Thiourea

{{Short description|1=Organosulfur compound (S=C(NH2)2)}} {{see also|Thioureas}} {{chembox |verifiedrevid = 477863582 |ImageFile1 = Thioharnstoff.svg |ImageClass1 = skin-invert |ImageFile2 = Thiourea-3D-vdW.png |ImageClass2 = bg-transparent |ImageCaption2 = {{legend|black|Carbon, C}}{{legend|white|Hydrogen, H}}{{legend|blue|Nitrogen, N}}{{legend|yellow|Sulfur, S}} |PIN = Thiourea<ref name=iupac2013>{{cite book|first1=Henri A.|last1=Favre|first2=Warren H.|last2=Powell|title=Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book)|url=https://books.google.com/books?id=4USgAgAAQBAJ|publisher=Royal Society of Chemistry|date=2014|location=Cambridge|pages=98, 864|doi=10.1039/9781849733069|oclc=1077224056|isbn=9780854041824}}</ref> |OtherNames = Thiocarbamide |Section1={{Chembox Identifiers |CASNo = 62-56-6 |CASNo_Ref = {{cascite|correct|CAS}} |ChEBI_Ref = {{ebicite|correct|EBI}} |ChEBI = 36946 |PubChem = 2723790 |ChEMBL_Ref = {{ebicite|correct|EBI}} |ChEMBL = 260876 |UNII_Ref = {{fdacite|correct|FDA}} |UNII = GYV9AM2QAG |SMILES = C(=S)(N)N |UNNumber = 2811 |RTECS = YU2800000 |KEGG_Ref = {{keggcite|correct|kegg}} |KEGG = C14415 |ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |ChemSpiderID = 2005981 |InChI = 1/CH4N2S/c2-1(3)4/h(H4,2,3,4) |InChIKey = UMGDCJDMYOKAJW-UHFFFAOYAJ |StdInChI_Ref = {{stdinchicite|correct|chemspider}} |StdInChI = 1S/CH4N2S/c2-1(3)4/h(H4,2,3,4) |StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |StdInChIKey = UMGDCJDMYOKAJW-UHFFFAOYSA-N |Beilstein = 605327 |Gmelin = 1604 }} |Section2={{Chembox Properties |Formula = {{chem2|SC(NH2)2}} |C=1|H=4|N=2|S=1 |Appearance = white solid |Density = 1.405 g/mL |MeltingPtC= 182 |Solubility = 142 g/L (25 °C) |MagSus = {{val|-4.24e-5}} cm³/mol }} |Section7={{Chembox Hazards | GHSPictograms = {{GHS07}}{{GHS08}}{{GHS09}} | GHSSignalWord = Warning | HPhrases = {{H-phrases|302|351|361|411}} | PPhrases = {{P-phrases|201|202|264|270|273|281|301+312|308+313|330|391|405|501}} |NFPA-H = 3 |NFPA-F = 1 |NFPA-R = 0 }} |Section8={{Chembox Related | OtherCompounds = Urea<br>Selenourea }} }}

'''Thiourea''' ({{IPAc-en|ˌ|θ|aɪ|.|oʊ|j|ʊəˈr|iː|.|ə|,_|-|ˈ|jʊər|i|-}}){{refn|{{cite encyclopedia |url=http://www.lexico.com/definition/thiourea |archive-url=https://web.archive.org/web/20200322184329/https://www.lexico.com/definition/thiourea |url-status=dead |archive-date=2020-03-22 |title=thiourea |dictionary=Lexico UK English Dictionary |publisher=Oxford University Press}}}}{{refn|{{cite Merriam-Webster|thiourea|access-date=2016-01-21}}}} is an organosulfur compound with the formula {{chem2|SC(NH2)2}} and the structure {{chem2|H2N\sC(\dS)\sNH2}}. It is structurally similar to urea ({{chem2|H2N\sC(\dO)\sNH2}}), with the oxygen atom replaced by sulfur atom (as implied by the ''thio-'' prefix). The properties of urea and thiourea differ significantly. Thiourea is a reagent in organic synthesis. Thioureas are a broad class of compounds with the formula {{chem2|SC(NHR)(NH2), SC(NHR)2, etc}}

==Structure and bonding== Thiourea is a planar molecule. The C=S bond distance is 1.71 Å. The C-N distances average 1.33 Å.<ref>{{cite journal|title=A Simple Refinement of Density Distributions of Bonding Electrons. IX. Bond Electron Density Distribution in Thiourea, CS(NH₂)₂, at 123K|author=D. Mullen |author2=E. Hellner|journal=Acta Crystallogr.|year=1978|volume=B34|issue=9 |pages=2789–2794|doi=10.1107/S0567740878009243|doi-access=|bibcode=1978AcCrB..34.2789M }}</ref> The weakening of the C-S bond by C-N pi-bonding is indicated by the short C=S bond in thiobenzophenone, which is 1.63 Å.

Thiourea occurs in two tautomeric forms, of which the thione form predominates in aqueous solutions. The equilibrium constant has been calculated as ''K''_eq is {{val|1.04e-3}}.<ref>{{cite journal|last1=Allegretti|first1=P.E|last2=Castro|first2=E.A|last3=Furlong|first3=J.J.P|title=Tautomeric equilibrium of amides and related compounds: theoretical and spectral evidences|journal=Journal of Molecular Structure: THEOCHEM|date=March 2000|volume=499|issue=1–3|pages=121–126|doi=10.1016/S0166-1280(99)00294-8}}</ref> The thiol form, which is also known as an isothiourea, can be encountered in substituted compounds such as isothiouronium salts.

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==Production== The global annual production of thiourea is around 8,000&nbsp;tonnes, mostly in China. Thiourea is manufactured by the reaction of hydrogen sulfide with calcium cyanamide in the presence of carbon dioxide.<ref name=Ullmann/>

:{{chem2|CaCN2 + 3 H2S → Ca(SH)2 + (NH2)2CS}} :{{chem2|2 CaCN2 + Ca(SH)2 + 6 H2O → 2 (NH2)2CS + 3 Ca(OH)2}} :{{chem2|Ca(OH)2 + CO2 → CaCO3 + H2O}}

==Applications== ===Thiox precursor=== Thiourea is a precursor to thiourea dioxide, which is achieved using hydrogen peroxide: :{{chem2|(NH2)2CS + 2 H2O2 → (NH)(NH2)CSO2H + 2 H2O}} Thiourea dioxide is a common reducing agent in textile processing.<ref name=Ullmann>{{cite encyclopedia|first1=Bernd|last1=Mertschenk|first2=Ferdinand|last2=Beck|first3=Wolfgang|last3=Bauer|title=Thiourea and Thiourea Derivatives|encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry|year=2002|publisher=Wiley-VCH|doi=10.1002/14356007.a26_803.pub3|isbn=3527306730}}</ref>

===Pharmaceuticals=== Thiourea has utility in practical heterocyclic chemistry. It is a precursor to sulfathiazoles, tetramisole, and cephalosporins.

===Other uses=== Other industrial uses of thiourea include production of flame retardant resins, and vulcanization accelerators. Thiourea is building blocks to pyrimidine derivatives. Thus, thioureas condense with β-dicarbonyl compounds.<ref>{{cite journal |last1 = Foster|first1=H. M.|last2=Snyder|first2=H. R. | title = 4-Methyl-6-hydroxypyrimidine |journal=Organic Syntheses | volume = 35 | page = 80 | year = 1955 | doi = 10.15227/orgsyn.035.0080}}</ref> The amino group on the thiourea initially condenses with a carbonyl, followed by cyclization and tautomerization. Desulfurization delivers the pyrimidine. The pharmaceuticals thiobarbituric acid and sulfathiazole are prepared using thiourea.<ref name="Ullmann"/> 4-Amino-3-hydrazino-5-mercapto-1,2,4-triazole is prepared by the reaction of thiourea and hydrazine.

Thiourea is used as an auxiliary agent in diazo paper, light-sensitive photocopy paper and almost all other types of copy paper.

It is also used to tone silver-gelatin photographic prints (see Sepia Toning).

Thiourea is used in the Clifton-Phillips and Beaver bright and semi-bright electroplating processes.<ref>{{cite journal|title=81st Universal Metal Finishing Guidebook|journal=Metal Finishing, Guidebook and Directory Issue|date=Fall 2013|publisher=Metal Finishing Magazine|issn=0026-0576|pages=285|url=http://metalfinishing.epubxp.com/t/12238-metal-finishing-guide-book|access-date=2016-10-11|archive-date=2017-11-17|archive-url=https://web.archive.org/web/20171117133018/http://metalfinishing.epubxp.com/t/12238-metal-finishing-guide-book|url-status=live}}</ref> It is also used in a solution with tin(II) chloride as an electroless tin plating solution for copper printed circuit boards.

Thiourea has been proposed as a fertilizer especially under conditions of environmental stress.<ref>{{cite journal|last=Wahid|first=Abdul|date=2017-08-01|title=Thiourea: A Molecule with Immense Biological Significance for Plants|url=https://www.fspublishers.org/published_papers/27245_..pdf|journal=International Journal of Agriculture and Biology|volume=19|issue=4|pages=911–920|doi=10.17957/ijab/15.0464|issn=1560-8530|doi-access=free|access-date=2020-12-09|archive-date=2020-02-15|archive-url=https://web.archive.org/web/20200215101725/http://www.fspublishers.org/published_papers/27245_..pdf|url-status=live}}</ref>

It is an ingredient in some metal polishes, such as Tarn-X, in combination with sulfamic acid and other ingredients to chemically remove tarnish from precious metals like silver, gold, and platinum.

==Reactions== Thiourea exists in dynamic equilibrium with ammonium thiocyanate at 150 °C. This equilibrium was once exploited as a route to thiourea, but the separation of the mixture is problematic.<ref name=Ullmann/> Thiourea is basic, sustaining protonation at sulfur. According to X-ray crystallography, the product is {{chem2|[HSC(NH2)2]+}}, a planar cation. Protonation does not substantially perturb the bond distances.<ref>{{cite journal |doi=10.1107/S0567740868004255 |title=The crystal structure of thiourea nitrate |date=1968 |last1=Feil |first1=D. |last2=Song Loong |first2=W. |journal=Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry |volume=24 |issue=10 |pages=1334–1339 |bibcode=1968AcCrB..24.1334F |url=https://research.utwente.nl/en/publications/the-crystal-structure-of-thiourea-nitrate(e9781ec8-c971-4ed0-b173-5b8f1ca16b7e).html }}</ref>

===Oxidation=== When treated with a variety of oxidants, thiourea forms a cationic disulfide. Oxidation with iodine proceeds as follows:<ref>{{cite journal |doi=10.1039/C3DT53302F |title=Fundamental chemistry of iodine. The reaction of di-iodine towards thiourea and its methyl-derivative: Formation of aminothiazoles and aminothiadiazoles through dicationic disulfides |date=2014 |last1=Biesiada |first1=M. |last2=Kourkoumelis |first2=N. |last3=Kubicki |first3=M. |last4=Owczarzak |first4=A. M. |last5=Balas |first5=V. |last6=Hadjikakou |first6=S. K. |journal=Dalton Trans |volume=43 |issue=12 |pages=4790–4806 |pmid=24477281 |doi-access=free }}</ref> :{{chem2|S\dC(NH2)2 + I2 -> [(H2N)2C\sS\sS\sC(NH2)2](2+) + 2 I-}} Oxidized with hydrogen peroxide gives thiourea dioxide.<ref name= Makarov14>{{cite journal |doi=10.1002/chem.201403453 |title=Recent Developments in the Chemistry of Thiourea Oxides |date=2014 |last1=Makarov |first1=Sergei V. |last2=Horváth |first2=Attila K. |last3=Silaghi-Dumitrescu |first3=Radu |last4=Gao |first4=Qingyu |journal=Chemistry – A European Journal |volume=20 |issue=44 |pages=14164–14176 |pmid=25265917 }}</ref>

===Reductant=== Thiourea reduces peroxides to the corresponding diols.<ref>{{cite journal|first1=C.|last1=Kaneko|first2=A.|last2=Sugimoro|first3=S.|last3=Tanaka|title=A facile one-step synthesis of ''cis''-2-cyclopentene and ''cis''-2-cyclohexene-1,4-diols from the corresponding cyclodienes|url=https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-1974-23462|journal=Synthesis|pages=876–877|year=1974|doi=10.1055/s-1974-23462|volume=1974|issue=12|s2cid=93207044 |access-date=2022-06-18|archive-date=2021-06-12|archive-url=https://web.archive.org/web/20210612083502/https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-1974-23462|url-status=live|url-access=subscription}}</ref> :File:PeroxideRednTU.svg

Thiourea is also used in the reductive workup of ozonolysis to give carbonyl compounds.<ref>{{cite journal | author = Gupta, D., Soman, G., and Dev, S. | title = Thiourea, a convenient reagent for the reductive cleavage of olefin ozonolysis products | journal = Tetrahedron | pages = 3013–3018 | year = 1982 | doi = 10.1016/0040-4020(82)80187-7 | volume = 38 | issue = 20}}</ref> Dimethyl sulfide is also an effective reagent for this reaction, but it is highly volatile (boiling point&nbsp;{{val|37|u=°C}}) and has an obnoxious odor whereas thiourea is odorless and conveniently non-volatile (reflecting its polarity). :File:CyclohexenetrioxalaneRednTU.svg

===Precursor to thiols=== Thiourea is employed as a source of sulfide, such as for converting alkyl halides to thiols. The reaction capitalizes on the nucleophilicity of the sulfur center and is reminiscent of the protonation of thiourea. S-alkylation gives a isothiouronium salt: :{{chem2|CS(NH2)2 + RX → RSC(NH2)2+X−}} Isothiouronium cations are prone to base hydrolysis to give the thiolate, which can undergo protonation to give the thiol. :{{chem2|RSC(NH2)2+X− + 2 NaOH → RSNa + OC(NH2)2 + NaX + H2O}} :{{chem2|RSNa + HCl → RSH + NaCl}}

In one example, ethane-1,2-dithiol is prepared from 1,2-dibromoethane:<ref>{{OrgSynth | author = Speziale, A. J. | title = Ethanedithiol | collvol = 4 | collvolpages = 401 | year = 1963 | prep = cv4p0401}}</ref> :{{chem2|C2H4Br2 + 2 SC(NH2)2 → [C2H4(SC(NH2)2)2]Br2}} :{{chem2|[C2H4(SC(NH2)2)2]Br2 + 2 KOH → C2H4(SH)2 + 2 OC(NH2)2 + 2 KBr}}

===Precursor to metal sulfides=== Like other thioamides, thiourea can serve as a source of sulfide upon reaction with metal ions. For example, mercury sulfide forms when mercuric salts in aqueous solution are treated with thiourea: :{{chem2|Hg(2+) + SC(NH2)2 + H2O → HgS + OC(NH2)2 + 2 H+}} These sulfiding reactions have been applied to the synthesis of many metal sulfides..<ref>{{cite journal|last1=Liang|first1=Y.|last2=et|first2=al.|title=An Efficient Precursor to Synthesize Various FeS₂ Nanostructures via a Simple Hydrothermal Synthesis Method |journal=CrystEngComm |date=2016|volume=18|issue=33|pages=6262–6271|doi=10.1039/c6ce01203e|bibcode=2016CEG....18.6262L }}</ref><ref>{{cite journal|last=Bao, N. |display-authors=etal |date=2007|title=Facile Cd−Thiourea Complex Thermolysis Synthesis of Phase-Controlled CdS Nanocrystals for Photocatalytic Hydrogen Production under Visible Light|journal=The Journal of Physical Chemistry C|volume=111|issue=47 |pages=17527–17534|doi=10.1021/jp076566s}}</ref>

=== Precursor to heterocycles === Thiourea is a building block for many heterocycles. It is a precursor to pyrimidine derivatives via condensation with β-dicarbonyl compounds.<ref>{{OrgSynth | author = Foster, H. M., and Snyder, H. R. | title = 4-Methyl-6-hydroxypyrimidine | volume = 35 | page = 80 | year = 1955 | doi = 10.15227/orgsyn.035.0080}}</ref> :500px

Similarly, aminothiazoles can be synthesized by the reaction of α-haloketones and thiourea.<ref>{{cite journal |author1=Dodson, R. M. |author2=King, L. C. |name-list-style=amp | title = The reaction of ketones with halogens and thiourea | journal = J. Am. Chem. Soc. | volume = 67 | pages = 2242–2243 | year = 1945 | doi = 10.1021/ja01228a059 | pmid=21005695 | issue = 12|bibcode=1945JAChS..67.2242D }}</ref>

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The pharmaceuticals thiobarbituric acid and sulfathiazole are prepared using thiourea.<ref name=Ullmann/> 4-Amino-3-hydrazino-5-mercapto-1,2,4-triazole is prepared by the reaction of thiourea and hydrazine.

===With metals=== Being a soft nucleophile, thiourea has an affinity for metal ions, forming coordination complexes. Representative is {{chem2|[Tc(SC(NH2)2]6]Cl3}}.<ref>{{cite journal |doi=10.1021/acs.inorgchem.2c03258 |title=Thiourea as a Stabilizer of Reduced Forms of Technetium─Tc(III) and Tc(IV): Experimental and Theoretical Studies of Complexes |date=2023 |last1=Volkov |first1=Mikhail A. |last2=Novikov |first2=Anton P. |last3=Grigoriev |first3=Mikhail S. |last4=Nevolin |first4=Yuri M. |last5=German |first5=Konstantin E. |journal=Inorganic Chemistry |volume=62 |issue=1 |pages=256–265 |pmid=36525584 }}</ref> One practical consequence of its affinity for metals, thiourea is used as a silver polish.<ref name=Ullmann/> Another potential application is the use of thiourea as a lixiviant for gold and silver leaching, bypassing the steps of cyanide use and smelting.<ref>{{cite web|first=Anthony|last=Esposito|archive-url=https://web.archive.org/web/20090217115008/http://www.bnamericas.com/story.jsp?idioma=I&sector=7&noticia=399641|archive-date=17 February 2009|url=http://www.bnamericas.com/story.jsp?idioma=I&sector=7&noticia=399641|url-status=dead|title=Peñoles, UAM unveil pilot thiourea Au-Ag leaching plant in Mexico|publisher=Business News Americas|date=July 13, 2007}}</ref>

Thiourea is a reagent in the Kurnakov test used to differentiate cis- and trans- isomers of certain square planar platinum complexes. The reaction was discovered in 1893 by Russian chemist Nikolai Kurnakov and is still performed as an assay for compounds of this type.<ref>{{cite journal|last=Kauffman|first=George B.|date=January 1983|title=Nikolaĭ Semenovich Kurnakov, the reaction (1893) and the man (1860–1941) a ninety-year retrospective view|url=https://www.sciencedirect.com/science/article/pii/S027753870081400X|journal=Polyhedron|language=en|volume=2|issue=9|pages=855–863|doi=10.1016/S0277-5387(00)81400-X|issn=0277-5387|access-date=2020-12-09|archive-date=2021-03-28|archive-url=https://web.archive.org/web/20210328190216/https://www.sciencedirect.com/science/article/abs/pii/S027753870081400X|url-status=live|url-access=subscription}}</ref>

==Safety== The {{LD50}} for thiourea is {{val|125|u=mg/kg}} for rats (oral).<ref name="msds">{{cite web|url=http://gis.dep.wv.gov/tri/cheminfo/msds1385.txt|title=Thiourea and its properties|date=September 11, 1986|access-date=January 6, 2012|archive-date=May 27, 2010|archive-url=https://web.archive.org/web/20100527182536/http://gis.dep.wv.gov/tri/cheminfo/msds1385.txt|url-status=live}}</ref>

A goitrogenic effect (enlargement of the thyroid gland) has been reported for chronic exposure, reflecting the ability of thiourea to interfere with iodide uptake.<ref name=Ullmann/>

"Thiourea and its metabolites (probably oxidized thiourea) are tumorigenic and cause lung edema."<ref>{{cite encyclopedia|doi=10.1002/047084289X.ra091|encyclopedia=Encyclopedia of Reagents for Organic Synthesis|entry=Aminoiminomethanesulfonic acid|first1=Audrey|last1=Miller|first2=David C.|last2=Palmer|date=15 April 2001}}</ref>

==See also== *Thioureas

==References== {{reflist|30em}}

==Further reading== *{{cite book|title=The Chemistry of Double-Bonded Functional Groups|url=https://books.google.com/books?id=5h8SAQAAMAAJ|url-access=limited |first=Saul|last=Patai|pages=[https://archive.org/details/chemistryfunctio01pata/page/n1360 1355]–1496|publisher=John Wiley & Sons|location=New York, NY|date=1977|oclc=643207498|isbn=9780471924937}}

==External links== *[https://www.inchem.org/documents/cicads/cicads/cicad49.htm INCHEM assessment of thiourea] *[https://www.inchem.org/documents/icsc/icsc/eics0680.htm International Chemical Safety Card 0680]

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Category:Functional groups Category:Thioureas