6928-85-4

Basic information

• Product Name: 1-Amino-4-methylpiperazine
• Synonyms: LABOTEST-BB LT00005082;1-METHYL-4-AMINOPIERAZINE;1-METHYL-4-AMINOPIPERAZINE;1-AMINO-4-METHYLPIERAZINE;1-AMINO-4-METHYLPIPERAZINE;4-AMINO-1-METHYLPIPERAZINE;4-methylpiperazin-1-ylamine;AMPRZ
• CAS NO: 6928-85-4
• Molecular Formula: C₅H₁₃N₃
• Molecular Weight: 115.18
• EINECS: 230-053-7
• Product Categories: Piperaizine;Piperazine derivates;Building Blocks;Heterocyclic Building Blocks;Piperazines
• Mol File: 6928-85-4.mol
• Article Data: 13

Chemical Properties

• Boiling Point: 172-175 °C
• Flash Point: 62 °C
• Appearance: Clear/Viscous Solution
• Density: 0.957 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.29hPa at 25℃
• Refractive Index: 1.4835-1.4855
• Storage Temp.: Store at +2°C to +8°C.
• Solubility: water: soluble
• PKA: 7?+-.0.42(Predicted)
• Water Solubility: miscible
• Sensitive: Air & Light Sensitive
• BRN: 103334
• CAS DataBase Reference: 1-Amino-4-methylpiperazine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Amino-4-methylpiperazine(6928-85-4)
• EPA Substance Registry System: 1-Amino-4-methylpiperazine(6928-85-4)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 24/25-36-26
• RIDADR: 2733
• WGK Germany: 3
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 6928-85-4(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless to light yellow liquid

Uses

1-Amino-4-methylpiperazine has been used:in synthesis of pyrazolo-pyrazine, -pyridine derivatives and 2-[(4-methylpiperazin-1-yl)iminomethyl]phenolas a solvating and stabilizing agent in the preparation of uniform Ag nanoparticles (<10nm)synthesis of N-(4-Fluorobenzylidene)-4-methylpiperazin1-aminesynthesis of 4-Methyl-N-(3,4,5-trimethoxybenzylidene) piperazin-1-aminesynthesis of N-(3,4-Dichlorobenzylidene)-4- methylpiperazin-1-aminesynthesis of N-(4-(Diethylamino)benzylidene)-4- methylpiperazin-1-aminesynthesis of N-(2,5-Dimethoxybenzylidene)-4- methylpiperazin-1-aminesynthesis of 4-Methyl-N-((5-nitrofuran-2- yl)methylene)piperazin-1-amine

Application

1-Amino-4-methylpiperazine, a derivative of piperazine, is used widely as an intermediate in the synthesis of pharmaceutical agents. It is an important intermediate for Rifampicin. Rifampicin , known as rifampin, is an antibiotic used to treat a several kinds of bacterial infections such as tuberculosis, leprosy and Legionnare's disease.

Preparation

1-Amino-4-methylpiperazine is obtained from piperazine hexahydrate through the steps of methylation, hydrolysis, nitrosation and reduction.1-Amino-4-methylpiperazine is synthesized by chlorination of methyl(diethanol)amine (I) and subsequent cyclization of the di(chloroethyl)amine (II) obtained in aqueous hydrazine.

Flammability and Explosibility

Notclassified

InChI:InChI=1/C5H13N3/c1-7-2-4-8(6)5-3-7/h2-6H2,1H3

Synthetic route

1-methyl-4-nitroso-piperazine (16339-07-4) → 1-methyl-piperazine (109-01-3) + N-amino-N'-methylpiperazine (6928-85-4)

Conditions	Yield
With carbon dioxide; water; ammonium chloride; zinc at 35℃; under 1500.15 Torr; for 1.5h; Reagent/catalyst; Temperature; Pressure; Autoclave; Green chemistry;	A n/a B 96%
With hydrogen In water at 50℃; under 37503.8 Torr; for 5h; Autoclave; Green chemistry;	A n/a B 38%

1-methyl-4-nitroso-piperazine (16339-07-4) → N-amino-N'-methylpiperazine (6928-85-4)

Conditions	Yield
With hydrogen In dichloromethane; water at 50℃; under 37503.8 Torr; for 5h; Solvent; Autoclave; Green chemistry;	94%
With lithium aluminium tetrahydride In diethyl ether for 10h; Heating;	88%
With acetic acid; zinc In water Cooling with ice;	78%

mechlorethamine hydrochloride (55-86-7) → N-amino-N'-methylpiperazine (6928-85-4)

Conditions	Yield
With hydrazine hydrate	87%

mechlorethamine hydrochloride (55-86-7) → N,N-bis(2-hydrazinoethyl)methylamine + N-amino-N'-methylpiperazine (6928-85-4)

Conditions	Yield
With hydrazine hydrate at 50℃; for 2h;	A 2% B 87%

N-Methyldiethanolamine (105-59-9) → N-amino-N'-methylpiperazine (6928-85-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96 percent / SOCl2 / CHCl3 / 2 h / 20 °C 2: 87 percent / aq. NH2NH2 View Scheme

4-chlorocarbonyl-4,9-dihydro-1-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one (118306-22-2) → N-amino-N'-methylpiperazine (6928-85-4) + 4,9-dihydro-1-methyl-4-{[(4-methyl-1-piperazinyl)amino]carbonyl}-10H-thieno[3,4-b][1,5]benzodiazepin-10-one

4-(chlorocarbonyl)-4,9-dihydro-3-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one (118306-21-1) → N-amino-N'-methylpiperazine (6928-85-4) + 4,9-dihydro-3-methyl-4-{[(4-methyl-1-piperazinyl)amino]carbonyl}-10H-thieno[3,4-b][1,5]benzodiazepin-10-one

4-(chlorocarbonyl)-4,9-dihydro-1,3-dimethyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one (118306-23-3) → N-amino-N'-methylpiperazine (6928-85-4) + 4,9-dihydro-1,3-dimethyl-4-{[(4-methyl-1-piperazinyl)amino]carbonyl}-10H-thieno[3,4-b][1,5]benzodiazepin-10-one

3-chloro-4-(chlorocarbonyl)-4,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one (118306-24-4) → N-amino-N'-methylpiperazine (6928-85-4) + 3-chloro-4,9-dihydro-4-{[(4-methyl-1-piperazinyl)amino]carbonyl}-10H-thieno[3,4-b][1,5]benzodiazepin-10-one

CH3N(CH2CH2)2NNH2*BH3 (21223-19-8) + water (7732-18-5) → N-amino-N'-methylpiperazine (6928-85-4) + hydrogen (1333-74-0) + boric acid (11113-50-1)

Conditions	Yield
In water
In water

1-methyl-piperazine (109-01-3) → N-amino-N'-methylpiperazine (6928-85-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride; sodium nitrite / water; tetrahydrofuran / 4 h / 20 °C 2: acetic acid; zinc / water / Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: sodium nitrite; hydrogenchloride / water; tetrahydrofuran / 4 h / 0 - 25 °C 2: zinc; acetic acid / water / 5 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: sodium nitrite; hydrogenchloride / water; tetrahydrofuran / 4 h / 25 °C 2: zinc; acetic acid / water / 5 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water / 0.17 h / 40 °C 1.2: 1.5 h / 20 - 30 °C 2.1: hydrogen / water / 5 h / 50 °C / 37503.8 Torr / Autoclave; Green chemistry View Scheme

N-amino-N'-methylpiperazine (6928-85-4) + chloro-diphenylphosphine (1079-66-9) → 1-diphenylphosphinoamino-4-methylpiperazine (849371-46-6)

Conditions	Yield
With triethylamine In diethyl ether at 20℃; for 1h;	100%
With triethylamine In tetrahydrofuran for 5h;	85%

N-amino-N'-methylpiperazine (6928-85-4) + (l)-N-[3-(4-(4'-acetylphenyl)phenyl)-2-oxooxazolidin-5-ylmethyl]acetamide → (l)-N-[3-(4-(4'-Acetylphenyl)phenyl)-2-oxooxazolidin-5-ylmethyl]acetamide 4-Methylpiperazinylhydrazone

Conditions	Yield
With trifluoroborane diethyl ether In 1,4-dioxane	100%

N-amino-N'-methylpiperazine (6928-85-4) + 2-(4-isocyanatophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → N-(4-methylpiperazin-1-yl)-N'-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-urea (879486-81-4)

Conditions	Yield
In dichloromethane at 20℃; for 6h;	100%

N-amino-N'-methylpiperazine (6928-85-4) + (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-4-(methylthio)thiazol-2(5H)-one (1407543-46-7) → (4Z,5Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-4-((4-methylpiperazin-1-yl)imino)thiazolidin-2-one (1408060-02-5)

Conditions	Yield
In ethanol at 85℃;	100%

N-amino-N'-methylpiperazine (6928-85-4) + N-(1H-1,2,3-benzotriazol-1-ylmethylene)-N-methylmethanaminium chloride → N,N-dimethyl-N'-(4-methylpiperazino)iminoformamide dihydrochloride

Conditions	Yield
With hydrazine In tetrahydrofuran for 4h; Condensation; Heating;	98%

N-amino-N'-methylpiperazine (6928-85-4) + difluoro(diethoxyphosphinyl)acetyl chloride (97480-49-4) → diethyl 1,1-difluoro-2-(4-methylpiperazin-1-ylamino)-2-oxoethylphosphonate (1217898-90-2)

Conditions	Yield
With pyridine; dmap In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	98%

N-amino-N'-methylpiperazine (6928-85-4) + N-tert-1,3-oxazine(5,6-c)rifamycin → rifampicin (13292-46-1)

Conditions	Yield
With acetic acid In butan-1-ol at 70℃; for 2h; Temperature; Solvent; Large scale;	97.87%
In water; N,N-dimethyl-formamide at 75℃; for 0.333333h; Temperature; Time;	92%
In N,N-dimethyl-formamide at 80℃; for 0.333333h; Concentration;

N-amino-N'-methylpiperazine (6928-85-4) + (3,4,5-trimethoxyphenyl)isothiocyanate (35967-24-9) → 1-(4-methylpiperazin-1-yl)-3-(3,4,5-trimethoxyphenyl)thiourea

Conditions	Yield
In ethanol for 1h; Reflux;	97%

N-amino-N'-methylpiperazine (6928-85-4) + sulindac sulfide (49627-27-2) → (Z)-2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)-N-(4-methylpiperazin-1-yl)acetamide

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In acetonitrile at 20℃; Inert atmosphere;	96%

N-amino-N'-methylpiperazine (6928-85-4) + carbon disulfide (75-15-0) + 2-(chloromethyl)-3-methylnaphthalene-1,4-dione (31599-79-8) → (4-methylpiperazin-1-yl)dithiocarbamic acid 3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-ylmethyl ester

Conditions	Yield
In tetrahydrofuran at 20℃;	95.9%

N-amino-N'-methylpiperazine (6928-85-4) + C26H14BrNO10 (609353-50-6) → C31H25BrN4O9

Conditions	Yield
In N,N-dimethyl-formamide; trifluoroacetic acid for 5h;	95%

N-amino-N'-methylpiperazine (6928-85-4) + chlorobenzene (108-90-7) → 4-methyl-N-phenylpiperazin-1-amine

Conditions	Yield
With 5-(di-tert-butylphosphino)-1′, 3′, 5′-triphenyl-1′H-[1,4′]bipyrazole; bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; sodium t-butanolate at 110℃; for 12h; Buchwald-Hartwig Coupling;	95%
With potassium tert-butylate; tris(dibenzylideneacetone)dipalladium (0) In 1,4-dioxane at 120℃; for 5h;	88%
With C38H49N2P*C9H10ClPd In 1,4-dioxane at 20℃; for 7h; Inert atmosphere; Schlenk technique;	77%

N-amino-N'-methylpiperazine (6928-85-4) + dimethylcadmium (506-82-1) → Cd(2+)*2CH3(1-)*NH2N(CH2)4NCH3=Cd(CH3)2(NH2N(CH2)4NCH3)

Conditions	Yield
In hexane hexane soln. of Me2Cd added to hexane; then 1-amino-4-methylpiperazine added; mixt. stirred; elem. anal.;	94%

N-amino-N'-methylpiperazine (6928-85-4) + 2-((2'-iodo-[1,1'-biphenyl]-2-yl)methyl)benzaldehyde → (E)-1-(2-((2'-iodo-[1,1'-biphenyl]-2-yl)methyl)phenyl)-N-(4-methylpiperazin-1-yl)methanimine

Conditions	Yield
With sodium sulfate In dichloromethane at 20℃; for 12h;	94%

N-amino-N'-methylpiperazine (6928-85-4) + 2-thiocyanato-cyclohex-1-enecarbaldehyde (42141-25-3) → 2-(4-methyl-piperazin-1-yl)-4,5,6,7-tetrahydro-1,2-benzisothiazolium perchlorate

Conditions	Yield
Stage #1: N-amino-N'-methylpiperazine; 2-thiocyanato-cyclohex-1-enecarbaldehyde With acetic acid for 0.25h; Stage #2: With perchloric acid; acetic acid for 1h;	93%

N-amino-N'-methylpiperazine (6928-85-4) + 4,4'-(4-formyl-1H-pyrazole-1,3-diyl)dibenzoic acid → 4,4'-{4-[((E)-(4-methylpiperazin-1-yl)imino)methyl]-1H-pyrazole-1,3-diyl}dibenzoic acid

Conditions	Yield
In ethanol for 8h; Reflux;	93%

N-amino-N'-methylpiperazine (6928-85-4) + 1-bromo-2-(phenylethenyl)benzene (21375-88-2) → 1-(4-methyl-piperazin-1-yl)-2-phenyl-1H-indole (1264670-27-0)

Conditions	Yield
With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; OTips-DalPhos; potassium tert-butylate In toluene at 90℃; for 12h; Inert atmosphere; Sealed vial;	92%
With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; OTips-DalPhos; potassium tert-butylate In toluene at 90℃; for 12h; Buchwald-Hartwig Coupling; Inert atmosphere; Sealed tube;	92%
With caesium carbonate; palladium dichloride; tri tert-butylphosphoniumtetrafluoroborate In N,N-dimethyl-formamide at 110℃; for 3h; Inert atmosphere;	74%

N-amino-N'-methylpiperazine (6928-85-4) + carbon disulfide (75-15-0) + 2-(1-chloromethyl-2,6-dioxo-piperidine-3-yl)-1,3-dihydro-2H-isoindole-1,3-dione (359869-12-8) → [3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2,6-dioxopiperidin-1-yl]methyl 4-methylpiperazin-1-yldithiocarbamate (1083189-99-4)

Conditions	Yield
In acetonitrile at 20℃; for 48h;	91%

N-amino-N'-methylpiperazine (6928-85-4) + C44H48FN3O8 → C43H56FN5O5

Conditions	Yield
With dimethyl sulfoxide In tetrahydrofuran for 0.416667h;	90%

N-amino-N'-methylpiperazine (6928-85-4) + 2-(4-chlorophenyl)-2-methyl-1,3-dioxolane (36881-02-4) → C15H23N3O2

Conditions	Yield
With potassium tert-butylate; tris(dibenzylideneacetone)dipalladium (0) In 1,4-dioxane at 120℃; for 2.5h;	90%

N-amino-N'-methylpiperazine (6928-85-4) + 2,6-dimethyl-1-chlorobenzene (6781-98-2) → C13H21N3

Conditions	Yield
With potassium tert-butylate; tris(dibenzylideneacetone)dipalladium (0) In 1,4-dioxane at 120℃; for 5.5h;	90%

N-amino-N'-methylpiperazine (6928-85-4) + 2-chloro-N,N-diphenylacetamide (5428-43-3) → C19H24N4O

Conditions	Yield
With triethylamine In acetone for 8h;	90%

N-amino-N'-methylpiperazine (6928-85-4) + 4-[3-(2,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid → 4-{3-(2,4-difluorophenyl)-4-[(E)-(methylimino)-N-(4-methylpiperazin-1-yl)]-1H-pyrazol-1-yl}benzoic acid

Conditions	Yield
With acetic acid In methanol for 12h; Reflux;	90%

N-amino-N'-methylpiperazine (6928-85-4) + pyridoxal (66-72-8) → 5-(hydroxymethyl)-2-methyl-4-(((4-methylpiperazine-1-yl)imino)methyl)pyridine-3-ol

Conditions	Yield
In ethanol at 20℃; for 5h;	90%
at 50℃;	53%

N-amino-N'-methylpiperazine (6928-85-4) + 1-formyl-5-nitroisoquinoline (20335-60-8) → (4-Methyl-piperazin-1-yl)-[1-(5-nitro-isoquinolin-1-yl)-meth-(Z)-ylidene]-amine

Conditions	Yield
In ethanol for 3h; Heating;	89%

N-amino-N'-methylpiperazine (6928-85-4) + acetic anhydride (108-24-7) + anthranilic acid (118-92-3) → 2-methyl-3-(4-methylpiperazin-1-yl)quinazolin-4(3H)-one

Conditions	Yield
With titanium dioxide nanoparticles at 80℃; for 7h; Neat (no solvent);	89%

N-amino-N'-methylpiperazine (6928-85-4) + rimonabant acid (162758-35-2) → 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(4-methylpiperazin-1-yl)-1H-pyrazole-3-carboxamide (953758-69-5)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 6h; Inert atmosphere;	89%

N-amino-N'-methylpiperazine (6928-85-4) + o-nitrophenylisothiocyanate (2719-30-4) → 1-(4-methylpiperazin-1-yl)-3-(2-nitrophenyl)thiourea

Conditions	Yield
In ethanol for 1h; Reflux;	89%

Upstream product

• 16339-07-4 1-methyl-4-nitroso-piperazine 
• 109-01-3 1-methyl-piperazine 
• 21223-19-8 CH₃N(CH₂CH₂)2NNH₂*BH₃ 
• 7732-18-5 water 
• 118306-24-4 3-chloro-4-(chlorocarbonyl)-4,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one 
• 118306-23-3 4-(chlorocarbonyl)-4,9-dihydro-1,3-dimethyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one 
• 118306-21-1 4-(chlorocarbonyl)-4,9-dihydro-3-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one 
• 118306-22-2 4-chlorocarbonyl-4,9-dihydro-1-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one 
• 105-59-9 N-Methyldiethanolamine 
• 55-86-7 mechlorethamine hydrochloride 

Downstream Products

• 197979-66-1 methyl (Z)-3-(3',5'-dimethoxyphenyl)-2-[(E)-1-(4-methylpiperazin-1-ylcarbamoyl)-2-phenylvinyl]-2-butenoate 
• 1254359-53-9 4-(4-methyl-piperazin-1-yl)-5-(3,5-dimethoxyphenyl)-2,4-dihydro-[1,2,4]triazole-3-thione 
• 879486-81-4 N-(4-methylpiperazin-1-yl)-N'-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-urea 
• 13292-46-1 rifampicin 
• 65504-18-9 4-amino-5-chloro-2-methoxy-N-(4-methyl-piperazin-1-yl)-benzamide 
• 90832-34-1 3-(4-Trifluoromethylphenyl)-7-chloro-10-hydroxy-3,4-dihydroacridine-1,9(2H,10H)-dione 1-(N-methyl-N'-piperazinyl)imine 
• 364734-03-2 3-(4-methoxyphenyl)-5-((4-methylpiperazino)-thionocarbamoylamino)indeno[1,2-c]pyrazol-4-one 

Relevant articles and documents

Cyclization of N,N-bis(2-chloroethyl)methylamine in aqueous hydrazine

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Method for synthesizing 1-amino-4-methylpiperazine through catalytic hydrogenation

The invention relates to a method for synthesizing 1-amino-4-methylpiperazine through catalytic hydrogenation. The invention discloses the green synthesis method for synthesizing 1-amino-4-methylpiperazine by hydrogenating 1-methyl-4-nitrosopiperazine in a water and organic mixed solvent system under the catalysis of an iron oxide and ferrous oxide supported palladium catalyst, wherein the methodcomprises the steps: adding 1-methyl-4-nitrosopiperazine into a paramagnetic Pd/Fe3O4-FeO catalyst, carrying out a hydrogenation reaction in a three-phase system of water, an organic solvent and the catalyst at a certain temperature, and finally, carrying out reduced pressure distillation separation to obtain the target product 1-amino-4-methylpiperazine. The 1-amino-4-methylpiperazine is preparedby innovatively using a catalytic hydrogenation method in a three-phase system, and compared with a traditional synthesis method, the method is more environmentally friendly and safer, and the cost is saved.

Selective reduction of N-nitroso aza-aliphatic cyclic compounds to the corresponding N-amino products using zinc dust in CO2–H2O medium

[Figure not available: see fulltext.] A new method for reduction of N-nitroso aza-aliphatic cyclic compounds employing zinc in pressurized CO2–H2O medium has been developed. H2O and NH4Cl were used as hydrogen donors, and reduction was performed under environmentally benign conditions. The presented approach allowed to obtain the respective N-amino products selectively and in excellent yields (up to 97%).