5147-80-8

Basic information

• Product Name: 2-[DI(METHYLTHIO)METHYLIDENE]MALONONITRILE
• Synonyms: [BIS(METHYLTHIO)METHYLENE]MALONONITRILE;[BIS(METHYLTHIO)METHYLENE]PROPANEDINITRILE;AKOS UB-20051;2-[DI(METHYLTHIO)METHYLIDENE]MALONONITRILE;2-(bis(methylthio)methylene)malononitrile;[Bis(Methylthio)Methylene]Malo;2-[DI(METHYLTHIO)METHYLIDENE]MALONONITRILE,98+%;3,3-BIS(METHYLTHIO)-2-CYANOACRYLONITRILE
• CAS NO: 5147-80-8
• Molecular Formula: C₆H₆N₂S₂
• Molecular Weight: 170.26
• Product Categories: Small molecule;Aliphatics
• Mol File: 5147-80-8.mol
• Article Data: 32

Chemical Properties

• Melting Point: 76-78°C
• Boiling Point: 248.3 °C at 760 mmHg
• Flash Point: 103.9 °C
• Appearance: orange
• Density: 1.256 g/cm³
• Vapor Pressure: 0.0245mmHg at 25°C
• Refractive Index: 1.584
• Storage Temp.: 2-8°C
• CAS DataBase Reference: 2-[DI(METHYLTHIO)METHYLIDENE]MALONONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[DI(METHYLTHIO)METHYLIDENE]MALONONITRILE(5147-80-8)
• EPA Substance Registry System: 2-[DI(METHYLTHIO)METHYLIDENE]MALONONITRILE(5147-80-8)

Safety Data

• Hazard Codes: T,Xi,Xn
• Statements: 20/21/22-36/37/38-22
• Safety Statements: 26-36/37/39
• RIDADR: 3439
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 5147-80-8(Hazardous Substances Data)

Usage

Uses

2-[Bis(methylthio)methylene]malononitrile is used as pharmaceutical intermediate.

InChI:InChI=1/C6H6N2S2/c1-9-6(10-2)5(3-7)4-8/h1-2H3

Synthetic route

carbon disulfide (75-15-0) + malononitrile (109-77-3) + methyl iodide (74-88-4) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
With potassium carbonate; tetrabutylammomium bromide In benzene at 60℃; for 3h;	100%
Stage #1: malononitrile With potassium carbonate In dimethyl sulfoxide at 20℃; for 0.166667h; Large scale reaction; Stage #2: carbon disulfide In dimethyl sulfoxide at 0 - 22℃; for 0.5h; Large scale reaction; Stage #3: methyl iodide In dimethyl sulfoxide at 5 - 20℃; Large scale reaction;	99%
Stage #1: carbon disulfide; malononitrile With potassium carbonate In dimethyl sulfoxide at 0 - 20℃; for 2h; Stage #2: methyl iodide In dimethyl sulfoxide at 0 - 20℃; for 12h;	93.9%

potassium 1,1-dicyanoethylene-2,2-ditholate (4777-48-4) + methyl iodide (74-88-4) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
In water at 25 - 30℃; for 72h;	89%

disodium iso-maleonitriledithiolate monohydrate (106719-99-7) + methyl iodide (74-88-4) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
	86%

carbon disulfide (75-15-0) + dimethyl sulfate (77-78-1) + malononitrile (109-77-3) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
Stage #1: carbon disulfide; malononitrile With sodium ethanolate In ethanol at 20℃; for 1h; Stage #2: dimethyl sulfate In ethanol	85%
Stage #1: malononitrile With potassium hydroxide In water; N,N-dimethyl-formamide at 0 - 20℃; for 2h; Stage #2: carbon disulfide In water; N,N-dimethyl-formamide at 20℃; for 1.5h; Stage #3: dimethyl sulfate In water; N,N-dimethyl-formamide at 0 - 20℃; for 4h;	85%
(i) NaOMe, MeOH, (ii) /BRN= 635994/; Multistep reaction;
Stage #1: malononitrile With potassium hydroxide at 20℃; Stage #2: carbon disulfide Stage #3: dimethyl sulfate

(S,S)-dimethyl trithiocarbonate (2314-48-9) + C3Ag2N2 → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
In methanol

dimethyl sulfate (77-78-1) + 2-Dimercaptomethylene-malononitrile; compound with ammonia → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
With sodium hydroxide

2,2-Dicyano-1-mercapto-ethenethiolatetetrabutyl-ammonium; (42717-51-1) + methyl iodide (74-88-4) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
In N,N-dimethyl-formamide

potassium (2,2-dicyano-1-methylsulfanylethen-1-yl)thiolate (20602-68-0) + methyl iodide (74-88-4) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
In ethanol

dimercaptomethylene-malononitrile (18771-14-7) + dimethyl sulfate (77-78-1) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
In dimethyl sulfoxide for 2h; Ambient temperature; Yield given;

2-(2,4-dithia-1,5-disodapentan-3-ylidene)propanedinitrile (4885-93-2) + CH3X, X=halogen → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
In isopropyl alcohol Heating;

carbon disulfide (75-15-0) + malononitrile, sodium-compound → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
With diethyl ether; methyl iodide Einwoechiges Erwaermen des Reaktionsgemisches mit Methyljodid.;

dimethyl sulfate (77-78-1) + malononitrile (109-77-3) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
With carbon disulfide; sodium methylate In methanol	18.6 g (11%)

carbon disulfide (75-15-0) + malononitrile (109-77-3) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
alcoholic sodium methoxide
alcoholic sodium methoxide

2-(2,4-dithia-1,5-disodapentan-3-ylidene)propanedinitrile (4885-93-2) + methyl iodide (74-88-4) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
In ice-water
In methanol
In ethanol at 20℃;

potassium 1,1-dicyanoethylene-2,2-ditholate (4777-48-4) + dimethyl sulfate (77-78-1) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
In water

dimercaptomethylene-malononitrile (18771-14-7) + methyl iodide (74-88-4) → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
With tetrabutylammomium bromide In N,N-dimethyl-formamide at 60℃; for 64h; Inert atmosphere;	3.4 g
In dimethyl sulfoxide at 5 - 20℃; for 12h;	18.2 g

carbon disulfide (75-15-0) + methyl iodide (74-88-4) + 1,3-dicyano-1,3-propanedione → [Bis(methylthio)methylene]malononitrile (5147-80-8)

Conditions	Yield
Stage #1: carbon disulfide; 1,3-dicyano-1,3-propanedione With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 8.25h;

[Bis(methylthio)methylene]malononitrile (5147-80-8) + benzylamine (100-46-9) → 2-benzylamino-2-methylthio-1,1-ethylenedicarbonitrile (152588-23-3)

Conditions	Yield
at 20℃;	100%
Heating;
In ethyl acetate

4-piperidinopiperidin (4897-50-1) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → [(methylthio)(4-piperidinopiperidino)methylene]malononitrile (904677-87-8)

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 0.25h;	100%

C18H18N2O + [Bis(methylthio)methylene]malononitrile (5147-80-8) → C23H20N4OS

Conditions	Yield
In xylene Heating;	100%

9-amino-9-deoxy-epihydroquinine (852913-53-2) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → C25H29N5OS

Conditions	Yield
In tetrahydrofuran for 24h; Reflux;	100%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + propan-1-ol-3-amine (156-87-6) → [1-(1-benzylpiperidin-4-ylamino)-2-(3-hydroxypropylamino)methylene]malononitrile (904678-69-9)

Conditions	Yield
Stage #1: 4-amino-1-benzylpiperidine; [Bis(methylthio)methylene]malononitrile In tetrahydrofuran at 20℃; for 2.5h; Stage #2: propan-1-ol-3-amine In tetrahydrofuran at 60℃; for 16h;	99.5%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + dibutylamine (111-92-2) → 2-(Dibutylamino-methylsulfanyl-methylene)-malononitrile (85106-65-6)

Conditions	Yield
In benzene Ambient temperature;	99%
In dichloromethane Heating;

[Bis(methylthio)methylene]malononitrile (5147-80-8) + Methyl thioglycolate (2365-48-2) → methyl 3-amino-4-cyano-5-(methylsulfanyl)-2-thiophenecarboxylate (129332-45-2)

Conditions	Yield
With triethylamine In methanol for 2h; Reflux;	99%
With triethylamine In methanol for 1h; Heating;	84%
With triethylamine In methanol at 130℃; for 0.0666667h; Microwave irradiation;	82%
With triethylamine In methanol

m-Anisidine (536-90-3) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → 2-cyano-3-(3-methoxyphenylamino)-3-methylsulfanylacrylonitrile (155557-30-5)

Conditions	Yield
In methanol for 15h; Heating;	99%
With 4-methoxy-aniline at 100℃; for 2h;	70%
Heating;
Stage #1: m-Anisidine; [Bis(methylthio)methylene]malononitrile In pyridine for 1h; Reflux; Stage #2: In pyridine

[Bis(methylthio)methylene]malononitrile (5147-80-8) + ethyl 2-sulfanylacetate (623-51-8) → 3-amino-4-cyano-5-(methylthio)thiophene-2-carboxylic acid ethyl ester (116170-90-2)

Conditions	Yield
With triethylamine In methanol for 2h; Reflux;	99%
With triethylamine In methanol for 2h; Reflux;	99%
With triethylamine In ethanol at 0 - 20℃; for 12h;	72.6%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + phosphonic acid diethyl ester (762-04-9) → (2,2-Dicyano-1-methylsulfanyl-vinyl)-phosphonic acid diethyl ester (194095-91-5)

Conditions	Yield
With sodium hydride In tetrahydrofuran	99%

Cyanothioacetamide (7357-70-2) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → 2-amino-6-mercapto-4-(methylthio)pyridine-3,5-dicarbonitrile

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃;	99%
With triethylamine In N,N-dimethyl-formamide at 20℃; for 18h;	93%
With triethylamine In N,N-dimethyl-formamide at 20℃;	89%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + phenylhydrazine (100-63-0) → 5-amino-3-(methylsulfanyl)-1-phenyl-1H-pyrazole-4-carbonitrile (59334-11-1)

Conditions	Yield
In methanol Heating;	98%
for 3h; Reflux;	96%
In ethanol
In ethanol Heating;
In ethanol

4-(2-methylpyrrolidin-1-ylmethyl)piperidine dihydrochloride + [Bis(methylthio)methylene]malononitrile (5147-80-8) → {[4-(2-methylpyrrolidin-1-ylmethyl)piperidino](methylthio)methylene}malononitrile (904677-53-8)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃; for 0.25h;	98%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + 3,5-bis-trifluoromethylbenzylamine (85068-29-7) → 2-(((3,5-bis(trifluoromethyl)benzyl)amino)(methylthio)methylene)malononitrile (1598411-35-8)

Conditions	Yield
In tetrahydrofuran for 23h; Reflux; Green chemistry; stereoselective reaction;	98%
In methanol Reflux;
In tetrahydrofuran Reflux;

[Bis(methylthio)methylene]malononitrile (5147-80-8) → 5-amino-3-(methylsulfanyl)-1H-pyrazole-4-carbonitrile (72760-85-1)

Conditions	Yield
With hydrazine hydrate In methanol for 3h; Heating;	97%
With hydrazine hydrate In ethanol Cooling with ice; Reflux;	85%
With hydrazine hydrate In methanol for 3h; Reflux;	80%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + 1,2-diamino-benzene (95-54-5) → 2-(2,3-dihydro-1H-benzo[d]imidazolylidene)malononitrile (4933-40-8)

Conditions	Yield
In ethanol for 24h; Heating;	97%
Stage #1: [Bis(methylthio)methylene]malononitrile; 1,2-diamino-benzene In ethanol for 8h; Reflux; Stage #2: With sodium ethanolate; N-Cyanoguanidine In ethanol for 5h; Reflux;	84%
In ethanol at 70℃; for 4h;	77.6%
In ethanol for 24h; Heating;

4-(N-methyl-N-phenylamino)piperidine dihydrochloride + [Bis(methylthio)methylene]malononitrile (5147-80-8) → {[4-(N-methyl-N-phenylamino)piperidino](methylthio)methylene}malononitrile (904677-47-0)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; water at 20℃; for 0.25h;	97%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + Trimethylenediamine (109-76-2) → 2-(hexahydropyrimidin-2-ylidene)malononitrile

Conditions	Yield
In water at 25℃; regioselective reaction;	97%
	85%

1-phenyl-2-pyridin-2-ylethanone (1620-53-7) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → 1-Benzoyl-4-imino-2-methylsulfanyl-4H-quinolizine-3-carbonitrile (123366-01-8)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide Ambient temperature;	96%

N-trimethylsilylmethylamine (18166-02-4) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → 2-[Methylsulfanyl-(trimethylsilanylmethyl-amino)-methylene]-malononitrile (129757-45-5)

Conditions	Yield
In methanol for 0.166667h; Heating;	96%

1-methyl-3-(2-ethoxy-2-oxoethyl)-1H-imidazol-3-ium bromide (109833-18-3) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → 1-methylimidazolium N-(3,3-dicyano-1-ethoxycarbonyl-2-methylthio)allylide (139038-43-0)

Conditions	Yield
With potassium carbonate In chloroform for 168h; Ambient temperature;	96%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + Cysteamine (60-23-1) → 2-(thiazolidin-2-ylidene)malononitrile (5718-93-4)

Conditions	Yield
In ethanol for 2h; Heating;	96%
In ethanol at 20℃; for 4h;	73%
In water Reflux; regioselective reaction;	73%
In ethanol at 20℃; for 4h;	73%
In ethanol at 20℃; for 4h;

N,N'-bis(2-hydroxyethyl)ethylene diamine (4439-20-7) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → [1,3-bis(2-hydroxyethyl)imidazolidin-2-ylidene]malononitrile (111161-06-9)

Conditions	Yield
In tetrahydrofuran for 1h; Heating;	95.3%
In methanol for 14h; Heating;	92%

N,N-bis(2-hydroxyethyl)ethylidenediamine (3197-06-6) + [Bis(methylthio)methylene]malononitrile (5147-80-8) → [1,3-bis(2-hydroxyethyl)imidazolidin-2-ylidene]malononitrile (111161-06-9)

Conditions	Yield
In tetrahydrofuran for 1h; Heating / reflux;	95.3%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + 2-(2-Aminoethylamino)ethanol (111-41-1) → <1-(2-hydroxyethyl)-2-imidazolidinylidene>malononitrile (149138-82-9)

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 3h;	95.2%
In tetrahydrofuran at 20℃; for 2h;	95%
In toluene for 20h; Ambient temperature;	90%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + 2-amino-benzenethiol (137-07-5) → (2,3-dihydrobenzothiazol-2-ylidenyl)malonodinitrile (4464-52-2)

Conditions	Yield
In ethanol for 24h; Heating;	95%
In ethanol for 6h; Heating;	90%
With piperidine In ethanol for 5h; Heating;	52%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + methylhydrazine (60-34-4) → 1H-1-methyl-3-amino-4-cyano-5-methylsulfanylpyrazole (151291-05-3)

Conditions	Yield
In ethanol for 6h; Heating;	95%
In ethanol for 1h; Heating;	40%
In water
In water
Heating / reflux;

[Bis(methylthio)methylene]malononitrile (5147-80-8) + 4-((4-methoxyphenyl)diazenyl)-1H-pyrazole-3,5-diamine (6975-75-3) → 2,5-diamino-3-((4-methoxyphenyl)diazenyl)-7-(methylthio)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (155375-48-7)

Conditions	Yield
In N,N-dimethyl-formamide at 154℃; for 0.166667h; Microwave irradiation;	95%
With piperidine In ethanol for 4h; Heating;	85%

[Bis(methylthio)methylene]malononitrile (5147-80-8) + 3,5-diamino-4-phenylazopyrazole (3656-02-8) → 2, 5-diamino-7-(methylthio)-3-(phenyldiazenyl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (155375-38-5)

Conditions	Yield
In N,N-dimethyl-formamide at 154℃; for 0.166667h; Microwave irradiation;	95%
With piperidine In ethanol for 4h; Heating;	90%

Upstream product

• 42717-51-1 2,2-Dicyano-1-mercapto-ethenethiolatetetrabutyl-ammonium; 
• 74-88-4 methyl iodide 
• 20602-68-0 potassium (2,2-dicyano-1-methylsulfanylethen-1-yl)thiolate 
• 4777-48-4 potassium 1,1-dicyanoethylene-2,2-ditholate 
• 77-78-1 dimethyl sulfate 
• 75-15-0 carbon disulfide 
• 18771-14-7 dimercaptomethylene-malononitrile 
• 4885-93-2 2-(2,4-dithia-1,5-disodapentan-3-ylidene)propanedinitrile 
• 109-77-3 malononitrile 
• 106719-99-7 disodium iso-maleonitriledithiolate monohydrate 
• 2314-48-9 (S,S)-dimethyl trithiocarbonate 

Downstream Products

• 123366-01-8 1-Benzoyl-4-imino-2-methylsulfanyl-4H-quinolizine-3-carbonitrile 
• 103184-06-1 2-[Methylsulfanyl-(4-phenyl-piperazin-1-yl)-methylene]-malononitrile 
• 116931-42-1 C₂₁H₁₂N₄S 
• 135017-65-1 <1-<2-<(p-tolylsulfonyl)oxy>ethyl>-2-imidazolidinylidene>propanedinitrile 
• 4464-52-2 (2,3-dihydrobenzothiazol-2-ylidenyl)malonodinitrile 
• 130224-38-3 5-amino-3-methylthio-1-(4-nitrophenyl)pyrazole-4-carbonitrile 
• 114361-51-2 3-cyano-1,2-dihydro-4-methylthio-2-oxo-6-phenyl-2H-pyran-5-ylacetic acid 
• 174749-94-1 7-Amino-2-(4-chloro-phenyl)-5-methylsulfanyl-4-nitro-pyrazolo[1,5-a]pyridine-6-carbonitrile 
• 155557-31-6 2-cyano-3-(2-methoxyphenylamino)-3-methylsulfanylacrylonitrile 
• 824397-58-2 2-cyano-3-(3,5-dimethoxyphenylamino)-3-methylsulfanylacrylonitrile 
• 101476-79-3 5-Amino-3-p-tolylamino-1H-pyrazole-4-carbonitrile 
• 61380-87-8 6-(4-bromophenyl)-4-methylsulfanyl-2H-pyran-2-one-3-carbonitrile 
• 68192-60-9 6-(p-bromophenyl)-3-cyano-4-methylthio-2(1H)-pyridone 
• 15908-64-2 3,4-dihydro-6-methymercapto-4-oxo-2-phenylpyrimidine-5-carbonitrile 

Relevant articles and documents

Synthesis of Polysubstituted Pyrimidines from Ketene Dithioacetals Using KF/Al2O3 Catalyst

KF/Al2O3 was first used to catalyze the synthesis of 2-alkylthio-4-amino-5-cyano-6-methylthiopyrimidines 3a-f via the reaction of the ketene dithioacetals 1 (prepared from malononitrile) with isothiuronium salts 2a-f. Six pyrimidine compounds were prepared and all of their structures were confirmed by elemental analysis, 1H NMR, and IR. The reaction conditions (solvents, catalyst amounts, and temperature) were investigated for the first time. The separation yield reached 89%.

Preparation method and use of thiophene compound

The invention belongs to the technical field of pharmaceutical chemistry, and relates to thiophene compounds shown by general formula I, pharmaceutically acceptable salts, solvates or prodrugs and preparation methods thereof. In which substituents L, Ar, R have the meanings given in the specification. The invention also relates to a strong PI3K inhibitory effect of a compound of the general formula I, and also relates to the use of such compounds and pharmaceutically acceptable salts, solvates or prodrugs thereof in the preparation of drugs for the treatment and/or prevention of diseases caused by abnormally high expression of PI3K, in particular in the preparation of drugs for the treatment and/or prevention of cancer.

Tailored-design Synthesis of Sulfapyrimidine Derivatives

In this paper, we report an efficient and convenient approach for the synthesis of tailored-design target sulfapyrimidine derivatives expected to show remarkable antimicrobial activities. The approach is based on reacting arylsulfonyl guanidine with α,β-unsaturated carbonyl compounds to afford N-(4,6-diarylpyrimidin-2-yl)arylsulfonamide or with ylidene derivatives to afford N-(6-aryl-5-cyanopyrimidin-2-yl)arylsulfonamide, N-(4-amino-5-cyano-6-(methylthio)-pyrimidin-2-yl)-arylsulfonamide, and N-(5-cyanopyrimidin-2-yl)arylsulfonamide compounds through Michael addition reaction. The structure of the newly synthesized compounds was confirmed from spectral data and elemental analysis.