aza-crown ether
{{short description|Ring molecule with several amine (–N– or >N–) groups}}
File:Co((CH2CH2NH)6)+++(BIGNOU01).png
In organic chemistry, an aza-crown ether is an aza analogue of a crown ether (cyclic polyether).{{cite journal |doi=10.1016/S0010-8545(98)00243-4|title=Proton coordination by polyamine compounds in aqueous solution|year=1999|last1=Bencini|first1=Andrea|last2=Bianchi|first2=Antonio|last3=Garcia-España|first3=Enrique|last4=Micheloni|first4=Mauro|last5=Ramirez|first5=José Antonio|journal=Coordination Chemistry Reviews|volume=188|pages=97–156}}{{cite journal |doi=10.1039/b106367g|title=Metal complexes of azacrown ethers in molecular recognition and catalysis|year=2002|last1=Reichenbach-Klinke|first1=Roland|last2=König|first2=Burkhard|journal=Journal of the Chemical Society, Dalton Transactions|issue=2|pages=121–130}} That is, it has a nitrogen atom (amine linkage, {{chem2|\sNH\s}} or {{chem2|>N\s}}) in place of each oxygen atom (ether linkage, {{chem2|\sO\s}}) around the ring. While the parent crown ethers have the formulae {{chem2|(CH2CH2O)_{n} }}, the parent aza-crown ethers have the formulae {{chem2|(CH2CH2NH)_{n} }}, where n = 3, 4, 5, 6. Well-studied aza crowns include triazacyclononane (n = 3), cyclen (n = 4),{{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}} and hexaaza-18-crown-6 (n = 6).
File:Me3TACN.png|1,4,7-Trimethyl-1,4,7-triazacyclononane, a tridentate ligand used in coordination chemistry.
File:Cyclam.png|Cyclam is a tetraaza crown ether with alternating {{chem2|(CH2)2}} and {{chem2|(CH2)3}} linkers between amine centers.
File:Plerixafor.svg|Plerixafor, a derivative of cyclam, is used to treat lymphoma and multiple myeloma.{{Cite journal | title = Plerixafor | journal = Drugs in R&D | volume = 8 | issue = 2| pages = 113–119 | year = 2007 | doi = 10.2165/00126839-200708020-00006| pmid = 17324009 | last1 = }}
File:Cryptand.svg| 2.2.2-Cryptand is an aza-crown of the mixed ether-amine variety.
Synthesis
The synthesis of aza crown ethers are subject to the challenges associated with the preparation of macrocycles.{{cite journal |doi=10.1021/cr00094a008|title=Synthesis of aza-crown ethers|year=1989|last1=Krakowiak|first1=Krzysztof E.|last2=Bradshaw|first2=Jerald S.|last3=Zamecka-Krakowiak|first3=Daria J.|journal=Chemical Reviews|volume=89|issue=4|pages=929–972}} The 18-membered ring in (CH2CH2NH)6 can be synthesized by combining two triamine components.{{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}} By reaction with tosyl chloride, diethylene triamine is converted to a derivative with two secondary sulfonamides. This compound serves as a building block for macrocyclizations.
Variants
Many kinds of aza crown ethers exist.
;Variable length linkers
Aza crowns often feature trimethylene ((CH2)3) as well as ethylene ((CH2)2) linkages. One example is cyclam (1,4,8,11-tetraazacyclotetradecane).
;Tertiary amines
In many aza-crown ethers some or all of the amines are tertiary. One example is the tri(tertiary amine) (CH2CH2NCH3)3, known as trimethyltriazacyclononane. Cryptands, three-dimensional aza crowns, feature tertiary amines.
;Mixed ether-amine ligands
Another large class of macrocyclic ligands feature both ether and amines.{{cite journal |doi=10.1021/ja00732a007|title=Stability constants of cyclic polyether complexes with univalent cations|year=1971|last1=Frensdorff|first1=Hans K.|journal=Journal of the American Chemical Society|volume=93|issue=3|pages=600–606}} One example is the diaza-18-crown-6, [(CH2CH2O)2(CH2CH2NH)]2.{{cite journal |journal=Organic Syntheses| first1= Vincent J.|last1= Gatto|first2= Steven R.|last2= Miller|first3= George W.|last3= Gokel | title = 4,13-Diaza-18-Crown-6 | volume = 68 | pages = 227| year = 1990 | doi = 10.15227/orgsyn.068.0227}}
;Lariate crowns
The presence of the amine allows the formation of Lariat crown ethers, which feature sidearms that augment complexation of cation.{{cite journal|first1=G. W.|last1= Gokel|first2= L. J. |last2=Barbour|first3= R. |last3=Ferdani |first4=J.|last4= Hu |title=Lariat Ether Receptor Systems Show Experimental Evidence for Alkali Metal Cation Interactions|journal=Acc. Chem. Res. |year=2002 |volume=35|issue= 10|pages= 878–886 |doi=10.1021/ar000093p|pmid= 12379140}}