Squaramide

Squaramide
Names
	IUPAC name 3,4-diaminocyclobut-3-ene-1,2-dione
Identifiers
CAS Number	5231-89-0;
3D model (JSmol)	Interactive image;
PubChem CID	2781329;
CompTox Dashboard (EPA)	DTXSID40381784 ;
	InChI InChI=1S/C4H4N2O2/c5-1-2(6)4(8)3(1)7/h5-6H2 Key: WUACDRFRFTWMHE-UHFFFAOYSA-N;
	SMILES C1(=C(C(=O)C1=O)N)N;
Properties
Chemical formula	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). Infobox references

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 amines^[3]^[4]

Squaramide is prepared by ammonolysis of diesters of squaric acid:^[5]^[6]

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]

References

^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ Storer, R. Ian (2013). "Squaramide". e-EROS Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rn01531. ISBN 978-0-471-93623-7.
^ 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.

[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.

[Busschaert-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.

[1]

[2]

[3]

[4]

[5]

[6]