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Structure of 2420-16-8

Chemical Structure| 2420-16-8

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Product Details of [ 2420-16-8 ]

CAS No. :2420-16-8
Formula : C7H5ClO2
M.W : 156.57
SMILES Code : C1=C(C(=CC=C1C=O)O)Cl
MDL No. :MFCD00016981
InChI Key :VGSOCYWCRMXQAB-UHFFFAOYSA-N
Pubchem ID :17022

Safety of [ 2420-16-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 2420-16-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
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 38.86
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.42
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.89
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.86
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.39
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.74

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.38
Solubility 0.654 mg/ml ; 0.00417 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.3
Solubility 0.792 mg/ml ; 0.00506 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.37
Solubility 0.663 mg/ml ; 0.00424 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.91 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.02

Application In Synthesis of [ 2420-16-8 ]

* 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.

  • Downstream synthetic route of [ 2420-16-8 ]

[ 2420-16-8 ] Synthesis Path-Downstream   1~7

  • 2
  • [ 2420-16-8 ]
  • [ 74-88-4 ]
  • [ 4903-09-7 ]
YieldReaction ConditionsOperation in experiment
97% REFERENCE EXAMPLE 4 3-Chloro-4-methoxybenzaldehyde Following a similar procedure to that described in reference example 3, but starting from 3-chloro-4-hydroxybenzaldehyde instead of 4-hydroxybenzaldehyde and using methyl iodide instead of 2-iodopropane, the title compound of the example was obtained as an oil (97% yield). 1H-NMR (300 MHz, CD3OD delta TMS): 3.98 (s, 3H), 7.04 (d, J=8.4 Hz, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.89 (s, 1H), 9.84 (s, 1H).
96% With potassium carbonate; In N,N-dimethyl-formamide; at 25 - 80℃; for 1.5h; Toa mixture of 3-chloro-4-hydroxybenzaldehyde(10.00 g, 63.87 mmol, 1.0 eq) and potassium carbonate (26.48g, 191.61 mmol, 3.0 eq) in DMF (150 mL) was added dropwiseiodomethane (43.23 g, 304.57 mmol,18.96 mL, 4.8 eq) over 30 min at 25 C. The mixture was heated at80 Cfor 1 h. It was cooled to rt, diluted with water (500 mL) and extracted with ethyl acetate (3x500 mL). The combined organic layerswere washedwith saturated brine (3x200 mL), driedover anhydrous sodium sulfate,filtered and concentrated under reduced pressure. The crude product waspurified by flash column chromatography (silica gel, petroleum ether/ethylacetate = 20: 1 to 5: 1) to give the title compound (10.50 g, 61.55 mmol, 96%yield) as a yellow solid.1H NMR: (CDCl3,400 MHz) delta 9.87 (s, 1H), 7.92 (d, J =2.0 Hz, 1H), 7.79 (dd, J =2.0,8.4 Hz, 1H), 7.06 (d, J =8.4 Hz, 1H), 4.00 (s, 3 H).
93% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 1h;Inert atmosphere; To a stirred solution of 3-chloro-4-hydroxybenzaldehyde (2.9 g, 18.412 mmol) in DMF (30 mL) was added K2CO3 (7.6 g, 55.238 mmol). CH3I (7.80 g, 55.238 mmol) was then added slowly at RT under an inert atmosphere. After addition was completed, the reaction mixture was brought to 80 0C and stirred for 1 h. The reaction mixture was quenched with water (20 mL) and extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to obtain crude product. The crude material was purified via silica gel column chromatography to afford 3-chloro-4-methoxybenzaldehyde (2.78 g, 93%) as a yellow solid.
56% In diethyl ether; acetone; 3-Chloro-4-methoxybenzaldehyde A mixture of 3-chloro-4-hydroxybenzaldehyde (25 g, 160 mmol), iodomethane (27.25 g, 192 mmol), KCO3 (granular, anhydrous) (110.6 g, 800 mmol), and acetone (300 mL) was refluxed for 3 hours. The reaction mixture was then cooled to room temperature. Diethyl ether (500 mL) was added and the mixture was filtered through paper to remove the inorganic solids. The filtrate was evaporated under reduced pressure, dissolved in diethyl ether (800 mL), and washed with 0.1 N NaOH (3*100 mL). The organic layer was dried (Na2SO4) and evaporated under vacuum to yield 24 g, 92% yield of crude product. This material was further purified by chromatography on silica gel (50 mm*30 cm) (elution with hexane-EtOAc, 5:1) to give 15.02 g, 56% yield of a white solid: TLC (hexane-EtOAc, 5:1) Rf=0.24; GC Rt=4.75 min; MS (EI) m/z 170(M+), 172(M+2).
With potassium carbonate; In N-methyl-acetamide; PREPARATION 43 To a solution of 3-chloro-4-hydroxybenzaldehyde (153 g) in dimethylformamide (500 ml) was added potassium carbonate (203 g) under ice-cooling, followed by iodomethane (91.3 ml). After stirring at ambient temperature for 2 hours, the mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer were washed with water and brine, dried over magnesium sulfate and evaporated in vacuo. The oily residue was triturated with n-hexane to obtain 3-chloro-4-methoxybenzaldehyde (156 g) as a white powder. NMR(CDCl3, delta): 4.00 (3H, s), 7.05 (1H, d, J=8 Hz), 7.78 (1H, dd, J=2 Hz, 8 Hz), 7.92 (1H, d, J=2 Hz), 9.86 (s, 1H).

  • 3
  • [ 2420-16-8 ]
  • [ 584-08-7 ]
  • [ 74-88-4 ]
  • [ 4903-09-7 ]
YieldReaction ConditionsOperation in experiment
56% In diethyl ether; acetone; 3-Chloro-4-methoxybenzaldehyde A mixture of 3-chloro-4-hydroxybenzaldehyde (25 g, 160 mmol), iodomethane (27.25 g, 192 mmol), K2 CO3 (granular, anhydrous) (110.6 g, 800 mmol), and acetone (300 mL) was refluxed for 3 hours. The reaction mixture was then cooled to room temperature. Diethyl ether (500 mL) was added and the mixture was filtered through paper to remove the inorganic solids. the filtrate was evaporated under reduced pressure, dissolved in diethyl ether (800 mL), and washed with 0.1 N NaOH (3*100 mL). The organic layer was dried (Na2 SO4) and evaporated under vacuum to yield 24 g, 92percent yield of crude product. This material was further purified by chromatography on silica gel (50 mm*30 cm) (elution with hexane-EtOAc, 5:1) to give 15.02 g, 56percent yield of a white solid: TLC (hexane-EtOAc, 5:1) Rf =0.24; GC Rt =4.75 min; MS (EI) m/z 170(M+), 172(M+2).
56% In diethyl ether; acetone; 3-Chloro-4-methoxybenzaldehyde A mixture of 3-chloro-4-hydroxybenzaldehyde (25 g, 160 mmol), iodomethane (27.25 g, 192 mmol), K2 CO3 (granular, anhydrous) (110.6 g, 800 mmol), and acetone (300 mL) was refluxed for 3 hours. The reaction mixture was then cooled to room temperature. Diethyl ether (500 mL) was added and the mixture was filtered through paper to remove the inorganic solids. the filtrate was evaporated under reduced pressure, dissolved in diethyl ether (800 mL), and washed with 0.1N NaOH (3*100 mL). The organic layer was dried (Na2 SO4) and evaporated under vacuum to yield 24 g, 92percent yield of crude product. This material was further purified by chromatography on silica gel (50 mm*30 cm) (elution with hexane-EtOAc, 5:1) to give 15.02 g, 56percent yield of a white solid: TLC (hexane-EtOAc, 5:1) Rf =0.24; GC Rt =4.75 min; MS (EI) m/z 170(M+), 172(M+2).
  • 4
  • [ 2420-16-8 ]
  • [ 77-78-1 ]
  • [ 4903-09-7 ]
YieldReaction ConditionsOperation in experiment
85% Finely powdered potassium carbonate (18.1 g, 0.131 mol, 2 eq) was added to a well stirred solution of 3-chloro-4-hydroxybenzaldehyde (10 g, 0.064 mol, 1 eq) in acetone (80 mL) under nitrogen. After 10 min., dimethylsulphate (8 g, 0.064 mol, 1 eq) was added slowly at room temperature and stirred for 30 min. The reaction mixture was allowed to reflux for 2h. Reaction progress was monitored by TLC, Reaction mixture cooled to room temperature and K2CO3 was filtered, acetone was distilled out in vacuo to obtain residue and was triturated with hexane (20 mL) at O0C for 30 min. to result pale green colored solid. Yield 9.2 g (85percent).
  • 5
  • [ 2420-16-8 ]
  • [ 76350-90-8 ]
  • 3-chloro-4-((2-methyl-[1,1'-biphenyl]-3-yl)methoxyl)benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.97 g With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; Diisopropyl azodicarboxylate (1.01 g, 5 mmol) in THF (30 mL) was added dropwise to a cooled (0 C) solution of 4-hydroxy-3-chlorobenzaldehyde (0.782 g, 5 mmol), triphenylphosphine (1.3 g, 4.99 mmol) and intermediate 1A, 2 -methyl- [1,1 '- biphenyl]-3-yl)methanol (0.90 g, 4.54 mmol) in dry THF (30 mL). The resulting yello solution was allowed to slowly warm to room temperature with stirring overnight. Solvent was removed by rotary evaporator. The residue was purified on a 40 g silica gel column with 10: 1 Hexane:Ethyl acetate. Isolated 0.97 g of the desired product as white solid. 1H NMR (400MHz, CHLOROFORM-d) delta 9.90 (s, 1H), 7.98 (d, J=2.0 Hz, 1H), 7.81 (dd, J=8.6, 2.0 Hz, 1H), 7.53 - 7.49 (m, 1H), 7.49 - 7.43 (m, 2H), 7.39 (d, J=7.1 Hz, 1H), 7.36 - 7.29 (m, 4H), 7.20 (d, J=8.3 Hz, 1H), 5.30 (s, 2H), 2.30 (s, 3H).
  • 6
  • [ 7504-94-1 ]
  • [ 2420-16-8 ]
  • C11H9ClN4O [ No CAS ]
  • 7
  • [ 2420-16-8 ]
  • [ 15469-97-3 ]
  • 2-chloro-4-[(1-trityl-1H-imidazol-2-yl)hydroxymethyl]phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% General procedure: To a solution of 1-tritylimidazole (8.12 g, 26.160 mmol) in anhydrous THF (165 mL) was added n-BuLi (1.28 M in THF, 20.0 mL, 1.67 g, 13.08 mmol) at -20°C over a period of 20 min under nitrogen atmosphere. The red solution was allowed to attain room temperature and stirred for 1 h, then cooled to -78°C. In a separate flask the appropriate aldehyde 1a?c (10.47 mmol) was dissolved in anhydrous THF (4 mL) and added to the red solution dropwise at -78 °C. The reaction mixture was stirred at -78°C for 1 h and slowly brought to room temperature during which red color tuned to yellow and then to colorless. After complete reaction, saturated NH4Cl (250 mL) was added to the reaction mixture at -78°C. The resulting mixture was extracted with EtOAc (3 x 100 mL); the organic layer was separated, washed with water, saturated NaCl, and dried over anhydrous Na2SO4. The organic layer was evaporated in vacuo and the residue washed with cold CH2Cl2.
 

Historical Records

Technical Information

• Acidity of Phenols • Alkyl Halide Occurrence • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Electrophilic Substitution of the Phenol Aromatic Ring • Etherification Reaction of Phenolic Hydroxyl Group • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Halogenation of Phenols • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Julia-Kocienski Olefination • Kinetics of Alkyl Halides • Knoevenagel Condensation • Kumada Cross-Coupling Reaction • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nozaki-Hiyama-Kishi Reaction • Oxidation of Phenols • Passerini Reaction • Paternò-Büchi Reaction • Pechmann Coumarin Synthesis • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reformatsky Reaction • Reimer-Tiemann Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Stetter Reaction • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

Categories

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[ 2420-16-8 ]

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