Structure of 781-17-9
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CAS No. : | 781-17-9 |
Formula : | C16H14 |
M.W : | 206.28 |
SMILES Code : | C1(CCC2=CC=CC(CC3)=C42)=C4C3=CC=C1 |
MDL No. : | MFCD00267195 |
InChI Key : | XDFUNRTWHPWCKO-UHFFFAOYSA-N |
Pubchem ID : | 69906 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 67.51 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.44 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.18 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.28 |
Solubility | 0.0108 mg/ml ; 0.0000522 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.85 |
Solubility | 0.0293 mg/ml ; 0.000142 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.02 |
Solubility | 0.000196 mg/ml ; 0.000000951 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
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) |
Yes |
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 |
-4.62 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.38 |
* 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 |
---|---|---|
90% | With palladium 10% on activated carbon; hydrogen; In tetrahydrofuran; methanol; at 90℃; under 7500.75 Torr; for 168h;Autoclave; | A solution of pyrene 1 (2.5 g, 12.2 mmol) in a THF:MeOH mixture (1:5) (60 mL) was hydrogenated over 10 % Pd/C (850 mg) in an autoclave at 90C and with H2, at 10 Bar, for 7 days. The reaction mixture was filtered through Celite and washed several times with THF. The filtrate was concentrated, then diluted with dichloromethane (2 x 25 mL) and washed with water (2 x 50 mL) and brine. The organic extract was dried over anhydrous MgSO4, filtered, and evaporated. The crude residue was crystallized from DCM:EtOH (1:9) to give the product as a shiny white crystalline solid (2.26 g, 10.9 mmol, 90 %); mp. 129-131C (lit,14 mp 133C); 1H NMR (400 MHz, CDCl3): δ 7.11 (m, 6H), 2.91 (s, 8H); EIMS calculated for [C16H14]: 206.11; Found: 206.10; 1,2,3,6,7,8-Hexahydropyrene 3 (present in the mixture): 1H NMR (400 MHz, CDCl3): δ 7.14 (s, 4H), 3.09 (d, 8H, J=5.3Hz), 2.07 (d, 4H, J=5.0Hz). |
85% | With palladium 10% on activated carbon; hydrogen; for 12h; | To the reaction in which 4.04 g (20 mmol) of pyrene was dissolved in 50 ml of MC, 100 mg (0.2 mmol) of 10% palladium was added.After the reaction solution was stirred under hydrogen gas for 12 hours,Filtration under celite filtered the palladium precipitate and the solvent was removed under vacuum to afford 3.50 g (yield 85%) of intermediate I-12(1). |
1Og of pyrene was put into a flask, 500ml of ethyl acetate and 5g of Raney nickel were added thereto, and then the mixture solution was stirred under N2 at room temperature for 3 days. The reaction solution was filtered, the solvent was removed from the filtrate, and then the residual solid was dried. The dried solid was put into a flask, 250ml of ethanol and 0.15g of Pd/C were added thereto, and then the mixture solution was reacted at a pressure of 45psi H2 for 6 days. The reaction solution was filtered, the solvent was removed from the filtrate, and then the residual solid was dried to obtain 8g of tetrahydropyrene.GC-Mass (theoretical value: 206.11g/mol, measured value: 206g/mol) |
With hydrogen;5%-palladium/activated carbon; In decalin; at 160℃; under 51490.1 Torr; for 21h; | Into an autoclave, 195 g of pyrene (available from HIROSHIMA WAKO Co., Ltd.), 1 liter of decaline (available from HIROSHIMA WAKO Co., Ltd.) and 78 g of 5% palladium carbon (available from HIROSHIMA WAKO Co., Ltd.) were placed, and the reaction was allowed to proceed at 160C for 21 hours under a hydrogen pressure of 70 kg/cm2. After the reaction was completed, the catalyst was separated by filtration and washed with 3 liters of chloroform. Then, chloroform was removed under a reduced pressured, and the remaining decaline solution was cooled with ice. The formed crystals were separated by filtration, washed with ethanol and dried, thereby obtaining 130 g of crystals.The obtained crystals in an amount of 126 g was suspended in 6.3 liters of purified water, and 2 g of ferric chloride monohydrate (available from HIROSHIMA WAKO Co., Ltd.) was added to the suspension. Then, an aqueous solution obtained from 30 milliliter of bromine and 3 liters of purified water was added dropwise at the room temperature over 4 hours. The reaction was then allowed to proceed at the room temperature for 12 hours. The formed crystals were separated by filtration, washed with water and ethanol and dissolved into 3 liters of chloroform. The resultant solution was washed with an aqueous solution of sodium hydrogencarbonate and water and dried with anhydrous magnesium sulfate, and the solvent was then removed. To the obtained residue, 1.5 liters of hexane was added. The formed crystals were separated by filtration, and 71.5 g of the crystals were obtained. Since m/z=286 and 284 in the field desorption mass analysis (FD-MS) of the obtained compound, which corresponded to C10H12Br=285, the compound was identified to be 4,5,9,10-tetrahydro-2-bromopyrene (the yield: 41%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With bromine;iron(III) chloride; In water; at 20℃; for 16h; | Into an autoclave, 195 g of pyrene (available from HIROSHIMA WAKO Co., Ltd.), 1 liter of decaline (available from HIROSHIMA WAKO Co., Ltd.) and 78 g of 5% palladium carbon (available from HIROSHIMA WAKO Co., Ltd.) were placed, and the reaction was allowed to proceed at 160C for 21 hours under a hydrogen pressure of 70 kg/cm2. After the reaction was completed, the catalyst was separated by filtration and washed with 3 liters of chloroform. Then, chloroform was removed under a reduced pressured, and the remaining decaline solution was cooled with ice. The formed crystals were separated by filtration, washed with ethanol and dried, thereby obtaining 130 g of crystals. The obtained crystals in an amount of 126 g was suspended in 6.3 liters of purified water, and 2 g of ferric chloride monohydrate (available from HIROSHIMA WAKO Co., Ltd.) was added to the suspension. Then, an aqueous solution obtained from 30 milliliter of bromine and 3 liters of purified water was added dropwise at the room temperature over 4 hours. The reaction was then allowed to proceed at the room temperature for 12 hours. The formed crystals were separated by filtration, washed with water and ethanol and dissolved into 3 liters of chloroform. The resultant solution was washed with an aqueous solution of sodium hydrogencarbonate and water and dried with anhydrous magnesium sulfate, and the solvent was then removed. To the obtained residue, 1.5 liters of hexane was added. The formed crystals were separated by filtration, and 71.5 g of the crystals were obtained. Since m/z=286 and 284 in the field desorption mass analysis (FD-MS) of the obtained compound, which corresponded to C10H12Br=285, the compound was identified to be 4,5,9,10-tetrahydro-2-bromopyrene (the yield: 41%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.3% | With nitric acid; In acetic acid; for 0.0833333h; | More specifically, after dissolving the 4,5,9,10-tetrahydro-pyrene 211 in glacial acetic acid, by reacting the solution with fuming nitric acid, the 2-nitro-4,5,9,10-tetrahydro-pyrene 215 was synthesised according to the first step 210. A water bath that can maintain reactants and a reactor temperature at 20 C. is prepared. 3.1g (15mmol) of tetrahydro-pyrene 211 was poured in a two-circle rounded bottom flask having a magnetic stirrer placed in the water bath, and the reactant was dissolved adding 200 ml of glacial acetic acid. 13.5 ml of fuming acid was slowly added to the solution extending over 5 minutes while stirring the solution. After mixing the reactants for 5 more minutes, the solution was quenched by adding 100 ml of ice water, then yellow solids were formed. The solution containing yellow solid was further stirred for approximately one hour. After filtering the solution, the obtained yellow solids were washed with cold water. The yellow solids were dissolved in dichloromethane solvent. Afterward, 3.56 g (14.2 mmol) of a light yellow solid, i.e., 2-nitro-4,5,9,10-tetrahydro-pyrene 215 was obtained by purifying the solution passing through a silica gel chromatography column using 10% acetylactate and a hexane group solvent. In this case, yield was 94.3%. The structure of the product was examined using a hydrogen nuclear magnetic resonance (NMR), and found that it matched the structure of compound numeral 215 depicted in FIG. 2. The hydrogen NMR obtained was [1H NMR (400 MHz, CDCl3) (ppm): 7.98 (2H, s), 7.26 (1H, dd), 7.16 (2H, t), 2.97 (8H, m); MS: m/z (%) 189 (10), 202 (15), 221 (M+, 100)] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 24h; | NBS (N-Bromosuccinimide,3.56 g (20 mmol) of N-bromosuccinimide was completely dissolved in 50 ml of DMF (Dimethylformamide), and then 2.06 g (10 mmol) of intermediate I-12(1) was added to the solution and stirred at room temperature for 24 hours.The reaction solution was extracted twice with 50 ml of water and 50 ml of dichloromethane.The collected organic layer was dried over magnesium sulfate, and the residue obtained by evaporating the solvent was separated and purified through silica gel tube chromatography to obtain 2.51 g (yield 69%) of intermediate I-12(2). |
65% | With bromine; In water; at 20℃; for 48h; | 5g of tetrahydropyrene obtained in Preparation Example 1-1 was put into a flask, 100ml of distilled water was added thereto, to which 3.5ml of Br2(2.1eq, 0.05mol) was further added slowly, <n="24"/>and then the mixture solution was stirred at room temperature for 2 days. After completion of the reaction, the reaction solution was filtered, and then the filtrate was washed several times with distilled water. The washed filtrate was purified using a sublimator to obtain 5.7g of dibromo-tetrahydropyrene (yield 65%) .GC-Mass (theoretical value: 364.07g/mol, measured value: 364g/mol) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With aluminum (III) chloride; In carbon disulfide; at -10 - 20℃; for 51h; | A mixture of acetyl chloride (1.1 eq, 0.21 g, 2.67 mmol) and anhydrous AlCl3 (1.2 eq, 0.39 g, 2.92 mmol) in CS2 was cooled to -10C and a solution of <strong>[781-17-9]4,5,9,10-tetrahydropyrene</strong> 2 (0.5 g, 2.43 mmol) in CS2 was gradually added during 3 hours. The reaction mixture was stirred at room temperature for 2 days, then poured on ice and the mixture was extracted with diethyl ether (3 x 25 mL). The combined extracts were dried over MgSO4 and concentrated to dryness under reduced pressure to give an oily residue. Purification by column chromatography (silica gel, ethyl acetate: n-hexane 1:9). Crystallization from DCM:EtOH (1:9) yielded 7 as yellow crystals afforded the product (0.53 g, 2.14 mmol, 88 %); mp 110-111C (lit,14 mp 113-114C); 1H NMR (400 MHz, CDCl3): δ 7.70 (s, 2H), 7.19 (d, 1H), 7.12 (d, 2H), 2.93 (d, 8H), 2.62 (s, 3H); MS (MALDI-TOF, positive ion mode), m/z 249.07 [M]+. The structure of 7 was investigated by single crystalX-ray crystallography. |
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