organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...

, an aza-crown ether is an aza analogue of a

crown ether In organic chemistry, crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups (). The most common crown ethers are cyclic oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., . Impor ...

(cyclic polyether). That is, it has a

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

atom (

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

linkage, or ) in place of each

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

atom (

ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...

linkage, ) around the

ring Ring may refer to: * Ring (jewellery), a round band, usually made of metal, worn as ornamental jewelry * To make a sound with a bell, and the sound made by a bell :(hence) to initiate a telephone connection Arts, entertainment and media Film and ...

. While the

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crown ethers have the formulae , the parent ''aza''-crown ethers have the formulae , where n = 3, 4, 5, 6. Well-studied aza crowns include

triazacyclononane 1,4,7-Triazacyclononane, known as "TACN" which is pronounced "tack-en," is an aza-crown ether with the formula (C2H4NH)3. TACN is derived, formally speaking, from cyclononane by replacing three equidistant CH2 groups with NH groups. TACN is one of ...

(n = 3),

cyclen Cyclen (1,4,7,10-tetraazacyclododecane) is a aza-crown ether with the formula (CH2CH2NH)4. It is a white solid. Synthesis Some syntheses exploit the Thorpe-Ingold effect to facilitate ring-formation. Illustrative is the reaction of the depro ...

(n = 4), and

hexaaza-18-crown-6 Hexaaza-18-crown-6 is the macrocyclic ligand with the formula (CH2CH2NH)6. A white solid, this compound has attracted attention as the N6-analogue of 18-crown-6. It functions as a hexadentate ligand in coordination chemistry. It is the parent hexaa ...

(n = 6). File:Me3TACN.png,

1,4,7-Trimethyl-1,4,7-triazacyclononane 1,4,7-Trimethyl-1,4,7-triazacyclononane is the aza-crown ether with the formula (CH2CH2NCH3)3. This colorless liquid is the N-methylated derivative of triazacyclononane (TACN), a face-capping tridentate ligand that is popular in coordination chem ...

, a tridentate ligand used in

coordination chemistry A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...

. File:Cyclam.png,

Cyclam Cyclam (1,4,8,11-tetraazacyclotetradecane) is an organic compound with the formula (NHCH2CH2NHCH2CH2CH2)2. Classified as an aza-crown ether, it is a white solid that is soluble in water. As a macrocyclic ligand, it binds strongly to many transitio ...

is a tetraaza crown ether with alternating and linkers between amine centers. File:Plerixafor.svg,

Plerixafor Plerixafor (INN and USAN, trade name Mozobil) is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients into the bloodstream. The stem cells are then extracted from the blood and transplanted back to the patient. The drug ...

, a derivative of cyclam, is used to treat

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

and

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...

. File:Cryptand.svg,

2.2.2-Cryptand .2.2ryptand is the organic compound with the formula N(CH2CH2OCH2CH2OCH2CH2)3N. This bicyclic molecule is the most studied member of the cryptand family of chelating agents. It is a white solid. Many analogous compounds are known. Their high a ...

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

macrocycle Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry. ...

s. The 18-membered ring in (CH₂CH₂NH)₆ can be synthesized by combining two triamine components. By reaction with

tosyl chloride 4-Toluenesulfonyl chloride (''p''-toluenesulfonyl chloride, toluene-''p''-sulfonyl chloride) is an organic compound with the formula CH3C6H4SO2Cl. This white, malodorous solid is a reagent widely used in organic synthesis. Abbreviated TsCl or To ...

diethylene triamine Diethylenetriamine (abbreviated Dien or DETA) and also known as 2,2’-Iminodi(ethylamine)) is an organic compound with the formula HN(CH2CH2NH2)2. This colourless hygroscopic liquid is soluble in water and polar organic solvents, but not simple ...

is converted to a derivative with two secondary

sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...

s. This compound serves as a building block for

macrocyclization Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry. ...

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 Cyclam (1,4,8,11-tetraazacyclotetradecane) is an organic compound with the formula (NHCH2CH2NHCH2CH2CH2)2. Classified as an aza-crown ether, it is a white solid that is soluble in water. As a macrocyclic ligand, it binds strongly to many transitio ...

(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 In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such a ...

) (CH₂CH₂NCH₃)₃, known as

trimethyltriazacyclononane 1,4,7-Trimethyl-1,4,7-triazacyclononane is the aza-crown ether with the formula (CH2CH2NCH3)3. This colorless liquid is the N-methylated derivative of triazacyclononane (TACN), a face-capping tridentate ligand that is popular in coordination chem ...

Cryptand In chemistry, cryptands are a family of synthetic, bicyclic and polycyclic, multidentate ligands for a variety of cations. The Nobel Prize for Chemistry in 1987 was given to Donald J. Cram, Jean-Marie Lehn, and Charles J. Pedersen for their e ...

s, 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, CH₂CH₂O)₂(CH₂CH₂NH)sub>2. ;Lariate crowns The presence of the amine allows the formation of

Lariat A lasso ( or ), also called lariat, riata, or reata (all from Castilian, la reata 're-tied rope'), is a loop of rope designed as a restraint to be thrown around a target and tightened when pulled. It is a well-known tool of the Spanish an ...

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

References

Polyamines Secondary amines Tertiary amines Ethyleneamines Chelating agents Macrocycles