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Chemical Structure| 262-12-4 Chemical Structure| 262-12-4

Structure of 262-12-4

Chemical Structure| 262-12-4

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Product Citations

Gustavo Muñoz ; Kari M. Chamberlain ; Maxim E. Solovyev ; Dennis W. Smith Jr. ; Charles U. Pittman Jr. ;

Abstract: Since the seminal work presented by Olah in 1966 on fluorinated carbocations, several strategies have been presented to introduce fluorinated moieties in polymer backbones via carbocation chemistry. The hexafluoroisopropylidene (6F) group is well known for its ability to enhance thermal properties and processability of polymers. However, its direct electrophilic incorporation into polymers has been largely ignored due to the challenges posed by activating hexafluoroacetone monomer for electrophilic aromatic substitution (EAS). In this article, we review the role of fluorinated carbocations from 1966 up to our recent versatile fluoroalkylation strategy to directly enchain the 6F group in polymers. Via EAS interfacial polymerization we reacted hexafluoroacetone trihydrate (HFAH) with aromatic monomers in triflic anhydride (Tf2O) and 1,2-dichloroethane (DCE) with Aliquat® 336. In addition, the polymerization of dibenzo-1,4-dioxin with HFAH is presented. A semi-fluorinated diol, 4,4′-bis(2-hydroxyhexafluoroisopropyl)diphenyl ether, was synthesized by this method and used to prepare the first reported polycarbonate with hexafluoroisopropoxy groups –C(CF3)2O– incorporated in the main chain via polycondensation. Polysilyl ethers were also prepared from this diol. Additionally, we briefly mention Carraher’s legacy in the synthesis of metal-containing polymers via reactions of group IVB metallocene dichloride with dinucleophiles (diamines, diol, dicarboxylic acids, and dithiols) in solution and interfacial conditions in terms of electrophilic vs nucleophilic polycondensation. The new acidic, sterically hindered semi-fluorinated diol and bisphenol AF were reacted with group IVB metallocene dichloride in attempts to form metallocene condensation polymers with improved solubility.

Keywords: Semi-fluorinated polyaryl ether ; Electrophilic polymerization ; Fluorinated diol ; Fluorinated metallopolymer ; Hexafluoroacetone trihydrate ; High-performance polymer

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Product Details of [ 262-12-4 ]

CAS No. :262-12-4
Formula : C12H8O2
M.W : 184.19
SMILES Code : C12=CC=CC=C1OC3=CC=CC=C3O2
MDL No. :MFCD00022282
InChI Key :NFBOHOGPQUYFRF-UHFFFAOYSA-N
Pubchem ID :9216

Safety of [ 262-12-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P264-P270-P301+P312+P330-P501

Computational Chemistry of [ 262-12-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 53.03
TPSA ?

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

18.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.53
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

4.3
Log Po/w (WLOGP)?

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

3.58
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.

2.56
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

3.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.2

Water Solubility

Log S (ESOL):?

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

-4.33
Solubility 0.00871 mg/ml ; 0.0000473 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.4
Solubility 0.00732 mg/ml ; 0.0000397 mol/l
Class?

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

Moderately 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

-4.39
Solubility 0.00754 mg/ml ; 0.0000409 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

Yes
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

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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-4.37 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

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<2.0
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)

2.55

Application In Synthesis of [ 262-12-4 ]

* 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 [ 262-12-4 ]

[ 262-12-4 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 262-12-4 ]
  • [ 105906-36-3 ]
  • [ 105836-96-2 ]
  • [ 39073-07-9 ]
 

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