108-13-4

Basic information

• Product Name: Malonamide
• Synonyms: MALONODIAMIDE;MALONIC ACID DIAMIDE;MALONDIAMIDE;MALONIC ACID AMIDE;MALONAMIDE;METHANEDICARBOXYLIC ACID DIAMIDE;DICARBOXYMETHANE DIAMIDE;LABOTEST-BB LT01598526
• CAS NO: 108-13-4
• Molecular Formula: C₃H₆N₂O₂
• Molecular Weight: 102.09
• EINECS: 203-553-8
• Product Categories: API intermediates;Aliphatics;Miscellaneous Reagents;Amides;Biochemicals and Reagents;Building Blocks;C2 to C7;Carbonyl Compounds;Chemical Synthesis;Derivatization agents;Luminescent Compounds/Detection;Organic Building Blocks;Wavelength Index
• Mol File: 108-13-4.mol
• Article Data: 21

Chemical Properties

• Melting Point: 172-175 °C(lit.)
• Boiling Point: 191.38°C (rough estimate)
• Flash Point: 232.5 °C
• Appearance: white crystalline powder
• Density: 1.3516 (rough estimate)
• Vapor Pressure: 1.13E-08mmHg at 25°C
• Refractive Index: 1.5110 (estimate)
• Storage Temp.: Store below +30°C.
• Solubility: Soluble in HCl.
• PKA: 7.00±0.70(Predicted)
• Water Solubility: 180 g/L (20 ºC)
• BRN: 1751401
• CAS DataBase Reference: Malonamide(CAS DataBase Reference)
• NIST Chemistry Reference: Malonamide(108-13-4)
• EPA Substance Registry System: Malonamide(108-13-4)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 2
• RTECS: ON9125000
• TSCA: Yes
• Hazardous Substances Data: 108-13-4(Hazardous Substances Data)

Usage

Description

Malonamide is a dicarboxylic acid diamide that is malonic acid in which both carboxy groups have been replaced by carbamoyl groups. It is functionally related to a malonic acid.

Chemical Properties

White crystalline powder

Uses

Different sources of media describe the Uses of 108-13-4 differently. You can refer to the following data:
1. Malonamide is used in the synthesis of malonamic acid, malonamate and malonamide derivative of some heterocyclic compounds with antiinflammatory activity.
2. Malonamide is a reagent for fluorimetric determination of reducing carbohydrates. The malonamide-based ionic liquid extractant was used in the extraction of europium(iii) and other trivalent rare earth elements from nitric acid medium.
3. The malonamide-based ionic liquid extractant was used in the extraction of europium(iii) and other trivalent rare-earth ions from nitric acid medium.

General Description

The malonamide derivatives are obtained by the one-pot, five-component condensation reaction of isocyanide, Meldrum′s acid, arylidene malononitrile, and two amine molecules in CH2Cl2.

Hazard

Mildly toxic by ingestion.

Synthesis

The synthesis of?Malonamide is as follows:A typical reaction was carried out in a 10 mL flask. Benzonitrile (2 mmol), CuII-4 ? (0.2 g), acetaldoxime (6 mmol) and MeOH (4 mL) were stirred at 65 °C for 4 h. The solid was filtered, washed with MeOH and the filtrate evaporated. The residue was subjected to GC-MS analysis and NMR spectroscopy. The filtered catalyst can be recycled after drying at about 150 °C for 1 h.

Purification Methods

Crystallise the amide from water. [Beilstein 2 IV 1887.]

InChI:InChI=1/C3H6N2O2/c4-2(6)1-3(5)7/h1H2,(H2,4,6)(H2,5,7)

Synthetic route

malononitrile (109-77-3) → malonodiamide (108-13-4)

Conditions	Yield
With Acetaldehyde oxime In methanol at 65℃; for 4h;	98%
With manganese(IV) oxide; water In isopropyl alcohol at 100℃; under 5171.62 Torr; for 0.5h;	98%
Stage #1: malononitrile With acetamide; acetic acid at 50℃; under 760.051 Torr; for 0.5h; Stage #2: With tetrakis(acetonitrile)palladium(II) tetrafluoroborate at 50℃; under 1 - 3 Torr; for 2h;	43%

cyanoacetic acid amide (107-91-5) → malonodiamide (108-13-4)

Conditions	Yield
With sodium hydroxide	91%
With Amberlyst A-26 (OH- form); dihydrogen peroxide In methanol at 20℃; for 4h; Hydrolysis;	85%
With urea-hydrogen peroxide; potassium carbonate In water; acetone for 1.25h; Ambient temperature;

2-benzylidenepropanediamide (19411-83-7) + ethyl (E)-3-aminobut-2-enoate (41867-20-3) → malonodiamide (108-13-4) + Diethyl 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate (1165-06-6) + 3-carbamoyl-4-phenyl-5-ethoxycarbonyl-6-methyl-3,4-dihydropyridin-2-one (89434-90-2)

Conditions	Yield
In ethanol; acetic acid for 1h; Heating;	A 34% B 27% C 13%

carbon suboxide (504-64-3) → malonodiamide (108-13-4)

Conditions	Yield
With diethyl ether; ammonia
With ammonia at 0℃;
With ammonia In diethyl ether temperatures below 0°C;;

ethyl malonamate (7597-56-0) → malonodiamide (108-13-4)

Conditions	Yield
With ammonia; ammonium chloride at 0℃;

methanetricarboxylic acid triethyl ester (6279-86-3) → malonodiamide (108-13-4)

Conditions	Yield
With ammonia
With ammonia In ethanol for 24h; Ambient temperature;

methanetetracarboxylic acid tetraethyl ester (39000-70-9) → malonodiamide (108-13-4)

Conditions	Yield
With ammonia

propene-1,1,3,3-tetracarboxylic acid tetraethyl ester (49597-05-9) → malonodiamide (108-13-4) + iminomethyl-malonic acid diethyl ester

Conditions	Yield
With ammonium hydroxide 14-taegiges Stehen;

diethyl malonoimidate dihydrochloride (10344-69-1) → chloroethane (75-00-3) + malonodiamide (108-13-4)

Conditions	Yield
at 150 - 160℃;

malonic acid dimethyl ester (108-59-8) → malonodiamide (108-13-4)

Conditions	Yield
With ammonium hydroxide

diethyl malonate (105-53-3) → malonodiamide (108-13-4)

Conditions	Yield
With ammonium hydroxide
With ammonia at 25℃;
With ammonia; ammonium chloride at 0℃;
With ammonium hydroxide
With hydrazine hydrate

BARBITURIC ACID (67-52-7) → malonodiamide (108-13-4)

Conditions	Yield
With water Irradiation;

(Z)-3-Amino-3-hydroxy-acrylamide → malonodiamide (108-13-4)

Conditions	Yield
With perchloric acid In water at 25℃; Equilibrium constant;

4-hydroxy-6-methoxy-2-oxo-2H-pyran-3-carboxylic acid methyl ester (855654-96-5) + ammonium hydroxide → malonodiamide (108-13-4)

1,3-Dihydro-3-oxo-2-isobenzofuranylidenmalonsaeurediethylester (897-38-1) + ammonia (7664-41-7) → malonodiamide (108-13-4) + phthalamide (88-96-0)

ammonia (7664-41-7) + diethyl malonate (105-53-3) → malonodiamide (108-13-4)

Conditions	Yield
at 0℃; Beschleunigung der Reaktion durch verschiedene Ammoniumsalze; Geschwindigkeit;
at -33℃; Beschleunigung der Reaktion durch verschiedene Ammoniumsalze; Geschwindigkeit;

ammonium hydroxide + diethyl malonate (105-53-3) → malonodiamide (108-13-4)

diethyl malonate (105-53-3) + liquefied ammonia → malonodiamide (108-13-4)

formamide (77287-34-4, 77287-35-5, 60100-09-6) + polyoxymethylene → malonodiamide (108-13-4)

ethanol (64-17-5) + ammonia (7664-41-7) + diethyl malonate (105-53-3) → malonic acid (141-82-2) + malonodiamide (108-13-4) + ethyl malonamate (7597-56-0) + malonic acid monoamide(?)

ethanol (64-17-5) + ammonia (7664-41-7) + water (7732-18-5) + diethyl malonate (105-53-3) → malonic acid (141-82-2) + malonodiamide (108-13-4) + ethyl malonamate (7597-56-0) + malonic acid monoamide(?)

Conditions	Yield
Kinetics;

formaldehyd (50-00-0) + formamide (77287-34-4, 77287-35-5, 60100-09-6) + polyoxymethylene → malonodiamide (108-13-4)

carbon suboxide (504-64-3) + ammonia (7664-41-7) → malonodiamide (108-13-4)

ethyl malonamate (7597-56-0) + ammonia (7664-41-7) → malonodiamide (108-13-4)

Conditions	Yield
at 0℃; Geschwindigkeit;

ethyl malonamate (7597-56-0) + ammonium chloride + ammonia (7664-41-7) → malonodiamide (108-13-4)

Conditions	Yield
at 0℃; Geschwindigkeit;

isopropenyl-malonic acid diethyl ester (38806-12-1) + ammonium hydroxide → malonodiamide (108-13-4)

2-bromomalonamide (1186-67-0) + acetic acid (64-19-7) + potassium iodide → malonodiamide (108-13-4)

Conditions	Yield
at 25℃; bei 60grad rasch;

2,2-dibromomalonamide (73003-80-2) + acetic acid (64-19-7) + potassium iodide → malonodiamide (108-13-4)

Conditions	Yield
at 25℃; oberhalb 60grad rasch;

propene-1,1,3,3-tetracarboxylic acid tetraethyl ester (49597-05-9) + ammonium hydroxide → malonodiamide (108-13-4) + β-amino-ethylene-α.α-dicarboxylic acid ester + 2.6-dioxy-pyridinecarboxylic acid-(3.5)-diamide

malonodiamide (108-13-4) → dithiomalonamide (6944-34-9)

Conditions	Yield
With Lawessons reagent In toluene at 100℃; for 4h;	100%
With Lawessons reagent In tetrahydrofuran for 10h; Heating;	47%
With tetraphosphorus decasulfide In 1,4-dioxane for 2h; Heating;	21%
With tetraphosphorus decasulfide In 1,4-dioxane for 1.5h; Heating;
With Lawessons reagent In toluene for 3h; Heating; Yield given;

2-Aminonicotinaldehyde (7521-41-7) + malonodiamide (108-13-4) → 2-Amino-1,8-naphthyridine-3-carboxamide (15935-96-3)

Conditions	Yield
With piperidine In methanol for 0.0333333h; Friedlander condensation; microwave irradiation;	100%

phosphonic Acid (13598-36-2) + uranyl(VI) nitrate + malonodiamide (108-13-4) → UO2(2+)*HPO3(2-)*H2NCOCH2CONH2=[(UO2)(HPO3)(H2NCOCH2CONH2)]

Conditions	Yield
In water pptn. from stoich. mixt. of U-salt, phosphorous acid and amide solns. (c(DAMA) 0.1 M); X-ray diffraction; elem. anal.;	99%

malonodiamide (108-13-4) + dimethyl sulfate (77-78-1) → C5H10N2O2*2CH4O4S

Conditions	Yield
With boron trifluoride; tetra(n-butyl)ammonium hydrogensulfate at 80℃; for 15h; Temperature; Reagent/catalyst; Large scale;	98.8%

malonodiamide (108-13-4) → dichloro-malonic acid diamide (30989-14-1)

Conditions	Yield
With lead(IV) acetate; aluminium trichloride In acetonitrile for 0.916667h; Heating;	95%
With chlorine
With water; chlorine
With chloroform; Iodine monochloride
With sulfuryl dichloride

malonodiamide (108-13-4) → hydroxyimino-malonic acid diamide (71721-66-9)

Conditions	Yield
With hydrogenchloride; 1-butyl-3-methylimidazolium nitrite; water at 20℃;	95%
With bromide; hydrogen cation; cis-nitrous acid In water at 25℃; Rate constant; also in the presence of SCN- ions; var. conc. of the malonamide, Br and SCN ions;
With water; acetic acid; sodium nitrite
With nitrosylchloride

malonodiamide (108-13-4) + 5-chloro-1,3-dimethyluracil (31217-00-2) → 5-Chloro-2-hydroxy-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid amide (75993-42-9)

Conditions	Yield
	95%

cadmium(II) chloride monohydrate + malonodiamide (108-13-4) → dichloro(malonamide)cadmium(II) monohydrate

Conditions	Yield
In methanol; ethanol refluxing (8 h); crystals deposited by cooling the soln., washed several times with diethyl ether; elem. anal.;	95%

malonodiamide (108-13-4) + 1-butoxy-4,4,5,5,5-pentafluoropent-1-en-3-one (1072027-60-1) → 2-Oxo-6-(pentafluoroethyl)-1,2-dihydropyridine-3-carboxamide (1072021-29-4)

Conditions	Yield
With ethanol; sodium for 7h; Heating / reflux;	94%

malonodiamide (108-13-4) + 1,2-diamino-benzene (95-54-5) → bis(1H-benzo[d]imidazol-2-yl)methane (5999-14-4)

Conditions	Yield
With hydrogenchloride In water at 150℃; for 1h; Microwave irradiation;	92%
With 1,2,3-trichlorobenzene
With ethylene glycol

malonodiamide (108-13-4) + ethyl pelargonate (123-29-5) → 2-octylpyrimidine-4,6-diol

Conditions	Yield
With ethanol; sodium for 3h; Reflux;	91%
With sodium ethanolate In ethanol for 2h; Inert atmosphere; Reflux;	26%

malonodiamide (108-13-4) + 9-benzylidene-9,10-dihydroanthracene (63650-28-2) → 9-(α-Acetoxybenzylidene)-9,10-dihydroanthracene (96784-21-3) + 9-Acetoxy-9-benzoyl-9,10-dihydroanthracene (96784-20-2) + 4'-Carbamoyl-3'-phenyl-1',5'-dihydrospiropyrrol>-5'-one (96784-19-9)

Conditions	Yield
With manganese triacetate; acetic acid for 0.00333333h; Heating;	A 5% B 2% C 90%

malonodiamide (108-13-4) + N-(3,4-dimethoxybenzylidene)aniline (27895-67-6) → 3,4-dimethoxybenzalmalonamide (86213-21-0)

Conditions	Yield
With piperidine In benzene Ambient temperature;	90%

malonodiamide (108-13-4) + 4-n-butoxy-1,1,1-trifluorobut-3-en-2-one (109317-78-4) → 2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carboxamide (116548-03-9)

Conditions	Yield
With hydrogenchloride; sodium ethanolate In ethanol Heating;	90%

malonodiamide (108-13-4) + 3-benzyl-6-methyl-[1,3]oxazine-2,4-dione (10128-99-1) → 3-benzyl-5-methylpyrido<4,3-d>pyrimidine-2,4,7(1H,3H,6H)-trione (141946-12-5)

Conditions	Yield
With tetra(n-butyl)ammonium hydrogensulfate; potassium carbonate In N,N-dimethyl-formamide at 40 - 50℃; for 3.5h;	90%

malonodiamide (108-13-4) → 2-bromomalonamide (1186-67-0)

Conditions	Yield
With bromine In acetic acid at 60℃; for 5h;	89%
With perchloric acid; iodine In water at 25℃; Rate constant; var. HClO4 conc.;
With bromine; acetic acid
With dibromomalononitrile; boron trifluoride In ethanol Heating;
With bromine In acetic acid

malonodiamide (108-13-4) + 1-cyclohexyl-3-methyl-5-nitrouracil (78999-59-4) → 5-carbamoyl-1-cyclohexyluracil (37721-35-0)

Conditions	Yield
With sodium ethanolate In ethanol for 1h; Heating;	89%
With sodium ethanolate In ethanol for 1h; Heating;	86%

malonodiamide (108-13-4) + 3-cyclohexyl-1-methyl-5-nitrouracil (78999-60-7) → 5-carbamoyl-1-methyluracil (78999-61-8)

Conditions	Yield
With sodium ethanolate In ethanol for 2h; Heating;	89%
With sodium ethanolate In ethanol for 1h; Heating;	86%

malonodiamide (108-13-4) + ethyl coumarin-3-carboxylate (1846-76-0) → 2-oxo-2H-chromene-3-carboxamide (1846-78-2)

Conditions	Yield
With piperidine In ethanol for 6h; Michael reaction; Heating;	88%

malonodiamide (108-13-4) + 1-phenyl-3-(1-methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-2-propynone (1244024-26-7) → 4-(1-methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-6-phenylpyridin-2(1H)-one

Conditions	Yield
Stage #1: malonodiamide With potassium hydroxide In dimethyl sulfoxide at 20 - 25℃; for 0.5h; Stage #2: 1-phenyl-3-(1-methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-2-propynone In dimethyl sulfoxide at 20 - 25℃; for 24h;	88%

malonodiamide (108-13-4) + (E)-2-benzoyl-3-(4-methoxyphenyl)acrylonitrile (20413-06-3, 88137-32-0, 88137-31-9) → 3-carbamoyl-5-cyano-6-hydroxy-4-(p-methoxyphenyl)-6-phenylpiperidin-2-one (100784-42-7)

Conditions	Yield
With piperidine In methanol for 16h; Ambient temperature;	87%

malonodiamide (108-13-4) → 2-nitromalonamide (69645-51-8)

Conditions	Yield
With nitric acid; acetic acid at 15 - 20℃; for 1h;	86%
With nitric acid
With sulfuric acid; nitric acid

malonodiamide (108-13-4) → malononitrile (109-77-3)

Conditions	Yield
With phosphorus pentoxide under 15.0015 - 37.5038 Torr; for 1h; Temperature; Heating;	86%
With phosphorus pentaoxide
With phosphorus pentoxide at 250℃; under 15001.5 - 37503.8 Torr; for 1h; Temperature;
under 15.0015 - 37.5038 Torr; for 1h; Temperature; Heating;

malonodiamide (108-13-4) + (E)-2-Benzoyl-3-phenyl-acrylonitrile (20413-05-2, 101220-34-2, 101220-25-1) → 3-carbamoyl-5-cyano-6-hydroxy-4,6-diphenylpiperidin-2-one (75238-88-9)

Conditions	Yield
With piperidine In methanol for 16h; Ambient temperature;	86%
With piperidine In methanol

malonodiamide (108-13-4) + 3-aminopropyltriethoxysilane (919-30-2) → N,N'-bis(3-triethoxysilylpropyl)malonic amide (223476-24-2)

Conditions	Yield
With ammonium sulfate at 145 - 150℃; for 21h;	86%

malonodiamide (108-13-4) + 3-benzoyl-chromen-2-one (1846-74-8) → 2-oxo-2H-chromene-3-carboxamide (1846-78-2)

Conditions	Yield
With piperidine In ethanol Michael reaction; Heating;	86%

malonodiamide (108-13-4) → 2,2-dibromomalonamide (73003-80-2)

Conditions	Yield
With lead(IV) acetate; zinc dibromide In acetonitrile at 20℃; for 0.25h;	85%
With water; bromine at 70 - 80℃;
With bromine

1,3-dimethyl-5-nitrouracil (41613-26-7) + malonodiamide (108-13-4) → N-methylnitroacetamide (72078-82-1) + 5-carbamoyl-1-methyluracil (78999-61-8)

Conditions	Yield
With sodium ethanolate In ethanol for 1h; Heating; other derivatives;	A n/a B 84%
With sodium ethanolate In ethanol for 1h; Product distribution; Mechanism; Heating;	A 0.02 g B 84%
With sodium ethanolate In ethanol for 1h; Heating;	A n/a B 84%
With sodium ethanolate In ethanol for 1h; Heating;	A 0.02 g B 84%

Upstream product

• 504-64-3 carbon suboxide 
• 6279-86-3 methanetricarboxylic acid triethyl ester 
• 10344-69-1 diethyl malonoimidate dihydrochloride 
• 108-59-8 malonic acid dimethyl ester 
• 19411-83-7 2-benzylidenepropanediamide 
• 41867-20-3 ethyl (E)-3-aminobut-2-enoate 
• 7664-41-7 ammonia 
• 105-53-3 diethyl malonate 
• 77287-34-4 formamide 
• 64-17-5 ethanol 
• 7732-18-5 water 
• 50-00-0 formaldehyd 
• 49597-05-9 propene-1,1,3,3-tetracarboxylic acid tetraethyl ester 
• 3377-20-6 diethyl methylenemalonate 

Downstream Products

• 67-52-7 BARBITURIC ACID 
• 642-04-6 2,3,5,6-tetraphenylpyrazine 
• 5999-14-4 bis(1H-benzo[d]imidazol-2-yl)methane 
• 4599-42-2 malonic acid bis-(N'-phenyl-hydrazide) 
• 1113-63-9 2-methyl-malonamide 
• 62062-03-7 6-(6-ethoxy-4-methoxy-benzofuran-5-yl)-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyridine-3-carboxylic acid amide 
• 62062-04-8 6-(6-ethoxy-4,7-dimethoxy-benzofuran-5-yl)-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyridine-3-carboxylic acid amide 
• 69211-08-1 C₁₆H₁₇N₅O 
• 69210-95-3 p-tolylhydrazono-malonic acid diamide 
• 69210-99-7 2-[(3-Chloro-phenyl)-hydrazono]-malonamide 
• 69211-07-0 C₁₆H₁₇N₅O 
• 69211-02-5 2-[(4-Iodo-phenyl)-hydrazono]-malonamide 
• 69210-96-4 2-[(4-Ethyl-phenyl)-hydrazono]-malonamide 
• 16601-44-8 Di-benzylmercapto-malonsaeure-diamid 

Relevant articles and documents

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Transfer Hydration of Dinitriles to Dicarboxamides

We present a robust method for double transfer hydration of dinitriles to afford diamides. The transfer hydration of 1, n -dinitriles (n = 1-6) proceeds smoothly in the presence of a palladium(II) catalyst with acetamide as a water donor, affording the corresponding diamides in moderate to high yields, without involving significant side reactions such as monohydration or cyclization. The equilibrium was shifted in the forward direction by removing coproduced acetonitrile under reduced pressure.

Corresponding amine nitrile and method of manufacturing thereof (by machine translation)

The present invention relates to a nitrile manufacturing method, which has characteristics of significantly-reduced ammonia source consumption, low environmental pressure, low energy consumption, low production cost, high nitrile purity, high nitrile yield and the like compared with the method in the prior art, wherein nitrile having a complicated structure can be obtained through the method. The present invention further relates to a method for producing a corresponding amine from the nitrile.

Modulation of Nitrile Hydratase Regioselectivity towards Dinitriles by Tailoring the Substrate Binding Pocket Residues

The regioselective hydration of dinitriles is one of the most attractive approaches to prepare ω-cyanocarboxamides or diamides and such regioselectivity is often beyond the capability of chemical catalysts. The use of nitrile hydratase to biotransform dinitriles selectively would be highly desirable. Molecular docking of two aliphatic dinitriles and two aromatic dinitriles into the active site of a nitrile hydratase (NHase) from Rhodococcus rhodochrous J1 allowed the identification of proximal NHase substrate binding pocket residues. Four residues (βLeu48, βPhe51, βTyr68, and βTrp72) were selected for single- and double-point mutations to modulate the NHase regioselectivity towards dinitriles. Several NHase mutants with an altered regioselectivity were obtained, and the best one was Y68T/W72Y. Docking experiments further indicated that the poor binding affinity of aliphatic and aromatic ω-cyanocarboxamides to the NHase variants resulted in distinct regioselectivity between wild-type and mutated NHases.