Thioureas

In organic chemistry, thioureas are members of a family of organosulfur compounds with the formula S=C(NR2)2 and structure R2N−C(=S)−NR2. The parent member of this class of compounds is thiourea (S=C(NH2)2). Substituted thioureas are found in several commercial chemicals.

Structure and bonding

Thioureas have a trigonal planar molecular geometry of the N2C=S core. The C=S bond distance is near 1.71 Å, which is 0.1 Å longer than in normal ketones (R2C=O). The C–N bond distances are short.[1] Thioureas occurs in two tautomeric forms.

On the other hand, some compounds depicted as isothioureas and in fact thioureas, one example being mercaptobenzimidazole.[2]

Synthesis

N,N′-unsubstituted thioureas can be prepared by treating the corresponding cyanamide with hydrogen sulfide or similar sulfide sources.[3] Organic ammonium salts react with potassium thiocyanate as the source of the thiocarbonyl (C=S).[4]

Alternatively, N,N′-disubstituted thioureas can be prepared by coupling two amines with thiophosgene:[5]

HNR2 + S=CCl2 → 2 S=C(NR2)2 + 2 HCl

Amines also condense with organic thiocyanates to give thioureas:[6]

HNR2 + S=C=NR' → S=C(NR2)(NHR')

Cyclic thioureas are prepared by transamidation of thiourea with diamines. Ethylene thiourea is synthesized by treating ethylenediamine with carbon disulfide.[7] In some cases, thioureas can be prepared by thiation of ureas using phosphorus pentasulfide.

Reactions

Thioureas are susceptible to tautomerization. For the parent thiourea, the thione tautomer predominates in aqueous solutions.[8] The thiol form, known as an isothiourea, can be encountered in substituted compounds such as isothiouronium salts.

Thioureas are nucleophilic at sulfur. When they contain a pair of N-H substituents, thioureas engage in hydrogen bonding. This interaction is the basis of a research theme called thiourea organocatalysis.[9]Thioureas are often found to be stronger hydrogen-bond donors (i.e., more acidic) than ureas.[10][11]

Applications and occurrence

Agrichemicals that feature the thiourea functional group include diafenthiuron, methimazole, carbimazole (converted in vivo to methimazole), and propylthiouracil.[12] α-Naphthylthiourea is a commercial rodenticide.

Some thioureas are vulcanization accelerators.

Ergothioneine, which is derived from histidine, is a rare example of a thiourea found in nature.

The cyclic of thiourea called thiamazole is used to treat overactive thyroid

References

  1. ↑ D. Mullen; E. Hellner (1978). "A Simple Refinement of Density Distributions of Bonding Electrons. IX. Bond Electron Density Distribution in Thiourea, C=S(NH2)2, at 123K". Acta Crystallogr. B34 (9): 2789–2794. doi:10.1107/S0567740878009243.
  2. ↑ Form, G. R.; Raper, E. S.; Downie, T. C. (1976). "The crystal and molecular structure of 2-mercaptobenzimidazole". Acta Crystallographica Section B: Structural Crystallography and Crystal Chemistry. 32 (2): 345–348. doi:10.1107/S0567740876003026.
  3. ↑ Koketsu, Mamoru; Kobayashi, Chikashi; Ishihara, Hideharu (2003). "Synthesis of N-aryl-S-alkylthiocarbamates". Heteroatom Chemistry. 14 (4): 374–378. doi:10.1002/hc.10163.
  4. ↑ Herr, R. J.; Kuhler, L.; Meckler, H.; Opalka, C. J. (2000). "A Convenient Method for the Preparation of Primary and Symmetrical N,N′-Disubstituted Thioureas". Synthesis. 2000 (11): 1569–1574. doi:10.1055/s-2000-7607.
  5. ↑ Yi-Bo Huang; Wen-Bin Yi; Chun Cai (2012). "Thiourea Based Fluorous Organocatalyst". Topics in Current Chemistry. 308: 191–212. doi:10.1007/128_2011_248. ISBN 978-3-642-25233-4. PMID 21972024.
  6. ↑ Miyabe, H.; Takemoto, Y. (2008). "Discovery and Application of Asymmetric Reaction by Multifunctional Thioureas". Bull Chem Soc Jpn. 81 (7): 785. doi:10.1246/bcsj.81.785.
  7. ↑ C. F. H. Allen; C. O. Edens; James VanAllan. "Ethylene Thiourea". Org. Syntheses. 26: 34. doi:10.15227/orgsyn.026.0034.
  8. ↑ Allegretti, P.E; Castro, E.A; Furlong, J.J.P (March 2000). "Tautomeric equilibrium of amides and related compounds: theoretical and spectral evidences". Journal of Molecular Structure: THEOCHEM. 499 (1–3): 121–126. doi:10.1016/S0166-1280(99)00294-8.
  9. ↑ R. Schreiner, Peter (2003). "Metal-free organocatalysis through explicit hydrogen bonding interactions". Chem. Soc. Rev. 32 (5): 289–296. doi:10.1039/b107298f. PMID 14518182.
  10. ↑ Jakab, Gergely; Tancon, Carlo; Zhang, Zhiguo; Lippert, Katharina M.; Schreiner, Peter R. (2012). "(Thio)urea Organocatalyst Equilibrium Acidities in DMSO". Organic Letters. 14 (7): 1724–1727. doi:10.1021/ol300307c. PMID 22435999.
  11. ↑ Nieuwland, Celine; Fonseca Guerra, Célia (2022). "How the Chalcogen Atom Size Dictates the Hydrogen-Bond Donor Capability of Carboxamides, Thioamides, and Selenoamides". Chemistry – A European Journal. 28 (31): e202200755. doi:10.1002/chem.202200755. PMC 9324920. PMID 35322485.
  12. ↑ Yi, Qi-Qi; Sun, Ping; Zhang, Xinyi; Wang, Hao; Wu, Jian (2025). "Thiourea Derivatives in Agrochemical Discovery and Development". Journal of Agricultural and Food Chemistry. 73 (15): 8756–8774. doi:10.1021/acs.jafc.5c00430. PMID 40190191.

Further reading

  • Patai, S., ed. (1977). The Chemistry of double-bonded functional groups. New York, NY: John Wiley & Sons. pp. 1355–1496. ISBN 0-471-92493-8.
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