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Chemical Structure| 85-52-9 Chemical Structure| 85-52-9

Structure of 2-Benzoylbenzoic acid
CAS No.: 85-52-9

Chemical Structure| 85-52-9

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Aspen X.-Y. Chen ; Tanay Kesharwani Yong Wu ; Haoyuan Chen ; Dengke Shen ; J. Fraser Stoddart ;

Abstract: Confinement is a unifying element in selective enzymic reactions but has rarely been used to control site selectivity of carbon-hydrogen (C-H) bond functionalization in artificial receptors. Herein, we demonstrate the selective functionalization of one of seven C(sp3)-H bonds on a D-glucopyranosyl residue of (γ-CD) by irradiating 2-benzoylbenzoate in a γ-cyclodextrin-containing metal-organic framework (CD-MOF-1). Both 1H NMR spectroscopy and X-ray crystallog. of the products confirm that functionalization occurs selectively at one of the two C(sp3)-H bonds on the C6 position of a D-glucopyranosyl residue. The alignment of 2-benzoylbenzoate inside (γ-CD)2 tunnels in CD-MOF-1, as revealed by X-ray crystallog., precludes C-H functionalization on the outer surface of the γ-CD tori. Theoretical calculations indicate less steric hindrance associated with C6-functionalized (γ-CD)2 tunnels in CD-MOF-1 compared with C3 and C5, leading to the observed site selectivity.

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Product Details of [ 85-52-9 ]

CAS No. :85-52-9
Formula : C14H10O3
M.W : 226.23
SMILES Code : O=C(O)C1=CC=CC=C1C(C2=CC=CC=C2)=O
MDL No. :MFCD00002472
InChI Key :FGTYTUFKXYPTML-UHFFFAOYSA-N
Pubchem ID :6813

Safety of [ 85-52-9 ]

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

Computational Chemistry of [ 85-52-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 63.28
TPSA ?

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

54.37 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.54
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

2.37
Log Po/w (WLOGP)?

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

2.62
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.

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

2.79
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.35

Water Solubility

Log S (ESOL):?

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

-3.06
Solubility 0.197 mg/ml ; 0.000871 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.

-3.15
Solubility 0.159 mg/ml ; 0.000704 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

-4.24
Solubility 0.0129 mg/ml ; 0.000057 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

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.

-6.0 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.

0.56

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)

1.87

Application In Synthesis of [ 85-52-9 ]

* 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 [ 85-52-9 ]

[ 85-52-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 85-52-9 ]
  • compound C36H30O2 [ No CAS ]
  • [ 7510-28-3 ]
  • 2
  • [ 85-52-9 ]
  • [ 119692-59-0 ]
  • [ 1214748-82-9 ]
YieldReaction ConditionsOperation in experiment
With 2,6-di-tert-butyl-4-methyl-phenol; tetrabutylammomium bromide; In ISOPROPYLAMIDE; acetonitrile; for 16.0h;Reflux; Synthesis of BP-3; [0145] Synthesis of 2-benzoyl-benzoic acid 3-(4-acryloyloxy-butoxy)-2-hydroxy- propyl ester:A reaction mixture containing 2-benzoyl benzoic acid (40.0 g), acetonitrile(300 mL), dimethylacetamide (10 ml_), tetrabutylammonium bromide (5.6 g)and 2,6-di-tert-butyl-4-methylphenol (0.3 g) was heated to reflux.At this temperature 4-hydroxybutylacrylate glycidylether (28.0 g) was added and the mixture was allowed to stir at reflux temperature for 16 hours.The mixture was cooled to room temperature and the solvent was evaporated under reduced pressure.The residual oil was dissolved in methyl-tert-butylether (300 mL) and extracted 3 times with a mixture of an aqueous solution of sodium hydroxide (1 N) and distilled water (1/2.4)The organic layer was separated, dried on MgSO4, filtered and evaporated to provide 45.2 g of a brown oil.
With 2,6-di-tert-butyl-4-methyl-phenol;tetrabutylammomium bromide; In N,N-dimethyl acetamide; acetonitrile; for 16.0h;Reflux; A reaction mixture containing 2-benzoyl benzoic acid (40.0 g), acetonitrile (300 mL), dimethylacetamide (10 mL), tetrabutylammonium bromide (5.6 g)and 2,6-di-tert-butyl-4-methylphenol (0.3 g) was heated to reflux. At this temperature 4-hydroxybutylacrylate glycidylether (28.0 g) was added and the mixture was allowed to stir at reflux temperature for 16 hours. The mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The residual oil was dissolved in methyl-tert-butylether (300 mL) and extracted 3 times with a mixture of an aqueous solution of sodium hydroxide (1N) and distilled water (1/2.4). The organic layer was separated, dried on MugsO4, filtered and evaporated to provide 45.2 g of a brown oil.
45.2 g With 2,6-di-tert-butyl-4-methyl-phenol; tetrabutylammomium bromide; In N,N-dimethyl acetamide; acetonitrile; for 16.0h;Reflux; Synthesis of 2-benzoyl-benzoic acid 3-(4-acryloyloxy-butoxy)-2-hydroxy-propyl ester A reaction mixture containing 2-benzoyl benzoic acid (40.0 g, 0.1722 mol), acetonitrile (300 mL), dimethylacetamide (10 mL), tetrabutylammonium bromide (5.6 g, 17.22 mmol) and 2,6-di-tert-butyl-4-methylphenol (0.3 g, 1.4 mmol) was heated to reflux. At this temperature 4-hydroxybutylacrylate glycidylether (28.0 g, 140 mmol) was added and the mixture was allowed to stir at reflux temperature for 16 hours. The mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The residual oil was dissolved in methyl-tert-butylether (300 mL) and extracted 3 times with a mixture of an aqueous solution of sodium hydroxide (1N) and distilled water (1/2.4) The organic layer was separated, dried on MgSO4, filtered and evaporated to provide 45.2 g of a brown oil.
  • 3
  • [ 85-52-9 ]
  • [ 128-37-0 ]
  • [ 119692-59-0 ]
  • [ 1214748-82-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; tetrabutylammomium bromide; In tert-butyl methyl ether; ISOPROPYLAMIDE; water; acetonitrile; Synthesis of BP-3 Synthesis of 2-benzoyl-benzoic acid 3-(4-acryloyloxy-butoxy)-2-hydroxy-propyl ester: A reaction mixture containing 2-benzoyl benzoic acid (40.0 g, 0.1722 mol), acetonitrile (300 mL), dimethylacetamide (10 mL), tetrabutylammonium bromide (5.6 g, 17.22 mmol) and 2,6-di-tert-butyl-4-methylphenol (0.3 g, 1.4 mmol) was heated to reflux. At this temperature 4-hydroxybutylacrylate glycidylether (28.0 g, 140 mmol) was added and the mixture was allowed to stir at reflux temperature for 16 hours. The mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The residual oil was dissolved in methyl-tert-butylether (300 mL) and extracted 3 times with a mixture of an aqueous solution of sodium hydroxide (1N) and distilled water (1/2.4) The organic layer was separated, dried on MgSO4, filtered and evaporated to provide 45.2 g of a brown oil.
 

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