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Structure of 637-87-6

Chemical Structure| 637-87-6

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Product Citations

Chapel Hill ;

Abstract: Photoredox catalysis has traditionally been accomplished by using ruthenium or iridium polypyridyl complexes. These complexes, while robust in their application, can prove to be quite cost prohibitive. Additionally, their respective redox windows are relatively narrow, limiting the scope of substrates with which they can undergo photoinduced electron transfer. Visible light absorbing organic chromophores have proven to be cost effective alternatives to precious transition metal photoredox catalysts. Additionally, the excited state redox potentials of organic photoredox catalysts can be significantly greater than that of their inorganic counterparts allowing for the development of new methodologies on substrates that could not otherwise undergo photoinduced electron transfer. In particular, organic acridinium dyes possess photophysical properties that make them extremely potent excited state oxidants. More recently it has been demonstrated that the acridine radical in the excited state possesses and excited state oxidation potential comparable to that of dissolving metal reductants making it an excellent excited state reductant. Herein, we describe methods developed that leverage the 5.51 V of redox potential that acridinium complexes can access. Nucleophilic aromatic substitution (SNAr) is a common method for arene functionalization; however, reactions of this type are typically limited to electron-deficient aromatic halides. Herein, we describe a mild, metal_x005f_x0002_free, cation-radical accelerated nucleophilic aromatic substitution (CRA-SNAr) using a potent acridinium photoredox catalyst as an excited state oxidant. Selective substitution of arene C−O bonds on a wide array of aryl ether substrates was shown with a variety of primary amine nucleophiles. Mechanistic evidence is also presented that supports the proposed CRA-SNAr pathway. Ketone–olefin coupling reactions are common methods for the formation of carbon–carbon bonds. This reaction class typically requires stoichiometric or super stoichiometric quantities of metal reductants and catalytic variations are limited in application. Photoredox catalysis has offered an alternative method towards ketone–olefin coupling reactions, although most methods are limited in scope to easily reducible aromatic carbonyl compounds. Herein, we describe a mild, metal-free ketone–olefin coupling reaction using an excited state acridine radical super reductant as a photoredox catalyst. We demonstrate both intra and intermolecular ketone–olefin couplings of aliphatic and aromatic ketones and aldehydes. Mechanistic evidence is also presented supporting an “olefin first”ketone–olefin coupling mechanism.

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Product Details of [ 637-87-6 ]

CAS No. :637-87-6
Formula : C6H4ClI
M.W : 238.45
SMILES Code : IC1=CC=C(Cl)C=C1
MDL No. :MFCD00001053
InChI Key :GWQSENYKCGJTRI-UHFFFAOYSA-N
Pubchem ID :12510

Safety of [ 637-87-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332
Precautionary Statements:P280

Computational Chemistry of [ 637-87-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 44.17
TPSA ?

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

0.0 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

3.62
Log Po/w (WLOGP)?

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

2.94
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.

3.79
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

3.51
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.22

Water Solubility

Log S (ESOL):?

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

-4.15
Solubility 0.0167 mg/ml ; 0.0000701 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.

-3.31
Solubility 0.117 mg/ml ; 0.000492 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

-3.97
Solubility 0.0256 mg/ml ; 0.000107 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

Low
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

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

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.

-5.18 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<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)

2.08

Application In Synthesis of [ 637-87-6 ]

* 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.

  • Upstream synthesis route of [ 637-87-6 ]
  • Downstream synthetic route of [ 637-87-6 ]

[ 637-87-6 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 637-87-6 ]
  • [ 105-53-3 ]
  • [ 19677-37-3 ]
References: [1] Organic Letters, 2002, vol. 4, # 2, p. 269 - 272.
  • 2
  • [ 637-87-6 ]
  • [ 41252-95-3 ]
References: [1] Bulletin des Societes Chimiques Belges, 1927, vol. 36, p. 375,376[2] Chemisches Zentralblatt, 1927, vol. 98, # I, p. 886.
[3] Bulletin de la Classe des Sciences, Academie Royale de Belgique, 1926, vol. &lt;5&gt;12, p. 829[4] Bulletin des Societes Chimiques Belges, 1927, vol. 36, p. 372[5] Chemisches Zentralblatt, 1927, vol. 98, # I, p. 885.
 

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