67-42-5

Basic information

• Product Name: Ethylenebis(oxyethylenenitrilo)tetraacetic acid
• Synonyms: 3,6-DIOXAOCTAMETHYLENEDINITRILOTETRAACETIC ACID;1,2-DI(2-AMINOETHOXY)ETHANE-NNN'N'-TETRA-ACETIC ACID;1,2-BIS[2-[BIS(CARBOXYMETHYL)AMINO]ETHOXY]ETHANE;2,2'-ETHYLENEDIOXYBIS[ETHYLIMINODI(ACETIC ACID)];GLYCOLETHERDIAMINE-N,N,N',N'-TETRAACETIC ACID;GLYCOL ETHER DIAMINE TETRAACETIC ACID;IDRANAL(R) VI;GEDTA
• CAS NO: 67-42-5
• Molecular Formula: C₁₄H₂₄N₂O₁₀
• Molecular Weight: 380.35
• EINECS: 200-651-2
• Product Categories: Analytical Chemistry;Chelating Reagents;Complexones;EDTA Analogs
• Mol File: 67-42-5.mol
• Article Data: 3

Chemical Properties

• Melting Point: 241 °C (dec.)(lit.)
• Boiling Point: 507.99°C (rough estimate)
• Flash Point: 363.851 °C
• Appearance: White/Crystalline Powder
• Density: 1.2838 (rough estimate)
• Vapor Pressure: 3.76E-20mmHg at 25°C
• Refractive Index: 1.4590 (estimate)
• Storage Temp.: Store at RT.
• Solubility: 0.1 M NaOH: 0.1 M at 20 °C, clear, colorle
• PKA: 1.47±0.10(Predicted)
• Water Solubility: slightly soluble
• Merck: 14,3529
• BRN: 1717370
• CAS DataBase Reference: Ethylenebis(oxyethylenenitrilo)tetraacetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Ethylenebis(oxyethylenenitrilo)tetraacetic acid(67-42-5)
• EPA Substance Registry System: Ethylenebis(oxyethylenenitrilo)tetraacetic acid(67-42-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 24/25-36-26
• WGK Germany: 2
• RTECS: AH3760000
• TSCA: Yes
• Hazardous Substances Data: 67-42-5(Hazardous Substances Data)

Usage

Description

Ethylenebis(oxyethylenenitrilo)tetraacetic acid is also named as Egtazic acid. It works as a chelating agent for the determination of calcium in the presence of magnesium.

Uses

Different sources of media describe the Uses of 67-42-5 differently. You can refer to the following data:
1. Pharmaceutic aid. EGTA.
2. Ethylene glycol-O,O'-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid is a chelating agent used for making complexes, especially for calcium ions, which help to determine calcium in the presence of magnesium. It can be used experimentally for treating animals possessing cerium poisoning. It is useful in the separation of thorium from monazite. It also acts as a buffer and is used in protein purification.
3. A chelating agent useful for the determination of calcium in the presence of magnesium.

Definition

ChEBI: A diether that is ethylene glycol in which the hydrogens of the hydroxy groups have been replaced by 2-[bis(carboxymethyl)amino]ethyl group respectively.

Biological Activity

Calcium chelator; protects against cell death caused by nitric oxide-induced calcium influx into nerve cells.

Safety Profile

Poison by intraperitoneal route. Moderately toxic by ingestion. When heated to decomposition it emits toxic fumes of NOx. See also GLYCOL ETHERS.

Purification Methods

Dissolve EGTA in aqueous NaOH, precipitate it by adding aqueous HCl, wash it with water and dry at 100o in vacuo.[Beilstein 4 IV 217.]

InChI:InChI=1/C14H24N2O10/c17-11(18)7-15(8-12(19)20)1-3-25-5-6-26-4-2-16(9-13(21)22)10-14(23)24/h1-10H2,(H,17,18)(H,19,20)(H,21,22)(H,23,24)/p-2

Synthetic route

3,6-dioxa-1,8-diaminooctane (929-59-9) + chloroacetic acid (79-11-8) → ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5)

Conditions	Yield
With sodium hydroxide

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → dianhydride of ethylene bis(oxyethylenenitrilo)tetraacetic acid (23910-62-5)

Conditions	Yield
With acetic anhydride In pyridine at 65℃; for 20h; Dehydration;	98%
Stage #1: ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid With pyridine for 0.25h; Inert atmosphere; Stage #2: With acetic anhydride at 65℃; for 24h; Inert atmosphere; Sealed tube;	91%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + (S)-2-aminobutan-1-ol (5856-62-2) → (-)-N,N,N',N'-tetrakis{[4-(S)-ethyloxazolin-2-yl]methyl}ethylene glycol bis(2-aminoethyl) ether (850410-82-1)

Conditions	Yield
Stage #1: ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid; (S)-2-aminobutan-1-ol In toluene for 20h; Reflux; Stage #2: at 135℃; for 8h;	93%

europium(III) oxide + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → K(1+)*Eu(C6H12O2N2(CH2COO)4)(1-) = K[Eu(C6H12O2N2(CH2COO)4)]

Conditions	Yield
With potassium hydroxide In water suspn. stirring, heating (80°C); filtration, evapn. (vac.);	90%

gadolinium(III) oxide + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → K(1+)*Gd(C6H12O2N2(CH2COO)4)(1-) = K[Gd(C6H12O2N2(CH2COO)4)]

Conditions	Yield
With potassium hydroxide In water suspn. stirring, heating (80°C); filtration, evapn. (vac.);	90%

holmium(III) oxide + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → K(1+)*Ho(C6H12O2N2(CH2COO)4)(1-) = K[Ho(C6H12O2N2(CH2COO)4)]

Conditions	Yield
With potassium hydroxide In water suspn. stirring, heating (80°C); filtration, evapn. (vac.);	90%

ytterbium(III) oxide + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → K(1+)*Yb(C6H12O2N2(CH2COO)4)(1-) = K[Yb(C6H12O2N2(CH2COO)4)]

Conditions	Yield
With potassium hydroxide In water suspn. stirring, heating (80°C); filtration, evapn. (vac.);	90%

1H-imidazole (288-32-4) + malachite + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → (3,12-bis(carboxylatomethyl)-6,9-dioxa-3,12-diazatetradecanedioate)bis(imidazole)dicopper(II)

Conditions	Yield
In water soln. of Cu salt and ligand in H2O heated under stirring (vac.), imidazole added; filtered, filtrate evapd. at room temp., recrystd. from H2O; elem. anal.;	90%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + 1,2-diamino-benzene (95-54-5) → ethylene glycol-bis-(β-aminoethylether) N,N,N',N'-tetrakis<2-benzimidazolyl> (89735-41-1)

Conditions	Yield
at 180℃; for 5h;	87%
at 180℃; for 3h;	87%
at 180 - 190℃; for 1h; Acetylation;	70%

yttrium(III) oxide + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + water (7732-18-5) + ethylenediamine (107-15-3) → (ethylenediamine*H2)[YIII(ethyleneglycol-bis(2-aminoethylether)-N,N,N',N'-tetraacarboxylate)H2O]2*6H2O

Conditions	Yield
Stage #1: yttrium(III) oxide; ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid; water for 18h; Heating; Reflux; Stage #2: ethylenediamine pH=6;	86.25%

neodymium(III) oxide + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + water (7732-18-5) + ethylenediamine (107-15-3) → (ethylenediamine-H2)0.5[NdIII(ethyleneglycol-bis-(2-aminoethylether)-N,N,N′,N'-tetraacetate)H2O]2·6H2O

Conditions	Yield
Stage #1: neodymium(III) oxide; ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid; water for 18h; Reflux; Stage #2: ethylenediamine pH=6;	81.92%

lutetium(III) oxide + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + water (7732-18-5) + ethylenediamine (107-15-3) → (ethylenediamine*H)[LuIII(ethyleneglycol-bis(2-aminoethylether)-N,N,N',N'-tetraacarboxylate)]*2H2O

Conditions	Yield
Stage #1: lutetium(III) oxide; ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid; water for 18h; Heating; Reflux; Stage #2: ethylenediamine pH=6;	79.86%

1H-imidazole (288-32-4) + malachite + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + water (7732-18-5) → (3,12-bis(carboxylatomethyl)-6,9-dioxa-3,12-diazatetradecanedioate)tetrakis(imidazole)dicopper(II) tetrahydrate

Conditions	Yield
In water soln. of Cu salt and ligand in H2O heated under stirring (vac.), imidazole (10% excess) added; filtered, filtrate evapd.; elem. anal.;	79.5%

malachite + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + water (7732-18-5) → diaqua(3,12-bis(carboxylatomethyl)-6,9-dioxa-3,12-diazatetradecanedioate)dicopper(II) dihydrate

Conditions	Yield
In water soln. of Cu salt and ligand in H2O heated under stirring (vac.); filtered, filtrate allowed to evap. at room temp., crystals collected, washed with cold H2O, dried in air; elem. anal.;	76.46%

hafnium hydroxide (12027-05-3) + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → {hafnium(IV)(ethylenedioxydiethylenedinitrilotetraacetate)}*3H2O

Conditions	Yield
In water Zr(OH)4 (prepared from HfOCl2*8H2O and NH4OH) added to a suspension of H4egta, refluxed for 18 h; the clear soln. evapd., cooled, crystals filtered off, dried in a desiccator over anhyd. CaCl2; elem. anal.;	73%

2-acetamido-2-deoxy-β-D-glucopyranosylamine (4229-38-3, 102039-79-2, 115350-20-4, 133677-75-5, 137493-97-1) + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → C46H80N10O26 (1214718-89-4)

Conditions	Yield
Stage #1: ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide for 0.5h; Stage #2: 2-acetamido-2-deoxy-β-D-glucopyranosylamine In dimethyl sulfoxide at 20℃; for 72h;	55%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → strontium(II) ethylene-bis(oxyethylenenitrilo)tetraacetic acid complex

Conditions	Yield
With strontium(II) carbonate In water at 70℃; for 6.5h;	49%

silicotungstic acid hydrate + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + copper(II) acetate monohydrate (6046-93-1) → [Cu4(ethyleneglycol-bis-(2-aminoethylether)-tetraacetate)2(H2O)4Cu2(H2O)8][SiW12O40]*14H2O

Conditions	Yield
With HCl In water aq. soln. of H4SiW12O40*14H2O (0.2 mmol) and Cu(OAc)2*H2O (1 mmol) stirred at room temp. for 30 min; aq. soln. of ligand (0.2 mmol) added; pH adjusted to 3.1 with 1 M HCl; mixt. heated at 60°C for 2 h; filtered; crystn. from filtrate by evapn. at room temp. in air for 2 wk;TGA; elem. anal.;	41%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + zirconium tetrahydroxide (756456-88-9, 14475-63-9) → {zirconium(IV)(ethylenedioxydiethylenedinitrilotetraacetate)}*3H2O

Conditions	Yield
In water Zr(OH)4 (prepared from ZrOCl2*8H2O and NH4OH) added to a suspension of H4egta, refluxed for 72 h; the clear soln. evapd., cooled, crystals filtered off, dried in a desiccator over anhyd. CaCl2; elem. anal.;	40%

cadmium(II) nitrate tetrhydrate + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → C14H20N2O10(4-)*3Cd(2+)*5H2O*2NO3(1-)

Conditions	Yield
With sodium hydroxide In water at 140℃; for 48h; High pressure;	39.39%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + (5)-N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (1234368-17-2) + trifluoroacetic acid (76-05-1) → 3,12-bis(14-(3-((S)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)-2-oxo-6,9,12-trioxa-3-azatetradecyl)-N1,N14-bis(2-(2-(2-(2-(3-((S)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-6,9-dioxa-3,12-diazatetradecane-1,14-diamide trifluoroacetate

Conditions	Yield
Stage #1: ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid; (5)-N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: trifluoroacetic acid	29%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + N,N'-diacetylchitobiosamine (102039-77-0) → C78H132N14O46 (1214718-90-7)

Conditions	Yield
Stage #1: ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide for 0.5h; Stage #2: N,N'-diacetylchitobiosamine In dimethyl sulfoxide at 20℃; for 72h;	27%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + N-1-(ε-aminocaproyl)-β-N-acetyl-2-deoxyglucopyranosyl (53517-87-6) → C70H124N14O30 (1214718-92-9)

Conditions	Yield
Stage #1: ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide for 0.5h; Stage #2: N-1-(ε-aminocaproyl)-β-N-acetyl-2-deoxyglucopyranosyl In dimethyl sulfoxide at 20℃; for 72h;	26%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + W3S4(H2O)9(4+)*4Cl(1-)=[W3S4(H2O)9]Cl4 → Na4[(W3S4)2(ethylene glycol bis(2-aminoethyl) tetraacetate)3] * 16 H2O

Conditions	Yield
With DMF In N,N-dimethyl-formamide 165°C, stirring for 3 h (pptn.); collection, pptn. of second crop from filtrate on i-PrOH addn., dissoln.in water, filtration, pH-adjustment to 7 (NaOH), evapn., chromy. (ion e xchanger, Na-form; then repeatedly on Sephadex G25, water), evapn. (reduced pressure); elem. anal.;	25%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + β-amino lactose → C78H132N14O46

Conditions	Yield
Stage #1: ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide for 0.5h; Stage #2: β-amino lactose In dimethyl sulfoxide at 20℃; for 72h;	23%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) + W3SO3(H2O)9(4+)*4Cl(1-)=(W3SO3(H2O)9)Cl4 → Na4((W3SO3)2(EGTA)3)*10H2O

Conditions	Yield
In water; N,N-dimethyl-formamide to soln. (W3SO3(H2O)9)Cl4 in DMF was added H4EGTA and refluxed for 3 h, solid was filtered, dissolved in water and passed through cation exchange column (Na+); eluate was evapd. to dryness under vac., residue was dissolved in water and loaded on Sephadex G-25 column, aq. eluate was concd. to dryness in vacuo; elem. anal.;	14%

ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → formaldehyd (50-00-0) + carbon dioxide (124-38-9) + {2-[2-(2-Amino-ethoxy)-ethoxy]-ethylamino}-acetic acid

Conditions	Yield
With sodium bismuthate In water at 80℃; Mechanism; Product distribution; further products;

4-amino-5,6-dichloro-benzene-1,3-disulfonic acid diamide (5250-72-6) + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → {(2-{2-[2-(bis-carboxymethyl-amino)-ethoxy]-ethoxy}-ethyl)-[(2,3-dichloro-4,6-disulfamoyl-phenylcarbamoyl)-methyl]-amino}-acetic acid

Conditions	Yield
Stage #1: 4-amino-5,6-dichloro-benzene-1,3-disulfonic acid diamide; ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetone at 20℃; for 0.25h; Stage #2: With triethylamine In acetone at 4℃; Further stages.;

chloraminophenamide (121-30-2) + ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid (67-42-5) → {(2-{2-[2-(bis-carboxymethyl-amino)-ethoxy]-ethoxy}-ethyl)-[(5-chloro-2,4-disulfamoyl-phenylcarbamoyl)-methyl]-amino}-acetic acid

Conditions	Yield
Stage #1: chloraminophenamide; ethylene glycol-bis(2-aminoethyl)-N,N,N'N,'-tetraacetic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetone at 20℃; for 0.25h; Stage #2: With triethylamine In acetone at 4℃; Further stages.;

Upstream product

• 929-59-9 3,6-dioxa-1,8-diaminooctane 
• 79-11-8 chloroacetic acid 

Downstream Products

• 50-00-0 formaldehyd 
• 124-38-9 carbon dioxide 
• 99590-87-1 diethyl 3,12-bis(2-ethoxy-2-oxoethyl)-6,9-dioxa-3,12-diazatetradecanedioate 

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