Cyclen

Cyclen (1,4,7,10-tetraazacyclododecane) is a aza-crown ether with the formula (CH₂CH₂NH)₄. It is a white solid. Being structurally simple, symmetrical, and polyfunctional, cyclen has been widely investigated.^[1]

Cyclen

Names
Preferred IUPAC name 1,4,7,10-Tetrazacyclododecane
Other names Tetraaza-12-crown-4
Identifiers
CAS Number	294-90-6 Y
3D model (JSmol)	Interactive image Interactive image
ChEBI	CHEBI:37391 Y
ChEMBL	ChEMBL19880 Y
ChemSpider	58488 Y
ECHA InfoCard	100.102.391
PubChem CID	64963
UNII	964584YO2O Y
CompTox Dashboard (EPA)	DTXSID60183621
InChI InChI=1S/C8H20N4/c1-2-10-5-6-12-8-7-11-4-3-9-1/h9-12H,1-8H2 Y Key: QBPPRVHXOZRESW-UHFFFAOYSA-N Y InChI=1/C8H20N4/c1-2-10-5-6-12-8-7-11-4-3-9-1/h9-12H,1-8H2 Key: QBPPRVHXOZRESW-UHFFFAOYAQ
SMILES N1CCNCCNCCNCC1 C1CNCCNCCNCCN1
Properties
Chemical formula	C8H20N4
Molar mass	172.276 g·mol−1
Appearance	White solid
Melting point	110–113 °C (230–235 °F; 383–386 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Synthesis

Some syntheses exploit the Thorpe-Ingold effect to facilitate ring-formation. Illustrative is the reaction of the deprotonated tosylamides with ditosylates:^[2]

TsN(CH₂CH₂NTsNa)₂ + TsN(CH₂CH₂OTs)₂ → (TsNCH₂CH₂)₄

The resulting macrocycle can be deprotected with strong acid. Base gives the tetramine.

High dilution conditions result in a low reaction rate penalty and this disadvantage is removed in an alternative procedure starting from triethylenetetraamine and dithiooxamide to a bisamidine – also a bis(imidazoline) – followed by reduction and ring expansion with DIBAL.^[3]

Coordination complexes

Structure of [Ni(cyclen)(OH₂)₂]²⁺. Color code: O = red, N = blue, Ni = dark blue, white = H, gray = C.^[4]

Coordination complexes of cyclen have been studied extensively.^[5][6] With a 12-membered ring, it tends to bind to four contiguous sites on octaheral metal centers. In contrast the larger cyclam ligand tens to form attach to four coplanar sites. It also forms complexes of the type [Ln(cyclen)₂]³⁺ where Ln = lanthanide.^[7]

References

1. Lejault, Pauline; Duskova, Katerina; Bernhard, Claire; Valverde, Ibai E.; Romieu, Anthony; Monchaud, David (2019). "The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation" (PDF). European Journal of Organic Chemistry. 2019 (36): 6146–6157. doi:10.1002/ejoc.201900870. S2CID 201220297.
2. Atkins, T. J.; Richman, J. E.; Oettle, W. F. (1978). "1,4,7,10,13,16-Hexaazacyclooctadecane". Org. Synth. 58: 86. doi:10.15227/orgsyn.058.0086.
3. Reed, David P.; Weisman, Gary R. (2002). "1,4,7,10-Tetraazacyclododecane". Org. Synth. 78: 73. doi:10.15227/orgsyn.078.0073.
4. Scott, Brian; Brewer, Karen J.; Spreer, Larry O.; Craig, Carl A.; Otvos, John W.; Calvin, Melvin; Taylor, Scott (1990). "A Novel Conformation for a Coordinated Macrocycle: The Crystal Structure of [Ni(12-aneN₄)(OH₂)₂](CIO₄)₂·H₂O; (12-aneN₄= 1,4,7,10-Tetraazacyclododecane)". Journal of Coordination Chemistry. 21 (4): 307–313. doi:10.1080/00958979009408193.
5. Gunnlaugsson, Thorfinnur; Leonard, Joseph P. (2005). "Responsive lanthanide luminescent cyclen complexes: From switching/Sensing to supramolecular architectures". Chemical Communications (25): 3114–3131. doi:10.1039/b418196d. PMID 15968347.
6. Joshi, Tanmaya; Graham, Bim; Spiccia, Leone (2015). "Macrocyclic Metal Complexes for Metalloenzyme Mimicry and Sensor Development". Accounts of Chemical Research. 48 (8): 2366–2379. doi:10.1021/acs.accounts.5b00142. PMID 26244894.
7. Barraza, Ramiro; Sertage, Alexander G.; Kajjam, Aravind B.; Ward, Cassandra L.; Lutter, Jacob C.; Schlegel, H. Bernhard; Allen, Matthew J. (2022). "Properties of Amine-Containing Ligands That Are Necessary for Visible-Light-Promoted Catalysis with Divalent Europium". Inorganic Chemistry. 61 (49): 19649–19657. doi:10.1021/acs.inorgchem.2c02911. PMC 9771976. PMID 36417708.

Further reading

• Suchý, M.; Hudson, R. H. E. (2008). "Synthetic Strategies Toward N-Functionalized Cyclens". Eur. J. Org. Chem. 2008 (29): 4847–4865. doi:10.1002/ejoc.200800636.