Aza-crown ether
# 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.

