Structure of 2631-77-8
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CAS No. : | 2631-77-8 |
Formula : | C7H4I2O2 |
M.W : | 373.91 |
SMILES Code : | O=CC1=CC(I)=CC(I)=C1O |
MDL No. : | MFCD00003321 |
InChI Key : | MYWSBJKVOUZCIA-UHFFFAOYSA-N |
Pubchem ID : | 75829 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 59.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.88 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.41 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.57 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.44 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.63 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.31 |
Solubility | 0.0183 mg/ml ; 0.0000489 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.32 |
Solubility | 0.178 mg/ml ; 0.000475 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.61 |
Solubility | 0.0909 mg/ml ; 0.000243 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) |
Yes |
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 |
-6.54 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 |
0.0 |
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 |
2.0 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) |
1.82 |
* 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 |
---|---|---|
With piperidine; In ethanol; | General procedure: 3-Carbonyl coumarins were obtained by Knoevenagel cyclization between substituted salicylaldehydes (1 mmol) and methyl acetoacetate (1 mmol) or ethyl benzoylacetate (1 mmol) in ethanol (25 mL) with catalytic amounts of piperidine. The ethyl ester of coumarin-3-carboxylic acid was prepared by Knoevenagel reaction between diethyl malonate (1 mmol) and the appropriate salicylaldehyde (1 mmol) with catalytic amounts of piperidine in ethanol (50 mL). Then, if there was an hydroxyl group at position 7, etherification was performed by adding a suitable benzyl bromide (1 mmol) or cycloheptyl bromide (1 mmol), and potassium carbonate (1 mmol) in anhydrous acetone (100 mL), using N,N'-dicyclohexyl-18-crown-6-ether (1 mmol) as a chelating agent. Final products were purified by chromatography. Ethyl ester derivatives (1 mmol) were dissolved and stirred at room temperature in a solution of LiOH.H2O (6 mmol) in H2O/MeOH (1:5, v/v; 50 mL); then HCl 3 N (50 mL) was added. The suspension was filtered and the solid was dried under vacuum. 3-Carboxyhydrazido derivatives were obtained by dissolving at reflux 3-coumarin carboxylic acid (1 mmol) in thionyl chloride (20 mL). After solvent evaporation under vacuum, the reactive acyl chloride (1 mmol) was reacted with a suitable hydrazine hydrochloride (2 mmol) in the presence of sodium acetate (2 mmol) in H2O/CH3CN (1/4, v/v). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With sodium periodate; sulfuric acid; iodine; potassium iodide; sodium sulfite; In water; acetic acid; at 25℃; for 3h; | General procedure: Iodination of phenol (1d) in the presence of Na2SO3 (typical procedure). A 100-mL round-bottom flask was charged with a solution of 3 mmol of phenol in 10 mL of acetic acid, and a solution of KI3 and Na2SO3 (prepared preliminarily by addition of 3 mmol of iodine and 3 mmol of Na2SO3 to a solution of 3 mmol of potassium iodide in 3 mL of water) was added rapidly. At the same time, a solution of 3 mmol of NaIO4 in 5 mL of water was added, and 0.5 mL of sulfuric acid was rapidly added using a pressure-equalizing dropping funnel. The mixture was stirred at 25C, the progress of the reaction being monitored by TLC. When the reaction was complete, the mixture was poured into ice-cold water, and the solid product was separated by vacuum filtration, washed twice with deionized water, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; In ethanol; | General procedure: 3-Carbonyl coumarins were obtained by Knoevenagel cyclization between substituted salicylaldehydes (1 mmol) and methyl acetoacetate (1 mmol) or ethyl benzoylacetate (1 mmol) in ethanol (25 mL) with catalytic amounts of piperidine. The ethyl ester of coumarin-3-carboxylic acid was prepared by Knoevenagel reaction between diethyl malonate (1 mmol) and the appropriate salicylaldehyde (1 mmol) with catalytic amounts of piperidine in ethanol (50 mL). Then, if there was an hydroxyl group at position 7, etherification was performed by adding a suitable benzyl bromide (1 mmol) or cycloheptyl bromide (1 mmol), and potassium carbonate (1 mmol) in anhydrous acetone (100 mL), using N,N'-dicyclohexyl-18-crown-6-ether (1 mmol) as a chelating agent. Final products were purified by chromatography. Ethyl ester derivatives (1 mmol) were dissolved and stirred at room temperature in a solution of LiOH.H2O (6 mmol) in H2O/MeOH (1:5, v/v; 50 mL); then HCl 3 N (50 mL) was added. The suspension was filtered and the solid was dried under vacuum. 3-Carboxyhydrazido derivatives were obtained by dissolving at reflux 3-coumarin carboxylic acid (1 mmol) in thionyl chloride (20 mL). After solvent evaporation under vacuum, the reactive acyl chloride (1 mmol) was reacted with a suitable hydrazine hydrochloride (2 mmol) in the presence of sodium acetate (2 mmol) in H2O/CH3CN (1/4, v/v). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 10h; | General procedure: Salicylaldehyde was dissolved in DMF (5 mL, distilled from CaH2). Propargyl bromide andpotassium carbonate were added at 0 C, and the reaction mixture was stirred at roomtemperature for prescribed time indicated. After completion of the reaction (monitored byTLC), water (10 mL) was added and extracted with ethyl acetate (3x15 mL). The combinedorganic layers were washed with brine, dried over Na2SO4, filtered, and concentrated underreduced pressure. Subsequent column chromatography using silica gel with ethylacetate-hexanes yielded the corresponding 2-(prop-2-ynyloxy)benzaldehydes in good yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With sodium sulfate; In ethanol; for 16h;Reflux; | General procedure: Commercially available salicylaldehyde (1 mmol) and sodium sulfate(0.5 g) were added to a solution of (S)-tert-leucinol (1 mmol) or Lvalinol(1 mmol) in ethanol (20 mL). The reaction mixture was stirredunder reflux for 16 h, filtered, and concentrated under reducedpressure. The reaction mixture was then dissolved in dichloromethane(10 mL) and washed with water (3 × 10 mL) and brine (15 mL). Theorganic layer was dried and concentrated under reduced pressure toleave the crude product, which was purified by column chromatographyon silica gel (8:2 hexane/ethyl acetate) to yield the pure ligand. (S)-2-(N-3,5-Diiodosalicylidene)-amino-3,3-dimethyl-1-butanol(10, Table 4):.22,36 Yellow solid, 79%, mp 164-165 C (lit. mp163-164);22 1H NMR δH (300 MHz) 1.00 (9H, s), 2.53 (1H, brs),3.08 (1H, dd, J = 9.5 and 2.5 Hz), 3.68 (1H, dd, J = 11.1 and 9.8 Hz),3.93-4.07 (1H, brm), 7.51 (1H, d, J = 2.1 Hz), 8.01 (1H, d, J = 2.1Hz), 8.10 (1H, s); IR νmax/cm-1 (KBr) 3320, 2965, 1638, 1479, 1217,1060; [α]D20 = -18.5 (c 0.1, acetone), lit.22 [α]D20 = -16.6 (c 1.0 for S inacetone). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With formic acid; In ethanol; at 20℃; for 3h; | General procedure: To a stirred solution of 3,5-dichlorosalicylaldehyde (2.00 g,10.47 mmol) in ethanol (20 mL) was slowly added 2,6-difluoroaniline (1.37 g, 10.47 mmol) at room temperature in the presence of trace amount of formic acid as a catalyst. The reaction mixture was stirred at room temperature for 3 h. Orange crystals were formed and then filtered. The product was obtained in 64%yield (2.74 g). 1H NMR data (500.13 MHz, CDCl3, 298 K): δ 13.77(s, 1H, OH), 8.87 (s, 1H, NCH), 7.48 (d, 4JHH 2.5, 1H, salicyl-H), 7.31(d, 4JHH 2.5, 1H, salicyl-H), 7.23e7.16 (m, 1H, aniline-H), 7.06e6.98(m, 2H, aniline-H). 13C NMR data (125.77 MHz, CDCl3, 298 K):δ 166.50 (HCN), 157.61 (d, CF), 156.22 (COH), 155.57 (d, CF), 133.61(salicyl-CH), 130.50 (salicyl-CH), 128.15 (t, aniline-CN), 124.14(t, CCHN), 123.90 (CCl), 123.35 (CCl), 120.68 (aniline-CH), 112.64(d, aniline-CH). Elemental analysis for C13H7Cl2F2NO: C, 51.68; H,2.34; N, 4.64%. Found C, 51.89; H, 2.31; N, 4.66%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In ethanol;Reflux; | General procedure: To a stirred ethanolic (25 mL) solution of 3,5-dihalosalicylaldehyde(2 mmol) was added an ethanolic (25 mL) solutionof the diamine (1 mmol). The reaction mixture was refluxedfor 1-3 h at 80-90 C in a water bath. The resulting solutionwas cooled to room temperature, and the resulting precipitatewas collected by suction filtration and washed withcold ethanol (3 × 10 mL) to afford the desired Schiff base. Single crystals of the isen, bspn and isbn suitable for X-ray diffraction experiments were obtained by slow evaporationof the hot ethanolic solution of the compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; In ethanol; at 20℃; | General procedure: To a stirred solution of salicylaldehyde (1 mmol) and malononitrile (1 mmol) in ethanol (5 ml), was added piperidine (40 mol %) and allowed stirring until the formation of precipitate. To this formed precipitate, was added azido ketone (1.5 mmol) and stirring was continued for the specified time. The progress of the reaction was monitored by thin layer chromatography using ethyl acetate: pet ether (3: 7) as an eluent. After the specified reaction time the ethanol was removed under vacuo and the crude product was purified by flash chromatography on silica gel (neutralized with five drops triethyl amine) (petroleum ether-ethyl acetate, 90/10-75/25). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In methanol; at 30℃; for 0.5h; | The ligand (L) was prepared by a slow addition of 2-picolyamine(0.1446 g, 1 mmol) in methanol to 3,5-diiodosalicyaldehyde (0.5 g,1 mmol). The mixture was stirred for 30 min at 30 C and the progressof reaction was monitored by TLC. The obtained yellow precipitatewas filtered off, washed thoroughly with methanol anddried in vacuo: Yield: 84%; M.P: 110 C; Color: yellow. IR (KBr,cm1): 3448 (AOH), 1633 (CHN), 1573(m), 1462(w) (CC),1437 (CN), 1429, 1356(m), 1276(m) (CAO).1H NMR (300 MHz, CDCl3) d:14.70 (s, 1H, OH), 8.56 (d, J = 4.8 Hz,1H, ArH), 8.32 (s, 1H, ACN), 8.04 (d, J = 2.1 Hz, 1H, ArH), 7.69 (td, J= 7.7, 1.8 Hz, 1H, ArH), 7.55 (d, J = 2.1 Hz, 1H, ArH), 7.33 (d, J= 7.8 Hz, 1H, ArH), 7.24-7.16 (m, 1H, ArH), 4.93 (s, 2H, ACH2).UV-vis (MeOH, nm) 235, 344, 406; ESI-MS (MeOH) Foundm/z = 464.75 [M + H] (calculated m/z = 463.89 for M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With diphenyl hydrogen phosphite; In toluene; for 3h;Reflux; | General procedure: Taking I-4a for example, 2-hydroxybenzaldehye (1 mmol), ethylamine (1 mmol), and diphenyl phosphite (1.2 mmol) were ordinally added in a single-port round bottom flask (25 mL), equipped with a reflux condenser and a drying tube, and then anhydrous toluene (3 mL) was added. The residue was precipitated after 2 h under reflux. Reflux the reaction mixture gently for a further hour. After cooling, methanol (3 mL) was added to the reaction and was filtered out. Then the filtered residue was washed with methanol (44 mL). The pure product I-4a could be obtained and dried in a vacuum dryer. The other products were obtained by this similar method. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With diphenyl hydrogen phosphite; In toluene; for 3h;Reflux; | General procedure: Taking I-4a for example, 2-hydroxybenzaldehye (1 mmol), ethylamine (1 mmol), and diphenyl phosphite (1.2 mmol) were ordinally added in a single-port round bottom flask (25 mL), equipped with a reflux condenser and a drying tube, and then anhydrous toluene (3 mL) was added. The residue was precipitated after 2 h under reflux. Reflux the reaction mixture gently for a further hour. After cooling, methanol (3 mL) was added to the reaction and was filtered out. Then the filtered residue was washed with methanol (44 mL). The pure product I-4a could be obtained and dried in a vacuum dryer. The other products were obtained by this similar method. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | In methanol; at 20℃; for 72h; | To a solution of (1S,2R)-(+)-2-amino-1,2-diphenylethanol (200.0 mg, 0.94 mmol, 1.0 equiv) in anhydrous methanol (3 mL) and MgSO4 (564.4 mg, 5.0 equiv) a solution of <strong>[2631-77-8]3,5-diiodosalicylaldehyde</strong> (350.6 mg, 0.94 mmol, 1.0 equiv) in methanol (14 mL) was added dropwise. After the reaction mixture was stirred for 3 d at room temperature, MgSO4 was filtered off, and the solution was concentrated and purified by flash column chromatography (SiO2, PE/EtOAc 3:1) to afford the desired product in 56% yield (300.0 mg) as an orange foam. 1H NMR (300 MHz, CDCl3): δ=2.04 (br s, 1H), 4.48 (d, J=7.3 Hz, 1H), 5.00 (d, J=7.3 Hz, 1H), 7.19-7.39 (m, 11H), 7.77 (s, 1H), 7.98 (d, J=2.0 Hz, 1H), 14.44 (s, 1H). 13C NMR (100 MHz, CDCl3): 78.0, 79.3, 79.7, 87.3, 119.8, 127.0, 127.9, 128.3, 128.4, 128.9, 138.4, 139.7, 139.9, 148.7, 160.4, 163.6. FAB: m/z=570 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With piperdinium acetate; In ethanol; for 2h;Reflux; | General procedure: A mixture of the appropriate aldehyde (8.06 mmol), Meldrum’s acid (1) (1.16 g, 8.06 mmol) and piperidinium acetate (29 mg, 0.2 mmol) in ethanol (25 mL) was stirred at room temperature for 20 mins and then heated under reflux for 2 h. The reaction mixture was allowed to cool to room temperature before being stirred at 0 C for another hour. The solid which precipitated out of solution was filtered off, washed thoroughly with ethanol and dried in vacuo to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 20℃; | Step 1: Synthesis of Intermediate, 2-[4-(diethylamino)piperidin-1-yl]methyl}- 4,6-diiodophenol 1: Sodium triacetoxyborohydride (8.56g, 38.4mmol) was added portionwise to a solution of <strong>[2631-77-8]2-hydroxy-3,5-diiodobenzaldehyde</strong> (9.8g, 26.0mmol),/V,/V-diethylpiperidin-4-amine (4.0g, 26.0mmol) and acetic acid (1 .5ml_, 26.0mmol) in dichloromethane (60ml_). After 4-5h of stirring at rt, the reaction was diluted with dichloromethane before being washed with saturated aqueous solution of NaHC03. The organic layer was dried over Na2S04, filtered and evaporated. The residue was purified on silica gel (dichloromethane/methanol 99/1 to 95/5 with 1 % triethylamine) to provide 2-[4-(diethylamino)piperidin-1 -yl]methyl}-4,6- diiodophenol (8.5g, 1 6.5mmol, 64% yield) as a beige foam. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In ethanol; at 20℃;Inert atmosphere; Schlenk technique; Molecular sieve; | General procedure: To a mixture of salicylaldehyde 1a-f, 1,3-dihydro-α,β-diphenyl-2H-isoindole -2-ethanamine 2 (equivalent to 1a-f), and several 4 Å sieves in a septum capped Schlenk tube was added anhydrous ethanol (ca. 10 mL per mmol of 1a-f) via syringe at 20 C with stirring under nitrogen. After stirring the resulting mixture overnight, the solvent was removed under vacuum, and the residue was purified by flash chromatography on silica gel (Vethyl acetate/Vpetroleum ether = 1/20) to give the brown target ligands 3a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | In methanol; at 40℃; for 12h;Inert atmosphere; | General procedure: To a solution of 8 (1.73 g, 5 mmol) in MeOH (20 mL) was added salicylaldehyde (5 mmol) 9a-d and the resulting mixture was warmed to 40 C and stirred for 12 h. After cooling to 0 C, the precipitate was filtered off and washed with cold methanol to give the target ligand precursors H(La-d). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In methanol; for 3h;Reflux; | The ligand was prepared by the following method. A solution of <strong>[2631-77-8]3,5-diodosalicylaldehyde</strong> (1 mmol, 0.4 g) in methanol (15 ml) was added dropwise to a solution of 4-phenylthiosemicarbazide (1 mmol, 0.17 g) in methanol (15 ml) with stirring at reflux. After being stirred for 3 h, the resulting white solids were removed by filtration, washed with cold ethanol and dried in vacuo over anhydrous CaCl2. M.p: 192 C, Yield: 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With acetic acid; In ethanol;Reflux; | Schiff base ligand were synthesized by refluxing of 3,5 diiodosalicylaldehyde (0.01M) and 4-bromo-2,6-dichlorobenzenamine (0.01 M) in 50ml ethanol on water bath for 4-5 hours inpresence of 2-3 drops of glacial acetic acid. The reaction mixture was kept for overnight, where yellow color precipitate was obtained. It was filtered by whatmann paper, washed with distilled water then alcohol, dried in vacuum dessicator. Pure Schiff base was recrystallized from ethanol. The purity ofligand was checked by TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | General procedure: A mixture of salicylaldehyde (1 mmol), 4-hydroxycoumarin (1mmol), and L-proline (0.1 mmol) in EtOH (5 mL) was heated to reflux for 6 h. Indole or barbituric acid (1 mmol) was then added to the reaction mixture and reflux continued with stirring for a further 6-8 h (monitoring by TLC). The solid formed was filtered washed with EtOH then with H2O to afford analytically pure product. |
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