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Chemical Structure| 1951-36-6 Chemical Structure| 1951-36-6

Structure of 1951-36-6

Chemical Structure| 1951-36-6

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Product Details of [ 1951-36-6 ]

CAS No. :1951-36-6
Formula : C8H6O4
M.W : 166.13
SMILES Code : O=CC1=CC(O)=C(C=O)C=C1O
MDL No. :MFCD22055335
InChI Key :PIWMYUGNZBJTID-UHFFFAOYSA-N
Pubchem ID :11084236

Safety of [ 1951-36-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 1951-36-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 41.26
TPSA ?

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

74.6 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.5
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

1.24
Log Po/w (WLOGP)?

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

0.72
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.

-0.43
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

1.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.64

Water Solubility

Log S (ESOL):?

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

-1.89
Solubility 2.14 mg/ml ; 0.0129 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-2.4
Solubility 0.654 mg/ml ; 0.00394 mol/l
Class?

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

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

-1.14
Solubility 12.1 mg/ml ; 0.0729 mol/l
Class?

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

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

No
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

No
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

No
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

No
Log Kp (skin permeation)?

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

-6.43 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

1.0
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)

1.0

Application In Synthesis of [ 1951-36-6 ]

* 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 [ 1951-36-6 ]

[ 1951-36-6 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 7310-97-6 ]
  • [ 1951-36-6 ]
YieldReaction ConditionsOperation in experiment
96% With boron tribromide; In dichloromethane; at 0 - 20℃;Inert atmosphere; To a solution of 4 (1.0 g) in dry DCM (150 mL), BBr3(2.0 mL) in 50 mL of CH2Cl2 was added dropwise at 0 C under N2 atmosphere. After being stirred overnight at room temperature, the mixture was cooled to 0 C and water (20 mL) was added in drops to quench the reaction. The residue was extracted with CH2Cl2, washed with brine, dried over MgSO4, and evaporated under reduced pressure, giving the crude compound which was purified by flash chromatography with hexane/ethyl acetate (5:1) as eluent to afford the title compound as an orange solid. Yield: 0.83 g (96%).1H NMR (400 MHz, d6-DMSO, 298K, TMS) delta10.30 (d, 4H, J=8.8 Hz), 7.23 (s, 2H). 13CNMR (100 MHz, d6-DMSO, 298K, TMS) 190.66, 153.25, 128.13, 115.56 ppm.
94% With boron tribromide; In dichloromethane; at -40 - 25℃; for 3h;Inert atmosphere; A three-necked reactor equipped with a thermometer was charged with 3.32 g (17.10 mmol) of the intermediate A synthesized in the step 1 and 160 ml of dichloromethane under a nitrogen stream to prepare a solution, which was cooled to -40 C. After the addition of 51.3 ml (51.29 mmol) of boron tribromide (17% dichloromethane solution) dropwise to the solution, the mixture was stirred at -40 C. for 1 hour. The reaction mixture was then heated to 25 C., and stirred for 2 hours. 600 ml of ice water was added to the reaction mixture, followed by extraction twice with 500 ml of ethyl acetate. The organic layer was collected, and dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. The solvent was evaporated from the filtrate under reduced pressure using a rotary evaporator. The resulting solid was added to 100 ml of toluene. After stirring the mixture for 5 minutes, the resulting crystals were filtered off to obtain 2.67 g of an intermediate B as yellow crystals (yield: 94%). The structure of the target product was identified by 1H-NMR. 1H-NMR (500 MHz, CDCl3, TMS, delta ppm): 10.23 (s, 2H), 9.96 (s, 2H), 7.24 (s, 2H).
70% With boron tribromide; In chlorobenzene; (1) Synthesis of 2,5-dihydroxybenzene-1,4-dicarboaldehyde (AD) 0.5 g of 2,5-dimethoxybenzene-1,4-dicarboaldehyde (AD) and 25 mL of boron tribromide were dissolved in 150 mL of chlorobenzene and stirred at room temperature for 12 hours. After complete reaction, the reacted mixture was neutralized with sodium carbonate, followed by extraction with water and dichloromethane and recrystallization within dichloromethane, thereby obtaining 2,5-dihydroxybenzene-1,4-dicarboaldehyde. The obtained product exhibited yield, property and NMR analysis result as follows. 70% Yield, Yellow crystal, H-NMR (300 MHz, DMSO, TMS): delta=10.30 (s, 2H), 7.20 (s, 2H; aromatic)
68% With boron tribromide; In dichloromethane; at 0℃; for 3h;Inert atmosphere; To a solution of 1-2 <strong>[7310-97-6]2,5-dimethoxyterephthalaldehyde</strong> (6.59 g, 33.93 mmol, 1 eq) in distilled DOM (156 mL) was added at 000 BBr3 at 1 M in distilled DOM (133.7 mL, 133.7mmol, 4 eq). The mixture was stirred for 3 hour under N2. Distilled water (300 mL) was then added at 0O. The mixture was extracted with hot 0H013 (300 mLx4) and washed with Rochelle?s salt (300 mL) and water (2*300 mL). The organic phase was dried over anhydrous Na2SO4 and filtered. After removing the solvent, the remaining residue was purified by recrystallization in 0H013 to give a yellow solid (3.82 g, 68 %).1H NMR (300 MHz, 0D013) 6 ppm = 10.23 (s, 2 H, OHO), 9.97 (s, 2 H, OH), 7.25 (s, 2 H, Ar) data matched with literature reference

References: [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 8670 - 8675.
    Angew. Chem.,2019,vol. 131,p. 8762 - 8767,6.
[2]Chem,2019,vol. 5,p. 3184 - 3195.
[3]Journal of the American Chemical Society,2018,vol. 140,p. 984 - 992.
[4]Journal of the American Chemical Society,2019,vol. 141,p. 15693 - 15699.
[5]Patent: US2015/274647,2015,A1 .Location in patent: Paragraph 0027-0230.
[6]Journal of Physical Chemistry A,2019,vol. 123,p. 8674 - 8689.
[7]Chemistry - A European Journal,2019,vol. 25,p. 12394 - 12404.
[8]Angewandte Chemie - International Edition,2018,vol. 57,p. 11310 - 11315.
    Angew. Chem.,2018,vol. 130,p. 11480 - 11485,6.
[9]Journal of the American Chemical Society,2018,vol. 140,p. 12677 - 12681.
[10]Journal of the American Chemical Society,2019,vol. 141,p. 11253 - 11258.
[11]Journal of Organic Chemistry,2016,vol. 81,p. 10922 - 10929.
[12]Patent: US2012/276651,2012,A1 .
[13]Zeitschrift fur Naturforschung, B: Chemical Sciences,2007,vol. 62,p. 66 - 74.
[14]Patent: WO2017/211985,2017,A1 .Location in patent: Page/Page column 36.
[15]Journal of Polymer Science, Part A: Polymer Chemistry,2014,vol. 52,p. 2412 - 2421.
[16]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 2755 - 2756.
[17]Tetrahedron Letters,2013,vol. 54,p. 3419 - 3423.
[18]Chemical Physics Letters,1997,vol. 267,p. 132 - 140.
[19]Journal of the Chemical Society,1965,p. 438,443.
[20]Journal of Physical Chemistry,1996,vol. 100,p. 19303 - 19309.
[21]Journal of Materials Chemistry A,2018,vol. 6,p. 374 - 382.
  • 2
  • [ 1951-36-6 ]
  • [ 77-78-1 ]
  • [ 7310-97-6 ]
  • 3
  • [ 7310-97-6 ]
  • [ 1951-36-6 ]
  • 2-Hydroxy-5-methoxy-benzene-1,4-dicarbaldehyde [ No CAS ]
 

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