Structure of 3-Iodophenol
CAS No.: 626-02-8
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CAS No. : | 626-02-8 |
Formula : | C6H5IO |
M.W : | 220.01 |
SMILES Code : | OC1=CC=CC(I)=C1 |
MDL No. : | MFCD00002261 |
InChI Key : | FXTKWBZFNQHAAO-UHFFFAOYSA-N |
Pubchem ID : | 12272 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.93 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.39 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.6 |
Solubility | 0.0546 mg/ml ; 0.000248 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.02 |
Solubility | 0.212 mg/ml ; 0.000963 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.78 |
Solubility | 0.366 mg/ml ; 0.00166 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 |
-5.56 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 |
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) |
1.9 |
* 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 |
---|---|---|
50% | With triethylamine; magnesium chloride; In acetonitrile;Cooling with ice; | 10 g (45 mmol) of 3-iodobenzoic acid was dissolved in 160 ml of anhydrous acetonitrile, 12.8 g (134 mmol) of anhydrous magnesium chloride was added thereto in portions under ice-cooling, followed by addition of 25.3 ml of triethylamine, (636 mmol) of paraformaldehyde was added in batches, and the reaction was quenched by adding 1 M HC1 to adjust the pH to 5. After the reaction, the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and the solvent was passed through 100- 200 mesh silica gel column chromatography, eluting with petroleum ether to give 15.6 g of intermediate, 50% yield |
40% | With triethylamine; magnesium chloride; In acetonitrile; at 85℃; for 24h; | In a 100ml reaction bottle,1.5 g (6.8 mmol) of 3-iodophenol and 2 g (21.1 mmol) of anhydrous magnesium chloride were dissolved in 50 ml of anhydrous acetonitrile and 6 ml (43.2 mmol) of triethylamine solution.Then 2g (66.7mmol) of paraformaldehyde was added,The reaction was carried out at 85 C for 24 hours; the reaction was cooled to room temperature.It was then neutralized with 1 N HCl solution and extracted three times with dichloromethane.Drying anhydrous Na2SO4, steaming to obtain crude product,Finally, it was separated and purified by silica gel column chromatography to obtain 0.69 g of product.The yield was 40%. |
36% | With triethylamine; magnesium chloride; In acetonitrile;Reflux; Inert atmosphere; | To a dry CH3CN solution (10 mL) of the 1.1 g phenol (5 mmol), anhydrous magnesium chloride (1.42 g, 15 mmol), triethylamine (5.5 mL, 40 mmol) and paraformaldehyde (2.1 g, 70 mmol) were added. The reaction mixture was heated to reflux under an argon atmosphere for overnight and monitored by TLC. Upon cooling, the reaction mixture was dilute with diethyl ether (20 mL). The organic layer was washed successively with HCl (1 M, 2*10 mL) and water (2*10 mL), and then dried (MgSO4). The product was puried by column chromatography (PE EA = 50:1) to afford 0.451 g (36%) 4b? as white solid. |
To a solution of 3-iodophenol (3.00 g, 13.6 MMOL) in acetonitrile (50 mL) was added magnesium chloride (3.89 g, 40.9 MMOL), triethylamine (7.6 mL, 55 MMOL), and PARAFORMALDEHYDE (1.64 g, 55 MMOL). The reaction mixture was REFLUXED overnight, then neutralized with saturated aqueous ammonium chloride. The resultant red precipitate was removed by filtration, and the filtrate was extracted with ethyl acetate. The precipitate was dissolved in methanol and added to the combined organic extracts, which were then dried over magnesium sulfate. The solvent was removed under reduced pressure to provide an orange solid (5.4 g) as the crude product. This material was used in the subsequent step without further purification. | ||
3-Iodophenol (1Og, 45mmol) was dissolved in anhydrous acetonitrile (160ml), cooled in an ice bath and magnesium chloride (12.8g, 134mmol) added portionwise over 1010 mins. Triethylamine (25.3ml, 363mmol) was added to this mixture over 5 mins, followed by portionwise addition of paraformaldehyde (5.47g, 636mmol). After complete addition the mixture was heated at reflux for 18.5 hours. The mixture was cooled and quenched by the addition of sat. NH4Cl (350ml) and extracted with EtOAc (3 xl50ml). The combined EtOAc layers were washed with sat. NaHCO3 (2 x 150mml), IN HCl (2 x 150ml), and sat. NaCl (2 x15 100ml), dried over Na2SO4, filtered and evaporated. The residue was purified by MPLC on silica gel eluting with a gradient rising from 100% hexanes to 20% EtOAc in hexanes. Product containing fractions were combined and evaporated and recrystallised from hot hexanes to give of the title compound. 1HNMR (500 MHz, CDCl3) delta: 11.02 (s, IH), 9.87 (s, IH), 7.46 (d, IH), 7.42 (dd, IH), 7.25 (d, IH).20 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The reaction was carried out in a large flask equipped with a stirrer and reflux condenser. A solution of 3-Iodophenol (1Og; 45,4 mmol) in acetonitrile (160 ml) was cooled in an ice-water bath and magnesium chloride (12.8g; 134.4 mmol) was added to the phenol in small batches over 10 minutes to give a pink cloudy solution. Triethylamine (50.6 ml; 363.2 mmol) was added to the acetonitrile solution gradually over 5 minutes keeping the solution at ~0 0C and this was followed with the addition of paraformaldehyde (19.2g; 636 mmol) in small 0.5-lg batches over 10 minutes. Once the addition of the paraformaldehyde was complete the reaction vessel with the reflux condenser in place was removed from the cooling bath and warmed quickly to 80 0C (bath temperature). After 0.25 h of heating the solids started to dissolve and around 1 h of heating the reaction solution was almost a homogeneous golden yellow color which slowly started to turn to an orange color. The reaction was kept at 80 0C for 18.5 hours; the reaction had become a deep orange in color. The reaction mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride solution (350 ml). The aqueous acetonitrile mixture was shaken with EtOAc (150 ml) and transferred into a separatory funnel. The layers were separated and the aqueous layer extracted with EtOAc (2 x 150 ml). The three EtOAc layers were combined and washed successively with saturated aqueous NaHCO3 (2 x 150 ml), IN hydrochloric acid (2 x 150 ml) and lastly with saturated brine (2 x 100 ml). The orange colored solution with the crude product was dried over anhydrous Na2SO4 powder, filtered through a Celite pad and the filtrate concentrated under reduced pressure to leave an orange colored oil that slowly solidified on standing. The solid was purified in 3 batches on a Biotage SPl system on 4OM Flash silica cartridge using a gradient of EtOAc and hexanes 0->2% (350 ml), 2->15% (1250 ml) 15->20% (350 ml). The aldehyde fractions were concentrated down to leave an off-white feathery solid. This solid was crystallized from hexanes to give 6g of the pure aldehyde. The mother liqours were purified on silica gel preparative tic plates eluted with EtOAc and hexanes (7:93 v/v) from which a further 300 of the desired aldehyde was recovered (Total 6.3g). There was also -800 mg of the isomeric aldehyde obtained from the purification. The NMR data for 2-hydroxy-4-iodobenzaldehyde is as follows :- 1H-NMR (400 MHz, CDCl3) delta: 7.25 (d, J = 8 Hz, IHO, 7.42 (dd, J = 8 & 1.5 Hz, IH), 7.46 (d, J - 1.5Hz, IH), 9.87 (s, IH)5 11.04 (s, IH).The NMR data for the isomeric 2-hydroxy-6-iodobenzaldehyde was:- 1H-NMR (400 MHz, CDCl3) delta: 6.99 (d, J = 8 Hz, IH), 7.15 (t, J = 8 Hz, IH)3 7.50 (d, J = 8 Hz, IH), 10.09 (s, IH), 12.07 (s, IH). |
Tags: 626-02-8 synthesis path| 626-02-8 SDS| 626-02-8 COA| 626-02-8 purity| 626-02-8 application| 626-02-8 NMR| 626-02-8 COA| 626-02-8 structure
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