Cyclen
Verifiedrevid443545290
Pin1,4,7,10-Tetrazacyclododecane
OthernamesTetraaza-12-crown-4
[12]aneN₄[1]

Cyclen (1,4,7,10-tetraazacyclododecane) is an aza-crown ether with the formula (CH2CH2NH)4. It is a white solid. It forms coordination complexes with metal cations and is used to synthesize the chelating agent DOTA which has several medical applications. Being structurally simple, symmetrical, and polyfunctional, cyclen has been widely investigated.[2]

Synthesis

Some syntheses exploit the Thorpe-Ingold effect to facilitate ring-formation. Illustrative is the reaction of the deprotonated tosylamides with ditosylates:[3]

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.[4]

Coordination complexes

Coordination complexes of cyclen have been studied extensively.[5][6] With a 12-membered C8N4 ring, it tends to bind to four contiguous sites on octahedral metal centers, forming four 5-membered chelate rings (see figure). Cyclen also forms "bis complexes", e.g. of the type [Ln(cyclen)2]3+ where Ln = lanthanide.[7]

  • The cyclam ligands are also tetraaza macrocycles but consist of a more flexible C10N4 ring.

References

  1. ^
  2. ^ Lejault, Pauline; Duskova, Katerina; Bernhard, Claire; Valverde, Ibai E.; Romieu, Anthony; Monchaud, David (2019). "The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation". European Journal of Organic Chemistry. 2019 (36): 6146–6157. doi:10.1002/ejoc.201900870. S2CID 201220297
  3. ^ 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
  4. ^ Reed, David P. & Weisman, Gary R. (2002). "1,4,7,10-Tetraazacyclododecane". Org. Synth.. 78: 73. doi:10.15227/orgsyn.078.0073
  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