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Chemical Structure| 1141-88-4 Chemical Structure| 1141-88-4

Structure of 2,2′-Dithiodianiline
CAS No.: 1141-88-4

Chemical Structure| 1141-88-4

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Product Details of [ 1141-88-4 ]

CAS No. :1141-88-4
Formula : C12H12N2S2
M.W : 248.37
SMILES Code : NC1=CC=CC=C1SSC2=CC=CC=C2N
MDL No. :MFCD00007703
InChI Key :YYYOQURZQWIILK-UHFFFAOYSA-N
Pubchem ID :14358

Safety of [ 1141-88-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H318-H410
Precautionary Statements:P264-P270-P280-P305+P351+P338-P310-P330-P403-P501
Class:9
UN#:3077
Packing Group:

Computational Chemistry of [ 1141-88-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 0.0
Num. H-bond donors 2.0
Molar Refractivity 73.41
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

102.64 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.29
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.05
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

3.67
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.95
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.22
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.84

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.66
Solubility 0.0545 mg/ml ; 0.00022 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.87
Solubility 0.00334 mg/ml ; 0.0000134 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.42
Solubility 0.00938 mg/ml ; 0.0000378 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

Yes
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

Yes
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.65 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

2.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.55

Application In Synthesis of [ 1141-88-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1141-88-4 ]

[ 1141-88-4 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 105-53-3 ]
  • [ 1141-88-4 ]
  • [ 5325-20-2 ]
  • [ 13920-91-7 ]
  • 2
  • [ 6668-24-2 ]
  • [ 1141-88-4 ]
  • [ 120-75-2 ]
  • [ 124530-83-2 ]
  • [ 93-55-0 ]
  • 3
  • [ 104-87-0 ]
  • [ 1141-88-4 ]
  • [ 16112-21-3 ]
YieldReaction ConditionsOperation in experiment
97% With sodiumsulfide nonahydrate; acetic acid; In N,N-dimethyl-formamide; at 100℃; for 8h; In a parallel synthesizer reaction tube, 0.40 mmol was added 2,2' -dithio diphenylamine, 0.80 mmol of p-methylbenzaldehyde, 0.20 mmol of Na2S · 9H20 and 0.20 mmol of AcOH, Then, 3 mL of DMF was added as the reaction solvent, and the reaction was stirred at 100 C for 8 hours. LC detection found that the reaction of disulfide material completely, cooled to room temperature, The solvent was removed under reduced pressure using a rotary evaporator to give the crude product. The crude product was eluted with petroleum ether and ethyl acetate as eluant and subjected to column elution (200-300 mesh silica gel) to give 175 mg of white powder 2- (4-methylphenyl) benzothiazole having a purity of more than 99%, the separation yield was 97% and the melting point was 84-86 C.
97% General procedure: 2,2′-Disulfanediyldianiline or 5,5′-dichloro-2,2′-dithiobisaniline (0.4mmol), corresponding aryl aldehydes (0.8mmol), Na2S·9H2O (0.2mmol), and NaHCO3 or AcOH (0.2mmol) in DMF (3mL) were put into a reaction tube of parallel reactor (Wattecs). The reaction mixture was stirred at 100C under N2 atmosphere for the indicated time until the starting materials was consumed completely as monitored by TLC and LC-MS analysis. The reaction mixture was then washed with aqueous sodium bisulfite solution to remove the excess aldehyde and extracted with CH2Cl2. The organic layers were dried over anhydrous MgSO4. After filtering to remove the MgSO4, the solvent was removed under reduced pressure. The crude product was purified by column chromatography through a silica-gel column to afford the desired products.
87% With sodium hydrogen sulfide; at 190℃; for 0.333333h;Microwave irradiation; Green chemistry; General procedure: 2,2-Disulfanediyldianiline (1a) or 5,5-dichloro-2,2-dithiobisaniline (1b) (0.50 mmol), the corresponding aldehydes(2a-p) (1.1 mmol), NaSH (0.3 mmol) and PEG-300 (2 mL) wereput into a round-bottomed ask, and the reaction mixture wasirradiated for 20 min at 25 W. After completion of the reactionmonitored by TLC with a mixture of petroleum ether and ethylacetate as eluent, the mixture was allowed to cool to roomtemperature. Distilled water (25 mL) was added into the ask,and then the solid was precipitated from the aqueous phaseafter stirring by magnetic stirrers in 5 min. The solid precipitatewas isolated by fltration, washed twice by distilled water (5 mL)and dried for 3 h. The pure targetproducts3a-3o were obtaineddirectly. The pure products 3p and 3q were obtained by columnchromatography(PE/EtOAc as eluent).Complete characterization of the products (all known) is found in the SupplementalMaterials (Figures S 1-S 34).
84% With sodiumsulfide nonahydrate; carbon dioxide; In water; at 50 - 80℃; for 24h;Autoclave; (1) Synthesis of 2- (4-methylphenyl) benzothiazoleWas added to the autoclave 0.40mmol 2,2'-dithiobis aniline, 0.80mmol of methyl benzaldehyde and 0.2mmol of Na2S · 9H2O, placed magneton, then add 2mL of water as a reaction solvent, after heating to 50 2MPa charged carbon dioxide gas. And continue to heat to 80 After stirring for 24h, LC detected disulfide starting material the reaction was complete, cooled to room temperature, using a rotary evaporator to give the crude product obtained after the solvent was removed under reduced pressure. The crude product with petroleum ether and ethyl acetate as the eluent, using a gradient elution by column chromatography (200-300 mesh silica gel) was obtained with a purity greater than 99% of the white powder of 2- (4-methylphenyl ) benzothiazole 151.2mg, isolated in 84% yield,
76% With tert.-butylhydroperoxide; copper dichloride; In chloroform; water; at 80℃; for 24h;Inert atmosphere; Schlenk technique; A 25 mL reaction vessel was charged with 2,2'-disulfanediyldianiline 7 (0.483 mmol, 0.57 equiv), p-methylbenzaldehyde 2a (0.845 mmol), CuCl2 (0.254mmol, 0.3 equiv), tert-butylhydroperoxide (0.507 mmol, 0.6 equiv, 70% aqueous solution) and 0.1 mL CHCl3 under nitrogen. The reaction mixture was stirred in an ice bath for 30 min, andthen stirred at 80C for 24 h. After cooling to room temperature, the mixture was purified by column chromatography using silica gel (petroleum ether/ethylacetate) to afford the product 3a.

  • 4
  • [ 99-94-5 ]
  • [ 1141-88-4 ]
  • [ 16112-21-3 ]
  • C22H19NO2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% General procedure: 2,2'-Disulfanediyldianiline 1a or 6,6'-disulfanediylbis(3-chloroaniline) 1b (0.5 mmol) and carboxylic acid (1.0 mmol, except 0.5mmol for 2k) were added to a three-neck flask under an atmosphere of Ar, and 5 mL dry toluene was added, then the mixture was stirred for 2.5 h at 70 C to allow the solid to dissolve in toluene solvent completely. After the reaction solution was cooled down to 30 C, PCl3 (1.2 mmol, 0.165 g) was added dropwise. When the PCl3 was added completely, the reaction mixture was further stirred for 4 - 6 h at 100C until no 2,2'-disulfanediyldianiline or 6,6'-disulfanediylbis(3-chloroaniline) was detected by TLC analysis. The reaction solution was washed with saturated aqueous sodium bicarbonate solution and extracted with CH2Cl2. The collected organic layers were dried over anhydrous MgSO4. After filtered toremove the MgSO4 and the solvent was removed under reduced pressure. The crude product was purifiedby flash chromatography on silica gel using PE / EtOAc.
  • 5
  • [ 7163-50-0 ]
  • [ 1141-88-4 ]
  • [ 16112-21-3 ]
  • 6
  • [ 26767-16-8 ]
  • [ 1141-88-4 ]
  • [ 22901-00-4 ]
  • 7
  • [ 2557-78-0 ]
  • [ 137-07-5 ]
  • [ 14135-38-7 ]
  • 2-((2-fluorophenyl)disulfaneyl)aniline [ No CAS ]
  • [ 1141-88-4 ]
  • 8
  • [ 1141-88-4 ]
  • [ 1015248-96-0 ]
 

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