Cyclen

{{chembox | verifiedrevid = 443545290 | ImageFile=Cyclen.svg | ImageSize=150px | PIN=1,4,7,10-Tetrazacyclododecane | OtherNames= Tetraaza-12-crown-4<br/> [12]aneN₄<ref>{{RedBook2005|page=261}}</ref> |Section1={{Chembox Identifiers | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 58488 | InChI = 1/C8H20N4/c1-2-10-5-6-12-8-7-11-4-3-9-1/h9-12H,1-8H2 | InChIKey = QBPPRVHXOZRESW-UHFFFAOYAQ | SMILES1 = C1CNCCNCCNCCN1 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 19880 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C8H20N4/c1-2-10-5-6-12-8-7-11-4-3-9-1/h9-12H,1-8H2 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = QBPPRVHXOZRESW-UHFFFAOYSA-N | CASNo_Ref = {{cascite|correct|??}} | CASNo=294-90-6 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 964584YO2O | PubChem=64963 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 37391 | SMILES = N1CCNCCNCCNCC1 }} |Section2={{Chembox Properties | C=8 | H=20 | N=4 | Appearance=White solid | Density= | MeltingPtC= 110-113 | BoilingPt= | Solubility= }} |Section3={{Chembox Hazards | MainHazards= | FlashPt= | AutoignitionPt = }} }}

'''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.<ref>{{cite journal |doi=10.1002/ejoc.201900870 |title=The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation |date=2019 |last1=Lejault |first1=Pauline |last2=Duskova |first2=Katerina |last3=Bernhard |first3=Claire |last4=Valverde |first4=Ibai E. |last5=Romieu |first5=Anthony |last6=Monchaud |first6=David |journal=European Journal of Organic Chemistry |volume=2019 |issue=36 |pages=6146–6157 |s2cid=201220297 |url=https://hal.archives-ouvertes.fr/hal-02268694v2/file/Lejault%20et%20al%20-%20EurJOC%202019.pdf }}</ref>

== Synthesis == Some syntheses exploit the Thorpe-Ingold effect to facilitate ring-formation. Illustrative is the reaction of the deprotonated tosylamides with ditosylates:<ref name = atkins>{{cite journal|journal=Org. Synth. | title = 1,4,7,10,13,16-Hexaazacyclooctadecane | first1= T. J.|last1= Atkins|first2= J. E.|last2= Richman|first3= W. F.|last3= Oettle | volume = 58 | page = 86 | year = 1978 | doi = 10.15227/orgsyn.058.0086}}</ref> :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.<ref>{{cite journal|journal=Org. Synth. | title = 1,4,7,10-Tetraazacyclododecane | first1= David P.|last1= Reed |first2=Gary R. |last2=Weisman | volume = 78 | pages = 73 | year = 2002 | doi = 10.15227/orgsyn.078.0073}}</ref>

:500px|Cyclen synthesis dithiooxamide method

==Coordination complexes== [[File:CSD CIF JIKJUI.jpg|thumb|left|Structure of [Ni(cyclen)(OH₂)₂]²⁺. Color code: O = red, N = blue, Ni = dark blue, white = H, gray = C.<ref>{{cite journal |doi=10.1080/00958979009408193 |title=A Novel Conformation for a Coordinated Macrocycle: The Crystal Structure of &#91;Ni(12-aneN₄)(OH₂)₂&#93;(CIO₄)₂·H₂O; (12-aneN₄= 1,4,7,10-Tetraazacyclododecane) |date=1990 |last1=Scott |first1=Brian |last2=Brewer |first2=Karen J. |last3=Spreer |first3=Larry O. |last4=Craig |first4=Carl A. |last5=Otvos |first5=John W. |last6=Calvin |first6=Melvin |last7=Taylor |first7=Scott |journal=Journal of Coordination Chemistry |volume=21 |issue=4 |pages=307–313 }}</ref>]] Coordination complexes of cyclen have been studied extensively.<ref>{{cite journal |doi=10.1039/b418196d |title=Responsive lanthanide luminescent cyclen complexes: From switching/Sensing to supramolecular architectures |date=2005 |last1=Gunnlaugsson |first1=Thorfinnur |last2=Leonard |first2=Joseph P. |journal=Chemical Communications |issue=25 |pages=3114–3131 |pmid=15968347 }}</ref><ref>{{cite journal |doi=10.1021/acs.accounts.5b00142 |title=Macrocyclic Metal Complexes for Metalloenzyme Mimicry and Sensor Development |date=2015 |last1=Joshi |first1=Tanmaya |last2=Graham |first2=Bim |last3=Spiccia |first3=Leone |journal=Accounts of Chemical Research |volume=48 |issue=8 |pages=2366–2379 |pmid=26244894 }}</ref> 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.<ref>{{cite journal |doi=10.1021/acs.inorgchem.2c02911 |title=Properties of Amine-Containing Ligands That Are Necessary for Visible-Light-Promoted Catalysis with Divalent Europium |date=2022 |last1=Barraza |first1=Ramiro |last2=Sertage |first2=Alexander G. |last3=Kajjam |first3=Aravind B. |last4=Ward |first4=Cassandra L. |last5=Lutter |first5=Jacob C. |last6=Schlegel |first6=H. Bernhard |last7=Allen |first7=Matthew J. |journal=Inorganic Chemistry |volume=61 |issue=49 |pages=19649–19657 |pmid=36417708 |pmc=9771976 }}</ref>

==Related compounds== *The cyclam ligands are also tetraaza macrocycles but consist of a more flexible C₁₀N₄ ring.

== References == {{reflist}}

==Further reading== * {{cite journal |author1=Suchý, M. |author2=Hudson, R. H. E. | journal = Eur. J. Org. Chem. | volume = 2008 | year = 2008 | pages = 4847–4865 | title = Synthetic Strategies Toward ''N''-Functionalized Cyclens | doi = 10.1002/ejoc.200800636 | issue = 29}}

Category:Ethyleneamines Category:Macrocycles Category:Chelating agents Category:Nitrogen heterocycles Category:Secondary amines