Aza-crown ether

In organic chemistry, an aza-crown ether is an aza analogue of a crown ether (cyclic polyether).^[2][3] 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 (CH₂CH₂O)_n, the parent aza-crown ethers have the formulae (CH₂CH₂NH)_n, where n = 3, 4, 5, 6. Well-studied aza crowns include triazacyclononane (n = 3), cyclen (n = 4),^[4] and hexaaza-18-crown-6 (n = 6).^[5]

• 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 (CH₂)₂ and (CH₂)₃ linkers between amine centers.
• 
  Plerixafor, a derivative of cyclam, is used to treat lymphoma and multiple myeloma.^[6]
• 
  2.2.2-Cryptand is an aza-crown of the mixed ether-amine variety.

The structure of [Co(III)(CH₂CH₂NH)₆]³⁺.^[1] Color code: blue = N, gray = C, black = C, white = H.

Synthesis

The synthesis of aza crown ethers are subject to the challenges associated with the preparation of macrocycles.^[7] The 18-membered ring in (CH₂CH₂NH)₆ can be synthesized by combining two triamine components.^[5] 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.^[8] One example is the diaza-18-crown-6, [(CH₂CH₂O)₂(CH₂CH₂NH)]₂.^[9]

Lariat crowns

The presence of the amine allows the formation of Lariat crown ethers, which feature sidearms that augment complexation of cation.^[10]