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Chemical Structure| 622-47-9 Chemical Structure| 622-47-9
Chemical Structure| 622-47-9

2-(p-Tolyl)acetic acid

CAS No.: 622-47-9

4.5 *For Research Use Only !

Cat. No.: A349592 Purity: 98%

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Product Details of [ 622-47-9 ]

CAS No. :622-47-9
Formula : C9H10O2
M.W : 150.17
SMILES Code : O=C(O)CC1=CC=C(C)C=C1
MDL No. :MFCD00004353

Safety of [ 622-47-9 ]

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

Calculated chemistry of [ 622-47-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 42.95
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.

1.51
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

1.86
Log Po/w (WLOGP)?

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

1.62
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.

1.98
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

2.01
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.8

Water Solubility

Log S (ESOL):?

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

-2.21
Solubility 0.916 mg/ml ; 0.0061 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.

-2.26
Solubility 0.817 mg/ml ; 0.00544 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

-2.54
Solubility 0.429 mg/ml ; 0.00286 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

No
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.

-5.9 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.

0.56

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)

1.02

Application In Synthesis of [ 622-47-9 ]

* 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.

  • Downstream synthetic route of [ 622-47-9 ]

[ 622-47-9 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 622-47-9 ]
  • [ 611-14-3 ]
  • [ 699-02-5 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; COMPARATIVE EXAMPLE 1 In the same manner as in Example 1 but not using triethylamine, the reaction was carried out to give the following results: conversion of p-methylphenylacetic acid, 99.2%; yield of p-methylphenethyl alcohol, 74.3%; selectivity to p-methylphenethyl alcohol, 74.9%; yield of ethyltoluene, 10.2%.
  • 2
  • dirhenium heptoxide [ No CAS ]
  • [ 622-47-9 ]
  • [ 611-14-3 ]
  • [ 699-02-5 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In 1,4-dioxane; EXAMPLE 1 Into a 50 ml volume stainless steel made autoclave equipped with a magnetic stirrer and inserted with a glass tube, p-methylphenylacetic acid (0.6 g), dehydrated dioxane (10 ml), dirhenium heptoxide (60 mg) and triethylamine (4.3 mg) were charged, and the inner atmosphere was replaced by nitrogen gas. Hydrogen gas was pressurized therein up to 100 atm. The reaction was carried out at 162 C. for 5 hours while stirring. After cooling to room temperature, the reaction mixture was subjected to gas chromatographic analysis to give the following results: conversion of p-methylphenylacetic acid, 98.5%; yield of p-methylphenethyl alcohol, 92.4%; selectivity to p-methylphenethyl alcohol, 93.8%; yield of ethyltoluene, 0.5%.
  • 3
  • [ 622-47-9 ]
  • [ 74-88-4 ]
  • [ 20430-18-6 ]
YieldReaction ConditionsOperation in experiment
To a solution of diisopropylamine (ALDRICH, 15.2 mL, 109 mmol) in 108 mL of anhydrous THF at -20C under N2 was added n-BuLi (55.7 mL, 106 mmol, 1.9M solution in hexane) droDwise via cannula. After stirrina for 2 hours. D-tolvlacetic acid (ALDRICH. 3.99 a. 26.5mmol) was added in 26 mL of THF. The mixture was stirred at -5C for 2 hours and, then, treated with iodomethane (9.9 mL, 159 mmol). The reaction mixture was allowed to gradually warm up to room temperature, stirred at that temperature for 15 hours, and then, quenched by pouring it into 20 mL of HCI (1N). The aqueous layer was extracted with Et20 (3x100 mL). The organic layer was treated with brine and dried over MgS04 and concentrated in vacuo to give 4.86 g of the title compound as a brown oil. 1H NMR (300 MHz, DMSO-d6) 8 ppm: 12.22 (br.s, 1H), 7.21 (m, 2H), 7.12 (m, 2H), 2.25 (s, 3H), 1.43 (s, 6H). No molecular peak is detected by MS.
  • 4
  • [ 622-47-9 ]
  • [ 88-73-3 ]
  • [ 16112-21-3 ]
  • 5
  • [ 622-47-9 ]
  • [ 615-43-0 ]
  • [ 16112-21-3 ]
YieldReaction ConditionsOperation in experiment
74% With copper(II) acetate monohydrate; sulfur; sodium hydroxide; In dimethyl sulfoxide; at 130℃; for 24h;Sealed tube; Inert atmosphere; General procedure: A mixture of o-iodoaniline (0.5 mmol, 1 equiv), arylacetic acid (0.6 mmol), elemental sulfur (1.5mmol), Cu(OAc)2·H2O (20 mmol%), and NaOH (1.0 mmol) in DMSO (3 mL) was put into a sealed pressure vessel (25 mL) containing a magnetic stirring bar. The tube was purged with nitrogen three times, and then capped and stirred in a preheated oil bath at 130 C for 24 h. The reaction mixture then cooled to room temperature and extracted with ethyl acetate (3x10 mL), the organic layer was washed with saturated NaCl (2x10 mL), dried over anhydrous Na2SO4, evaporated under vacumm and then purified by silica gel column chromatography by using petroleum ether and ethyl acetate (PE:EA=200:1) as eluent.
  • 6
  • [ 622-47-9 ]
  • [ 137-07-5 ]
  • [ 16112-21-3 ]
 

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