Structure of 2,6-Dihydroxynaphthalene
CAS No.: 581-43-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 581-43-1 |
Formula : | C10H8O2 |
M.W : | 160.17 |
SMILES Code : | OC1=CC2=C(C=C1)C=C(O)C=C2 |
MDL No. : | MFCD00004082 |
InChI Key : | MNZMMCVIXORAQL-UHFFFAOYSA-N |
Pubchem ID : | 93552 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 47.99 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.36 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.9 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.25 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.88 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.65 |
Solubility | 0.361 mg/ml ; 0.00226 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.37 |
Solubility | 0.679 mg/ml ; 0.00424 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.91 |
Solubility | 0.197 mg/ml ; 0.00123 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.93 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.0 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With N-Bromosuccinimide; In tetrahydrofuran; at 0 - 60℃; for 3h; | In a more detailed embodiment, the method begins by taking a solution of 2,6-naphthalene diol (10.16 g, 63.43 mmol) in tetrahydrofuran (110 mL) and cooling the solution to about 0 C., then treated slowly with N-bromosuccinimide (22.58 g, 0.13 mol). The flask was then topped with a water condenser and heated to around 60 C. for around 3 hours, then cooled to room temperature. This reaction mixture A was diluted with a saturated aqueous Na2S2O3 solution (250 mL) and water (1.5 L), and the resulting solid was collected by filtration, and then left under vacuum for around 18 hours. The desired product, (0082) (19.5 g, 0.061 mol, 97% yield), was obtained as a tan solid. The 1H NMR spectrum of (0083) is shown in FIG. 2. |
97% | With N-Bromosuccinimide; In tetrahydrofuran; at 0 - 60℃; for 3h; | In a more detailed embodiment of producing al,2,5,6-naphthalenediimide monomer, the method can begin by taking a solution of 2,6-naphthalene diol (10.16 g, 63.43 mmol) in tetrahydrofuran (110 mL) and cooling the solution to about 0 C, then treated slowly with N- bromosuccinimide (22.58 g, 0.13 mol). The flask was then topped with a water condenser and heated to around 60C for around 3 hours, then cooled to room temperature. This reaction mixture A was diluted with a saturated aqueous Na2S203 solution (-250 mL) and water (-1.5 L), and the resulting solid was collected by filtration, and then left under vacuum for around 18 hours. The desired product, mol, 97% yield), was obtained as a tan solid. The 1H NMR spectrum of is shown in Figure 2. |
90% | With N-Bromosuccinimide; In tetrahydrofuran;Reflux; | Example 1 - l,5-dibromonaphthalene-2,6-diol [00123] To a solution of naphthalene -2, 6-diol (1) (5.1 g) in 50 mL of Tetrahydrofuran (THF), was added N-Bromosuccinimide (NBS, 1 1.4 g). The mixture was re fluxing and monitored by GCMS. The reaction was quenched with saturated sodium thiosulfate, and filtered. The solid was washed by water to afford 1 ,5- dibromonaphthalene-2,6-diol (90%). LRMS (ESI): Calcd. for Ci0H6Br2O2: 317.8714, Found: 317.9. |
With bromine; In acetic acid; at 120 - 125℃; | Synthesis of 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene2,6-dihydroxynaphthalene (2 g, 12.5 mol) was dissolved in acetic acid (60 ml). The acetic acid was used as a solvent. Bromine (2.6 ml. 50.7 mol) was dripped in the solution, and reaction was carried out under a reflux temperature (120 C. to 125 C.).As is explained in the embodiment for carrying out the present invention, in this stage, first and fifth hydrogen atoms with a high reactivity among hydrogen atoms contained in 2,6-dihydroxynaphthalene were substituted by bromine atoms, and 1,5-dibromo-2,6-dihydroxynaphthalene was merely produced. In order to obtain naphthodithiophene having a linear structure at last, it was further necessary to substitute the third and seventh hydrogen atoms with bromine.Next, bromine (2.6 ml) was further dripped into the reaction solution by five times at total, and iron powders (50 mg, 1.3 mol) as a catalyst were added thereto, and reaction was caused for 76 hours.Next, the reaction solution was cooled to a room temperature, and pure water (50 ml) was added thereto. A precipitated solid was separated and collected by filtering. This solid substance was rinsed by acetone, dried under a reduced pressure condition, thereby obtaining a rough product.The obtained rough product was caused to be recrystallized using 1,4-dioxane as a solvent, and purified. Accordingly, 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene (3.0 g, yield: 51%) with colorless needle crystals was obtained.As explained above, by dripping bromine several times and by adding iron powders as a catalyst, 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene was synthesized at a high yield.The reaction formula of the above-explained reaction is as follow. Various spectrum data of the obtained 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene are indicated below.1H-NMR (270 MHz, CDCl3) delta6.18 (s, 2H, OH), 8.31 (s, 2H, ArH); EIMS (70 eV) m/z=476 (M+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; | STR66 46.8 g (0.19 mole) of 3,4,5-trichloro-benzotrifluoride are added slowly and with stirring to a mixture which consists of 56.8 g (0.36 mole) of 2,6-dihydroxynaphthalene, 14.3 g (0.36 mole) of pulverulent sodium hydroxide and 170 ml of dimethyl sulphoxide and which has been heated to 120 C., and the reaction mixture is then stirred at 120 C. for approximately 3 hours and further at 20 C. for approximately 15 hours. The reaction mixture is then diluted with water to twice the volume, and acidified with 1N hydrochloric acid. The precipitate obtained is separated off and extracted with toluene, and the organic phase is separated off, washed with water, dried over sodium sulphate and filtered. The solvent is distilled off the filtrate in a waterpump vacuum. The residue is recrystallized from ethanol. 52 g (74% of theory) of 6-(2,6-dichloro-4-trifluoromethyl-phenoxy)-2-naphthol of melting point 158 C. are obtained. The starting substances of the formula (II) listed in Table 2 below can be prepared in analogy with Example (II-1). |