Cyclen Explained

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]

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)₄The 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

Coordination complexes of cyclen have been studied extensively.^{[4] [5]} 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.^[6]

Further reading

• Suchý, M. . Hudson, R. H. E. . . 2008 . 2008 . 4847–4865 . Synthetic Strategies Toward N-Functionalized Cyclens . 10.1002/ejoc.200800636 . 29.

Notes and References

1. 10.1002/ejoc.201900870 . The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation . 2019 . Lejault . Pauline . Duskova . Katerina . Bernhard . Claire . Valverde . Ibai E. . Romieu . Anthony . Monchaud . David . European Journal of Organic Chemistry . 2019 . 36 . 6146–6157 . 201220297 .
2. Org. Synth. . 1,4,7,10,13,16-Hexaazacyclooctadecane . T. J.. Atkins. J. E.. Richman. W. F.. Oettle . 58 . 86 . 1978 . 10.15227/orgsyn.058.0086.
3. Org. Synth. . 1,4,7,10-Tetraazacyclododecane . David P.. Reed . Gary R. . Weisman . 78 . 73 . 2002 . 10.15227/orgsyn.078.0073.
4. 10.1039/b418196d . Responsive lanthanide luminescent cyclen complexes: From switching/Sensing to supramolecular architectures . 2005 . Gunnlaugsson . Thorfinnur . Leonard . Joseph P. . Chemical Communications . 25 . 3114–3131 . 15968347 .
5. 10.1021/acs.accounts.5b00142 . Macrocyclic Metal Complexes for Metalloenzyme Mimicry and Sensor Development . 2015 . Joshi . Tanmaya . Graham . Bim . Spiccia . Leone . Accounts of Chemical Research . 48 . 8 . 2366–2379 . 26244894 .
6. 10.1021/acs.inorgchem.2c02911 . Properties of Amine-Containing Ligands That Are Necessary for Visible-Light-Promoted Catalysis with Divalent Europium . 2022 . Barraza . Ramiro . Sertage . Alexander G. . Kajjam . Aravind B. . Ward . Cassandra L. . Lutter . Jacob C. . Schlegel . H. Bernhard . Allen . Matthew J. . Inorganic Chemistry . 61 . 49 . 19649–19657 . 36417708 . 9771976 .