294-93-9

Basic information

• Product Name: 12-Crown-4
• Synonyms: Eoct;Ethylene oxide cyclic tetramer;1,4,7,10-TETRAOXYCYCLODODECANE;1,4,7,10-TETRAOXACYCLODODECANE;12-CROWN 4-ETHER;12-CROWN-4;LITHIUM IONOPHORE V;CROWN ETHER/12-CROWN-4
• CAS NO: 294-93-9
• Molecular Formula: C₈H₁₆O₄
• Molecular Weight: 176.21
• EINECS: 206-036-5
• Product Categories: Crown Ethers;Functional Materials;Macrocycles for Host-Guest Chemistry
• Mol File: 294-93-9.mol
• Article Data: 13

Chemical Properties

• Melting Point: 16 °C(lit.)
• Boiling Point: 61-70 °C0.5 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Clear colorless to slightly yellow/Liquid After Melting
• Density: 1.089 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0269mmHg at 25°C
• Refractive Index: n20/D 1.463(lit.)
• Storage Temp.: 2-8°C
• Water Solubility: MISCIBLE
• Sensitive: Air Sensitive
• BRN: 1363064
• CAS DataBase Reference: 12-Crown-4(CAS DataBase Reference)
• NIST Chemistry Reference: 12-Crown-4(294-93-9)
• EPA Substance Registry System: 12-Crown-4(294-93-9)

Safety Data

• Hazard Codes: T+,Xn,Xi
• Statements: 26-36/37/38-20/21/22
• Safety Statements: 28-36/37-45-36-26
• RIDADR: UN 2810
• WGK Germany: 3
• RTECS: XF0550000
• F: 3-9-23
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 294-93-9(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless to slightly yellow liquid after

Uses

Different sources of media describe the Uses of 294-93-9 differently. You can refer to the following data:
1. An aprotic "solvent" for alkali metals, the sodium solution is a strong reducing agent
2. It serves as an aprotic "solvent" for alkali metals, the sodium solution is a strong reducing agent.
3. 12-Crown-4 can be used as: A promoter in the synthesis of poly(diethylsiloxane) (PDES) from monomer hexaethylcyclotrisiloxane using NaOH as a catalyst via anionic ring-opening polymerization. As an additive in the preparation of triarylmethane derivatives by palladium-catalyzed cross coupling reaction of aryl bromides with diarylmethane derivatives. A phase transfer catalyst in organic synthesis.

Definition

ChEBI: A crown ether that is cyclododecane in which the carbon atoms at positions 1, 4, 7 and 10 have been replaced by oxygen atoms.

Synthesis Reference(s)

Tetrahedron Letters, 15, p. 4029, 1974 DOI: 10.1016/S0040-4039(01)92075-1

General Description

12-Crown-4 is a crown ether generally used as a ligand in coordination chemistry. It is also known as lithium ionophore because of its strong chelating property specific to lithium cation.

Purification Methods

The distilled crude product has to be recrystallised from pentane at -20o to remove acyclic material. It is then dried over P2O5. It complexes Li. [Anet et al. Acta Chem Scand 27 3395 1973, Beilstein 19/11 V 334.]

InChI:InChI=1/C8H16O4/c1-2-10-5-6-12-8-7-11-4-3-9-1/h1-8H2

Synthetic route

[Li(12-crown-4)][W(CO)5(P(CH(SiMe3)2)(OPh))] + phenylacetylene (536-74-3) + methyl trifluoromethanesulfonate (333-27-7) → (1,4,7,10-tetraoxacyclododecane) (294-93-9) + [W(CO)5(P(CHCMePh)(CH(SiMe3)2)(OPh))] (1416967-44-6)

Conditions

Yield

In tetrahydrofuran byproducts: LiOTf; under Ar, soln. of phenylacetylene (1.0 mmol) added to W complex in THF at -78°C, after 0.5 h of stirring, phenylacetylene added, mixt. heated at reflux for 2 h, cooled to ambient temp., MeOTf added; volatiles evapd. in vac. (ca. 0.01 mbar), raw product purified by columnchromy. (SiO2, -20°C, petroleum ether/Et2O, 10:1), product obtai ned from 2nd fraction, detd. by 1H NMR, 13C NMR, 31P NMR, 29Si NMR, IR, MS;

A n/a B 62%

ethylene glycol (107-21-1) + 1,2-bis(2-chloroethoxy)ethane (112-26-5) → (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
With potassium hydroxide for 0.1h; microwave irradiation;	37%

Tetraethylene glycol (112-60-7) → (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
With cyanomethylenetributyl-phosphorane In benzene at 60℃; sealed vessel;	30%
With p-toluenesulfonyl chloride; lithium tert-butoxide In tert-butyl alcohol Heating;	27%

3-oxa-1,5-dichloropentane (111-44-4) + diethylene glycol (111-46-6) → (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
With lithium hydride In dimethyl sulfoxide Heating; different basis as 'template' agents, other solvents;	24%
With lithium hydride In dimethyl sulfoxide Heating;	24%

Tetraethylene glycol (112-60-7) → (1,4,7,10-tetraoxacyclododecane) (294-93-9) + 24-crown-8 (33089-37-1) + <36>crown-12 (71092-59-6) + 48-Crown-16 (71092-61-0)

Conditions	Yield
With potassium hydroxide; p-toluenesulfonyl chloride In 1,4-dioxane at 65℃; Further byproducts given;	A 1.4% B 23% C 11% D 4.3%

Tetraethylene glycol (112-60-7) + diethylene glycol (111-46-6) → (1,4,7,10-tetraoxacyclododecane) (294-93-9) + 18-crown-6 ether (17455-13-9) + 24-crown-8 (33089-37-1)

Conditions	Yield
With potassium hydroxide; p-toluenesulfonyl chloride In 1,4-dioxane at 60℃;	A n/a B 23% C 3%

Tetraethylene glycol (112-60-7) → (1,4,7,10-tetraoxacyclododecane) (294-93-9) + 24-crown-8 (33089-37-1)

Conditions	Yield
With sodium hydroxide; p-toluenesulfonyl chloride In 1,4-dioxane at 20℃;	A 3% B 12%

C8H16O4*K(1+) → (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
In methanol at 25℃; Equilibrium constant; enthalpy-entropy compensation for the complexation reactions of crown ethers with alkaline cations;

2C8H16O4*K(1+) → (1,4,7,10-tetraoxacyclododecane) (294-93-9) + C8H16O4*K(1+)

Conditions	Yield
In methanol at 25℃; Equilibrium constant; enthalpy-entropy compensation for the complexation reactions of crown ethers with alkaline cations;

C8H16O4*C3H9N*H(1+) → (1,4,7,10-tetraoxacyclododecane) (294-93-9) + trimethylammonium (145384-53-8)

Conditions	Yield
Thermodynamic data; enthalpy and entropy changes for the complex dissociation reaction: ΔH0D, ΔS0D;

C8H16O4*C6H13N*H(1+) → cyclohexyl-ammonium cation (29384-28-9) + (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
Thermodynamic data; enthalpy and entropy changes for the complex dissociation reaction: ΔH0D, ΔS0D;

C8H16O4*C5H5N*H(1+) → (1,4,7,10-tetraoxacyclododecane) (294-93-9) + pyridin-1-ium (16969-45-2)

Conditions	Yield
Thermodynamic data; enthalpy and entropy changes for the complex dissociation reaction: ΔH0D, ΔS0D;

C8H16O4*C4H4N2*H(1+) → (1,4,7,10-tetraoxacyclododecane) (294-93-9) + 1,2-diazineH+ (17009-97-1)

Conditions	Yield
Thermodynamic data; enthalpy and entropy changes for the complex dissociation reaction: ΔH0D, ΔS0D;

12-Crown-4 lithium perchlorate → (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
In acetone Equilibrium constant; various solvents (MeNO2, MeCN, propylene carbonate, MeOH, pyridine), complex formation between crown ethers and lithim ion, effect of solvent of the stability of complexes, 7Li NMR study;

C8H16O4*2ClO4(1-)*2Li(1+) → (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
In nitromethane Equilibrium constant; various solvents (MeCN, propylene carbonate, Me2CO, MeOH, pyridine), complex formation between crown ethers and lithim ion, effect of solvent of the stability of complexes, formation of 1:1 and 1:2 complexes, 7Li NMR study;

1,4,7,10-Tetraoxa-cyclododecane; compound with GENERIC INORGANIC NEUTRAL COMPONENT → (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
With Iodine monochloride In benzene at 24.9℃; Equilibrium constant;

C8H16O4*C10H15(1-)*C24BF20(1-)*Si(2+) → 1,4-dioxane (123-91-1) + (1,4,7,10-tetraoxacyclododecane) (294-93-9)

Conditions	Yield
In dichloromethane-d2 for 480h;

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + Lu(N(SiMe3)2)3 + sodium trimethylsilanolate (18027-10-6) → [Na((CH2CH2O)4)2](1+)*[Lu(N(Si(CH3)3)2)3(OSi(CH3)3)](1-)=[Na((CH2CH2O)4)2][Lu(N(Si(CH3)3)2)3(OSi(CH3)3)]

Conditions	Yield
In hexane dry atm.; molar ratio 1:1:2, stirring (room temp., 6 h); filtn., washing (n-hexane), drying (vac.); elem. anal.;	100%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + sodium trimethylsilanolate (18027-10-6) + tris(bis(trimethylsilyl)amido)europium(III) → [Na((CH2CH2O)4)2](1+)*[Eu(N(Si(CH3)3)2)3(OSi(CH3)3)](1-)=[Na((CH2CH2O)4)2][Eu(N(Si(CH3)3)2)3(OSi(CH3)3)]

Conditions	Yield
In hexane dry atm.; molar ratio 1:1:2, stirring (room temp., 6 h); filtn., washing (n-hexane), drying (vac.); elem. anal.;	100%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + tris(bis(trimethylsilyl)amido)ytterbium(III) + sodium trimethylsilanolate (18027-10-6) → [Na((CH2CH2O)4)2](1+)*[Yb(N(Si(CH3)3)2)3(OSi(CH3)3)](1-)=[Na((CH2CH2O)4)2][Yb(N(Si(CH3)3)2)3(OSi(CH3)3)]

Conditions	Yield
In hexane dry atm.; molar ratio 1:1:2, stirring (room temp., 6 h); filtn., washing (n-hexane), drying (vac.); elem. anal.;	100%

tris(bis(trimethylsilyl)amido)samarium(III) + (1,4,7,10-tetraoxacyclododecane) (294-93-9) + sodium trimethylsilanolate (18027-10-6) → [Na((CH2CH2O)4)2](1+)*[Sm(N(Si(CH3)3)2)3(OSi(CH3)3)](1-)=[Na((CH2CH2O)4)2][Sm(N(Si(CH3)3)2)3(OSi(CH3)3)]

Conditions	Yield
In hexane dry atm.; molar ratio 1:1:2, stirring (room temp., 6 h); filtn., washing (n-hexane), drying (vac.); elem. anal.;	100%

tetrahydrofuran (109-99-9) + n-butyllithium (109-72-8, 29786-93-4) + (1,4,7,10-tetraoxacyclododecane) (294-93-9) + C12H20B10 → C12H19B10(1-)*Li(1+)*2C4H8O*2C8H16O4

Conditions	Yield
Stage #1: tetrahydrofuran; n-butyllithium; C12H20B10 Stage #2: (1,4,7,10-tetraoxacyclododecane) In tetrahydrofuran	100%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + [Li(THF)3][UO2(N(SiHMe2)tBu)3] → [Li(12-crown-4)2][UO2(N(SiHMe2)tBu)3]

Conditions	Yield
In tetrahydrofuran for 1h;	100%

beryllium(II) chloride (7787-47-5) + (1,4,7,10-tetraoxacyclododecane) (294-93-9) → [(BeCl)([12]crown-4)]Cl

Conditions	Yield
In dichloromethane at 20℃; Inert atmosphere; Schlenk technique;	100%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + C36H30Be3 + phenyllithium (591-51-5) → C16H32Li2O8(2+)*2C18H15Be(1-)

Conditions	Yield
Stage #1: (1,4,7,10-tetraoxacyclododecane); C36H30Be3; phenyllithium In benzene-d6 Stage #2: In benzene-d6 at 80℃;	100%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + C36H30Be3 → C14H21BeO4(1+)*C18H15Be(1-)

Conditions	Yield
Stage #1: (1,4,7,10-tetraoxacyclododecane); C36H30Be3 In benzene-d6 Stage #2: In benzene-d6 Heating;	100%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + {Na}{(4,5-bis(diisopropylphosphino)-2,7,9,9-tetramethyl-9H-acridin-10-ide)Ni(CO)} → {Na(12-crown-4)2}{(4,5-bis(diisopropylphosphino)-2,7,9,9-tetramethyl-9H-acridin-10-ide)Ni(CO)}

Conditions	Yield
In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;	99%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + [W(carbonyl)5([bis(trimethylsilyl)methyl]cyanophosphane)] (851576-85-7) + tert.-butyl lithium (594-19-4) → [(OC)5WP(CH(SiMe3)2)CNLi(12-crown-4)] (947333-61-1)

Conditions	Yield
In diethyl ether; hexane under Ar; soln. of t-BuLi in n-hexane added dropwise at -80°C to stirred soln. of W complex in Et2O and 12-crown-4; warmed slowly to roomtemp. for 3.5 h; solvent removed under vac.; washed with Et2O and n-pentane; dried under reduced pressure; elem. anal.;	98.3%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + (Si(o-C6H4PiPr2)3)Fe[(CO)Na(THF)3] (1277179-18-6) → [(Na(12-crown-4)2][(Si(o-C6H4PiPr2)3)Fe(CO)]

Conditions	Yield
In tetrahydrofuran (Schlenk or glovebox, N2) the soln. of 12-crown-4 in THF was added dropwise to a soln. of complex in THF, stirred for 30 min at room temp.; filtered, volatiles were removed under vac., the solid was washed with pentane; elem. anal.;	98%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + (4,5-bis(diisopropylphosphino)-2,7,9,9-tetramethyl-9H-acridin-10-ide)Ni-μ-CO2-Na*THF → {Na(12-crown-4)2}{(4,5-bis(diisopropylphosphino)-2,7,9,9-tetramethyl-9H-acridin-10-ide)Ni(CO2)}

Conditions	Yield
In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;	98%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + C42H51CrLi2O3 → C30H25Cr(2-)*2C12H24LiO5(1+)

Conditions	Yield
In tetrahydrofuran at 0℃; Solvent; Inert atmosphere; Schlenk technique;	98%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + [Na(tetrahydrofuran)x][(Mo(N[i-Pr](3,5-C6H3Me2)3)2N] + nitrogen (7727-37-9) → [Mo(N[i-Pr](3,5-C6H3Me2)3N] (394246-98-1) + [Na(12-crown-4)2][(Mo(N[i-Pr](3,5-C6H3Me2)3)N2]

Conditions	Yield
In not given at 25°C? 1 atm and in the presence of crown ether (2 equiv. per Na);	A n/a B 97%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + C24H48LiP2Si4(1-)*4C4H8O*Li(1+) → C12H24PSi2(1-)*2C8H16O4*Li(1+)

Conditions	Yield
In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; Glovebox;	97%

tin(II) trifluoromethanesulfonate + (1,4,7,10-tetraoxacyclododecane) (294-93-9) → bis([12]crown-4)tin(II) triflate

Conditions	Yield
In tetrahydrofuran standard inert-atmosphere techniques; soln. of (12)crown-4 (0.943 mmol) added to soln. of Sn(OTf)2 (0.479 mmol), stiired for 2 h; solvent removed (in vac.), washed with pentane; elem. anal.;	96%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + Ba((N,N-dimethylamino)diboranato)2(diethyl ether)(x) → bis[(N,N-dimethylamino)diboranato](12-crown-4) barium(II)

Conditions	Yield
In diethyl ether under Ar atm. using Schlenk techniques; to soln. of Ba complex in Et2O was added Lewis base; mixt. stirred overnight; solid filtered; washed (pentane); dried under vac.; elem. anal.;	96%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + potassium hexamethylsilazane (40949-94-8) → C28H68K2N2O8Si4

Conditions	Yield
In toluene Inert atmosphere; Schlenk technique;	96%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + C36H54FeGaN2P3(1-)*C12H24NaO3(1+) → C36H54FeGaN2P3(1-)*C16H32NaO8(1+)

Conditions	Yield
In tetrahydrofuran at 20℃; for 2h;	96%

triphenylboroxine (3262-89-3) + (1,4,7,10-tetraoxacyclododecane) (294-93-9) + water (7732-18-5) + lithium pyrazolide → Li[Li(tetrahydrofuran)(phenyl(pyrazolyl)B(μ-O)(μ-OB(phenyl)O)B(pyrazolyl)phenyl)]*(12-crown-4)*2H2O

Conditions	Yield
In tetrahydrofuran (N2); using Schlenk techniques; stirring of mixt. of Li(pz) (2 equiv.), Ph3B3O3 (1 equiv.) and 12-crown-4 (2 equiv.) in THF at room temp. for 30min; addn. of hexane; cooling to -5°C overnight; crystn.; rinsing withhexane; drying under reduced pressure;	95%

tetrahydrofuran (109-99-9) + triphenylboroxine (3262-89-3) + (1,4,7,10-tetraoxacyclododecane) (294-93-9) + lithium pyrazolide → C8H16LiO4(1+)*C28H29B3LiN4O4(1-)

Conditions	Yield
for 0.5h;	95%

selenium (7782-49-2) + (1,4,7,10-tetraoxacyclododecane) (294-93-9) + C44H69ClLiLuO3Si2 + pivalaldehyde (630-19-3) → C37H53ClLuOSeSi2(1-)*Li(1+)*2C8H16O4

Conditions	Yield
Stage #1: C44H69ClLiLuO3Si2; pivalaldehyde In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; Stage #2: selenium In tetrahydrofuran Inert atmosphere; Stage #3: (1,4,7,10-tetraoxacyclododecane) In tetrahydrofuran for 1h; Inert atmosphere;	95%

(1,4,7,10-tetraoxacyclododecane) (294-93-9) + uranium(III) tris(1,3-bis-(trimethylsilyl)cyclopentadienyl) (174090-55-2) + sodium (7440-23-5) → [Na(12-crown-4)2][(C5H3(SiMe3)2)3U]

Conditions	Yield
In tetrahydrofuran for 0.5h; Glovebox; Inert atmosphere; Schlenk technique;	95%

Upstream product

• 536-74-3 phenylacetylene 
• 333-27-7 methyl trifluoromethanesulfonate 
• 929-72-6 2-(2-(2-(vinyloxy)ethoxy)ethoxy)ethanol 
• 107-21-1 ethylene glycol 
• 112-26-5 1,2-bis(2-chloroethoxy)ethane 
• 112-60-7 Tetraethylene glycol 
• 111-46-6 diethylene glycol 
• 111-44-4 3-oxa-1,5-dichloropentane 

Downstream Products

• 95189-83-6 C₁₉H₁₅Li*2C₈H₁₆O₄*C₄H₈O 
• 117226-84-3 {Li(12-crown-4)}{V(DIPP)4} 
• 141293-54-1 {({12}crown-4)lithium} {acetyldicarbonyl(η5-(1-phenylborole))ferrate} 
• 866922-55-6 [Y(CH₂SiMe₃)2([12]-crown-4)(tetrahydrofuran)][B(CH₂SiMe₃)(C₆F₅)3] complex 

Relevant articles and documents

Solution Thermodynamic Studies. 6. Enthalpy-Entropy Compensation for the Complexation Reactions of Some Crown Ethers with Alkaline Cations: A Quantitative Interpretation of the Complexing Properties of 18-Crown-6

The interactions of 18-crown-6, 15-crown-5, and 12-crown-4 with Na+ and K+ were studied in methanol and water as solvents at 25 deg C. ΔG0 values for both 1:1 and 2:1 complexation reactions were determined by potentiometric titrations.Used in conjunction with these values, calorimetric measurements led to ΔH0 and ΔS0 values.The thermodynamic parameters obtained cannot be correlated with the cations or the crown ethers "hole" sizes in any 1:1 or 2:1 reactions.Moreover, the ΔG0 values are the results of quite different but permanently compensating combinations of the ΔH0 and ΔS0 values.These arise from several thermodynamic processes in which the role of the solvent must be considered.In the case of 18-crown-6, we present a quantitative interpretation in which this crown ether develops interactions that are stronger with Na+ than with K+.

12-crown ether-4 lithium salt complex as well as preparation method and application thereof

The invention discloses a 12-crown ether-4 lithium salt complex and a preparation method thereof, and a method for preparing 12-crown ether-4 by adopting the complex. The preparation method of the 12-crown ether-4 comprises the following steps: by taking a compound triethylene glycol monovinyl ether in a formula 1 as a raw material, adding an alkaline substance into a first reaction solvent for catalytic reaction with a compound lithium alkoxide containing a substituent group in a formula 2 under the condition of air isolation, and obtaining a compound 12-crown ether-4 lithium salt complex in a formula 3 after the reaction is completed; and then adding a compound 12-crown ether-4 lithium salt complex as shown in a formula 3 and an acidic material into a second reaction solvent, reacting at the reaction temperature of-20 to 100 DEG C, and after the reaction is completed, obtaining a compound 12-crown ether-4 as shown in a formula 4. The design route is reasonable in design, the raw materials are safe and easy to obtain, the process safety is high, the reaction selectivity is high, the product purity is high, the method is friendly to operators, the production cost is greatly reduced, and the requirements of industrial production of products can be fully met.

The pentamethylcyclopentadienylsilicon(II) cation as a catalyst for the specific degradation of oligo(ethyleneglycol) diethers

Catalytic open sandwiches: Oligo(ethyleneglycol) diethers RO(CH 2CH2O)nR are degraded by the unusual catalyst Cp Si+ (see scheme). The open coordination sphere at silicon allows up to four Si-O contacts; crystal structure data of the reactive compounds [Cp Si(dme)]+BR4- and [Cp Si([12]crown-4)] +BR4- (R=C6F5) show weakly bound ether molecules. Copyright