10045-25-7

Basic information

• Product Name: 1,4,7,10-TETRAAZACYCLODODECANE TETRAHYDROCHLORIDE
• Synonyms: CYCLEN-4HCL;CYCLEN TETRAHYDROCHLORIDE;1,4,7,10-Tetraazacyclododecane tetrahydrochloride, 97+%;1,4,7,10-Tetraazacyclododecane (Cyclen) tetrahydrochloride;Cyclen tetrahydrochloride,98%;1,4,7,10-Tetraazacyclododecane,hydrochloride;1,4,7,10-Tetraazacyclododecane, hydrochloride(1:4);TETRAAZA-12-CROWN-4 TETRAHYDROCHLORIDE
• CAS NO: 10045-25-7
• Molecular Formula: C₈H₂₄N₄*4Cl
• Molecular Weight: 318.11
• Product Categories: Analytical Chemistry;Azacrown Ethers;Crown Ethers;Functional Materials;Ligands for Pharmaceutical Research;Macrocycles for Host-Guest Chemistry;Magnetic Resonance Imaging (Chelating Reagents);Ring Systems
• Mol File: 10045-25-7.mol
• Article Data: 10

Chemical Properties

• Melting Point: 297-300 °C
• Boiling Point: 283.8 °C at 760 mmHg
• Flash Point: 129.5 °C
• Appearance: White/Crystalline Solid
• Vapor Pressure: 0.00309mmHg at 25°C
• Storage Temp.: Inert atmosphere,Room Temperature
• Sensitive: Hygroscopic
• CAS DataBase Reference: 1,4,7,10-TETRAAZACYCLODODECANE TETRAHYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 1,4,7,10-TETRAAZACYCLODODECANE TETRAHYDROCHLORIDE(10045-25-7)
• EPA Substance Registry System: 1,4,7,10-TETRAAZACYCLODODECANE TETRAHYDROCHLORIDE(10045-25-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: XA5253000
• F: 10-21
• HazardClass: IRRITANT, MOISTURE SENSITIVE
• Hazardous Substances Data: 10045-25-7(Hazardous Substances Data)

Usage

Chemical Properties

white crystalline solid

Uses

Cyclen tetrahydrochloride may be used for the synthesis of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methyleneethylphosphinic acid), a new macrocyclic polyaza polyphosphinate ligand. It may also be used in the synthesis of anthraquinone-pendant cyclen.

General Description

Cyclen tetrahydrochloride is a macrocycle hydrochloride salt. It can be synthesized using perhydro-2a,4a,6a,8a-tetraazacyclopenteno[1,3-f,g]acenaphthylene as a precursor. Cyclen tetrahydrochloride has an orthorhombic crystal structure. Cations are reported to exhibit crystallographic two-fold rotation symmetry and [3333] quadrangular conformation, having protonated N atoms at corner positions. Synthesis of cyclen from the corresponding butanedione-protected linear tetramines has been reported.

InChI:InChI=1/C8H20N4.4ClH/c1-2-10-5-6-12-8-7-11-4-3-9-1;;;;/h9-12H,1-8H2;4*1H

Synthetic route

cyclen-glyoxal (74199-09-0, 79236-92-3) → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
With hydroxylamine hydrochloride In methanol for 36h; Heating;	87%
With hydrogenchloride; hydrazine hydrate In water pH=3 - Ca. 3.5; Solvent; Reflux;	38 g

cyclen tetratosylate (52667-88-6) → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
With hydrogenchloride; sulfuric acid; Amberlyst A26 at 120℃; for 48h;	66%
Stage #1: cyclen tetratosylate With sulfuric acid at 150℃; for 1h; Stage #2: With hydrogenchloride In ethanol	48%
With hydrogenchloride; sulfuric acid 1.) 100 deg C, 48 h; Yield given. Multistep reaction;
With hydrogenchloride; sulfuric acid 1.) 100 deg C, 70 h;	7.2 g
Stage #1: cyclen tetratosylate With sulfuric acid In water at 80℃; for 24h; Stage #2: With hydrogenchloride In water

8b,8c-dimethyl-decahydro-2a,4a,6a,8a-tetraaza-cyclopenta[fg]acenaphthylene → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
With hydrogenchloride In ethanol at 60℃; for 48h; Yield given;

cis-13-1,4,7,10-tetraazatetracyclo<5.5.2.04,14010,13>tetradecane (74199-09-0, 79236-92-3) → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
With hydrogenchloride; hydrazine hydrate at 100℃; for 20h; Yield given;

triethylentetramine (112-24-3) → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / acetonitrile / 2 h / -7 °C 2: 60 percent / K2CO3 / acetonitrile / 48 h / 60 °C 3: aq. HCl / ethanol / 48 h / 60 °C View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / water; acetone / 5 h / -2 - 0 °C 2: potassium carbonate / N,N-dimethyl-formamide / 24 h / 35 °C 3: sulfuric acid / water / 24 h / 80 °C View Scheme

5a,8b-dimethyloctahydro-2a,5,6,8a-tetraazaacenaphthylene (214195-92-3) → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 60 percent / K2CO3 / acetonitrile / 48 h / 60 °C 2: aq. HCl / ethanol / 48 h / 60 °C View Scheme

N,N',N'',N'''-tetrakis-(p-tolylsulphonyl)-triethylenetetramine (55442-07-4) → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) sodium hydride / 1.) DMF, 2.) DMF, 110 deg C, 6 h 2: 1.) sulphuric acid, 2.) hydrochloric acid / 1.) 100 deg C, 48 h View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 24 h / 35 °C 2: sulfuric acid / water / 24 h / 80 °C View Scheme

3H,6H-2a,5,6,8a-octahydrotetraaza-acenaphthylene (215540-27-5) → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate; potassium iodide / acetonitrile / 3.67 h / 40 - 75 °C / Inert atmosphere 2: hydrogenchloride; hydrazine hydrate / water / pH 3 - Ca. 3.5 / Reflux View Scheme

8b-methyldecahydro-2a,4a,6a,8a-tetraazacyclopenta[fg]acenaphthylene → 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7)

Conditions	Yield
With hydrogenchloride In water at 80 - 100℃; for 3h;	301 g

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + chloroformic acid ethyl ester (541-41-3) → 1,7-bis(ethoxycarbonyl)-1,4,7,10-tetraazacyclododecane (162148-43-8)

Conditions	Yield
With sodium hydroxide	98%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → 1,4,7,10-tetraazacyclododecan (294-90-6)

Conditions	Yield
With hydrogenchloride	95%
With potassium hydroxide In water at 0 - 10℃;	91.3%
With potassium hydroxide
With sodium hydroxide In toluene at 40℃; for 1h; Reflux;	13.77 g
With sodium hydroxide In water; toluene	12 g

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + methyl chloroformate (79-22-1) → 1,7-bis(methoxycarbonyl)-1,4,7,10-tetraazacyclododecane (162148-42-7)

Conditions	Yield
With sodium hydroxide	93%

Vinyl chloroformate (5130-24-5) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → 1,7-bis(vinyloxycarbonyl)-1,4,7,10-tetraazacyclododecane

Conditions	Yield
With sodium hydroxide	90%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + benzyl chloroformate (501-53-1) → 1,4,7,10-tetraaza-cyclododecane-1,7-dicarboxylic acid dibenzyl ester (162148-45-0) + 1,4,7,10-tetrakis(benzyloxycarbonyl)-1,4,7,10-tetraazacyclododecane

Conditions	Yield
With hydrogenchloride In 1,4-dioxane for 16h;	A 88% B 10%

4-nitrophenyl 2-(2-(dioctylamino)-2-oxoethoxy)acetate (1354344-55-0) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → 2,2′,2′′,2′′′-(((1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis (2-oxoethane-2,1-diyl))tetrakis(oxy))tetrakis(N,N-dioctylacetamide)

Conditions	Yield
With triethylamine In toluene for 15h; Reflux;	81%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + cucurbit[8]uril (259886-51-6) → C48H48N32O16*C8H20N4*4ClH

Conditions	Yield
In water at 100℃; for 2h;	73%

chloroacetic acid cholesterylester (3464-50-4) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → C124H204N4O8*ClNa

Conditions	Yield
With sodium carbonate In chloroform; acetonitrile for 7h; Heating;	71%

Chloressigsaeure-fluorenyl-(9)-ester (14159-51-4) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → 1,4,7,10-tetrakis[(fluorenoxycarbonyl)methyl]-1,4,7,10-tetraazacyclododecane-NaCl complex

Conditions	Yield
With sodium carbonate In acetonitrile Heating;	70%

formaldehyd (50-00-0) + phenylphosphinic acid (1779-48-2) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayltetramethylenetetrakis(phenylphosphinic acid) (138149-64-1)

Conditions	Yield
In hydrogenchloride at 100℃; for 2.5h; Condensation;	65%

manganese(II) chloride tetrahydrate + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → di-μ-oxo-bis(1,4,7,10-tetraazacyclododecane)dimanganese(III,IV) chloride lithium chloride pentahydrate

Conditions	Yield
With LiOH; LiCl In ethanol; water (NHCH2CH2)4*4HCl dissolved in aq. LiOH; ethanol added; MnCl2*4H2O added; air bubbled; LiCl (ethanol) added; solvent slowly evapd.; filtered off; washed (ethanol); H2O added to filtrate; evapd.; elem.anal.;	64%

tris(carbonato)cobaltate(III)(3-) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + sodium perchlorate → {Co(CO3)(1,4,7,10-tetraazacyclododecane)}ClO4

Conditions	Yield
In not given treatment of a tricarbonatocobaltate soln. with an equivalent amt. of C8H20N4*4HCl; concn.; removal of salts; addn. of aq. NaClO4 and ethanol to the filtrate;;	60%

manganese(II) nitrate hexahydrate + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → di-μ-oxo-bis(1,4,7,10-tetraazacyclododecane)dimanganese(III,IV) nitrate

Conditions	Yield
With LiOH In ethanol; water (NHCH2CH2)4*4HCl dissolved in aq. LiOH; ethanol added; Mn(NO3)2*6H2O added; air bubbled; evapd. to moist mass; treated with acetone; filtered; washed (acetone); elem.anal.;	60%

formaldehyd (50-00-0) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonic acid) (91987-74-5)

Conditions	Yield
With hydrogenchloride; phosphonic Acid In water for 1h; Heating;	54%
With hydrogenchloride; phosphonic Acid for 5h; Heating;	37.1%

2-chloro-N-ethylacetamide (105-35-1) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → 1,4,7,10-tetrakis[(ethylcarbamoyl)methyl]-1,4,7,10-tetraazacyclododecane-NaCl complex

Conditions	Yield
With sodium carbonate In acetonitrile Heating;	53%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + 1-[N-(tert-butoxycarbonyl)amino]-2-[N-(chloroacetyl)amino]ethane (149979-14-6) → 1,4,7-tris(2-(tert-butoxycarbonyl)-2-aminoethylamidemethyl)-1,4,7,10-tetraazacyclododecane (1315468-75-7)

Conditions	Yield
Stage #1: 1,4,7,10-tetraazacyclododecane tetrahydrochloride With N-ethyl-N,N-diisopropylamine In acetonitrile at 40℃; for 0.0833333h; Stage #2: 1-[N-(tert-butoxycarbonyl)amino]-2-[N-(chloroacetyl)amino]ethane In acetonitrile at 80℃; for 9h;	41%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + C18H17NO5S → C59H59N7O6

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile for 72h; Inert atmosphere; Reflux;	41%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + 2-Chloro-N,N-diethylacetamide (2315-36-8) → 1,4,7,10-tetrakis(N,N-diethylacetamido)-1,4,7,10-tetraazacyclododecane (136599-72-9)

Conditions	Yield
	40%

C101H83BrO6 + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → C412H348N4O24

Conditions	Yield
Stage #1: 1,4,7,10-tetraazacyclododecane tetrahydrochloride With 1-methyl-pyrrolidin-2-one; caesium carbonate at 130℃; for 5h; Inert atmosphere; Stage #2: C101H83BrO6 With 1-methyl-pyrrolidin-2-one for 24h; Inert atmosphere; Reflux;	37%

1,1'-(((5-(bromomethyl)-1,3-phenylene)bis(oxy))bis(butane-4,1-diyl))dipyrene + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → C196H172N4O8

Conditions	Yield
Stage #1: 1,4,7,10-tetraazacyclododecane tetrahydrochloride With 1-methyl-pyrrolidin-2-one; caesium carbonate at 130℃; for 5h; Inert atmosphere; Stage #2: 1,1'-(((5-(bromomethyl)-1,3-phenylene)bis(oxy))bis(butane-4,1-diyl))dipyrene With 1-methyl-pyrrolidin-2-one at 130℃; for 24h; Inert atmosphere;	36%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + 1-bromo-4-(1-pyrenyl)butane (117846-05-6) → C88H84N4

Conditions	Yield
Stage #1: 1,4,7,10-tetraazacyclododecane tetrahydrochloride With caesium carbonate In acetonitrile for 5h; Inert atmosphere; Reflux; Stage #2: 1-bromo-4-(1-pyrenyl)butane In acetonitrile for 24h; Inert atmosphere; Reflux;	30%

formaldehyd (50-00-0) + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrayltetramethylenetetrakis(phosphinic acid) (164858-92-8)

Conditions	Yield
With hypophosphorous acid In water at 40℃; for 3h;	29%

cobalt(II) chloride hexahydrate + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) → cis-dichloro(1,4,7,10-tetra-azacyclododecane)cobalt(III) chloride (15654-20-3)

Conditions	Yield
With air In methanol Li(OH)*H2O was added to suspn. of ligand in anhyd. methanol, soln. of CoCl2*6H2O in methanol was added and methanol-saturated air was passed through soln. for 1 h, soln. filtered and warmed to boiling point for 10 min; ppt. filtered off, washed with methanol and diethyl ether, dried; elem.anal.;	25%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + Chloro-acetic acid (R)-indan-1-yl ester → 1,4,7,10-tetrakis{[(R)-1-indanoxycarbonyl]methyl}-1,4,7,10-tetraazacyclododecane-NaCl complex

Conditions	Yield
With sodium carbonate In acetonitrile Heating;	24%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + Chloro-acetic acid (R)-(1,2,3,4-tetrahydro-naphthalen-1-yl) ester → 1,4,7,10-tetrakis{[(R)-tetrahydro-1-naphthoxycarbonyl]methyl}-1,4,7,10-tetraazacyclododecane-NaCl complex

Conditions	Yield
With sodium carbonate In acetonitrile Heating;	23%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + (O-(cyclopentyl))chloroacetate → 1,4,7,10-tetrakis[(cyclopentoxycarbonyl)methyl]-1,4,7,10-tetraazacyclododecane-NaCl complex

Conditions	Yield
With sodium carbonate In acetonitrile for 4h; Heating;	20%

1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + 2-chloromethylpyridine hydrochloride (6959-47-3) → 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (185130-32-9)

Conditions	Yield
With sodium hydroxide at 20℃; for 96h; pH=7 - 9;	20%
With sodium hydroxide In water at 20℃; for 96h; pH=7 - 9;	20%

dichloromethane (75-09-2) + 1-(4-pyridyl)pyridinium chloride hydrochloride hydrate + 1,4,7,10-tetraazacyclododecane tetrahydrochloride (10045-25-7) + water (7732-18-5) → 1,7-tetra(4-pyridyl)-1,4,7,10-tetraazacyclododecane hydrate dichloromethane solvate

Conditions	Yield
Stage #1: 1-(4-pyridyl)pyridinium chloride hydrochloride hydrate; 1,4,7,10-tetraazacyclododecane tetrahydrochloride at 170℃; for 3h; Inert atmosphere; Schlenk technique; Stage #2: water With sodium hydroxide for 2h; pH=> 11; Reflux; Stage #3: dichloromethane	19.3%

Upstream product

• 52667-88-6 cyclen tetratosylate 
• 809289-72-3 8b-methyldecahydro-2a,4a,6a,8a-tetraazacyclopenta[fg]acenaphthylene 
• 215540-27-5 3H,6H-2a,5,6,8a-octahydrotetraaza-acenaphthylene 
• 55442-07-4 N,N',N'',N'''-tetrakis-(p-tolylsulphonyl)-triethylenetetramine 
• 214195-92-3 5a,8b-dimethyloctahydro-2a,5,6,8a-tetraazaacenaphthylene 
• 112-24-3 triethylentetramine 
• 74199-09-0 cis-13-1,4,7,10-tetraazatetracyclo<5.5.2.0^4,140^10,13>tetradecane 
• 74199-09-0 cyclen-glyoxal 

Downstream Products

• 294-90-6 1,4,7,10-tetraazacyclododecan 
• 74199-09-0 cyclen-glyoxal 
• 18084-64-5 N,N’,N’’,N’’’-tetrabenzyl-1,4,7,10-tetraazacyclododecane 
• 48042-08-6 tetracyanonickelate(II) 
• 91987-74-5 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonic acid) 
• 175854-39-4 1,4,7-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecane 
• 170463-86-2 4,10-bis(p-toluenesulfonyl)-1,4,7,10-tetraazabicyclo<5.5.3>pentadecane 
• 52667-88-6 cyclen tetratosylate 
• 162148-45-0 1,4,7,10-tetraaza-cyclododecane-1,7-dicarboxylic acid dibenzyl ester 
• 134448-29-6 1,7-bis(4-toluenesulphonyl)-1,4,7,10-tetraazacyclododecane 
• 137076-54-1 1,4,7-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane-10-acetic acid 
• 192635-89-5 phenylmethyl 2-(1,4,7,10-Tetraaza-4,7,10-tris(((tert-butyl)oxycarbonyl)methyl)cyclododecyl)-acetate 

Relevant articles and documents

SYNTHESIS AND ACID-BASE AND COMPLEX-FORMING PROPERTIES OF 1,4,7,10-TETRAKIS(DIHYDROXYPHOSPHORYLMETHYL)-1,4,7,10-TETRAAZACYCLODODECANE

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Condensation of glyoxal with triethylenetetraamine. Stereochemistry, cyclization and deprotection

A mixture of bis-aminal isomers was obtained from aqueous glyoxal- triethylenetetraamine condensation. The irreversible isomerization of the species was observed and a new synthesis of cyclen proposed.

A new route to cyclen, cyclam and homocyclen

Cyclen, cyclam and homocyclen have been synthesized from the corresponding butanedione-protected linear tetramines. The cyclization step is followed by a facile deprotection of the rigidifying moiety.

Preparation method of cyclen

The invention provides a preparation method of cyclen. The method comprises the following step: taking triethylenetetramine (TETA) as a raw material to carry out refining, then carrying out a reactionon the refined triethylenetetramine with methylglyoxal to obtain an intermediate 2, carrying out cyclization on the intermediate 2 with glyoxal, carrying out reducing with sodium borohydride to obtain a cyclized intermediate 3, finally carrying out ring opening through acid hydrolysis, and then adjusting the pH value by using an alkali solution to free out the cyclen.

A high-purity torus cane rather method for the preparation of

The invention provides a preparation method of high-purity cyclen. The method comprises the following preparation paths. Cyclen obtained by the method of the invention has high purity. At the same time, the method greatly reduces the energy consumption and the power cost, and thereby reducing the raw material cost; the method greatly improves the reaction rate, reduces the catalyst amount and the reaction temperature, thereby shortening the consuming time of the process, and reducing the process cost; and the method greatly reduces the acid amount consumption, and thereby greatly reducing the equipment loss. The preparation method improves the production efficiency, and enables the product quality to reach more than 99.8%; hydrazine hydrate is used for replacing diethylenetriamine for a hydrolysis reaction, so the process is suitable for industrialized production. The method of the invention is environmentally friendly, is cost-saving, and is suitable for environment-friendly industrialization.