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Chemical Structure| 39515-51-0 Chemical Structure| 39515-51-0

Structure of 3-Phenoxybenzaldehyde
CAS No.: 39515-51-0

Chemical Structure| 39515-51-0

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Synonyms: m-Phenoxybenzaldehyde

4.5 *For Research Use Only !

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Product Details of [ 39515-51-0 ]

CAS No. :39515-51-0
Formula : C13H10O2
M.W : 198.22
SMILES Code : C1=C(C=CC=C1OC2=CC=CC=C2)C=O
Synonyms :
m-Phenoxybenzaldehyde
MDL No. :MFCD00003353
InChI Key :MRLGCTNJRREZHZ-UHFFFAOYSA-N
Pubchem ID :38284

Safety of [ 39515-51-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Computational Chemistry of [ 39515-51-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 58.35
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.23
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

3.38
Log Po/w (WLOGP)?

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

3.29
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.

2.61
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

3.22
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.95

Water Solubility

Log S (ESOL):?

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

-3.59
Solubility 0.0507 mg/ml ; 0.000256 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.

-3.61
Solubility 0.0486 mg/ml ; 0.000245 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

-4.61
Solubility 0.00489 mg/ml ; 0.0000247 mol/l
Class?

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

Moderately 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

Yes
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

Yes
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.

-5.11 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)

1.55

Application In Synthesis of [ 39515-51-0 ]

* 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 [ 39515-51-0 ]

[ 39515-51-0 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 2298-36-4 ]
  • [ 39515-51-0 ]
  • [4-(3-phenoxy-benzylamino)-phenoxy]-acetic acid [ No CAS ]
  • 2
  • [ 117011-70-8 ]
  • [ 39515-51-0 ]
  • 2-methyl-2-[4-(3-phenoxy-benzylamino)-phenoxy]-propionic acid [ No CAS ]
  • 3
  • [ 1135-40-6 ]
  • [ 51631-50-6 ]
  • [ 39515-51-0 ]
  • [ 51630-58-1 ]
YieldReaction ConditionsOperation in experiment
In n-heptane; water; EXAMPLE 2 Preparation of α-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methyl butanoate using 3-(cyclohexylamino)-propanesulfonic acid as the rate-promoting agent A flask was charged with 3-(cyclohexylamino)propanesulfonic acid (42 mg), 3-phenoxybenzaldehyde (1.90 g, 9.6 mmole), sodium cyanide (0.56 g, 12 mmole), 1 ml water, and 15 ml n-heptane. 2-(4-Chlorophenyl)-3-methylbutanoyl chloride (2.34 g, 10.1 mmole) in 5 ml n-heptane was added dropwise over a period of 24 minutes to the stirred mixture. Thirty minutes after the addition was complete, a total of 54 minutes, glpc indicated a 95.6% yield of the desired ester. After stirring overnight, the reaction mixture was filtered and extracted with ether. The ether was evaporated from the extract, affording α-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methyl butanoate (3.47 g).
In n-heptane; water; EXAMPLE 2 Preparation of α-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methyl butanoate using 3-(cyclohexylamino)propanesulfonic acid as the rate-promoting agent A flask was charged with 3-(cyclohexylamino)propanesulfonic acid (42 mg), 3-phenoxybenzaldehyde (1.90 g, 9.6 mmole), sodium cyanide (0.56 g, 12 mmole), 1 ml water, and 15 ml n-heptane. 2-(4-Chlorophenyl)-3-methylbutanoyl chloride (2.34 g, 10.1 mmole) in 5 ml n-heptane was added dropwise over a period of 24 minutes to the stirred mixture. Thirty minutes after the addition was complete, a total of 54 minutes, glpc indicated a 95.6% yield of the desired ester. After stirring overnight, the reaction mixture was filtered and extracted with ether. The ether was evaporated from the extract, affording α-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methyl butanoate (3.47 g).
  • 4
  • [ 3083-10-1 ]
  • [ 51631-50-6 ]
  • [ 39515-51-0 ]
  • [ 51630-58-1 ]
YieldReaction ConditionsOperation in experiment
In n-heptane; water; B. Using 2,5,8,11-tetramethyl-2,5,8,11-tetraazadodecane A flask was charged with 3-phenoxybenzaldehyde (1.98 g, 10 mmole), 20 ml n-heptane, 2,5,8,11-tetramethyl-2,5,8,11-tetraazadodecane (0.046 g), sodium cyanide (0.59 g, 12 mmole), and 1 ml. water. With stirring, 2-(4-chlorophenyl)-3-methylbutanoyl chloride (2.42 g, 10.5 mmole) was added dropwise over a period of 6 minutes. The reaction mixture was stirred at room temperature. Analysis by glpc 2.4 hr. after the acyl chloride had been added indicated a 67.7% yield of the desired ester. Stirring was continued overnight, and the desired ester (3.4 g) was isolated as described in the preceding Example.
  • 5
  • [ 51631-50-6 ]
  • [ 39515-51-0 ]
  • [ 51630-58-1 ]
YieldReaction ConditionsOperation in experiment
91% In tetrahydrofuran; n-heptane; water; A. Using Tetrahydrofuran To a stirred solution of sodium cyanide (0.74 g, 0.015 mole) in a 1:1 by volume mixture of water and tetrahydrofuran (20 ml) at 30 was added all at once 3-phenoxybenzaldehyde (1.98 g, 0.01 mole) in the same solvent system (5 ml), followed by the dropwise addition of 2-(4-chlorophenyl)-3-methylbutanoyl chloride (2.77 g, 0.012 mole). Stirring was continued at 30 for an additional 2 hours, after which the mixture was cooled to room temperature and extracted thrice with heptane (25 ml each). The combined organic layers were washed once with aqueous 2 N NaOH (25 ml), then four times with water (25 ml each) to a final wash pH of about 6, dried over Na2 SO4, and concentrated to give the desired product (3.90 g, 93% yield). When the experiment was repeated under substantially the same conditions the weight yield was 91%.
With NaCN; In n-heptane; water; toluene; EXAMPLE I. Preparation of α-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methylbutanoate A 50 ml round-bottomed flask equipped with a magnetic stirrer was charged with 10 mmol of 3-phenoxybenzaldehyde, 10 mmol of 2-(4-chlorophenyl)-3-methylbutanoyl chloride, 12 mmol of sodium cyanide, 1.00 ml of water and 20 ml of n-heptane. The molar ratio of water to sodium cyanide was 4.64, all NaCN being dissolved. The reaction mixture was stirred and analyzed. The yield of the ester wanted is presented in Table I (experiment 1). Experiment 2 is a repetition of experiment 1, the difference being that 20 ml of toluene was used instead of 20 ml of n-heptane and 10.5 mmol of the acyl halide instead of 10 mmol. The yield of the desired ester is presented in Table I. Comparisons of the yields show that n-heptane is the best solvent.
  • 6
  • [ 144-55-8 ]
  • [ 51631-50-6 ]
  • [ 39515-51-0 ]
  • [ 51630-58-1 ]
YieldReaction ConditionsOperation in experiment
99% In n-heptane; water; EXAMPLE IV Preparation of α-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methylbutanoate on an enlarged scale Methods A (not according to the invention), and B were compared for the preparation of the ester wanted. Method A, in the absence of a phase transfer catalyst. A 500 ml round-bottomed flask equipped with a paddle stirrer was charged with 100 mmol of 3-phenoxybenzaldehyde, 100 mmol of 2-(4-chlorophenyl)-3-methylbutanoyl chloride, 120 mmol of sodium cyanide, 10 ml of water (which dissolved all sodium cyanide) and 200 ml of n-heptane. After stirring for 45 hours the mixture was warmed to a temperature between 40 and 50 C and filtered. The filtrate was washed twice with 50 ml of a 1 M aqueous sodium bicarbonate solution, once with 50 ml of water, dried and the n-heptane was flashed from the dried solution to give the desired ester in a yield of 99% and a purity of 96%.
With NaCN; In n-heptane; water; EXAMPLE 6 Preparation of α-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methylbutanoate on an enlarged scale A 500 ml round-bottomed flask equipped with a paddle stirrer was charged with 100 mmol of 3-phenoxybenzaldehyde, 100 mmol of 2-(4-chlorophenyl)-3-methylbutanoyl chloride, 120 mmol of sodium cyanide, 10 ml of water, and 200 ml of n-heptane. The molar ratio of water to sodium cyanide was 4.64, all NaCN being dissolved. The mixture thus formed was stirred and analyzed. Table VI presents the yields and purities of the desired ester after the reaction time indicated. The reaction mixture obtained in experiment 1 was warmed to a temperature between 40 and 50 C and filtered. The filtrate was washed twice with 50 ml of a 1 M aqueous sodium bicarbonate solution, once with 50 ml of water, dried and n-heptane was flashed from the dried solution to give the desired ester.
  • 7
  • [ 57497-39-9 ]
  • [ 39515-51-0 ]
  • [ 1172128-74-3 ]
  • 8
  • [ 66230-04-4 ]
  • [ 1745-18-2 ]
  • [ 622-98-0 ]
  • [ 1875-88-3 ]
  • [ 2012-74-0 ]
  • [ 23853-78-3 ]
  • [ 3739-38-6 ]
  • [ 938-95-4 ]
  • [ 39515-51-0 ]
  • [ 873-76-7 ]
  • methyl N-hydroxybenzene carboximidoate [ No CAS ]
  • 9
  • [ 1198-14-7 ]
  • [ 55-21-0 ]
  • [ 39515-51-0 ]
  • N-((5-bromo-8-hydroxyquinolin-7-yl)(3-phenoxyphenyl)methyl)benzamide [ No CAS ]
  • 10
  • [ 1198-14-7 ]
  • [ 103-81-1 ]
  • [ 39515-51-0 ]
  • N-((5-bromo-8-hydroxyquinolin-7-yl)(3-phenoxyphenyl)methyl)-2-phenylacetamide [ No CAS ]
 

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