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Chemical Structure| 1667-12-5 Chemical Structure| 1667-12-5

Structure of 1667-12-5

Chemical Structure| 1667-12-5

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Product Details of [ 1667-12-5 ]

CAS No. :1667-12-5
Formula : C14H14O2
M.W : 214.26
SMILES Code : OCC1=CC=C(C2=CC=C(CO)C=C2)C=C1
MDL No. :MFCD00016713
InChI Key :SFHGONLFTNHXDX-UHFFFAOYSA-N
Pubchem ID :611786

Safety of [ 1667-12-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 1667-12-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.14
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 64.13
TPSA ?

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

40.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.12
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

2.59
Log Po/w (WLOGP)?

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

2.03
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.

2.41
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

3.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.48

Water Solubility

Log S (ESOL):?

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

-3.16
Solubility 0.149 mg/ml ; 0.000696 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.

-3.09
Solubility 0.175 mg/ml ; 0.000816 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

-4.58
Solubility 0.00562 mg/ml ; 0.0000262 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

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

Yes
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.

-5.77 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

0.0
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)

1.49

Application In Synthesis of [ 1667-12-5 ]

* 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 [ 1667-12-5 ]

[ 1667-12-5 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 792-74-5 ]
  • [ 7732-18-5 ]
  • [ 1667-12-5 ]
YieldReaction ConditionsOperation in experiment
96.6% With LiAlH4; In tetrahydrofuran; ethanol; acetone; a) Preparation of 4,4'-bis (Hydroxy-Methyl) Biphenyl 789 mg (20.8 mmoles) of LiAlH4 in 150 ml of anhydrous THF (tetrahydrofuran) are placed in a 2-liter flask which has a mechanical agitator, cooler, filler funnel and heating bath. A solution, heated to 50° C., of 7.5 g (27.7 mmoles) of 4,4'-bis (methoxycarbonyl)biphenyl in 500 ml of anhydrous THF is added dropwise, over a period of 1 hour, to the mixture, heated in an inert atmosphere to 50° C. under agitation. After a further 30 minutes of agitation in a heating bath, the mixture is cooled to ambient temperature and the excess LiAlH4 is destroyed by the careful addition of 15 ml of a THF/H2 O (80:20) mixture. The reaction mixture is filtered on Septum G2, washing the precipitate with anydrous ethanol (3*100 ml). The combined filtrate and washings are evaporated to dryness under vacuum with the heating bath at 40° C. The residue is then redissolved with 100 ml of hot acetone (50° C.), eliminating the insoluble residue by filtration, dried on anhydrous Na2 SO4 and evaporated to dryness. 5.74 g of 4,4'-bis (hydroxymethyl) biphenyl are obtained with a molar yield of 96.6percent. Analysis: Melting Point: 195.8°-196° C. 1 H-NMR (DMSOD6): delta4.53 (d, 4H, CH2); 5.20 (t, 2H, OH); 7.35-7.65 (8H, aromatic) MS-EI: (M+)214; m/e 196, 183, 167, 165, 155, 152, 77.
  • 2
  • [ 792-74-5 ]
  • [ 1667-12-5 ]
YieldReaction ConditionsOperation in experiment
96.6% With LiAlH4; In tetrahydrofuran; tetrahydrofuran-water; acetone; a) Preparation of 4,4'-bis (Hydroxy-Methyl) Biphenyl. 789mg (20.8 mmoles) of LiAlH4 in 150ml of anhydrous THF (tetrahydrofuran) are placed in a 2-litre flask which has a mechanical agitator, cooler, filler funnel and heating bath. A solution, heated to 50oC, of 7.5g (27.7 mmoles) of 4,4'-bis (methoxycarbonyl)biphenyl in 500ml of anhydrous THF is added dropwise, over a period of 1 hour, to the mixture, heated in an inert atmosphere to 50oC under agitation. After a further 30 minutes of agitation in a heating bath, the mixture is cooled to ambient temperature and the excess LiAlH4 is destroyed by the careful addition of 15ml of a THF/H2O (80:20) mixture. The reaction mixture is filtered on Septum G2, washing the precipitate with anydrous ethanol (3x100ml). The combined filtrate and washings are evaporated to dryness under vacuum with the heating bath at 40oC. The residue is then redissolved with 100ml of hot acetone (50oC), eliminating the insoluble residue by filtration, dried on anhydrous Na2SO4 and evaporated to dryness. 5.74g of 4,4'-bis (hydroxymethyl) biphenyl are obtained with a molar yield of 96.6percent.
 

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