Structure of 3,5-Dichlorobenzyl alcohol
CAS No.: 60211-57-6
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CAS No. : | 60211-57-6 |
Formula : | C7H6Cl2O |
M.W : | 177.03 |
SMILES Code : | C1=C(C=C(C=C1CO)Cl)Cl |
MDL No. : | MFCD00004634 |
InChI Key : | VSNNLLQKDRCKCB-UHFFFAOYSA-N |
Pubchem ID : | 43236 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.9 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.72 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.96 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.61 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.14 |
Solubility | 0.127 mg/ml ; 0.00072 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.99 |
Solubility | 0.183 mg/ml ; 0.00103 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.46 |
Solubility | 0.062 mg/ml ; 0.00035 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 |
-5.32 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 |
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) |
1.21 |
* 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 |
---|---|---|
82% | With thionyl chloride; at 60℃; for 2h; | (3,5-Dichlorophenyl)methanol 6a (7.5 g, 42.6 mmol) was dissolved in 50 mL of thionyl chloride and reacted at 60 ° C for 2 hours. The organic layer was extracted with EtOAc (EtOAc m. Analytical method (eluent: A system) purification,1,3-Dichloro-5-(chloromethyl)benzene 27a (6.8 g, pale yellow liquid) was obtained. Yield: 82percent. |
With pyridine; hydrogenchloride; thionyl chloride; In chloroform; water; | Step A Synthesis of 3,5-dichlorophenylmethyl chloride as an intermediate Under a nitrogen atmosphere, a stirred solution of 25.0 grams (0.141 mole) of 3,5-dichlorophenylmethanol and 11.4 mL (0.141 mole) of pyridine in 200 mL of chloroform was cooled to 5 C., and 15.9 mL (0.218 mole) of thionyl chloride was added dropwise during a 10 minute period. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it was stirred for about 18 hours. After this time, the reaction mixture was poured into 300 mL of water, and the mixture was extracted with 600 mL of diethyl ether. The ether solution was washed with 70 mL of an aqueous 6N hydrochloric acid solution, and then it was concentrated under reduced pressure to a residual oil. The oil was distilled under reduced pressure, yielding 25.6 grams of 3,5-dichlorophenylmethyl chloride, bp 95-100 C./0.1 mm Hg. | |
With thionyl chloride; In N,N-dimethyl-formamide; | (i) 3,5-Dichlorophenylacetonitrile A mixture of <strong>[60211-57-6]3,5-dichlorobenzyl alcohol</strong> (Aldrich, 25g), thionyl chloride (100ml) and DMF (0.5ml) was stirred and refluxed for 4 hours. After cooling the mixture was concentrated in vacuo , the residue was taken up in ether, washed with saturated aqueous NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to give 3,5-dichlorobenzylchloride as a light yellow solid, which was used without further purification, 28g, mp. 32-36C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.9% | With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 2h; | 3,5-Dichlorobenzoic acid 2a (5.0 g, 26.32 mmol) was dissolved in 50 mL of tetrahydrofuran, and a borane tetrahydrofuran solution (52.6 mL, 52.64 mmol, 1 M/THF) was added dropwise at 0 C, and the mixture was reacted at room temperature for 2 hours. At 0 C, 50 mL of 10% sodium hydroxide solution was added to quench the reaction. The organic layer was washed with a saturated sodium chloride solution (50 mL). Methanol 6a (4.0 g, white solid), yield: 86.9% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
All the aforementioned filtrates were combined, evaporated, and chromatographed on a column of silica gel eluted in 18 ml fractions with 49:1 (v/v) dichloromethane-methanol. Fractions 22-37 were combined and evaporated under vacuum to provide 1.28 g of solid 4-(4-chlorophenylthio)-3,5-dichlorobenzyl alcohol (B). Fractions 38-60 were combined, evaporated under vacuum, and the residue was triturated with diethyl ether, filtered, washed with diethyl ether, and dried under vacuum to provide 486 mg of A (total yield: 2.37 g); 60 MHz 'H NMR (DMSO-d6) A : 4.56 d (J=5Hs, 2H), 5.56 t (J=5Hz, 1H), 7.50 s (2H), 7.60 s (4H); B : 4.56 d (J=6Hz, 2H), 5.53 t (J=6Hz, 1H), 7.01 dm (J=8.5Hz, 2H), 7.34 dm (3=8.5Hz, 2H), 7.57 s (2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With bromine; triphenylphosphine; In tetrachloromethane; for 0.75h;Heating / reflux; | A solution of bromine (3.17ml, 61 mmol) in carbon tetrachloride (50ml) was added to a solution of triphenylphosphine (16.13g, 61 mmol) in carbon tetrachloride (250ml). <strong>[60211-57-6]3,5-Dichlorobenzyl alcohol</strong> (10.0g, 56mmol) was added as a solution in carbon tetrachloride (50ml) and the reaction mixture was heated at reflux for 45 minutes. Hexane was added. The mixture was filtered through silica and washed with hexane. The filtrate was concentrated under reduced pressure to provide the title compound (12.79g, 95%). 1H-NMR (400MHz, CDCl3) : delta = 4.37 (s, 2H), 7.24-7.28 (m, 3H). |
86% | Example 12. Benzyl-[l-(3,5-dichloro-benzyl)-lH-imidazol-2-yl]-amine EPO <DP n="72"/>12To a solution of <strong>[60211-57-6]3,5-dichlorobenzylalcohol</strong> in anhydrous THF at -30 0C was added Et3N. Mesyl chloride in THF was added to the solution dropwise. The reaction mixture was stirred at that temperature for 1 h until all the starting material was consumed. Then, LiBr was added to the reaction mixture and stirred for another 2 h. When the reaction was over, the reaction mixture was diluted with EtOAc and washed with water (x3). The organic phase was dried over Na2SO4 and concentrated to afford 1-bromomethy 1-3,5 -dichloro- benzene as a light brown solid (9.3 g, 86%). | |
With phosphorus tribromide; In dichloromethane; at 20℃; for 16h; | Reference example 9; (1) To 100 ml of a dichloromethane solution containing 10.0 g of 3, 5-dichlorobenzyl alcohol was added 15.3g of Phosphorus tribromide, and the mixture was stirred at room temperature for 16 hours. To the reaction mixture were added chloroform and water, the mixture was separated, and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 13.6 g of 3, 5-dichlorobenzylbromide shown in the following Table 72. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h; | To a solution of <strong>[60211-57-6](3,5-dichlorophenyl)methanol</strong> (10.0 g, 56.5 mmol) in methylene chloride (100 mL) at 0 0C was added 2,6-lutidine (16.4 mL, 141 mmol) followed by triisopropylsilyl triflate (19.7 mL, 73.4 mmol), and was stirred at 0 0C for 2 hours. The reaction was diluted with water and the organic layer was separated, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by chromatography on silica gel, eluting with hexane to provide the desired product (14.8 g, 79%). LC/MS: 333 (M+H)+, 1H NMR (CDCl3) delta 7.23 (s, 3H), 4.78 (s, 2H), 1.18 (m, 3H), 1.03 (s, 18H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -20℃; for 1h;Industry scale;Product distribution / selectivity; | Step 2aCharged methylene chloride to a portable reactor and cool to less than -20 C. Charged 1.1 eqs triflic anhydride to the portable reactor maintaining the temperature below -20 C.In a separate reactor, charged <strong>[60211-57-6]3,5-dichlorobenzyl alcohol</strong> (3) (1.1 eqs), methylene chloride and N,N-diisopropylethylamine (1.13 eqs) and mix for NLT 1 hour to dissolve solids. Cooled the solution to less than -10 C. and slowly transfer to the triflic anhydride solution in the portable reactor maintaining the internal temperature at less than -20 C., producing (4). Mixed the reaction solution at less than -20 C. for NLT 1 hour. |
Tags: 60211-57-6 synthesis path| 60211-57-6 SDS| 60211-57-6 COA| 60211-57-6 purity| 60211-57-6 application| 60211-57-6 NMR| 60211-57-6 COA| 60211-57-6 structure
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