Structure of 2-Naphthaldehyde
CAS No.: 66-99-9
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CAS No. : | 66-99-9 |
Formula : | C11H8O |
M.W : | 156.18 |
SMILES Code : | O=CC1=CC=C2C=CC=CC2=C1 |
MDL No. : | MFCD00004094 |
InChI Key : | PJKVFARRVXDXAD-UHFFFAOYSA-N |
Pubchem ID : | 6201 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.76 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.65 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.48 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.16 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.88 |
Solubility | 0.204 mg/ml ; 0.00131 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.42 |
Solubility | 0.593 mg/ml ; 0.00379 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.01 |
Solubility | 0.0154 mg/ml ; 0.0000984 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-5.53 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 |
2.0 |
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 |
1.0 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 |
---|---|---|
In methanol; at 20℃; for 3h; | Intermediate B (200mg, 1.01mml) was stirred in MeOH (10ml) at r.t. under N2 and 2- napthaldehyde (148mg, 0.96mmol) was added. The resultant solution was stirred for 3 h. After this time, NaBH4 (61 mg, 1.62mmol) was added, causing fizzing, and the solution stirred for 10 min. 1 M NaOH (20ml) was then added, forming an opaque white solution which was stirred for 20 min. H2O (50ml) was then added and the solution extracted with Et2O (2 x 100ml). The combined organic extracts were dried (MgSO4) and solvent removed in vacuo to give the title compound as a colourless oil (320mg, 100%). LCMS purity 98%, m/z 339 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydroxylamine hydrochloride; caesium carbonate; In water; dimethyl sulfoxide; at 125℃; for 48h; | General procedure: Aldehyde (0.5mmol), NH2OH·HCl (0.6mmol) and Cs2CO3 (0.6mmol) were stirred at 125C for 48h in a 3:1 mixture of DMSO-H2O (2mL) under air. The progress of the reaction was monitored by TLC using ethyl acetate and hexane as eluent. After completion, the reaction mixture was cooled to room temperature and treated with water (1mL). The resulting mixture was extracted with ethyl acetate (3×5mL). Drying (Na2SO4) and evaporation of the solvent gave a residue that was purified on silica gel column chromatography using ethyl acetate and hexane. The purified products were identified by 1H NMR spectra and the melting points comparison with the literature data. |
77% | With C49H54Cl2Ir2N2O6; hydroxylamine hydrochloride; sodium hydrogencarbonate; In toluene; at 110℃; for 12h;Inert atmosphere; Schlenk technique; | General procedure: The complexes (1-3) (0.002mmol), the aldehyde (1mmol), NH2OH·HCl (1mmol) and NaHCO3 (1mmol) were introduced in a dried schlenk tube and purged with N2. Then, to the mixture, dried and degassed toluene (2mL) was added, and the solution was refluxed for 12h. The mixture was cooled to room temperature and the products were extracted with methanol and dichloromethane before being filtered through Celite to remove the remaining complex. The amide was purified using column chromatography, and dried under vacuum. Characterization details for each amide are given in the Supporting information. |
74% | With hydroxylamine hydrochloride; caesium carbonate; In acetonitrile; at 60 - 65℃; | General procedure: To a stirred solution of acetonitrile (10 mL), aldehyde (1.0 mmol) and bioglycerol-based carbon catalyst (10 wt %) were added and stirred for 10 min. To this NH2OH·HCl (1.0 mmol) followed by Cs2CO3 (1.0 mmol) were added, after which the reaction mixture was heated at 60-65 C until completion of the reaction as indicated by TLC. The reaction mixture was cooled to room temperature and catalyst was filtered, the solvent was removed by rotary evaporator. The crude residue was extracted with ethyl acetate (3 × 10 mL). The combined organic layers were extracted with water, saturated brine solution, and dried over anhydrous Na2SO4. The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography using ethyl acetate and hexane (2:8) as eluents to give the corresponding substituted benzamide derivative in (71-78%) yield. The identity and purity of the product were confirmed by 1H, 13C NMR, and mass spectra. |
72% | With hydroxylamine; copper diacetate; In water; at 110℃; for 48h; | General procedure: To a solution of copper(II) acetate (0.04 mmol) in water (1 mL) were added the corresponding aldehyde (3, 2 mmol) and the hydroxylamine (4, 2 mmol). After 2 days stirring at 110 C the mixture was quenched with a saturated solution of ammonium chloride (10 mL), or added ether (2 mL) for the recycling process. The mixture was extracted with AcOEt (3×10 mL) and washed with brine (10 mL), after drying with anhydrous MgSO4, the organic layer was filtered on Celite and the solvents were removed under low pressure (15-18 Torr). The product was purified recrystallization from chloroform/hexane mixtures to give the corresponding product 2. Amides 2a,262b,272c, 272d,172e,282f,292g,272h,172j,302k,172l30 and 2m17 are commercially available and were characterized by comparison of their physical and spectroscopic data with those of pure examples. Yields are included in Table 4 (Fig. 1 for recycling processes). Physical and spectroscopic data, as well as literature data for known compounds, follow. |
With C33H27ClN3OPRu; hydroxylamine hydrochloride; sodium hydrogencarbonate; In toluene; at 20 - 110℃; for 8.25h;Inert atmosphere; Schlenk technique;Catalytic behavior; | General procedure: The reaction vessel was charged with aldehyde (1mmol), NH2OH·HCl (1 mmol), NaHCO3 (1 mmol),[Ru-NHC] catalyst (0.5 mol %) and the mixture wasplaced under an atmosphere of N2. About 2 mL of dryand degassed toluene was added and the mixture wasstirred for 15 min at room temperature followed byreflux for 8 h. On completion of the reaction, 2-3 mLmethanol was added to the mixture followed by filtrationthrough Celite to remove the catalyst and NaHCO3.The crude product was then purified by column chromatography(MeOH/CH2Cl2, 1:1) using silica (200-400 mesh) as solid phase provided the amide in goodyield. The resultant amide solution was subjected to GCanalysis and the product was identified in comparisonwith authentic samples | |
85%Chromat. | With C23H27Cl2N3Rh(1+)*C24H20B(1-); hydroxylamine hydrochloride; sodium hydrogencarbonate; In toluene; at 110℃; for 2h;Inert atmosphere; Schlenk technique; | General procedure: Compound 3 (0.002 mmol), the aldehyde (1 mmol), NH2OHHCl(1 mmol) and NaHCO3 (1 mmol) were introduced in a dried schlenktube and purged with N2. Then, to the mixture, dried and degassedtoluene (2 ml) was added and the mixture was stirred for about10 min at room temperature, before the solution was refluxed understirring for 2 h. The mixture was cooled and the products wereextracted with methanol and dichloromethane before beingfiltered through celite to remove the remaining catalyst andNaHCO3. The crude amide was purified using column chromatography,and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With ammonium acetate; In butan-1-ol; at 120℃; for 12h; | General procedure: Aldehyde 1 (0.5 mmol), 3-cynaoacetyl indole 2 (0.5 mmol), and 3-amino-2-enone 3 (0.5 mmol) at 120 C was stirred for 8 h or 12 h in 2 mL n-BuOH in the presence of NH4OAc (0.5 mmol). After the completion (monitored by TLC), water (50 mL) was added. The mixture was filtered and the solid product was washed with water (3×5 mL). The crude product was purified by recrystallization from EtOH to give 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With ammonium acetate; In butan-1-ol; at 120℃; for 12h; | General procedure: Aldehyde 1 (0.5 mmol), 3-cynaoacetyl indole 2 (0.5 mmol), and 3-amino-2-enone 3 (0.5 mmol) at 120 C was stirred for 8 h or 12 h in 2 mL n-BuOH in the presence of NH4OAc (0.5 mmol). After the completion (monitored by TLC), water (50 mL) was added. The mixture was filtered and the solid product was washed with water (3×5 mL). The crude product was purified by recrystallization from EtOH to give 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With triethylamine; In methanol; for 12h;Reflux; | General procedure: A solution of the corresponding aromatic aldehyde (0.8-10.3 mmol), 2-sulfanylacetic acid (1.0-1.3 equiv) and the corresponding aromatic nitrile (1.0-1.3 equiv) and triethylamine (1.5-15.0 equiv) in methanol was refluxed over night. The reaction mixture was evaporated under reduced pressure and the crude product was recrystallized from ethanol and washed with acetone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetraethylammonium tosylate; triethylamine; In acetonitrile; at 20℃;Electrolysis; | General procedure: A 0.3 M solution of Et4NOTs in CH3CN (15 mL) was placed in the cathodic chamber of a divided cell (40 mL beaker, 3 cm diameter, 6 cm height) equipped with a lead cathode (5×5 cm2), a platinum anode (2×1 cm2), and a ceramic cylindrical diaphragm (1.5 cm diameter). A 0.3 M solution of Et4NOTs in DMF (4 mL) was placed in the anodic chamber (inside the diaphragm). N-Methylphthalimide 1a (161 mg, 1 mmol), benzaldehyde (318 mg, 3 mmol), TMSCl (0.64 mL, 5 mmol), and TEA (0.70 mL, 5 mmol) were added to the cathodic chamber. After 300 C of electricity was passed at a constant current of 100 mA at room temperature, the catholyte was evaporated in vacuo. The residue was dissolved in ethyl acetate (20 mL) and insoluble solid was filtered off. After removal of the solvent, the residue was purified by column chromatography on silica gel (hexanes/ethyl acetate) to give 2a′ in a 70% yield with an 80:20 dr. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation; | General procedure: A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized to give compounds 3-29. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With sodium hydride; In tetrahydrofuran; at 35 - 80℃; for 8h; | General procedure: Anhydrous tetrahydrofuran (50 mL) was added into a round-bottomed flask (100 mL) containing<strong>[6882-68-4]sophoridine</strong> (0.005 mol) and sodium hydride (0.1 mol). The solution was stirred, and aldehyde(0.02 mol) was added at 35-40 C. The solution was then refluxed for 8 h. After cooling to roomtemperature, the mixture was treated with hydrochloric acid (5%, 20 mL) to hydrolyze the excesssodium hydride and then extracted with chloroform (3 x 20 mL). The combined organic layer wasconcentrated, and the residue was purified in a reverse-phase silica gel column (CH2Cl2:MeOH = 20:1,v/v) to give compounds 2a-2k. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | To a solution of <strong>[185342-88-5]1,3-dibromo-2,4-dimethoxybenzene</strong> (230) (375 mg, 1.27 mmols) in 10 mL of abs. THF, n-BuLi (1.6 M in hexane, 792 μL, 1.27 mmols) was added slowly at -78 C and the mixture was stirred at this temperature for a further 2 h. Subsequently, at -78 C., a -78 C cold solution of 2-naphthalenehyde (495 mg, 3.17 mmols) in 2 mL of abs. THF was added. The reaction mixture was stirred at the same temperature for 1 h and slowly brought to rt overnight. The reaction mixture was washed successively with 4 mL of water, 4 mL of sat. amMonium chloride solution and 30 mL EtOAc. After stirring for 10 min, the organic layer was separated off and the aqueous phase was extracted three times with in each case 10 mL of EtOAc. The combined organic layers were washed with 15 mL sat. sodium chloride solution and then dried over anhydrous magnesium sulfate. The solvent was completely removed in vacuo and the residue was purified by flash chromatography on silica gel (10% EtOAc/PE). The product (404 mg, 1.08 mmols, 85%) was obtained as a colorless oil. Rf: 0.14 (10% EtOAc/PE). 1H NMR (400 MHz, CDCl3) δ = 7.82 - 7.78 (m, 4H), 7.50 - 7.45 (m, 4H), 6.65 (d, 3J = 8.9 Hz, 1H), 6.44 (s, 1H), 3.74 (s, 3H), 3.63 (s, 3H). 13C NMR (101 MHz, CDCl3) δ = 157.57, 155.50, 141.88, 133.28, 132.91, 132.60, 128.10, 127.87, 127.64, 127.31, 126.05, 125.71, 124.42, 123.71, 109.06, 108.83, 69.34, 61.67, 56.17. ESI-MS: m/z = 354.90, 356.90 [(M-H2O)+H]+. HRMS (ESI): calculated for C19H16O2 79Br: m/z = 355.03282 [M+H]+, found: m/z = 355.03317 [M+H]+. calculated for C19H16O2 81Br: m/z = 357.03077 [M+H]+, found: m/z = 357.03049 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40.6% | With sodium methylate; In methanol; at 60℃; for 5h; | Using the method of synthesizing an intermediate similar to that of Example 1, Take 0.193 g (0.01 mol) of <strong>[13338-63-1]2-(3,4,5-trimethoxyphenyl)acetonitrile</strong> (5), 0.156 g (0.01 mol) of 2-naphthaldehyde, and 20 mL of methanol into a 50 mL three-necked flask. Stirring to 60 C, adding sodium methoxide 0.027 g (0.005 mol), Constant temperature reaction for about 5h, thin layer chromatography to follow the reaction, After the reaction is completed, cool to room temperature, filter, and wash. Dry and recrystallize from methanol to give a pale yellow solid. Yield: 40.6%, |
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