylamine (data page) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Diphenylamine is an organic compound with the formula (C6H5)2NH. The compound is a derivative of aniline, consisting of an amine bound to two phenyl groups. The compound is a colorless solid, but commercial samples are often yellow due to oxidized impurities.[5] Diphenylamine dissolves well in many common organic solvents, and is moderately soluble in water.[6] It is used mainly for its antioxidant properties. Diphenylamine is widely used as an industrial antioxidant, dye mordant and reagent and is also employed in agriculture as a fungicide and antihelmintic.[7]
Preparation and reactivity
[edit]Diphenylamine is manufactured by the thermal deamination of aniline over oxide catalysts:
- 2 C6H5NH2 → (C6H5)2NH + NH3
It is a weak base, with a Kb of 10−14. With strong acids, it forms salts. For example, treatment with sulfuric acid gives the bisulfate [(C6H5)2NH2]+[HSO4]− as a white or yellowish powder with m.p. 123-125 °C.[8]
Diphenylamine undergoes various cyclisation reactions. With sulfur, it gives phenothiazine, a precursor to pharmaceuticals.[9]
- (C6H5)2NH + 2 S → S(C6H4)2NH + H2S
With iodine, it undergoes dehydrogenation to give carbazole, with release of hydrogen iodide:
- (C6H5)2NH + I2 → (C6H4)2NH + 2 HI
Arylation with iodobenzene gives triphenylamine.[10] it is also used as a test reagent in the dische's test .
Applications
[edit]Testing for DNA
[edit]The Dische test uses diphenylamine to test for DNA, and can be used to distinguish DNA from RNA.
Apple scald inhibitor
[edit]Diphenylamine is used as a pre- or postharvest scald inhibitor for apples applied as an indoor drench treatment. Its anti-scald activity is the result of its antioxidant properties, which protect the apple skin from the oxidation products of α-farnesene during storage.[11] Apple scald is physical injury that manifests in brown spots after fruit is removed from cold storage.
Stabilizer for smokeless powder
[edit]In the manufacture of smokeless powder, diphenylamine is commonly used as a stabilizer,[12] such that the gunshot residue analysis seeks to quantify traces of diphenylamine.[13] Diphenylamine functions by binding nitrogen oxide degradation products, forming compounds like nitrodiphenylamine. In this way, DPA prevents these degradation products from accelerating further degradation.[14]
Antioxidant
[edit]Alkylated diphenylamines function as antioxidants in lubricants,[15] approved for use in machines, in which contact with food is not ruled out.[16] Alkylated diphenylamines and other derivatives are used as antiozonants in the manufacture of rubber products, reflecting the antioxidant nature of aniline derivatives.[5][17]
Redox indicator
[edit]Many diphenylamine derivatives are used as redox indicators that are particularly useful in alkaline redox titrations.[18] The diphenylaminesulfonic acid is a simple prototype redox indicator, owing to its improved aqueous solubility compared with diphenylamine.[19] Attempts have been made to explain the color changes associated with the oxidation of diphenylamine.[20][21]
In a related application, diphenylamine is oxidized by nitrate to give a similar blue coloration in the diphenylamine test for nitrates.
Dyes
[edit]Several azo dyes like Metanil Yellow, Disperse Orange 1, and Acid orange 5 are derivatives of diphenylamine. It is also used as a dye mordant. A dye mordant is any substance that helps dyes to adhere to fabrics.
History
[edit]Diphenylamine was discovered by A. W. Hofmann in 1864 amongst the products of dry distillation 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.[22]
In 1872, diphenylamine was suggested as a means to detect nitrous acid in sulfuric acid due to its blue coloration in the presence of oxidizing agents. By 1875, it was also being used to detect nitrites and nitrates in drinking water.[23]
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In 1924, diphenylamine is discovered to be useful in detecting DNA via the Dische test by Zacharias Dische.
Toxicity
[edit]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 system and can cause abnormal erythropoiesis in the spleen, and thus congestion of the spleen, and haemosiderosis. Changes in liver and kidneys were found upon longer exposure.[6] 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.[6] The U.S. CDC's NIOSH 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.[24]
The short-term NOAEL 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 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.[6]
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 [6][25] There is a data gap on presence or formation of nitrosamines in apple metabolism or during processing.[6] The carcinogen 4-Aminobiphenyl can accompany diphenylamine as an impurity.[24]
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.[6]
The impurity in commercial diphenylamine which induces polycystic kidney disease in rats was identified in 1981. Laboratory studies with highly purified diphenylamine indicated that the impurity can be formed by heating diphenylamine.[26]
Environmental fate
[edit]Diphenylamine is considered practically insoluble according to the 2014 MSDS. It exhibits very low persistence in direct water photolysis 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
[edit]Of 744 apples tested USDA 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. [27] A number of alternatives to the use of diphenylamine exist for the control of scald of apples.[28]
Regulation
[edit]Europe
[edit]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 (EC) review program covered by a regulation from 2002 requiring the European Food Safety Authority (EFSA) upon EC request to organize a peer review of the initial evaluation, i.e. a draft risk assessment, 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 [29] and it became law in 2013.[30]
WHO/FAO joint committee
[edit]The committee established an acceptable daily intake of 0.02 mg/kg/day in a meeting on pesticide residues.[25]
US EPA
[edit]After passage of the Food Quality Protection Act (FQPA) of 1996, the U.S. EPA 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 [31] 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".[32] EPA has not reviewed diphenylamine since then.
References
[edit]- ^ a b International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 671. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.
- ^ https://www.sigmaaldrich.com/Graphics/COfAInfo/SigmaSAPQM/SPEC/24/242586/242586-BULK_______SIAL_____.pdf [bare URL PDF]
- ^ a b c d e f NIOSH Pocket Guide to Chemical Hazards. "#0240". National Institute for Occupational Safety and Health (NIOSH).
- ^ "Diphenylamine".
- ^ a b P. F. Vogt, J. J. Gerulis, "Amines, Aromatic" in Ullmann’s Encyclopedia of Industrial Chemistry 2005, Wiley-VCH, Weinheim. doi:10.1002/14356007.a02_037
- ^ a b c d e f g "Conclusion on the peer review of the pesticide risk assessment of the active substance diphenylamine". EFSA Journal. 10: 2486. 25 January 2012. doi:10.2903/j.efsa.2012.2486.
- ^ Safe, S.; Hutzinger, O.; Crocker, J. F. S.; Digout, S. C. (1977). "Identification of toxic impurities in commercial Diphenylamine". Bulletin of Environmental Contamination and Toxicology. 17 (2): 204–207. Bibcode:1977BuECT..17..204S. doi:10.1007/BF01685551. PMID 843636.
- ^ The Merck Index, 10th Ed., (1983), p.485, Rahway: Merck & Co.
- ^ T. Kahl, K.-W. Schröder, F. R. Lawrence, W. J. Marshall, Hartmut Höke, Rudolf Jäckh, "Aniline" in Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH: Weinheim. doi:10.1002/14356007.a02_303
- ^ F. D. Hager (1941). "Triphenylamine". Organic Syntheses; Collected Volumes, vol. 1, p. 544.
- ^ Ingle, M; M. C. D'Souza (1989). "Physiology and control of superficial scald of apples: a review". HortScience. 24 (28): 31. doi:10.21273/HORTSCI.24.1.28. S2CID 89228904.
- ^ Cook, Stanley G (1935). "Determination of Diphenylamine in Smokeless Powders". Industrial & Engineering Chemistry Analytical Edition. 7 (4): 250–255. doi:10.1021/ac50096a019.
- ^ Leggett, Lana S; Lott, Peter F (1989). "Gunshot residue analysis via organic stabilizers and nitrocellulose". Microchemical Journal. 39: 76–85. doi:10.1016/0026-265X(89)90012-X.
- ^ Drzyzga, Oliver (2003). "Diphenylamine and derivatives in the environment: A review". Chemosphere. 53 (8): 809–818. Bibcode:2003Chmsp..53..809D. doi:10.1016/S0045-6535(03)00613-1. PMID 14505701.
- ^ Jun Dong; Cyril A. Migdal (2009). "1. Antioxidants". In Leslie R. Rudnick (ed.). Lubricant Additives: Chemistry and Applications (2nd ed.). CRC Press. pp. 3–50. ISBN 978-1420059656.
- ^ Canady, Richard; Richard Lane; Greg Paoli; Margaret Wilson; Heidi Bialk; Steven Hermansky; Brent Kobielush; Ji-Eun Lee; Craig Llewellyn; Joseph Scimeca (Oct 2013). "Determining the Applicability of Threshold of Toxicological Concern Approaches to Substances Found in Foods". Crit Rev Food Sci Nutr. 53 (12): 1239–1249. doi:10.1080/10408398.2012.752341. PMC 3809586. PMID 24090142.
- ^ Hans-Wilhelm Engels; Herrmann-Josef Weidenhaupt; Manfred Pieroth; Werner Hofmann; Karl-Hans Menting; Thomas Mergenhagen; Ralf Schmoll; Stefan Uhrlandt (2011). "Rubber, 9. Chemicals and Additives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a23_365.pub3. ISBN 978-3527306732.
- ^ Willard, H. H; Manalo, G. D (1947). "Derivatives of Diphenylamine as Oxidation-Reduction Indicators in Alkaline Solution". Analytical Chemistry. 19 (3): 167–170. doi:10.1021/ac60003a011.
- ^ Sarver, L. A; Kolthoff, I. M (1931). "Diphenylamine Sulfonic Acid as a New Oxidation-Reduction Indicator". Journal of the American Chemical Society. 53 (8): 2902–2905. doi:10.1021/ja01359a010.
- ^ Sarver, L. A; Kolthoff, I. M (1937). "Electrochemical Properties of Diphenylbenzidine Sulfonic Acid". Journal of the American Chemical Society. 59: 23–25. doi:10.1021/ja01280a007.
- ^ Sriramam, K (1977). "Mechanistic interpretation of the redox behaviour of diphenylamine". Talanta. 24 (1): 31–36. doi:10.1016/0039-9140(77)80181-1. PMID 18962017.
- ^ "The Chemical News and Journal of Industrial Science; with which is Incorporated the "Chemical Gazette.": A Journal of Practical Chemistry in All Its Applications to Pharmacy, Arts and Manufactures". 1866.
- ^ Withers, W. A. (1911). "A Modification of the Diphenylamine Test for Nitrous and Nitric Acids". Journal of the American Chemical Society. 33 (5): 708–711. doi:10.1021/ja02218a008 – via ACS Publications.
- ^ a b "Diphenylamine". NIOSH Pocket Guide to Chemical Hazards. CDC NIOSH. 4 April 2011. Retrieved 29 April 2014.
- ^ a b fao (2007). "2007 JMPR Evaluation, Diphenylamine (030) 155-189" (PDF). Joint FAO/WHO Meeting on Pesticide Residues. WHO, FAO. pp. 1–35. Retrieved 29 April 2014.
- ^ Clegg, S; Safe, S; Crocker, JF (1981). "Identification of a toxic impurity in commercial diphenylamine". J Environ Sci Health B. 16 (2): 125–30. Bibcode:1981JESHB..16..125C. doi:10.1080/03601238109372245. PMID 7252059.
- ^ "Pesticide Data Program's Summary for calendar year 2010". USDA. p. 189. Retrieved 29 April 2014.[permanent dead link]
- ^ 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.
- ^ "Conclusion on the peer review of the pesticide risk assessment of the active substance diphenylamine. European Food Safety Authority". EFSA Journal. 11 (3): 2486–2527. 2012. doi:10.2903/j.efsa.2013.3130.
- ^ "European Commission Regulation No 772/2012, 8 August 2013, amending Annexes II, III and V to Regulation (EC) No 396/2005 of the European Parliament and of the Council as regards maximum residue levels for diphenylamine in or on certain products". Official Journal of the European Union: L 217/2. 12 March 2013.
- ^ EPA (13 May 1999). "Diphenylamine; Pesticide Tolerance; 40 CFR Part 180" (PDF). Federal Register. 64 (92): 25842–25848. Retrieved 28 April 2014.
- ^ "diphenylamine Tolerance Actions 11/01". Federal Register. 4 December 2011. Retrieved 29 April 2014.
External links
[edit]- International Chemical Safety Card 0466
- NIOSH Pocket Guide to Chemical Hazards. "#0240". National Institute for Occupational Safety and Health (NIOSH).