title: Aza-crown ether
text: # Aza-crown ether
  
  In organic chemistry, an aza-crown ether is an aza analogue of a crown ether (cyclic polyether). That is, it has a nitrogen atom (amine linkage, −NH− or >N−) in place of each oxygen atom (ether linkage, −O−) around the ring. While the parent crown ethers have the formulae $(CH_2CH_2O)_n,$ the parent aza-crown ethers have the formulae $(CH_2CH_2NH)_n,$ where n = 3, 4, 5, 6. Well-studied aza crowns include triazacyclononane (n = 3), cyclen (n = 4), and hexaaza-18-crown-6 (n = 6).
  
  * Selected aza-crowns and their complexes
  * 1,4,7-Trimethyl-1,4,7-triazacyclononane, a tridentate ligand used in coordination chemistry.
  * Cyclam is a tetraaza crown ether with alternating $(CH_2)_2$ and $(CH_2)_3$ linkers between amine centers.
  * Plerixafor, a derivative of cyclam, is used to treat lymphoma and multiple myeloma.
  * 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. The 18-membered ring in $(CH_2CH_2NH)_6$ can be synthesized by combining two triamine components. 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 $((CH_2)_3)$ as well as ethylene $((CH_2)_2)$ 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) $(CH_2CH_2NCH_3)_3,$ 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.. One example is the diaza-18-crown-6, $[(CH_2CH_2O)_2(CH_2CH_2NH)]_2.$
  
  ### Lariate crowns
  
  The presence of the amine allows the formation of Lariat crown ethers, which feature sidearms that augment complexation of cation.
  
  