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Chemical Structure| 697-82-5 Chemical Structure| 697-82-5

Structure of 2,3,5-Trimethylphenol
CAS No.: 697-82-5

Chemical Structure| 697-82-5

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Synonyms: Isopseudocumenol

4.5 *For Research Use Only !

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Product Details of [ 697-82-5 ]

CAS No. :697-82-5
Formula : C9H12O
M.W : 136.19
SMILES Code : OC1=CC(C)=CC(C)=C1C
Synonyms :
Isopseudocumenol
MDL No. :MFCD00002228
InChI Key :OGRAOKJKVGDSFR-UHFFFAOYSA-N
Pubchem ID :12769

Safety of [ 697-82-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P260-P280-P303+P361+P353-P301+P330+P331-P304+P340+P310-P305+P351+P338+P310
Class:8
UN#:2430
Packing Group:

Computational Chemistry of [ 697-82-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 43.36
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.09
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

2.66
Log Po/w (WLOGP)?

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

2.32
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.

2.46
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

2.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.45

Water Solubility

Log S (ESOL):?

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

-2.8
Solubility 0.214 mg/ml ; 0.00157 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.

-2.74
Solubility 0.25 mg/ml ; 0.00184 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

-2.95
Solubility 0.152 mg/ml ; 0.00111 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.

-5.24 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

2.0
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

0.0 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)

1.0

Application In Synthesis of [ 697-82-5 ]

* 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 [ 697-82-5 ]

[ 697-82-5 ] Synthesis Path-Downstream   1~8

  • 2
  • [ 79-21-0 ]
  • [ 697-82-5 ]
  • [ 935-92-2 ]
  • [ 700-13-0 ]
  • [ 13038-87-4 ]
  • [ 20469-61-8 ]
  • [ 34649-27-9 ]
  • 5-acetoxy-2,4-dihydroxy-2,4,5-trimethyl-3,6-lacto-1-hexanoic acid [ No CAS ]
  • 3
  • [ 697-82-5 ]
  • [ 64-19-7 ]
  • [ 935-92-2 ]
  • [ 13038-87-4 ]
  • [ 20469-61-8 ]
  • [ 34649-27-9 ]
  • 1-acetoxy-4-methoxy-2,3,5-trimethylbenzene [ No CAS ]
  • [ 109576-73-0 ]
  • 4
  • [ 697-82-5 ]
  • [ 74-88-4 ]
  • [ 20469-61-8 ]
YieldReaction ConditionsOperation in experiment
48% General procedure: To a solution of the respective phenol derivative (23f-k, 15.0 mg, 0.11 mmol, 1 equiv) in dry DMF (2.2 mL), K2CO3 (15.2 mg, 0.11 mmol, 1 equiv) was added and the mixture was stirred at room temperature for 30 min. Methyl iodide (31 mg, 0.22 mmol, 2 equiv) was added and the reaction mixture was stirred at room temperature overnight. The reaction was quenched by addition of water and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel (cyclohexane/ethyl acetate 20:1).The pure products were obtained as pale yellow liquids.
In water; dimethyl sulfoxide; (1) Synthesis of 2,3,5-trimethylanisole In 100 ml of DMSO were dissolved 10 g of 2,3,5-trimethylphenol and 10.4 ml of methyl iodide. Under ice-cooling, 5.6 g of 60% sodium hydride in oil was added, and the mixture was stirred at room temperature for 10 hours. After addition of water, the extraction with ether was carried out. The ether layer was washed with water and dried over anhydrous sodium sulfate. Removal of the solvent by distillation leaves the oily substance. Yield 12.9 g (quantitative)
In water; dimethyl sulfoxide; (1) Synthesis of 2,3,5-trimethylanisole In 100 ml of dimethyl sulfoxide were dissolved 10 g of 2,3,5-trimethylphenol and 10.4 ml of methyl iodide and the solution was ice-cooled. To this solution was added 5.6 g of 60% oily sodium hydride and the mixture was stirred for 10 hours. Water was added and the resulting mixture was extracted with ether. The ether layer was washed with water and dried over anhydrous sodium sulfate. The solvent was then distilled off to give an oily substance. Yield 12.9 g (quantitative).
  • 6
  • [ 697-82-5 ]
  • phytyl bromide (1-bromo-3,7,11,15-tetramethyl-hexadec-2-ene [ No CAS ]
  • [ 80745-10-4 ]
  • 7
  • 3-N sodium hydroxide [ No CAS ]
  • [ 20469-61-8 ]
  • [ 697-82-5 ]
  • [ 74-88-4 ]
  • [ 54344-92-2 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; sodium acetate; trichlorophosphate; In N-methyl-acetamide; ethanol; water; benzene; EXAMPLE 1 The following procedure is illustrative of the synthesis of compounds represented by formula I. A total of 500 g of 2,3,5-trimethylphenol were introduced into 1840 ml of ethanol and 184 ml of water and treated with 240 g of potassium hydroxide with gentle stirring. 626 Grams of methyl iodide were added to the resulting clear solution at 0-5 over a period of 30-45 minutes. The mixture was stirred for 2 hours at room temperature, subsequently stirred under reflex conditions at 60 for 12 hours, then treated with 5 liters of water and thoroughly extracted with a total of 6 liters of ether. The extract was washed first with 3 liters of 3-N sodium hydroxide, then twice with 1 liter portions of water, dried over sodium sulfate and evaporated under reduced pressure. The residual <strong>[20469-61-8]<strong>[20469-61-8]2,3,5-trimethylanisol</strong>e</strong> boiled at 88-90 /10 Torr after rectification. 184 Grams of phosphorus oxychloride were added dropwise over 20-30 minutes to 87.1 g of dimethylformamide while at 10-20 with stirring. As the addition neared completion the temperature rose to 25. 150 Grams of <strong>[20469-61-8]<strong>[20469-61-8]2,3,5-trimethylanisol</strong>e</strong> were added over 20 minutes while cooling at 10-20. The mixture was slowly heated up to a maximum of 115, stirred at 100 for 6 hours in order to complete the reaction, cooled, poured into 2 kg of ice/water (1:1) and, after the addition of 1500 ml of benzene, treated with 500 g of sodium acetate. The water phase which formed was separated after stirring for 1 hour and again extracted with 1000 ml of benzene. The combined benzene extracts were washed successively with 480 ml of 1.5-N hydrochloric acid and 500 ml of water, dried over sodium sulfate and filtered over 20 g of decolorizing carbon. The filtrate was evaporated under reduced pressure. The residual 2,3,6-trimethyl-p-anisaldehyde melted at 65-66 after recrystallization from hexane.
  • 8
  • [ 697-82-5 ]
  • [ 616-38-6 ]
  • [ 20469-61-8 ]
YieldReaction ConditionsOperation in experiment
99% With dimanganese decacarbonyl; at 180℃; for 1h; General procedure: General procedure for the alkylation of phenols with dimethyl carbonate. A 17-mL stainless steel high-pressure micro reactor was charged with 3 mmol of Mn2(CO)10, W(CO)6, or Co2(CO)8, 100 mmol of the corresponding phenol, and 300 mmol of dimethyl carbonate, and the reactor was hermetically closed and heated for 1 h at 180C. The reactor was then cooled to room temperature and opened, and the mixture was filtered through a layer of alumina. Unreacted dimethyl carbonate was distilled off, and the residue was distilled under atmospheric or reduced pressure or recrystallized from ethanol. 1-Methoxy-2,3,5-trimethylbenzene. Yield 99%, bp 84.5-85C (7 mm). 13C NMR spectrum, deltaC, ppm: 11.60, 20.03, 21.38 (CH3); 110.52 (C6), 119.95 (C2), 124.92 (C4), 137.32 (C3), 137.54 (C5), 157.43 (C1). Found, %: C 79.87; H 9.35. C10H14O. Calculated, %: C 79.96; H 9.39.
 

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