722-27-0

Basic information

• Product Name: 4,4'-Dithiodianiline
• Synonyms: 4,4’-dithiobisaniline;4,4’-dithiobis-benzenamin;4,4’-dithiobisbenzenamine;4,4’-Dithiobis-benzenamine;4,4’-dithiodi-anilin;4,4'-Diaminodiphenyl disulphide;4-[(4-Aminophenyl)disulfanyl]phenylamine;4-aminophenyl
• CAS NO: 722-27-0
• Molecular Formula: C₁₂H₁₂N₂S₂
• Molecular Weight: 248.37
• EINECS: 211-961-2
• Product Categories: Amines
• Mol File: 722-27-0.mol
• Article Data: 61

Chemical Properties

• Melting Point: 77-78 °C(lit.)
• Boiling Point: 447 °C at 760 mmHg
• Flash Point: 224.2 °C
• Appearance: yellow powder
• Density: 1.2716 (rough estimate)
• Vapor Pressure: 3.47E-08mmHg at 25°C
• Refractive Index: 1.5700 (estimate)
• Solubility: soluble in Methanol
• PKA: 4.10±0.10(Predicted)
• Stability: Stable. Incompatible with acids, acid chlorides, acid anhydrides, chloroformates, strong oxidizing agents. Sensitive to air.
• CAS DataBase Reference: 4,4'-Dithiodianiline(CAS DataBase Reference)
• NIST Chemistry Reference: 4,4'-Dithiodianiline(722-27-0)
• EPA Substance Registry System: 4,4'-Dithiodianiline(722-27-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: BX9580000
• Hazardous Substances Data: 722-27-0(Hazardous Substances Data)

Usage

Chemical Properties

yellow powder

InChI:InChI=1/C12H12N2S2/c13-9-1-5-11(6-2-9)15-16-12-7-3-10(14)4-8-12/h1-8H,13-14H2

Synthetic route

4-aminotiophenol (1193-02-8) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With dihydrogen peroxide; sodium iodide In water; ethyl acetate at 20℃; for 24h;	99%
With cobalt(II)phthalocyanine-tetra-sodium sulfonate In water at 60℃; for 6h; Schlenk technique;	96%
With oxygen In water at 55℃; under 6750.68 Torr; for 7h;	96%

1-amino-4-({[amino(imino)methyl]amino}sulfonyl)benzene (57-67-0) → bis(4-aminophenyl)disulfide (722-27-0) + sulfanilamide (63-74-1) + aniline (62-53-3) + 4-aminobenzene sulfonic acid (121-57-3)

Conditions	Yield
In methanol for 76h; Product distribution; Mechanism; Irradiation; λ=254 nm;	A n/a B 4.4% C 95.1% D 2.7%

p-aminoiodobenzene (540-37-4) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
Stage #1: p-aminoiodobenzene With potassium 5-methyl-1,3,4-oxadiazole-2-thiolate In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: With copper(l) chloride In N,N-dimethyl-formamide at 130℃; for 7h;	94%
With dmap; nickel(II) chloride hexahydrate; potassium thioacyanate; N,N-dimethyl-formamide at 140℃; for 20h;	92%
With copper(l) iodide; water; oxygen; sodium hydrogencarbonate; thiourea at 115 - 120℃; for 16h; Green chemistry;	81%

4-thiocyanatoaniline (2987-46-4) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With ammonium hydroxide In 1,4-dioxane at 100℃; sealed ampoule;	93.5%
With hydrogenchloride beim Behandeln des Reaktionsprodukts mit Eisen(III)-chlorid oder mit wss.Wasserstoffperoxid;

4-bromo-aniline (106-40-1) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With dmap; nickel(II) chloride hexahydrate; potassium thioacyanate; N,N-dimethyl-formamide at 140℃; for 22h;	92%
With copper(l) iodide; hexachloroethane; sodium carbonate; thiourea In water at 120℃; for 18h;	85%
With copper(l) iodide; water; oxygen; sodium hydrogencarbonate; thiourea at 115 - 120℃; for 18h; Green chemistry;	82%

di(p-nitrophenyl) disulfide (100-32-3) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With iron; ammonium chloride In methanol at 80℃; for 6h;	90.6%
With bis(acetylacetonate)nickel(II) In 1,4-dioxane at 80℃;	88%
With ethanol; nickel Hydrogenation;

4-chlorobenzonitrile (100-00-5) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With sodium sulfide; water; dihydrogen peroxide
With sodium sulfide; water
With sodium disulfide; water
With sodium sulfide; water
With sodium sulfide; water

aniline hydrochloride (142-04-1) + aniline (62-53-3) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With sulfur

aniline (62-53-3) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With hydrogenchloride; sulfur at 150℃; laesst weitere 6-Stdn.gelinde Kochen;
With sulfur
With hydrogenchloride; sulfur

Acetanilid (103-84-4) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With disulfur dichloride at 100℃; entstehen 4.4'-Bis-acetamino-diphenyldisulfid (a) und 4.4'-Bis-acetamino-diphenyltrisulfid (b);aus der Loesung des Produktes in Eisessig krystallisiert das (b);das (a) zerlegt man durch Erhitzen mit verd.Schwefelsaeure;

piperidine (110-89-4) + 4-thiocyanatoaniline (2987-46-4) → 1-piperidinylcarbonnitrile (1530-87-6) + bis(4-aminophenyl)disulfide (722-27-0) + 1,1'-carbonimidoyl-bis-piperidine (52764-35-9) + 4-aminotiophenol (1193-02-8)

Conditions	Yield
at 70℃; Product distribution; Kinetics; various time;

Potassium p-aminothiophenolate (134251-08-4) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With air In water for 3h; Ambient temperature; Yield given;

bis-(4-amino-phenyl)-trisulfide (20057-94-7) → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
With triphenylphosphine In toluene at 68.4 - 87.7℃; Kinetics;

4-phenothiazin-3-yldisulfanyl-aniline + alcoholic-alkaline sodium sulfide → bis(4-aminophenyl)disulfide (722-27-0)

4-phenothiazin-3-yldisulfanyl-aniline + aqueous-alkaline sodium sulfide → bis(4-aminophenyl)disulfide (722-27-0)

hydrogenchloride (7647-01-0) + 4-phenothiazin-3-yldisulfanyl-aniline + tin → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
folgend Oxydation mit Luft in natron-alkalischer Loesung;

4-aminotiophenol (1193-02-8) + air → bis(4-aminophenyl)disulfide (722-27-0)

hydrogenchloride (7647-01-0) + aniline (62-53-3) + sulfur → bis(4-aminophenyl)disulfide (722-27-0)

Conditions	Yield
at 150℃; anschl. am Rueckflusskuehler;

aniline (62-53-3) + sulfur → bis(4-aminophenyl)disulfide (722-27-0) + 4,4'-thiobisaniline (139-65-1) + 2-[(4-aminophenyl)thio]benzenamine (6259-01-4)

Conditions	Yield
bei Siedetemperatur;

water (7732-18-5) + 4-chlorobenzonitrile (100-00-5) + sodium disulfide → bis(4-aminophenyl)disulfide (722-27-0) + 4-amino-4'-nitrodiphenyl sulfide (101-59-7) + di(p-nitrophenyl) disulfide (100-32-3) + 4-chloro-aniline (106-47-8)

water (7732-18-5) + 4-chlorobenzonitrile (100-00-5) + sodium sulfide → bis(4-aminophenyl)disulfide (722-27-0) + 4-amino-4'-nitrodiphenyl sulfide (101-59-7) + bis(4-nitrophenyl)sulfide (1223-31-0) + 4-chloro-aniline (106-47-8)

bis(4-aminophenyl)disulfide (722-27-0) + benzoyl chloride (98-88-4) → bis-(4-benzoylamino-phenyl)-disulfide (16766-10-2)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; for 0.583333h;	100%
With triethylamine In dichloromethane at 20℃; for 2h;

bis(4-aminophenyl)disulfide (722-27-0) + N-(tert-butoxycarbonyl)-D-proline (37784-17-1) → bis[4-[(R)-1-tert-butoxycarbonylpyrrolidin-2-ylcarbonylamino]phenyl]disulfide (877603-27-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 72h;	100%

bis(4-aminophenyl)disulfide (722-27-0) + pivaloyl chloride (3282-30-2) → 4,4'-dithiobis(N-phenyl-2,2-dimethylpropanamide) (143790-61-8)

Conditions	Yield
With pyridine In dichloromethane at 0℃;	99%
With pyridine In dichloromethane at 20℃; for 1h; Acylation;

bis(4-aminophenyl)disulfide (722-27-0) + methanesulfonyl chloride (124-63-0) → N-(4-((4-((methylsulfonyl)amino)phenyl)dithio)phenyl)methanesulfonamide (26272-22-0)

Conditions	Yield
With pyridine In chloroform; water	99%
With pyridine In dichloromethane at 20℃; for 3h;	92%
In pyridine; dichloromethane at 20℃; for 3h;	1.5 g

bis(4-aminophenyl)disulfide (722-27-0) + DPA dendron G3 → SS-DPA G3

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; titanium tetrachloride In chlorobenzene at 125℃; Inert atmosphere;	99%

2-methyl-1H-indole (95-20-5) + bis(4-aminophenyl)disulfide (722-27-0) → 4-((2-methyl-1H-indol-3-yl)thio)aniline

Conditions	Yield
With sodium tetrafluoroborate; potassium iodide In acetonitrile at 60℃; for 8h; Electrolysis;	92%
With sodium tetrafluoroborate; potassium iodide In acetonitrile at 60℃; for 8h; Electrochemical reaction;	92%
With sodium iodide In acetonitrile at 20℃; for 18h; Irradiation;	70%

2-Chloro-4,6-diamino-1,3,5-triazine (3397-62-4) + bis(4-aminophenyl)disulfide (722-27-0) → bis(4-melaminophenyl)disulfide

Conditions	Yield
With hydrogenchloride In water at 100℃; for 1h;	91.2%

bis(4-aminophenyl)disulfide (722-27-0) + phenyl isocyanate (103-71-9) → bis-[4-(N'-phenyl-ureido)-phenyl]-disulfide (52017-43-3)

Conditions	Yield
In dichloromethane Inert atmosphere; Reflux;	91%

maleic anhydride (108-31-6) + bis(4-aminophenyl)disulfide (722-27-0) → (Z)-3-{4-[4-((Z)-3-Carboxy-acryloylamino)-phenyldisulfanyl]-phenylcarbamoyl}-acrylic acid (86879-53-0)

Conditions	Yield
In toluene for 1h; Heating;	90%
In acetone at 20℃; for 1h;

bis(4-aminophenyl)disulfide (722-27-0) + trifluoroacetic anhydride (407-25-0) → 2,2,2-trifluoro-N-(4-{[4-(2,2,2-trifluoroacetylamino)phenyl]disulfanyl}phenyl)acetamide (131042-42-7)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 4h;	90%
With triethylamine In chloroform at 2 - 20℃; for 1h;

bis(4-aminophenyl)disulfide (722-27-0) + propionyl chloride (79-03-8) → N,N'-(4,4'-disulfanediylbis(4,1-phenylene))dipropionamide (52017-23-9)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 1.08333h;	90%
With triethylamine In dichloromethane at 0 - 20℃; for 1.08333h;	90%

bis(4-aminophenyl)disulfide (722-27-0) + di-tert-butyl disulfide (110-06-5) → 4-(tert-butyldisulfanyl)aniline

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 60℃; for 8h;	90%

2-chloro-4,6-dimethylpyrimidine (4472-44-0) + bis(4-aminophenyl)disulfide (722-27-0) → N,N'-[dithiobis(4,1-phenylene)]bis(4,6-dimethylpyrimidin-2-amine)

Conditions	Yield
In ethanol at 160℃; for 0.166667h; Microwave irradiation; Sealed tube; Green chemistry;	90%

bis(4-aminophenyl)disulfide (722-27-0) + C11H15NO3S (1173202-57-7) → C17H22N2S

Conditions	Yield
Stage #1: bis(4-aminophenyl)disulfide; C11H15NO3S With rongalite; potassium carbonate In N,N-dimethyl-formamide at 20℃; for 1.5h; Stage #2: In water at 20℃; for 12h; Acidic conditions;	89%

bis(4-aminophenyl)disulfide (722-27-0) + diethyl trimethylsilyl phosphite (13716-45-5) → O,O′-diethyl S-4-aminophenyl phosphorothioate (94409-35-5)

Conditions	Yield
In neat (no solvent) at 20℃; for 0.0333333h; Sealed tube; Green chemistry;	89%

bis(4-aminophenyl)disulfide (722-27-0) + α,α-difluorodibenzoylmethane (365-00-4) → 4-((difluoromethyl)thio)aniline (24933-60-6)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 12h;	88%

bis(4-aminophenyl)disulfide (722-27-0) + sodium benzenesulfonate (873-55-2) → S-(4-aminophenyl) benzenesulfonothioate (94934-06-2)

Conditions	Yield
With iodine In dichloromethane for 6h;	87%

Upstream product

• 1223-31-0 bis(4-nitrophenyl)sulfide 
• 103-84-4 Acetanilid 
• 1193-02-8 4-aminotiophenol 
• 7647-01-0 hydrogenchloride 
• 62-53-3 aniline 
• 7732-18-5 water 
• 100-00-5 4-chlorobenzonitrile 
• 540-37-4 p-aminoiodobenzene 
• 89415-43-0 (4-aminophenyl)boronic acid 
• 37434-06-3 1,2-bis(4-azidophenyl)disulfane 
• 106-40-1 4-bromo-aniline 
• 22948-02-3 3-aminothiophenol 
• 100-01-6 4-nitro-aniline 
• 710-24-7 4-acetamidobenzenesulfinic acid 

Downstream Products

• 52017-43-3 bis-[4-(N'-phenyl-ureido)-phenyl]-disulfide 
• 139-65-1 4,4'-thiobisaniline 
• 13908-73-1 C₁₈H₂₀Cl₂N₄O₂S₂ 
• 56934-71-5 N-{4-[4-(Ethoxyoxalyl-amino)-phenyldisulfanyl]-phenyl}-oxalamic acid ethyl ester 
• 74705-47-8 C₃₀H₂₂N₄O₄S₂ 
• 74705-49-0 C₂₆H₁₆N₆O₈S₂ 
• 31053-95-9 aminophenylthiyl radical 
• 6345-64-8 1,2-bis(4-Iodophenyl)disulfane 
• 143790-61-8 4,4'-dithiobis(N-phenyl-2,2-dimethylpropanamide) 
• 86879-53-0 (Z)-3-{4-[4-((Z)-3-Carboxy-acryloylamino)-phenyldisulfanyl]-phenylcarbamoyl}-acrylic acid 
• 885328-56-3 N,N'-dithiodi(4,1-phenylene)bis-(S)-2,3-bis[di(tert-butoxycarbonylmethyl)amino]propanamide 
• 885328-55-2 N,N'-dithiodi(4,1-phenylene)bis-(R)-2,3-bis[di(tert-butoxycarbonylmethyl)amino]propanamide 
• 55376-05-1 4,4'-disulfanyldibenzenediazonium 
• 1428846-92-7 N,N′-(3,3′-disulfanediylbis(3,1-phenylene))dimethanesulfonamide 

Relevant articles and documents

Direct visualization of photo-induced disulfide through oxidative coupling ofpara-aminothiophenol

Chemical transformations under visible irradiation are interesting in green preparation. Herein, a photo-oxidative coupling reaction ofpara-aminothiophenol (p-ATP) dimerizing to 4-aminophenyl disulfide (APDS) rather than 4,4′-dimercaptoazobenzene (DMAB) was achieved in water by visible light irradiation, producing monodispersed organic nanoparticlesin situwith strong light scattering visualized by the dark-field microscopy (DFM) imaging technique, owing to the formation of disulfide.

Accelerated reduction and solubilization of elemental sulfur by 1,2-aminothiols

Nucleophilic 1,2-aminothiol compounds readily reduce typically-insoluble elemental sulfur to polysulfides in both water and nonpolar organic solvents. The resulting anionic polysulfide species are stabilized through hydrogen-bonding interactions with the proximal amine moieties. These interactions can facilitate sulfur transfer to alkenes.

Synthesis and biological evaluation of disulfides as anticancer agents with thioredoxin inhibition

Altered redox homeostasis as a hallmark of cancer cells is exploited by cancer cells for growth and survival. The thioredoxin (Trx), an important regulator in maintaining the intracellular redox homeostasis, is cumulatively recognized as a promising target for the development of anticancer drugs. Herein, we synthesized 72 disulfides and evaluated their inhibition for Trx and antitumor activity. First, we established an efficient and fast method to screen Trx inhibitors by using the probe NBL-SS that was developed by our group to detect Trx function in living cells. After an initial screening of the Trx inhibitory activity of these compounds, 8 compounds showed significant inhibition activity against Trx. We then evaluated the cytotoxicity of these 8 disulfides, compounds 68 and 69 displayed high cytotoxicity to HeLa cells, but less sensitive to normal cell lines. Next, we performed kinetic studies of both two disulfides, 68 had faster inhibition of Trx than 69. Further studies revealed that 68 led to the accumulation of reactive oxygen species and eventually induced apoptosis of Hela cells via inhibiting Trx. The establishment of a method for screening Trx inhibitors and the discovery of 68 with remarkable Trx inhibition provide support for the development of anticancer candidates with Trx inhibition.