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Chemical Structure| 15231-91-1 Chemical Structure| 15231-91-1

Structure of 6-Bromo-2-naphthol
CAS No.: 15231-91-1

Chemical Structure| 15231-91-1

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Product Details of [ 15231-91-1 ]

CAS No. :15231-91-1
Formula : C10H7BrO
M.W : 223.07
SMILES Code : C1=C(C=CC2=C1C=CC(=C2)Br)O
MDL No. :MFCD00004081
InChI Key :YLDFTMJPQJXGSS-UHFFFAOYSA-N
Pubchem ID :27144

Safety of [ 15231-91-1 ]

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

Computational Chemistry of [ 15231-91-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 53.67
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.07
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

2.95
Log Po/w (WLOGP)?

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

3.31
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.

3.24
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

3.16
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.95

Water Solubility

Log S (ESOL):?

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

-3.7
Solubility 0.0447 mg/ml ; 0.0002 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.

-3.04
Solubility 0.205 mg/ml ; 0.000918 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

-4.36
Solubility 0.0098 mg/ml ; 0.000044 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

Yes
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

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

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

No
Log Kp (skin permeation)?

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

-5.57 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

0.0 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)

1.14

Application In Synthesis of [ 15231-91-1 ]

* 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 [ 15231-91-1 ]

[ 15231-91-1 ] Synthesis Path-Downstream   1~17

  • 1
  • [ 15231-91-1 ]
  • [ 7499-66-3 ]
YieldReaction ConditionsOperation in experiment
94% With ammonium bisulfite; ammonia; water; at 150℃; for 48h; 6-bromonaphthalen-2-amine (15)6-Bromonaphthalen-2-ol (1.5 g, 6.7 mmol) was heated with ammonium hydroxide (10ml) and ammonium sulfite (3.5 g, 26 mmol) in a seal tube at 150 0C for 48 h. After cooling to room temperature, ethyl acetate was added and organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and evaporated to obtain crude product 15 (1.4 g, Y; 94 %), which was pure enough and can be used directly for next step without further purification. 1H NMR (CDCl3): delta 7.84 (IH, br), 7.56 (IH, d, J= 9.6 Hz), 7.43 (2H, m), 6.95 (2H, m), 3.87 (2H, b). Leigh C. Anderson and Donald G. Thomas: Quinoidation of Triaryl Compounds - Hydroxynaphthyldiphenylcarbinols J. Am. Chem. Soc; 65; 1943; 239, 241.
33% With ammonium bisulfite; ammonia; In water; at 190℃; for 24h; Preparation of 6-Bromonaphthalen-2-amine (9) 6-Bromo-2-naphthol (2.0 g, 9 mmol), ammonium sulfite (10.4 g, 90 mmol) and 10 mL of ammonia solution were sealed in a tube. The reaction mixture was heated at 190 C. for 24 hrs and allowed to cool to room temperature, the reaction mixture was extracted with EtOAc. HCl (10%) was added to the organic layer to give a precipitate. After filtration, the solid was dissolved in 10% of Na2CO3 and extracted with EtOAc, the organic layer was dried over Na2SO4. The solvent was removed under reduced pressure to give the product as yellow solid (0.67 g, 33%). MS [M++43]=265, LC-MS: tR=20.14 min.
21% With ammonium hydroxide; ammonium sulfite monohydrate; In water; at 120℃; for 17h; General procedure: Ammonium hydroxide aqueous solution ( 841mg, 27.8 mmol, 2 equiv.) was added to a freshly prepared aqueous solution of ammonium sulfite monohydrate (3.2 g, 27.8 mmol, 2 equiv.) in a 35 ml high pressure reaction vessel. Appropriate 2-naphthol analog (1a or 1b) (13.9 mmol, 1 equiv.) was added, and the mixture was stirred for 17 h at 120 C. The reaction mixture was filtered and the precipitate was washed with cold 5% aq. NaOH and then dissolved in DCM. The organic layer was again washed with 5% aq. NaOH (3×30 mL) and dried over anh. sodium sulfate to afford 2-naphthylamines after the removal of solvent in vacuo.
  • 2
  • [ 15231-91-1 ]
  • [ 4163-60-4 ]
  • [ 15572-30-2 ]
  • 4
  • [ 15231-91-1 ]
  • [ 7664-41-7 ]
  • 4>2SO3 [ No CAS ]
  • [ 7499-66-3 ]
  • 8
  • [ 15231-91-1 ]
  • [ 175883-62-2 ]
  • [ 550998-12-4 ]
YieldReaction ConditionsOperation in experiment
1.56 g (73%) 6-(4-Methoxy-2-methylphenyl)-2-naphthol The title compound was prepared by reacting 6-bromo-2-naphthol (1.8 g, 5.4 mmol) with <strong>[175883-62-2]4-methoxy-3-methylphenylboronic acid</strong> (1.74 g, 7.0 mmol) according to method A to yield 1.56 g (73%) of yellowish solid: mp 124-126 C.; 1H NMR (DMDO-d6): delta 2.25(3H,s), 3.78 (3H, s), 6.85 (1H, dd, J=8.35 Hz, J=2.56 Hz), 6.90 (1H, d, J=2.37 Hz), 7.09 (1H, dd, J=8.75 Hz, J=2.25 Hz), 7.13 (1H, s), 7.20 (1H, d, J=8.33 Hz), 7.35 (1H, dd, J=8.39 Hz, J=1.37 Hz), 7.67 (1H,s), 7.70 (1H, d, J=8.53 Hz), 7.78 (1H, d, J=8.78 Hz), 9.74 (1H, s); MS (ESI) m/z263 (M-H)-. Anal. for C18H16O2: Calc'd: C: 81.79H: 6.10 Found: C: 81.43H: 6.01
  • 9
  • [ 15231-91-1 ]
  • [ 34667-88-4 ]
  • [ 526218-63-3 ]
YieldReaction ConditionsOperation in experiment
With potassium fluoride; In methanol; acetonitrile; Production Example 6-1 2-(6-bromo-2-naphthyloxy)-4-nitrobenzonitrile After heating to reflux <strong>[34667-88-4]2-fluoro-4-nitrobenzonitrile</strong> (1 g), 6-bromo-2-naphthol (1.41 g), potassium fluoride/alumina (0.7 g) and 18-crown-6 (0.16 g) in acetonitrile, the mixture was reacted for 12 hours. It was then cooled to room temperature, the insoluble portion was filtered using celite, the ethyl acetate layer was washed with water and saturated saline and then dried over magnesium sulfate, and the solvent was distilled off. Methanol was added to the residue for crystallization to obtain 1.43 g of 2-(6-bromo-2-naphthyloxy)-4-nitrobenzonitrile. 1H-NMR (CDCl3) delta:7.31 (1H, dd, J=2.4, 8.8 Hz), 7.54 (1H, d, J=2.0 Hz), 7.62-7.70 (3H, m), 7.88 (1H, s), 7.90 (1H, s), 8.01 (1H, dd, J=2.0, 8.4 Hz), 8.08 (1H, s).
  • 10
  • [ 15231-91-1 ]
  • [ 768-95-6 ]
  • [ 128272-29-7 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; In diethyl ether; n-heptane; dichloromethane; (a) Preparation of 3-(1-adamantyl)-6-bromo-2-naphthol 56 g (0.25 mol) of 6-bromo-2-naphthol, 38.2 g (0.25 mol) of 1-adamantanol and 500 ml of a mixture of dichloromethane and heptane (40/60) were introduced into a round-bottomed flask. 15 ml of concentrated sulfuric acid were added and the reaction mixture was stirred at room temperature for 48 hours. The solid was filtered off, washed with heptane (3*100 ml) and dissolved in ethyl ether and the organic phase was washed with water, separated by settling, dried over magnesium sulfate and evaporated. 60.1 g (67%) of the expected compound were collected, which compound had a melting point of 215-6 C.
With hydrogenchloride; In n-heptane; dichloromethane; water; (a) Synthesis of 7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene: 22.3 g (0.1 mol) of 6-bromo-2-naphthol, 15.2 g (0.1 mol) of 1-adamantanol and 100 ml of dichloromethane were introduced into a round-bottomed flask. 5.5 ml of concentrated hydrochloric acid were added and the mixture was stirred at room temperature for twelve hours. The mixture was evaporated to dryness and the residue was taken up in water and neutralized with sodium bicarbonate. The resulting mixture was extracted with ethyl acetate and the organic phase was separated out after settling of the phases had taken place, dried over magnesium sulfate and evaporated. The residue obtained was triturated in a mixture of dichloromethane and heptane (30/70), filtered and dried. 19 g (53%) of the expected compound, with a melting point of 215-6 C., were collected.
  • 11
  • [ 15231-91-1 ]
  • [ 22635-62-7 ]
  • [ 128272-29-7 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; In hexane; n-heptane; water; ethyl acetate; EXAMPLE 9 Preparation of 7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene In a 100 ml flask, under a nitrogen atmosphere, are placed 2 g of 1-acetoxyadamantane and 20 ml of n-heptane, and 0.5 g of concentrated sulfuric acid is introduced drop by drop. At a temperature of about 22.C, 2.3 of 6-hydroxy-2-bromonaphthalene are added slowly and the mixture is left in vigorous agitation. The solvent is eliminated by filtration and the solid residue in suspension in the water is collected. The residue is filtered and then washed until neutrality is obtained. The resulting reddish solid is washed again with hexane until a colorless filtrate is obtained. After drying in a vacuum oven for 24 hours at 30 C one obtains a raw product which is chromatographed with a silica column using an ethyl acetate and hexane mixture of 1:9 as the eluent. After evaporation of the solvents, 1.3 g of desired raw product were obtained (Melting point: 218-224 C.).
  • 12
  • [ 15231-91-1 ]
  • butyl halide [ No CAS ]
  • [ 66217-20-7 ]
  • 13
  • [ 15231-91-1 ]
  • [ 116332-54-8 ]
  • 6-(4-fluorobenzoyl)-2-naphthol [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% A solution of n-BuLi (11.76mL, 18.82mmol, 1.6M in hexane) was added dropwise to a cold (-78C) stirred solution of 6-bromo-2-naphthol (2g, 8.96mmol) in anhydrous THF (50mL). After 30min <strong>[116332-54-8]4-fluoro-N-methoxy-N-methylbenzamide</strong> 7a (1.640g, 8.96mmol) in anhydrous THF (20mL) was added slowly over 20min. The resulting mixture was stirred for 2h whilst warming to room temperature. Water (100mL) was added and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (3×50mL), and the combined organic extracts were dried over anhydrous Na2SO4, removal of the solvent under vacuum afforded the crude 6-(4-fluorobenzoyl)-2-naphthol8a. The crude product was purified by crystallisation from ethyl acetate and hexane, 52% yield, m. p. 142-143C; numax 531, 769, 804, 1127, 1299, 1458, 1648, 3271, 3550cm-1; deltaH 5.97 (1H, s, OH), 7.19 (4H, m, Ar-H), 7.75 (1H, d, J=8.6Hz, 4-H), 7.83 (1H, d, J=8.7Hz, 8-H), 7.88 (3H, m, Ar-H), 8.17 (1H, d, J=1.0Hz, 5-H); deltaC 109.61, 115.53 (d, J=21.7Hz), 119.10, 126.36, 126.81, 127.34, 131.54, 132.17, 132.27, 132.63, 132.72, 134.18 (d, J=3.1Hz), 137.09, 156.21, 165.30 (d, J=254Hz), 195.84; deltaF-106.58; Found [M+H]+=267.0821, C17H11FO2 requires [M+H]+=267.0816.
  • 14
  • [ 15231-91-1 ]
  • [ 924869-17-0 ]
  • methyl 2-(6-hydroxynaphthalen-2-yl)benzo[d]oxazole-5-carboxylate [ No CAS ]
  • 15
  • [ 15231-91-1 ]
  • [ 5419-55-6 ]
  • [ 18162-48-6 ]
  • [ 179942-45-1 ]
  • 17
  • [ 15231-91-1 ]
  • [ 71-36-3 ]
  • [ 66217-20-7 ]
YieldReaction ConditionsOperation in experiment
91.1% With triphenylphosphine; 1,1'-(azodicarboxylic)dipiperidide; In tetrahydrofuran; at 0 - 20℃; for 18.0h;Inert atmosphere; Under N2, to a solution of ADDP (2.27 g, 9.00 mmol) in THF (15 mL) at 0C was added triphenylphosphine (2.36 g, 9.00 mmol) dropwise and the mixture was kept stirring for additional 25 mins. Then, 6- bromonaphthalen-2-ol (1) (1 g, 4.5 mmol) and butan-1-ol (0.4 g, 5.3 mol) in THF (2 mL) was added slowly. The reaction mixture was stirred at room temperature for 18 h. H20 (100 mL) was added, extracted with EtOAc (50 mL x 3) and the combined organic phases were washed with brine (60 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (eluent: 10% EtOAc in PE) to afford 2- bromo-6-butoxynaphthalene (1.2 g, 95% purity, 91.1% yield) as ayellow solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ 8.10 (d, J= 1.6 Hz, 1 H), 7.79 (dd, J= 17.1, 8.9 Hz, 2 H), 7.55 (dd, J= 8.7, 1.9 Hz, 1 H), 7.35 (d, J= 2.3 Hz, 1 H), 7.20 (dd, J= 9.0, 2.4 Hz, 1 H), 4.08 (t, J = 6.5 Hz, 2 H), 1.83-1.71 (m, 2 H), 1.54-1.41 (m, 2 H), 0.95 (t, J= 7.4 Hz, 3 H).
91.1% With triphenylphosphine; 1,1'-(azodicarboxylic)dipiperidide; In tetrahydrofuran; at 0 - 20℃; for 18.0h;Inert atmosphere; Under N2, to a solution of ADDP (2.27 g, 9.00 mmol) in THF (15 mL) at 0C was added triphenylphosphine (2.36 g, 9.00 mmol) dropwise and the mixture was kept stirring for additional 25 mins. Then, 6- bromonaphthalen-2-ol (1) (1 g, 4.5 mmol) and butan-1-ol (0.4 g, 5.3 mol) in THF (2 mL) was added slowly. The reaction mixture was stirred at room temperature for 18 h. H20 (100 mL) was added, extracted with EtOAc (50 mL x 3) and the combined organic phases were washed with brine (60 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (eluent: 10% EtOAc in PE) to afford 2- bromo-6-butoxynaphthalene (1.2 g, 95% purity, 91.1% yield) as ayellow solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ 8.10 (d, J= 1.6 Hz, 1 H), 7.79 (dd, J= 17.1, 8.9 Hz, 2 H), 7.55 (dd, J= 8.7, 1.9 Hz, 1 H), 7.35 (d, J= 2.3 Hz, 1 H), 7.20 (dd, J= 9.0, 2.4 Hz, 1 H), 4.08 (t, J = 6.5 Hz, 2 H), 1.83-1.71 (m, 2 H), 1.54-1.41 (m, 2 H), 0.95 (t, J= 7.4 Hz, 3 H).
 

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