Article · Wikipedia archive · Last revised Jul 10, 2026

Squaramide

Squaramide is the organic compound with the formula O2C4(NH2)2. Not an amide in the usual sense, it is a derivative of squaric acid wherein the two OH groups are replaced by NH2 groups. Squaramides refer to a large class of derivatives wherein some of the H's are replaced by organic substituents. Exploiting their rigid planar structures, these compounds are of interest as hydrogen-bond donors in supramolecular chemistry and squaramide catalysis. Squaramides exhibit 10-50x greater affinity for halides than do thioureas. Squaramides also find application in medicinal chemistry, metabolomics and material science due to their ability to selectively conjugate amines

Last revised
Jul 10, 2026
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Citations
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Source
Wikipedia ↗
Squaramide
source ↗
Names
IUPAC name
3,4-diaminocyclobut-3-ene-1,2-dione
Identifiers
3D model (JSmol)
ChemSpider
EC Number
  • 848-257-5
UNII
  • InChI=1S/C4H4N2O2/c5-1-2(6)4(8)3(1)7/h5-6H2
    Key: WUACDRFRFTWMHE-UHFFFAOYSA-N
  • C1(=C(C(=O)C1=O)N)N
Properties
C4H4N2O2
Molar mass 112.088 g·mol−1
Appearance white solid
Melting point 338–340 °C (640–644 °F; 611–613 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Squaramide is the organic compound with the formula O2C4(NH2)2. Not an amide in the usual sense, it is a derivative of squaric acid wherein the two OH groups are replaced by NH2 groups. Squaramides refer to a large class of derivatives wherein some of the H's are replaced by organic substituents. Exploiting their rigid planar structures, these compounds are of interest as hydrogen-bond donors in supramolecular chemistry and squaramide catalysis.1 Squaramides exhibit 10-50x greater affinity for halides than do thioureas.2 Squaramides also find application in medicinal chemistry, metabolomics and material science due to their ability to selectively conjugate amines34

Squaramide is prepared by ammonolysis of diesters of squaric acid:56

O2C4(OEt)2 + 2 NH3 → O2C4(NH2)2 + 2 EtOH

N-Substituted squaramides are prepared similarly, using amines in place of ammonia.

Chloride-squaramide interaction in O2C4(NH(C6H4CF3)2. The characteristic planarity of a squaramide is evident.2 source ↗
References

References

  1. Chauhan, P.; Mahajan, S.; Kaya, U.; Hack, D.; Enders, D. (2015). "Bifunctional Amine-Squaramides: Powerful Hydrogen-Bonding Organocatalysts for Asymmetric Domino/Cascade Reactions". Adv. Synth. Catal. 357 (2–3): 253–281. doi:10.1002/adsc.201401003.
  2. Nathalie Busschaert; Isabelle L. Kirby; Sarah Young; Simon J. Coles; Peter N. Horton; Mark E. Light; Philip A. Gale (2012). "Squaramides as Potent Transmembrane Anion Transporters". Angew. Chem. Int. Ed. 51 (18): 4426–4430. doi:10.1002/anie.201200729. PMID 22461434. S2CID 34164978.
  3. Lin, Weifeng; Yang, Zhen; Kaur, Amanpreet; Block, Annika; Vujasinovic, Miroslav; Löhr, J.-Matthias; Globisch, Daniel (2021). "Squaric acid as a new chemoselective moiety for mass spectrometry-based metabolomics analysis of amines". RSC Chemical Biology. 2 (5): 1479–1483. doi:10.1039/D1CB00132A. ISSN 2633-0679. PMC 8496035. PMID 34704052.
  4. Wurm, Frederik R.; Klok, Harm-Anton (2013). "Be squared: expanding the horizon of squaric acid-mediated conjugations". Chemical Society Reviews. 42 (21): 8220–8236. doi:10.1039/c3cs60153f. ISSN 0306-0012. PMID 23873344.
  5. Storer, R. Ian (2013). "Squaramide". e-EROS Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rn01531. ISBN 978-0-471-93623-7.
  6. Ian Storer, R.; Aciro, Caroline; Jones, Lyn H. (2011). "Squaramides: Physical properties, synthesis and applications". Chemical Society Reviews. 40 (5): 2330–2346. doi:10.1039/c0cs00200c. PMID 21399835.