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Structure of 1818-27-5

Chemical Structure| 1818-27-5

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Product Details of [ 1818-27-5 ]

CAS No. :1818-27-5
Formula : C8H8O4
M.W : 168.15
SMILES Code : CC(C1=CC(O)=C(O)C=C1O)=O
MDL No. :MFCD00601422
InChI Key :WCJLAYDOJJYRHF-UHFFFAOYSA-N
Pubchem ID :74559

Safety of [ 1818-27-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 1818-27-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 3.0
Molar Refractivity 42.71
TPSA ?

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

77.76 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.22
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

1.09
Log Po/w (WLOGP)?

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

1.01
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.

-0.07
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

0.72
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.79

Water Solubility

Log S (ESOL):?

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

-1.87
Solubility 2.25 mg/ml ; 0.0134 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.

-2.32
Solubility 0.814 mg/ml ; 0.00484 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

-1.0
Solubility 16.7 mg/ml ; 0.0995 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

Yes
Log Kp (skin permeation)?

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

-6.55 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.

1.0 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)

1.35

Application In Synthesis of [ 1818-27-5 ]

* 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 [ 1818-27-5 ]

[ 1818-27-5 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 89-84-9 ]
  • [ 1818-27-5 ]
  • 3
  • [ 1818-27-5 ]
  • [ 127-09-3 ]
  • [ 108-24-7 ]
  • [ 55939-28-1 ]
  • 4
  • [ 533-73-3 ]
  • [ 108-24-7 ]
  • [ 64-19-7 ]
  • [ 1818-27-5 ]
  • 6
  • [ 613-03-6 ]
  • [ 64-19-7 ]
  • [ 1818-27-5 ]
  • 7
  • [ 1818-27-5 ]
  • [ 93-97-0 ]
  • [ 38183-04-9 ]
  • 8
  • [ 1818-27-5 ]
  • [ 93-97-0 ]
  • [ 38183-04-9 ]
  • 3-benzoyl-6,7-dihydroxy-2-phenyl-chromen-4-one [ No CAS ]
  • 10
  • [ 533-73-3 ]
  • [ 75-05-8 ]
  • [ 1818-27-5 ]
  • 11
  • [ 1818-27-5 ]
  • [ 139-85-5 ]
  • [ 526-12-5 ]
YieldReaction ConditionsOperation in experiment
(F) (2,4,5-Trihydroxyphenyl)ethanone A mixture of triacetoxybenzene (25.2 g, 0.10 mol) and p-toluenesulfonic acid (19.0 g, 0.10 mol) was heated at 140 C. with stirring under nitrogen for 15 minutes. Then water (150 ml) was added, and the reaction was refluxed for 10 minutes. The solution was cooled to 5 C. for 16 hours. The solid was filtered, washed with water (2*40 ml), and dissolved in ethyl acetate (200 ml). The organic solution was dried over sodium sulfate and filtered through silica gel (60-200 mesh, 200 ml). The desired material was eluted with ethyl acetate (4*200 ml). The fractions were combined and the solvent removed in vacuo to give 11.0 g of the title compound.
  • 15
  • [ 613-03-6 ]
  • [ 64-19-7 ]
  • ZnCl2 [ No CAS ]
  • [ 1818-27-5 ]
  • 16
  • [ 7446-70-0 ]
  • [ 613-03-6 ]
  • [ 1818-27-5 ]
  • [ 2999-24-8 ]
  • 21
  • [ 1818-27-5 ]
  • [ 94307-79-6 ]
  • 22
  • [ 1818-27-5 ]
  • [ 85288-45-5 ]
  • 23
  • [ 1818-27-5 ]
  • [ 42059-51-8 ]
YieldReaction ConditionsOperation in experiment
With acetic anhydride; In pyridine; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; hexane; chloroform; ethyl acetate; (G) [4,5-Bis(acetyloxy)-2-hydroxyphenyl]ethanone To a solution of <strong>[1818-27-5](2,4,5-trihydroxyphenyl)ethanone</strong> (4.0 g, 0.0238 mol) in pyridine (12 ml) at 0 C. was added acetic anhydride (4.5 ml, 0.0476 mol) in pyridine (1 ml) over 2 minutes. After 10 minutes of stirring, ice water (100 ml) was added and the product oiled out. The water layer was decanted and the product was washed with water and the water decanted (3*30 ml). The residue was dissolved in chloroform (100 ml) and the organic layer was washed with water (20 ml), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed twice on silica gel 60-200 mesh (100 ml) in ethyl acetate:hexane (4:1 to 1:1) to give 2.25 g of the desired product.
  • 24
  • [ 1818-27-5 ]
  • [ 541-41-3 ]
  • 4,5-Bis(ethoxycarbonyloxy)-2-hydroxyacetophenone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; sodium chloride; In ethyl acetate; (a) 4,5-Bis(ethoxycarbonyloxy)-2-hydroxyacetophenone <strong>[1818-27-5]2,4,5-Trihydroxyacetophenone</strong> (3.36 g) was dissolved in 150 ml of ethyl acetate, and 3.24 ml of pyridine was added at about -5 C. with stirring. Then, 50 ml of a solution of 3.8 ml of ethyl chloroformate in ethyl acetate was added dropwise over 30 minutes. The mixture was stirred for 10 minutes at the same temperature. The resulting precipitate was collected by filtration and washed three times with 10 ml of ethyl acetate. The washings and the filtrate were combined, and the mixture was washed with water (once) and a saturated aqueous solution of sodium chloride (three times) and dried over magnesium sulfate. The solvent was distilled off, and the residue was recrystallized from ethyl ether-ethanol. The crystals were collected by filtration, and washed with ethanol and n-hexane and dried to afford 4.60 g of the desired product. Melting point: 58-60 C.
  • 25
  • [ 1818-27-5 ]
  • [ 17341-93-4 ]
  • 2-Hydroxy-4,5-bis(2,2,2-trichloroethoxycarbonyloxy)-acetophenone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; sodium chloride; In ethyl acetate; (a) 2-Hydroxy-4,5-bis(2,2,2-trichloroethoxycarbonyloxy)-acetophenone <strong>[1818-27-5]2,4,5-Trihydroxyacetophenone</strong> (16.8 g) was dissolved in 500 ml of ethyl acetate, and 15.98 ml of pyridine was added at about -5 C. with stirring. Then, a solution of 26.82 ml of 2,2,2-trichloroethyl chloroformate in 70 ml of ethyl acetate was added dropwise over the course of 2.5 hours. The mixture was stirred at the same temperature for 15 minutes. The precipitate formed was collected by filtration and washed with ethyl acetate. The washing and the filtrate were combined, and the mixture was washed with water (once) and a saturated aqueous solution of sodium chloride (twice), and dried over magnesium sulfate. The solvent was distilled off, and the residue was recrystallized from ethyl ether-ethanol. The crystals were collected by filtration, washed with ethanol and n-hexane and dried to afford 43.6 g of the desired product. Melting point: 107.5-108 C.
  • 26
  • [ 66003-50-7 ]
  • [ 1818-27-5 ]
YieldReaction ConditionsOperation in experiment
66.9% With trichlorosilane; In chlorobenzene; at 20℃; for 24h;Inert atmosphere; Compound 2 (4 g, 19.03 mmol) was dissolved in chlorobenzene (20 mL) at room temperature, protected with nitrogen, and trichlorosilane (6.6 g 49.47 mmol) was slowly added dropwise; the mixture was heated at reflux for one day and the chlorobenzene was separated by rotary evaporation. The mixture was dissolved in ImoL/L hydrochloric acid (50 mL), extracted with ethyl acetate, and after-treated, and was purified by silica gel column chromatography to give a pale yellow solid 3 (2.1 g, 12.7 mmol). The yield was 66.9%.
  • 27
  • [ 1818-27-5 ]
  • [ 100-39-0 ]
  • [ 7298-38-6 ]
  • 28
  • [ 1818-27-5 ]
  • [ 18107-18-1 ]
  • [ 20628-06-2 ]
  • [ 22089-12-9 ]
  • 29
  • [ 1818-27-5 ]
  • [ 120-92-3 ]
  • [ 1227935-84-3 ]
  • 30
  • [ 1818-28-6 ]
  • [ 1818-27-5 ]
YieldReaction ConditionsOperation in experiment
76.6% With boron tribromide; In dichloromethane; at 20℃;Inert atmosphere; Step C: Compound 128 was dissolved in dichloromethane (20mL), N2 protection, was added dropwise under ice-cooling BBr3,After the addition was completed, the mixture was stirred at room temperature overnight. Pour the reaction solution into crushed ice and adjust the pH to 4-5 with 2N NaOH solution.Add ethyl acetate (50 mL × 2) for extraction.The combined organic phases were washed with saturated brine.Dry over anhydrous sodium sulfate. Evaporate the solvent under reduced pressure.The product is purified by column chromatography (200-300 mesh silica gel,Ethyl acetate: dichloromethane = 1:5 to 1:1 elution),1-(2,4,5-Trihydroxyphenyl)ethanone (129) (1.41 g),The yield was 76.6%.
75.87% With aluminum (III) chloride; In chlorobenzene; at 20℃; for 12h; A solution of 2,4,5-trimethoxyacetophenone (4.00 g,19.03 mmol) in chlorobenzene (20 mL) was treated with AlCl3(6.60 g, 49.47 mmol) at room temperature and then refluxed for12 h. The solvent was evaporated and the residue was hydrolyzedwith cooled 1 M HCl (50 mL) and extracted with ethyl acetate(3 50 mL). The organic layer was washed with water (2 50 mL), dried over sodium sulfate anhydrous and then filtered.After evaporation, the crude product was purified by column chromatography(methanol/dichloromethane [0.5:9.5]) to provide2,4,5-trihydroxyacetophenone as the pale yellow solid (2.42 g,75.87%); m.p. 206-207 C; FTIR (KBr) (cm1): 3405, 3238 (OAHst.), 1634 (CO st.) 1589, 1536 (CC st.), 1300, 1211, 1135 (CAOst.); 1H NMR 300 MHz (CD3OD): d 2.46 (s, 3H, CH3), 6.27 (s, 1H,H3), 7.14 (s, 1H, H6); HRMS (ESI) m/z calculated for C8H8O4,168.0428 [M]+, 167.0350 [MH]+; found 167.0356 [MH]+.
With aluminum (III) chloride; In toluene; for 24h;Reflux; A mixture of l-(2,4,5-trimethoxyphenyl)ethanone (10 g, 47.6 mmol, 1 eq) and AICI3 (16.5 g, 124 mmol, 2.6 eq) in toluene (48 mL) is stirred at reflux for 24 h. The mixture is concentrated to dryness and quenched with cooled 1 N HC1. The mixture is extracted with ethyl acetate. The organic layer is dried (Na2S04) and concentrated. The residue is purified by flash column chromatography (S1O2, dichloromethane/methanol 100:0 to 95:5) to afford the desired product.
  • 31
  • [ 1818-27-5 ]
  • C30H26O6 [ No CAS ]
  • 32
  • [ 1818-27-5 ]
  • 6,7-dihydroxy-2-(30-methoxyphenyl) chromone [ No CAS ]
  • 33
  • [ 1818-27-5 ]
  • [ 100-39-0 ]
  • [ 7298-39-7 ]
YieldReaction ConditionsOperation in experiment
70.19% To a solution of 2,4,5-trihydroxyacetophenone (1.50 g,8.93 mmol) in acetone (24 mL) was added anhydrous potassiumcarbonate (2.22 g, 16.07 mmol). The mixture was stirred at roomtemperature for 10 min. Then benzyl bromide (2.75 g, 16.08 mmol)was added and the reaction mixture was refluxed for 5 h. Aftercooling to room temperature, the solvent was evaporated andwater was added to the residue. The aqueous mixture wasextracted with ethyl acetate (3 40 mL). The combined organiclayer was washed with water (2 40 mL) and dried over sodiumsulfate anhydrous, then filtered. After removing the solvent, thecrude product was purified by column chromatography (ethyl acetate/hexane [1:4]) to provide 4,5-bis(benzyloxy)-2-hydroxyacetophenoneas the white solid (2.18 g, 70.19%); m.p. 99-100 C; FTIR(KBr) (cm1): 3065, 3037 (aromatic CAH st.), 2867 (aliphaticCAH st.), 1633 (CO st.), 1510, 1455 (CC st.), 1370 (CAH bending),1263, 1210, 1166 (CAO st.); 1H NMR 300 MHz (CDCl3): d 2.48 (s, 3H, CH3), 5.10 (s, 2H, CH2-Ph), 5.21 (s, 2H, CH2-Ph), 6.54 (s,1H, H3), 7.19 (s, 1H, H6), 7.34-7.48 (m, 10H, H20, H30, H40, H50, H60 ,H200, H300, H400, H500, H600); LRMS (ESI) m/z [M+Na]+ 371.29 (46.0),280.20 (100.0), 189.29 (10.0).
  • 34
  • [ 5350-57-2 ]
  • [ 1818-27-5 ]
  • C21H18N2O3 [ No CAS ]
  • 35
  • [ 1818-27-5 ]
  • [ 52249-88-4 ]
 

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