Diphenylamine

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]

Diphenylamine
Names
Preferred IUPAC name
N-Phenylaniline
Other names
(Diphenyl)amine
Diphenylamine (deprecated[1])
Diphenylazane
N-Phenylbenzenamine
Anilinobenzene
(Phenylamino)benzene
N,N-Diphenylamine
C.I. 10355
Phenylbenzenamine
Identifiers
3D model (JSmol)
Abbreviations DPA
508755
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.004.128
EC Number
  • 204-539-4
67833
KEGG
RTECS number
  • JJ7800000
UNII
UN number 2811 3077
Properties
C12H11N
Molar mass 169.23 g/mol
Appearance White, off-white[2]
Odor pleasant, 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
Main hazards Toxic. Possible mutagen. Possible teratogen. Harmful in contact with skin, and if swallowed or inhaled. Irritant.
Safety data sheet See: data page
GHS pictograms
GHS Signal word Danger
GHS hazard statements
 H301, H311, H319, H331, H373, H400, H410
P260, P261, P264, P270, P271, P273, P280, P301+310, P302+352, P304+340, P305+351+338, P311, P312, P314, P321, P322, P330, P337+313, P361, P363, P391, P403+233, P405, P501
NFPA 704 (fire diamond)
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilHealth code 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
3
0
Flash point 152 °C (306 °F; 425 K)
NIOSH (US health exposure limits):
PEL (Permissible)
 none[3]
REL (Recommended)
 TWA 10 mg/m3[3]
IDLH (Immediate danger)
 N.D.[3]
Related compounds
Related Amine
 Aniline
Supplementary data page
Refractive index (n),
Dielectric constant (εr), etc.
Thermodynamic
data
 Phase behaviour
solid–liquid–gas
UV, IR, NMR, MS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Preparation and reactivity

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]

Applications

Apple scald inhibitor

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

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 nitrocellulose degradation products (e.g. NO, NO2, and nitric acid), preventing these degradation products from accelerating further degradation.[14]

Antioxidant

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 anti-ozonants in the manufacture of rubber products, reflecting the antioxidant nature of aniline derivatives.[5][17]

Redox indicator

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

Several azo dyes including Metanil Yellow, Disperse Orange 1, and Acid orange 5 are derivatives of diphenylamine.

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 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.[22]

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][23] 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.[22]

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.[24]

Environmental fate

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

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. [25] A number of alternatives to the use of diphenylamine exist for the control of scald of apples.[26]

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 (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 [27] and it became law in 2013.[28]

WHO/FAO joint committee

The Committee established an acceptable daily intake of 0.02 mg/kg/day in a meeting on pesticide residues.[23]

US EPA

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 [29] 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".[30] EPA has not reviewed diphenylamine since then.

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gollark: Otherwise I would just use python.
gollark: It's part of a small project called "openring" I tweaked a bit.
gollark: You could probably work out *something* with channels, but honestly I think it would be harder to understand than some iterator-based approach.
gollark: No, the items are converted into entries which store that data.

References
  1. "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 671. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
  2. https://www.sigmaaldrich.com/Graphics/COfAInfo/SigmaSAPQM/SPEC/24/242586/242586-BULK_______SIAL_____.pdf
  3. NIOSH Pocket Guide to Chemical Hazards. "#0240". National Institute for Occupational Safety and Health (NIOSH).
  4. "Diphenylamine".
  5. 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
  6. "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.
  7. "Identification of toxic impurities in commercial Diphenylamine", Bulletin of Environmental Contamination and Toxicology, February 1977, Volume 17, Issue 2, pp 204–207. Authored by S Safe, O Hutzinger, JFS Crocker, SC Digout
  8. The Merck Index, 10th Ed., (1983), p.485, Rahway: Merck & Co.
  9. 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
  10. F. D. Hager (1941). "Triphenylamine". Organic Syntheses.; Collective Volume, 1, p. 544
  11. Ingle, M; M. C. D'Souza (1989). "Physiology and control of superficial scald of apples: a review". HortScience. 24 (28): 31.
  12. Cook, Stanley G (1935). "Determination of Diphenylamine in Smokeless Powders". Industrial & Engineering Chemistry Analytical Edition. 7 (4): 250–255. doi:10.1021/ac50096a019.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. "Diphenylamine". NIOSH Pocket Guide to Chemical Hazards. CDC NIOSH. 4 April 2011. Retrieved 29 April 2014.
  23. 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.
  24. Clegg, S; Safe, S; Crocker, JF (1981). "Identification of a toxic impurity in commercial diphenylamine". J Environ Sci Health B. 16: 125–30. doi:10.1080/03601238109372245. PMID 7252059.
  25. "Pesticide Data Program's Summary for calendar year 2010". USDA. p. 189. Retrieved 29 April 2014.
  26. 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.
  27. "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.
  28. EC (12 March 2013). "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". Journal of the European Union. L 217/2 (3): 3130. doi:10.2903/j.efsa.2013.3130.
  29. EPA (13 May 1999). "Diphenylamine; Pesticide Tolerance; 40 CFR Part 180" (PDF). Federal Register. 64 (92): 25842–25848. Retrieved 28 April 2014.
  30. "diphenylamine Tolerance Actions 11/01". Federal Register. 4 December 2011. Retrieved 29 April 2014.
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