Dinoseb

{{short description|Chemical compound used as a herbicide}} {{Distinguish|dinoterb}} {{chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 443695227 | ImageFile_Ref = {{chemboximage|correct|??}} | ImageFile=Dinoseb Grundstruktur V1.svg | ImageSize=200px | PIN = 2-(Butan-2-yl)-4,6-dinitrophenol | OtherNames = 2-(''sec''-Butyl)-4,6-dinitrophenol |Section1={{Chembox Identifiers | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 6684 | EC_number = 201-861-7 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C14302 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 34719 | InChI = 1/C10H12N2O5/c1-3-6(2)8-4-7(11(14)15)5-9(10(8)13)12(16)17/h4-6,13H,3H2,1-2H3 | InChIKey = OWZPCEFYPSAJFR-UHFFFAOYAU | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C10H12N2O5/c1-3-6(2)8-4-7(11(14)15)5-9(10(8)13)12(16)17/h4-6,13H,3H2,1-2H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = OWZPCEFYPSAJFR-UHFFFAOYSA-N | CASNo_Ref = {{cascite|correct|CAS}} | CASNo=88-85-7 | PubChem=6950 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = YD44ZEM22M | UNNumber = 2779 2902 | SMILES = [O-][N+](=O)c1cc(cc(c1O)C(CC)C)[N+]([O-])=O }} |Section2={{Chembox Properties | C=10 | H=12 | N=2 | O=5 | Appearance= | Density= {{val|1.35|u=g/cm3}} | MeltingPtC= 38-42 | BoilingPt= | Solubility= | pKa = 4.4<ref>{{cite journal |last1=Szeto |first1=Sunny Y. |last2=Price |first2=Patricia M. |title=Persistence of pesticide residues in mineral and organic soils in the Fraser Valley of British Columbia |journal=Journal of Agricultural and Food Chemistry |date=September 1991 |volume=39 |issue=9 |pages=1679–1684 |doi=10.1021/jf00009a027}}</ref> }} |Section3={{Chembox Hazards | GHS_ref=<ref name="sigma">{{Sigma-Aldrich|id=45453|name=Dinoseb|accessdate=2020-03-24}}</ref> | GHSSignalWord = Danger | GHSPictograms = {{GHS06}}{{GHS08}}{{GHS09}}{{GHS05}} | HPhrases = {{H-phrases|300|311|315|317|318|360|410}} | PPhrases = {{P-phrases|201|273|280|310|305+351+338|302+352}} | FlashPt= | AutoignitionPt = | LD50 = {{ubl |{{val|25|-|28|u=mg/kg}} (Oral, rat) |{{val|80|u=mg/kg}} (Dermal, rat) |{{val|20|u=mg/kg}} (Intravenous, rat) |{{val|7|-|9|u=mg/kg}} (Oral, bird)<ref name=":4" />{{translation needed inline}} }} }} }}

'''Dinoseb''' is a common industry name for 6-sec-butyl-2,4-dinitrophenol, a herbicide in the dinitrophenol family. It is a crystalline orange solid which does not readily dissolve in water. Dinoseb is banned as an herbicide in the European Union (EU) and the United States because of its toxicity.

It also finds use as a polymerisation inhibitor, where it is often referred to as DNBP. It is used to prevent the thermally induced polymerisation of styrene and other unsaturated monomers when they are being purified by distillation.{{cn|date=March 2026}}

==Chemistry== === Synthesis === The first step in the synthesis of dinoseb is the synthesis of 2-(1-methylpropyl)phenol from 1-butene and phenol.<ref>{{Cite book|title=Ashford's Dictionary of Industrial Chemicals|last=Ashford|first=R.D.|publisher=Wavelength Publications Ltd.|year=1994|isbn=978-0-9522674-3-0|location=London, England|pages=159}}</ref> First, 1-butene is protonated so that a secondary carbocation is formed. This can only happen under acidic conditions. The formed carbocation can undergo electrophilic aromatic substitution with phenol. The product of this reaction is 2-(1-methylpropyl)phenol.

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The second step in the synthesis of dinoseb is the nitration of 2-(1-methylpropyl)phenol. First, the nitronium ion is formed from nitric acid and sulfuric acid.<ref name=":0">{{Cite web|url=http://research.cm.utexas.edu/nbauld/teach/ch610bnotes/ch21.htm|title=Chapter 21:Reactions of Aromatics|website=research.cm.utexas.edu|access-date=2017-03-13}}</ref>

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2-(1-methylpropyl)phenol takes up the nitronium ion to form the arenium ion, which has three resonance structures. Water can cleave off the additional proton to form a neutral compound.<ref name=":0" />

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The product of this reaction can undergo a second nitration to form dinoseb.

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===Stereoisomerism=== Dinoseb is a racemic mixture of two enantiomers. {| class="wikitable" style="text-align:center" |- class="hintergrundfarbe6" ! colspan="2"| Dinoseb {{small|(2 stereoisomers)}} |- | 150px|''(S)''-Dinoseb {{small|(''S'')-configuration}} | 150px|''(R)''-Dinoseb {{small|(''R'')-configuration}} |}

==History== In 1892, dinitro-''ortho''-cresol (2,4-dinitro-6-methylphenol), a chemical compound closely related to dinoseb, was discovered in Germany and first used as an insecticide. It was later also used as an herbicide and also fungicide after those characteristics were discovered. In 1945 the ''ortho''-methyl group was replaced by a ''sec''-butyl group, producing dinoseb. This compound had a superior contact and stomach activity on insects and mites.<ref>{{Cite book|url=https://books.google.com/books?id=EZTMRzxg0qsC&pg=PA427|title=Quantitative Structure-Activity Relationships of Drugs|last=Topliss|first=John|date=2012-12-02|publisher=Elsevier|isbn=9780323146876|pages=427|language=en}}</ref>

Dinoseb became commercially available in 1945 and was approved for use in the United States based on safety data from Industrial Bio-Test Laboratories.<ref>{{Cite book|url=https://books.google.com/books?id=xGXEALaRC4sC&pg=PA149|title=Expert Witnessing: Explaining and Understanding Science|last=Meyer|first=Carl|date=1998-12-29|publisher=CRC Press|isbn=9780849311970|pages=149|language=en}}</ref> On January 13, 1984 the Danish ship Dana Optima lost 80 drums of Dinoseb during their trip from North Shields, England to Esbjerg, Denmark. After four months 72 drums were found and recovered.<ref>{{Cite book|url=https://books.google.com/books?id=R7_oCAAAQBAJ&pg=PA325|title=Chemical Spills and Emergency Management at Sea: Proceedings of the First International Conference on "Chemical Spills and Emergency Management at Sea", Amsterdam, the Netherlands, November 15–18, 1988|last1=Bockholts|first1=P.|last2=Heidebrink|first2=I.|date=2012-12-06|publisher=Springer Science & Business Media|isbn=9789400908871|pages=325–328|language=en}}</ref>

Dinoseb was withdrawn from the market in 1986 due to an increased threat of birth defects after female field workers were exposed to the chemical. It could also cause sterility in men who were exposed to the chemical.<ref>{{Cite news |url=https://www.nytimes.com/1986/10/08/us/emergency-order-bans-much-used-pesticide.html|title=Emergency Order Bans Much-Used Pesticide |last=Shabecoff |first=Philip |date=1986-10-08 |work=The New York Times |access-date=2017-03-13 |issn=0362-4331}}</ref>

== Uses == Dinoseb is an herbicide that was once widely used with crops like soybeans, vegetables, fruits, nuts, and citrus.{{cn|date=March 2026}} It has been banned in the EU and the United States due to its high toxicity.<ref name=":1">{{Cite journal|last1=Heusinkveld|first1=Harm J.|last2=van Vliet|first2=Arie C.|last3=Nijssen|first3=Peter C. G.|last4=Westerink|first4=Remco H. S.|date=2016-06-11|title=In vitro neurotoxic hazard characterisation of dinitrophenolic herbicides|journal=Toxicology Letters|volume=252|pages=62–69|doi=10.1016/j.toxlet.2016.04.014|issn=1879-3169|pmid=27106277|hdl=1874/345491 |hdl-access=free}}</ref> Dinoseb was also used as an insecticide to protect grapes.{{cn|date=March 2026}}

On the internet, dinoseb and other dinitrophenols are sold as weight loss pills,{{by whom?|date=March 2026}} though they are not useful for that purpose and are highly toxic.<ref name=":2">{{Cite journal|last1=Zaharia|first1=M.|last2=Tudorachi|first2=L.|last3=Pintilie|first3=O.|last4=Drochioi|first4=C.|last5=Gradinaru|first5=R.|last6=Murariu|first6=M.|year=2016|title=Banned dinitrophenols still trigger both legal and forensic issues|url=https://www.researchgate.net/publication/299373270|journal=Environmental Forensics|volume=17 |issue=1|pages=120–130|doi=10.1080/15275922.2015.1133735|bibcode=2016EnvFo..17..120Z |s2cid=112923764}}</ref>

== Mechanism of action ==

Dinoseb is an uncoupler of oxidative phosphorylation. It is a weak acid that can pass through lipid membranes when it's in the undissociated form.

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It uses this property to transport protons through the inner mitochondrial membrane (IMM).<ref>{{Cite book|url=https://books.google.com/books?id=l0lCPYkZhGEC&pg=PA237|title=Organic Pollutants: An Ecotoxicological Perspective|last=Walker|first=C. H.|date=2001-04-26|publisher=CRC Press|isbn=9780748409617|language=en}}</ref> Protons are taken up from the intermembrane space and after transport through the IMM, they are released again in the mitochondrial matrix. Dinoseb in the dissociated form is negatively charged, which causes it to move to the intermembrane space because of the electrochemical gradient that exists across the IMM. The negative charge is delocalized over the ring, increasing the anion's membrane permeability.

By lowering the proton gradient, dinoseb removes the cell's ability to produce ATP, resulting in the death of the cell.

Dinoseb is also a weak inhibitor of mitochondrial Complex III and Complex II of the respiratory chain.<ref>{{cite journal |title= Comparison of structure of quinone redox site in the mitochondrial cytochrome-bc1 complex and photosystem II (QB site) |last1=Saitoh |first1=I. |last2=Miyoshi |first2=H. |last3=Shimizu |first3=R. |last4=Iwamura |first4=H. | journal = Eur. J. Biochem.| volume =209| pages = 73–79| year = 1992|issue =1 | pmid =1327783|pmc = |doi=10.1111/j.1432-1033.1992.tb17262.x |doi-access=free}}</ref><ref>{{cite journal |title=The Carboxyl Terminus of the Saccharomyces cerevisiae Succinate Dehydrogenase Membrane Subunit, SDH4p, Is Necessary for Ubiquinone Reduction and Enzyme Stability* |author = K S Oyedotun, B D Lemire| journal = J Biol Chem| volume =272| pages = 31382–8| year =1997| issue=50 | pmid = 9395469 |pmc = |doi = 10.1074/jbc.272.50.31382 | doi-access=free }}</ref>

In plants, dinoseb also inhibits photosynthesis by inhibiting the electron flow from photocomplex II to plastoquinone.<ref>{{Cite book|url=https://books.google.com/books?id=bV39BAAAQBAJ&pg=PA86|title=Mode of Action, Metabolism and Toxicology: Pesticide Chemistry: Human Welfare and the Environment|last1=Matsunaka|first1=S.|last2=Hutson|first2=D. H.|last3=Murphy|first3=S. D.|date=2013-10-22|publisher=Elsevier|isbn=9781483150451|language=en}}</ref> As a result, the plastoquinone can't create a proton gradient and no ATP is produced by the ATP synthase. Also, NADP can't be reduced to form NADPH, which removes the ability to create glucose from carbon dioxide. This also leads to cell death.

== Toxicity == Dinoseb is highly toxic via ingestion, inhalation or when absorbed through the skin. Symptoms include fatigue, sweating, headaches, nausea, stomach aches and fever.<ref name=":3">{{Cite web|url=http://www.toxipedia.org/display/toxipedia/Dinoseb|title=Dinoseb - Toxipedia|website=www.toxipedia.org|access-date=2017-03-13}}</ref> It is also an irritant for the eyes. It causes burns on contact with skin and leaves yellow stains. For pregnant women this substance is especially dangerous as it can cause growth defects in unborn children (it is teratogenic).

Dinoseb interferes with the oxidative phosphorylation by acting as an uncoupler which disrupts the production of ATP in the mitochondria. This is done by making the inner membrane of the mitochondria more permeable to protons, which results in a lower proton gradient. As the membrane potential / gradient is the driving force for the production of ATP, the cell is unable to produce energy.<ref>{{Cite journal|last1=Palmeira|first1=C.M.|last2=Moreno|first2=A.J.|last3=Madeira|first3=V.M.C.|year=1994|title=Interactions of Herbicides 2,4-D and Dinoseb with Liver Mitochondrial Bioenergetics|journal=Toxicology and Applied Pharmacology|volume=127 |issue=1|pages=50–57|doi=10.1006/taap.1994.1138|pmid=8048053|bibcode=1994ToxAP.127...50P }}</ref>

Exposure to dinoseb also induces ER-mediated calcium release, resulting in increased intracellular calcium levels. This is followed by activation of caspase, which is a protease involved in cell apoptosis. The surviving cells have an increase of alpha-synuclein levels which leads to dopaminergic neurodegeneration.<ref name=":1" />

Dinoseb can cross biological membranes like the blood-brain barrier and the placental barrier..<ref name=":1" />

Oral {{LD50}} values of dinoseb range from {{val|14|to|114|u=mg/kg}} in rats, mice, rabbits, and guinea pigs.<ref name=":2" /> For humans, this is {{val|5|to|50|u=mg/kg}}.<ref name=":4">{{Cite book|title=Hoe gevaarlijk zijn milieugevaarlijke stoffen?|last=Copius Peereboom|first=J.W. |language=Dutch|year=1991|isbn=978-90-6009-477-8|pages=179–183}}</ref>{{translation needed inline |reason=Dutch source, won't be easy to find in the US, we need a translated quote or just nuke it...}}

== First aid measures == Because of the high toxicity, emergency services and poison control should be called immediately if anyone is exposed to this material.<ref>{{Cite web|url=http://www.cpcb.nic.in/divisionsofheadoffice/pci-ssi/MATERIAL_SAFETY-DATABASE/MSDS2008/222.pdf|title=Material safety data sheets 222: Dinoseb|website=Central Pollution Control Board|access-date=2017-03-16}}</ref>

==See also== * Dinoterb

==References== {{reflist}}

==External links== * [https://archive.today/20030625034953/http://www.epa.gov/OGWDW/contaminants/dw_contamfs/dinoseb.html US EPA datasheet]

{{Herbicides}}

Category:Herbicides Category:Dinitrophenol derivatives Category:Uncouplers Category:Sec-Butyl compounds Category:Group 24 herbicides