thiourea

Thiourea is a planar molecule. The C=S bond distance is 1.71 Å. The C-N distances average 1.33 Å.{{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 }} 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}}.{{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}} The thiol form, which is also known as an isothiourea, can be encountered in substituted compounds such as isothiouronium salts.

:300px

The global annual production of thiourea is around 10,000 tonnes. About 40% is produced in Germany, another 40% in China, and 20% in Japan. Thiourea is manufactured by the reaction of hydrogen sulfide with calcium cyanamide in the presence of carbon dioxide.

:{{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}}

Thiourea per se has few applications. It is mainly consumed as a precursor to thiourea dioxide, which is a common reducing agent in textile processing.{{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|isbn=3527306730}}

Recently thiourea has been investigated for its multiple desirable properties as a fertilizer especially under conditions of environmental stress.{{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}} It may be applied in various capacities, such as a seed pretreatment (for priming), foliar spray or medium supplementation.

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.{{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}} 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. 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.{{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}} It is also used in a solution with tin(II) chloride as an electroless tin plating solution for copper printed circuit boards.

Thioureas are used (usually as hydrogen-bond donor catalysts) in a research theme called thiourea organocatalysis.{{cite journal|first=Peter |last=R. Schreiner |title=Metal-free organocatalysis through explicit hydrogen bonding interactions |journal=Chem. Soc. Rev. |date=2003 |volume=32 |issue=5 |pages=289–296 |doi=10.1039/b107298f |pmid=14518182}} Thioureas are often found to be stronger hydrogen-bond donors (i.e., more acidic) than ureas.{{cite journal |last1=Jakab |first1=Gergely |last2=Tancon |first2=Carlo |last3=Zhang |first3=Zhiguo |last4=Lippert |first4=Katharina M. |last5=Schreiner |first5=Peter R. |title=(Thio)urea Organocatalyst Equilibrium Acidities in DMSO |journal=Organic Letters |date=2012 |volume=14 |issue=7 |pages=1724–1727 |doi=10.1021/ol300307c|pmid=22435999}}{{cite journal |last1=Nieuwland |first1=Celine |last2=Fonseca Guerra |first2=Célia |title=How the Chalcogen Atom Size Dictates the Hydrogen-Bond Donor Capability of Carboxamides, Thioamides, and Selenoamides |journal=Chemistry – A European Journal |date=2022 |volume=28 |issue=31 |page=e202200755 |doi=10.1002/chem.202200755|pmid=35322485 |pmc=9324920}}

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.

Thiourea reduces peroxides to the corresponding diols.{{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}} The intermediate of the reaction is an unstable endoperoxide.

Image:Diol.png

Thiourea is also used in the reductive workup of ozonolysis to give carbonyl compounds.{{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}} Dimethyl sulfide is also an effective reagent for this reaction, but it is highly volatile (boiling point {{val|37|u=°C}}) and has an obnoxious odor whereas thiourea is odorless and conveniently non-volatile (reflecting its polarity).

Image:Reduction cleavage.png

Thiourea is employed as a source of sulfide, such as for converting alkyl halides to thiols. The reaction capitalizes on the high nucleophilicity of the sulfur center and easy hydrolysis of the intermediate isothiouronium salt:

:{{chem2|CS(NH2)2 + RX → RSC(NH2)2+X−}}

:{{chem2|RSC(NH2)2+X− + 2 NaOH → RSNa + OC(NH2)2 + NaX + H2O}}

:{{chem2|RSNa + HCl → RSH + NaCl}}

In this example, ethane-1,2-dithiol is prepared from 1,2-dibromoethane:{{OrgSynth | author = Speziale, A. J. | title = Ethanedithiol | collvol = 4 | collvolpages = 401 | year = 1963 | prep = cv4p0401}}

:{{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}}

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, which have been applied to the synthesis of many metal sulfides, require water and typically some heating.{{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}}{{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}}

Thioureas are building blocks to pyrimidine derivatives. Thus thioureas condense with β-dicarbonyl compounds.{{OrgSynth | author = Foster, H. M., and Snyder, H. R. | title = 4-Methyl-6-hydroxypyrimidine | collvol = 4 | collvolpages = 638 | year = 1963 | prep = cv4p0638}}

The amino group on the thiourea initially condenses with a carbonyl, followed by cyclization and tautomerization. Desulfurization delivers the pyrimidine.

:500px

Similarly, aminothiazoles can be synthesized by the reaction of α-haloketones and thiourea.{{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}}

:500px

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

According to the label on consumer products TarnX{{cite web|url=https://cf1.bettymills.com/product/more_info/TX-4PRO.pdf|title=Tarn-X PRO Tarnish Remover|publisher=The Betty Mills Company, Inc.|access-date=2021-06-06|archive-date=2021-06-06|archive-url=https://web.archive.org/web/20210606174511/https://cf1.bettymills.com/product/more_info/TX-4PRO.pdf|url-status=live}} and Silver Dip,{{cite web|url=https://www.jlsmithco.com/wp-content/uploads/2020/05/hagerty-silver-dip-1-gal.jpg|title=Hagerty Silver Dip|publisher=J.L. Smith & Co.|access-date=2021-06-06|archive-date=2021-06-06|archive-url=https://web.archive.org/web/20210606174511/https://www.jlsmithco.com/wp-content/uploads/2020/05/hagerty-silver-dip-1-gal.jpg|url-status=live}} the liquid silver cleaning products contain thiourea along with a warning that thiourea is a chemical on California's list of carcinogens.{{cite report|url=https://oehha.ca.gov/media/downloads/proposition-65/report/expcancer.pdf|title=Expedited Cancer Potency Values and Proposed Regulatory Levels for Certain Proposition 65 Carcinogens|date=April 1992|access-date=2022-06-18|archive-date=2022-01-21|archive-url=https://web.archive.org/web/20220121224113/https://oehha.ca.gov/media/downloads/proposition-65/report/expcancer.pdf|url-status=live}} A lixiviant for gold and silver leaching can be created by selectively oxidizing thiourea, bypassing the steps of cyanide use and smelting.{{cite web|first=Anthony|last=Esposito|archive-url=https://web.archive.org/web/20090217115008/http://www.bnamericas.com/story.jsp?idioma=I§or=7¬icia=399641|archive-date=17 February 2009|url=http://www.bnamericas.com/story.jsp?idioma=I§or=7¬icia=399641|url-status=dead|title=Peñoles, UAM unveil pilot thiourea Au-Ag leaching plant in Mexico|publisher=Business News Americas|date=July 13, 2007}}

Thiourea is an essential 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.{{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}}

The {{LD50}} for thiourea is {{val|125|u=mg/kg}} for rats (oral).{{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}}

A goitrogenic effect (enlargement of the thyroid gland) has been reported for chronic exposure, reflecting the ability of thiourea to interfere with iodide uptake.

A cyclic derivative of thiourea called Thiamazole is used to treat overactive thyroid

• Thioureas

{{reflist|30em}}

• {{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}}

• [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]

{{Thyroid hormone receptor modulators}}

{{Authority control}}

Category:Functional groups