4730-54-5

Basic information

• Product Name: 1,4,7-Triazacyclononane
• Synonyms: 1,4,7-TRIAZACYCLONONANE;OCTAHYDRO-1H-1,4,7-TRIAZONINE;TRIETHYLENETRIAMINE;Triazacyclononanewhitextl;1,4,7-Triazacyclononane,97%;1,4,7-triazonane;Octahydro-1H-1,4,7-triazonine, Triethylenetriamine;1,4,7-Triazacyclonomane
• CAS NO: 4730-54-5
• Molecular Formula: C₆H₁₅N₃
• Molecular Weight: 129.2
• EINECS: 1592732-453-0
• Product Categories: organic amine;Achiral Nitrogen;Cy-N
• Mol File: 4730-54-5.mol
• Article Data: 26

Chemical Properties

• Melting Point: 42-45 °C(lit.)
• Boiling Point: 110-130 °C7 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: white/crystal
• Density: 0.9987 (rough estimate)
• Vapor Pressure: 0.0176mmHg at 25°C
• Refractive Index: 1.4620 (estimate)
• Storage Temp.: 2-8°C
• PKA: 10.57±0.20(Predicted)
• Water Solubility: Soluble in water
• BRN: 773877
• CAS DataBase Reference: 1,4,7-Triazacyclononane(CAS DataBase Reference)
• NIST Chemistry Reference: 1,4,7-Triazacyclononane(4730-54-5)
• EPA Substance Registry System: 1,4,7-Triazacyclononane(4730-54-5)

Safety Data

• Hazard Codes: C
• Statements: 34
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 3259 8/PG 2
• WGK Germany: 3
• F: 3-10-34
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 4730-54-5(Hazardous Substances Data)

Usage

Description

1,4,7-Triazacyclononane, known as "TACN" which is pronounced "tack-en," is a cyclic organic compound with the formula C6H12(NH)3. TACN is derived, formally speaking, from cyclononane by replacing three equidistant CH2 groups with NH groups. TACN is one of the oligomers derived from aziridine, C2H4NH. Other members of the series include diazacyclohexane, C4H8(NH)2, and the cyclic tetramer 1,4,7,10-tetraazacyclododecane.

Chemical Properties

White - light yellow solid

Uses

Different sources of media describe the Uses of 4730-54-5 differently. You can refer to the following data:
1. Starting material for the synthesis of 1,4,7-trifunctionalized derivatives which have applications in metal complexation.
2. 1,4,7-Triazacyclononane (TACN) is a versatile platform from which various ligands can be derived to form effective chelators for (radio)copper(II) complexation. The ability of TACN-derivatives to form highly stable complexes with copper(II) is greatly influenced by the number and type of substituents on the macrocyclic ring. The formed copper(II) complexes show a broad variability in their thermodynamic stability and kinetic inertness, varying in structure from square-pyramidal to distorted octahedral. TACN-based BFCAs have also been used for indirect radiolabelling of biomolecules, rendering them suitable for imaging and therapy.

Application

Starting material for the synthesis of 1,4,7-trifunctionalized derivatives which have applications in metal complexation.Possible reagent for compleximetric titrations with high cation-binding selectivity.

Preparation

The ligand is prepared from diethylene triamine as follows by macrocyclization using ethyleneglycol ditosylate.H2NCH2CH2NHCH2CH2NH2 + 3 TsCl → Ts(H)NCH2CH2N(Ts)CH2CHH2N(H)Ts + 3 HCl Ts(H)NCH2CH2N(Ts)CH2CH2N(H)Ts + 2 NaOEt → Ts(Na)NCH2CH2N(Ts)CH2CH2N(Na)Ts Ts(Na)NCHH2CH2N(Ts)CH2CH2N(Na)Ts + TsOCH2CH2OTs + → [(CH2CH2N(Ts)]3 + 2 NaOTs [(CH2CH2N(Ts)]3 + 3 H2O → [CH2CH2NH]3 + 3 HOTs

InChI:InChI=1/C6H15N3/c1-2-8-5-6-9-4-3-7-1/h7-9H,1-6H2

Synthetic route

N,N',N''-tribenzyl-1,4,7-triazacyclononane (125262-43-3) → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen; acetic acid In methanol at 50℃; under 760.051 Torr; for 3h;	100%
With methanol; palladium 10% on activated carbon at 50℃; for 3h;	100%
With palladium 10% on activated carbon; hydrogen; acetic acid	95%
With palladium 10% on activated carbon; hydrogen; acetic acid at 20℃; for 72h;	95%

1,4,7-triazacyclononane trihydrochloride (58966-93-1) → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
With sodium hydroxide In water; toluene Heating;	91%
With sodium hydroxide In water pH=12;	89%
With sodium hydroxide In water pH=13;	79.4%

N,N',N-tris(p-toluenesulfonyl)-1,4,7-triazacyclononane (52667-89-7) → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
Stage #1: N,N',N-tris(p-toluenesulfonyl)-1,4,7-triazacyclononane With sulfuric acid In water at 140℃; for 20h; Stage #2: With sodium hydroxide In water; toluene for 2h; Heating;	86%
With sulfuric acid at 100 - 105℃; Heating; 30-48 h;	73%
With sulfuric acid at 120℃; for 120h;	65%

N,N',N''-tris(β-trimethylsilylethanesulfonyl)-1,4,7-triazacyclononane (340970-58-3) → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
With cesium fluoride In N,N-dimethyl-formamide at 95℃; for 24h;	68%

1,4,7-Triazacyclononane trihydrobromide (35980-59-7) → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
With potassium hydroxide In methanol

1,4,7-triazacyclononane tritosylate → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
With sulfuric acid at 120℃; for 30h; Yield given;

octahydroimidazol[1,2-a]pyrazine (1610596-42-3) → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / acetonitrile / 24 h / 10 - 20 °C 1.2: 12 h / -10 °C 2.1: acetic acid; hydrogen; palladium 10% on activated carbon View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / acetonitrile / 24 h / 10 °C 2: sodium tetrahydroborate / ethanol / 12 h / -10 °C 3: palladium 10% on activated carbon; hydrogen; acetic acid / 72 h / 20 °C View Scheme

C27H32N3(1+)*Br(1-) → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol / 12 h / -10 °C 2: palladium 10% on activated carbon; hydrogen; acetic acid / 72 h / 20 °C View Scheme

N,N′-(ethane-1,2-diyl)bis(N-benzyl-2-chloroacetamide) (110330-98-8) → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium bromide; sodium carbonate / acetonitrile / 20 h / Inert atmosphere; Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 20 h / Inert atmosphere; Reflux 3: palladium 10% on activated carbon; acetic acid; hydrogen / methanol / 3 h / 50 °C / 760.05 Torr View Scheme
Multi-step reaction with 3 steps 1: lithium bromide / acetonitrile / 20 h / Inert atmosphere; Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 20 h / Reflux 3: palladium 10% on activated carbon; methanol / 3 h / 50 °C View Scheme

1,4,7-tribenzyl-1,4,7-triazacyclononane-2,6-dione → 1,4,7-triazacyclononane (4730-54-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 20 h / Inert atmosphere; Reflux 2: palladium 10% on activated carbon; acetic acid; hydrogen / methanol / 3 h / 50 °C / 760.05 Torr View Scheme
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 20 h / Reflux 2: palladium 10% on activated carbon; methanol / 3 h / 50 °C View Scheme

N,N-dimethyl-formamide dimethyl acetal (4637-24-5) + 1,4,7-triazacyclononane (4730-54-5) → tacnoa (67705-38-8)

Conditions	Yield
In toluene for 2h; Reflux;	100%
In chloroform; toluene at 20℃; for 12h;	99%
for 16h; Heating;	92%

(R)-2-isopropyloxirane (82378-47-0) + 1,4,7-triazacyclononane (4730-54-5) → N,N'N''-Tris<(2R)-2-hydroxy-3-methylbutyl>-1,4,7-triazacyclononane (151750-90-2)

Conditions	Yield
In ethanol for 240h; Ambient temperature;	100%

1,4,7-triazacyclononane (4730-54-5) + (S)-Propylene oxide (16088-62-3) → (2S,2'S,2”S)-1,1',1”-(1,4,7-triazonane-1,4,7-triyl)tris(propan-2-ol) (106610-88-2)

Conditions	Yield
In ethanol at 20℃;	100%
In ethanol for 48h;	100%
at 20℃; for 24h; Inert atmosphere; Schlenk technique;	97%

2-chloromethylpyridine hydrochloride (6959-47-3) + 1,4,7-triazacyclononane (4730-54-5) → 1,4,7-tris(pyridin-2-ylmethyl)-1,4,7-triazacyclononane (102851-50-3)

Conditions	Yield
With sodium hydroxide; hexadecylamine hydrochloride In water at 20℃; for 24h; Condensation;	100%
With sodium carbonate In acetonitrile at 20℃; for 120h;	83%
With triethylamine; sodium iodide In ethanol for 12h; Heating;	55%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 80℃; for 2h; Inert atmosphere;

1,2-epoxytetradecane (3234-28-4) + 1,4,7-triazacyclononane (4730-54-5) → 1-(2-hydroxytetradecyl)-1,4,7-triazacyclononane

Conditions	Yield
In ethanol for 168h;	100%
In ethanol Yield given;

H4(ruthenium)4(carbonyl)12 + 1,4,7-triazacyclononane (4730-54-5) → H(CH2)6(NH)3(1+)*H3Ru4(1-)*12CO=[H(CH2)6(NH)3][H3Ru4(CO)12]

Conditions	Yield
In hexane N2-atmosphere; addn. of slight excess of nonane derivative to Ru-complexsoln. at reflux, stirring (70°C, 2 h); cooling to room temp., filtration, extn. into hexane, drying (vac.); elem. anal.;	99.1%

4-Fluoronitrobenzene (350-46-9) + 1,4,7-triazacyclononane (4730-54-5) → 1,4-bis(4-nitrophenyl)[1,4,7]triazonane (848662-84-0)

Conditions	Yield
With potassium carbonate In water for 24h; Heating / reflux;	99%

2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile (58632-95-4) + 1,4,7-triazacyclononane (4730-54-5) → 1,4-di-tert-butyl 1,4,7-triazonane-1,4-dicarboxylate (174138-01-3)

Conditions	Yield
With triethylamine In chloroform at 20℃; for 8h;	98%
With triethylamine In chloroform at 0 - 20℃; Cooling with ice;	95%
With triethylamine In chloroform at 20℃; for 7h; Cooling with ice;	92%

perrhenic acid anhydride + 1,4,7-triazacyclononane (4730-54-5) → {(1,4,7-triazacyclononane)ReO3}ReO4

Conditions	Yield
In tetrahydrofuran N2-atmosphere; stirring equimolar amts. for 15 min (pptn.); decantation, washing (THF), drying (vac.); elem. anal.;	98%

rhenium(VII) oxide + 1,4,7-triazacyclononane (4730-54-5) → {(1,4,7-triazacyclononane)ReO3}ReO4

Conditions	Yield
In tetrahydrofuran ppt. washed with THF, dried in vac.;	98%

(3-bromopropyl)(phenyl)selane (118824-31-0) + 1,4,7-triazacyclononane (4730-54-5) → 1-[3-(phenylseleno)propyl]-1,4,7-triazacyclononanone

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	97.5%

1,4,7-triazacyclononane (4730-54-5) + p-methylbenzyl halide → 1,4,7-tris(4-methylbenzyl)-1,4,7-triazacyclononane

Conditions	Yield
With potassium hydroxide In toluene Heating;	97%

formaldehyd (50-00-0) + phosphonic acid diethyl ester (762-04-9) + 1,4,7-triazacyclononane (4730-54-5) → hexaethyl ((1,4,7-triazonane-1,4,7-triyl)tris(methylene))tris(phosphonate) (137145-65-4)

Conditions	Yield
In benzene Heating;	96.8%
With toluene-4-sulfonic acid In toluene for 6h; Reflux;	79%

dibutyl hydrogen phosphite (1809-19-4) + formaldehyd (50-00-0) + 1,4,7-triazacyclononane (4730-54-5) → N,N',N''-tris(dibutylphosphorylmethyl)-1,4,7-triazacyclononane (137145-67-6)

Conditions	Yield
In benzene Heating;	96%

1,4,7-triazacyclononane (4730-54-5) + 6-bromo-5'-bromomethyl-2,2'-bipyridine (334001-82-0) → 1,4,7-tris[(6-bromo-2,2'-bipyridine-5'-yl)methyl]-1,4,7-triazacyclononane (335594-42-8)

Conditions	Yield
With sodium carbonate In acetonitrile at 80℃; for 38h;	96%

formaldehyd (50-00-0) + di-n-propyl phosphonate (1809-21-8) + 1,4,7-triazacyclononane (4730-54-5) → [4,7-Bis-(dipropoxy-phosphorylmethyl)-[1,4,7]triazonan-1-ylmethyl]-phosphonic acid dipropyl ester (137145-66-5)

Conditions	Yield
In benzene Heating;	95%

acrylonitrile (107-13-1) + 1,4,7-triazacyclononane (4730-54-5) → 1,4,7-tris(2-cyanoethyl)-1,4,7-triazacyclononane (112995-08-1)

Conditions	Yield
Heating;	95%

2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile (74651-77-7) + 1,4,7-triazacyclononane (4730-54-5) → 1,4-di-tert-butyl 1,4,7-triazonane-1,4-dicarboxylate (174138-01-3)

Conditions	Yield
In chloroform for 72h;	95%

fac-[CoCl3(1,4,7-triazacyclononane)] (58723-65-2) + 1,4,7-triazacyclononane (4730-54-5) → [Co(1,4,7-triazacyclononane)2](ClO4)3

Conditions	Yield
In isopropyl alcohol refluxing, 85°C, 0.5h; cooled for 2-4 h; filtered; washed with ethanol and ether; dried;	95%

formaldehyd (50-00-0) + 1,4,7-triazacyclononane (4730-54-5) → 1,4,7-triazabicyclo[5.2.1]decane (133474-55-2)

Conditions	Yield
In ethanol at 20℃; for 4h; Molecular sieve;	95%

methyl 5-(2 formyl-1H-imidazol-1-yl)pentanoate + trifluoroacetic acid (76-05-1) + 1,4,7-triazacyclononane (4730-54-5) → trimethyl-5,5′,5″-(((1,4,7-triazonane-1,4,7-triyl)tris(methylene))tris(1H-imidazole-2,1-diyl))tripentanoate

Conditions	Yield
Stage #1: methyl 5-(2 formyl-1H-imidazol-1-yl)pentanoate; 1,4,7-triazacyclononane In tetrahydrofuran for 24h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran for 5h; Stage #3: trifluoroacetic acid In water; acetonitrile pH=2 - 3;	95%

α-bromo-γ-butyrolactone (5061-21-2) + 1,4,7-triazacyclononane (4730-54-5) → C18H27N3O6

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃;	94%

ethyl trifluoroacetate, (383-63-1) + 1,4,7-triazacyclononane (4730-54-5) → 1,4-bis (trifluoroacetyl)-1,4,7-triazacyclononane

Conditions	Yield
With triethylamine In methanol at 20℃;	94%
With triethylamine In methanol; dichloromethane	94%

dichlorotetrakis(dimethylsulfoxide)ruthenium (59091-96-2, 89395-66-4, 90698-13-8, 194497-67-1, 482618-33-7, 41290-68-0, 72904-47-3, 61779-29-1, 64376-67-6, 75766-08-4) + 1,4,7-triazacyclononane (4730-54-5) → ruthenium 1,4,7-triazacyclononane trichloride (93557-58-5)

Conditions	Yield
With concd. HCl; air In toluene addn. of triaza compd. to soln. of Ru complex in dry toluene, heated to reflux for 1 h, cooling to 0°C, (Ru(dmso)2Cl(tacn))Cl filtered off, dissolved in concd. HCl, heating to reflux in presence of air for 10 min, pptn.; microcrystals ppt. filtered off, washed (EtOH, Et2O), and air-dried;	94%

methyl hydrogen fumarate (2756-87-8) + 1,4,7-triazacyclononane (4730-54-5) → 4-methoxy-4-oxo-3-(1,4,7-triazonan-1-yl)butanoic acid

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 2h;	94%

1-(allyloxy)-6-(chloromethyl)-2(1H)-pyridinone + 1,4,7-triazacyclononane (4730-54-5) → N,N',N"-tris(1-allyloxy-6(1H)-pyridinone-2-methyl)-1,4,7-triazacyclononane

Conditions	Yield
With potassium carbonate In acetonitrile Reflux;	93%

2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile (58632-95-4) + 1,4,7-triazacyclononane (4730-54-5) → N,N'-diBoc-1,4,7-triazacyclononane

Conditions	Yield
In chloroform	92%

iron(II) chloride tetrahydrate + 1,4,7-triazacyclononane (4730-54-5) → bis(1,4,7-triazacyclononane)iron(II) perchlorate (111958-64-6)

Conditions	Yield
With NH4(CH3COO); NaClO4 In ethanol; water Ar atmosphere, addn. of ligand in EtOH to aq. soln. of ammonium acetate and FeCl2 (10 min, room temp.), addn. of NaClO4 (4°C), pptn.; pptn. filtered off, washed (cold ethanol, ether), dried (Ar atmosphere); elem. anal.;	92%

(99)TcCl(CO)3{P(C6H5)3}2 (139238-77-0, 15526-57-5) + 1,4,7-triazacyclononane (4730-54-5) → (C6H15N3)(99)Tc(CO)2{P(C6H5)3}(1+)*Cl(1-)={(C6H15N3)(99)Tc(CO)2{P(C6H5)3}}Cl (139131-25-2)

Conditions	Yield
In tetrahydrofuran byproducts: CO; Addn. of 1,4,7-triazacyclononane to a stirred soln. of Tc-complex under N2, heating (70°C), evolution of CO is observed.; Filtn. after 2 h, washing (cold THF), drying in vac., recrystn. (CH2Cl2/-n-hexane), elem. anal.;	92%

Upstream product

• 125262-43-3 N,N',N''-tribenzyl-1,4,7-triazacyclononane 
• 1610596-42-3 octahydroimidazol[1,2-a]pyrazine 
• 63632-68-8 N,N'-bis(2-chloroethyl)ethylenediamine dihydrochloride 
• 107-15-3 ethylenediamine 
• 110330-98-8 N,N′-(ethane-1,2-diyl)bis(N-benzyl-2-chloroacetamide) 
• 58966-93-1 1,4,7-triazacyclononane trihydrochloride 
• 340970-58-3 N,N',N''-tris(β-trimethylsilylethanesulfonyl)-1,4,7-triazacyclononane 
• 52667-89-7 N,N',N-tris(p-toluenesulfonyl)-1,4,7-triazacyclononane 
• 35980-59-7 1,4,7-Triazacyclononane trihydrobromide 

Downstream Products

• 193804-64-7 1-isopropyl-1,4,7-triazacyclononane 
• 169833-92-5 4,7-diisopropyl-1,4,7-triazacyclononane 
• 110076-36-3 1,4,7-tri(iso-propyl)-1,4,7-triazacyclononane 
• 138149-65-2 1,4,7-triazacyclononane-1,4,7-triyltris 
• 83834-39-3 1,4,7-triazacyclononane-1,4,7-triyl tris(methylenephosphonic acid) 
• 131060-53-2 1-(5-benzamido-1-ethoxycarbonylpentyl)-1,4,7-triazacyclononane 
• 131060-55-4 1,4-bis(5-benzamido-1-ethoxycarbonylpentyl)-1,4,7-triazacyclononane 
• 129865-73-2 tripotassium 1,4,7-tris-(5-t-butyl-2-hydroxylatobenzyl)-1,4,7-triazacyclononane 
• 146070-02-2 1,4,7-tris(4-acetylthiobenzoyl)-1,4,7-triazacyclononane 
• 141380-93-0 1-<<(3-benzamidopropyl)ethoxyphosphoryl>methyl>1,4,7-triazacyclononane 
• 143255-09-8 1,4,7-tris(β-diphenylphosphinylethyl)-1,4,7-triazacyclononane 
• 96556-05-7 N,N',N''-trimethyl-1,4,7-triazacyclononane 
• 174137-99-6 [1,4,7]Triazonan-1-yl-acetic acid tert-butyl ester 
• 174137-97-4 1,4-bis(tert-butoxycarbonylmethyl)-1,4,7-triazacyclononane 

Relevant articles and documents

Phosphoric triamides. 31Phosphorus NMR chemical shift as a function of the P-N bond characteristics

Six phosphoric triamides in which amide nitrogens are incorporated into an increasing number (from 0 to 3) of the 1,3,2-diazaphospholidin-2-one rings have been prepared and their crystal structures have been determined. The structural changes from the non-cyclic to the mono-, di- and tri-cyclic systems result in the decrease of the N-P-N bond angles and the increase of the P-N bond distance. These changes are paralleled by a strong deshielding of the 31P nucleus, leading to an exceptionally high δp value for the tricyclic derivative. The δp-structural parameters relationship is discussed in terms of the changes in hybridization of phosphorus and the variation in the P-N bond order.

Measurement of the rate of copper(II) exchange for 64Cu complexes of bifunctional chelators

Measurement of the rate of loss of 64Cu from the chelators used in the preparation of 64Cu-labeled proteins is critical to the development of effective 64Cu-labeled radiopharmaceuticals. Typically, however, this assessment has been made indirectly, by comparison of the relative uptake of the labeled proteins in the liver, or under non-physiological conditions such as hot 5 M HCl. In the present study, we measured the rate of loss of 64Cu from a series of chelators (DOTA, TETA, and NOTA) that are commonly used to label proteins as a function of [Cu2+] (1, 2, and 5 μM) and pH (7.5, 6.0. and 5.0). We found that 64Cu-NOTA is somewhat more kinetically stable than 64Cu-TETA and that both 64Cu-NOTA and 64Cu-TETA are much more kinetically stable than 64Cu-DOTA. Furthermore, the rate of loss of 64Cu from Cu-DOTA increased with higher [Cu 2+] and pH while the rate of loss of 64Cu from Cu-TETA and Cu-NOTA was minimally dependent on [Cu2+] and pH. These results suggest that NOTA is preferable to TETA and DOTA for the preparation of 64Cu-labeled proteins.

DINUCLEATING LIGAND OR DINUCLEAR METAL COMPLEX

To provide a dinuclear metal complex that can be synthesized simply and easily and has a proper anticancer action.SOLUTION: The present disclosure provides a dinucleating ligand represented by the following formula (I) and a dinuclear metal complex thereof (where X is H or a substituted carbamoyl group, R1, R2, R3, and R4 independently represent H or a C1-8 linear or branched alkyl group).SELECTED DRAWING: None

An Efficient Synthesis of N,N,N-Substituted 1,4,7-Triazacyclononane

A new and efficient synthetic approach is reported for various N,N,N-substituted 1,4,7-triazacyclononanes (TACN) in moderate to excellent yields, with optimization of the reaction sequences and conditions of the intermediate 1,4,7-tribenzyl-1,4,7-triazonane-2,6-dione reduction with LiAlH4, removal of benzyl with Pd/C, and alkylation reactions. This reaction scheme provides a convenient and flexible method to prepare various N,N,N-substituted TACN derivatives.