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Structure of 696-62-8

Chemical Structure| 696-62-8

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Sokolnicki, Tomasz ; Stefanowska-Kątna, Kinga ; Czapik, Agnieszka ; Walkowiak, Jędrzej ; Franczyk, Adrian ;

Abstract: A novel approach towards synthesizing new metalloid-substituted olefins has been accomplished by transforming (E)-1,2-diboryl-1-silylethenes through two consecutive Suzuki–Miyaura coupling reactions. This methodology provides an effective and selective way to obtain new, structurally different products, such as (E)-1-silyl-1-boryl-2-arylethens, (1E,3E)-1-silyl-1-boryl-2-alkenylethens, and (E)-1-silyl-1-aryl1-2-aryl2ethenes, which are difficult to synthesize through hydrometallation reactions and related processes. Due to the presence of reactive motifs (silyl group, Bpin moiety, and Csp2-H bond) in the structure of the final products, these molecules might be considered powerful building blocks in modern chemistry. With the aid of demetallation and cross-coupling reactions, they might be further functionalized into several invaluable chemicals, i.e., tetrasubstituted olefins (anti-cancer drugs, fluorescence materials), compounds with high π-conjugation, and polymers.

Keywords: (E)-1-silyl-1,2-diboryl-ethenes ; aryl iodides ; (E)-(2-iodovinyl)benzenes ; Suzuki–Miyaura cross-coupling ; substituted olefins ; building blocks

Purchased from AmBeed:

Zhao, Spencer ; Loh, Kang Yong ; Tyson, Jonathan ; Kadur, Chandan ; Bertozzi, Carolyn ; Deisseroth, Karl , et al.

Abstract: Catalytic reactions of a broad range of abiotic molecules and macromolecules are beyond the native capabilities of mammals. Natural enzymes from prokaryotes or plant-based eukaryotes have limited substrate scopes. Therefore, broadening the range of catalytic bond-forming reactions that function in physiological conditions would enable the syntheses of a vast array of molecules directly within biological systems. This approach may provide an alternative way to modulate cellular behaviors if such molecules can be synthesized with spatiotemporal control on specific cell types in living systems; furthermore, restricting synthesis to well-defined cells or cell-types would enable a potentially transformative approach of treating cells as separable reaction vessels within living organisms. Herein, we use genetic targeting to incorporate an organic photocatalytic dye onto specific cell types to enable in-situ light-controlled and spatially defined chemical synthesis of non-natural molecules. We demonstrate, for the first time, a photo-patterned organic coupling reaction in the extracellular matrix of living cells under dilute, aqueous, aerobic physiological conditions. A 6-fold contrast in reaction yield can be achieved between two adjacent HEK293FT cells with and without light exposure. The above photocatalysis can be initiated using mild confocal laser stimulation as low as 16 μW/mm2 at multiple wavelengths. Furthermore, the cell-type specific photocatalyzed C-H functionalization coupling reactions taking place on cell surfaces are used to demonstrate anabolic construction of non-natural products. The above findings lay an important foundation for developing future abiotic cell-type specific chemical syntheses in living organisms.

Purchased from AmBeed: ; ; ;

Alternative Products

Product Details of [ 696-62-8 ]

CAS No. :696-62-8
Formula : C7H7IO
M.W : 234.03
SMILES Code : COC1=CC=C(I)C=C1
MDL No. :MFCD00001056
InChI Key :SYSZENVIJHPFNL-UHFFFAOYSA-N
Pubchem ID :69676

Safety of [ 696-62-8 ]

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

Computational Chemistry of [ 696-62-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 45.65
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.26
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

2.95
Log Po/w (WLOGP)?

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

2.3
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.

2.72
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

2.81
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.61

Water Solubility

Log S (ESOL):?

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

-3.58
Solubility 0.062 mg/ml ; 0.000265 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.

-2.81
Solubility 0.366 mg/ml ; 0.00156 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

-3.48
Solubility 0.0771 mg/ml ; 0.00033 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

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

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.

-5.63 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)

2.0

Application In Synthesis of [ 696-62-8 ]

* 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 [ 696-62-8 ]
  • Downstream synthetic route of [ 696-62-8 ]

[ 696-62-8 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 547-63-7 ]
  • [ 696-62-8 ]
  • [ 6274-50-6 ]
YieldReaction ConditionsOperation in experiment
80%
Stage #1: With 2,2,6,6-tetramethylpiperidinyl-lithium In toluene at 20℃; for 0.25 h; Glovebox
Stage #2: With palladium(l) tri-tert-butylphosphine iodide dimer In toluene at 20℃; Glovebox
General procedure: Inside the glovebox, lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 70.7 mg, 0.48 mmol, 1.2 eq.) was dissolved in toluene (1.5 mL) and carbonyl compound (3, 0.48 mmol, 1.2 eq.) was added. After 15 min of stirring at ambient temperature a solution of Pd(I) iodo dimer (2, 3.5 mg, 0.004 mmol, 1 molpercent for aryl iodides; 17.4 mg, 0.02 mmol, 5 molpercent for aryl bromides) and aryl halide (4, X = I or Br, 0.4 mmol, 1.0 eq.) in toluene (0.5 mL) was added. After 4-18 h of further stirring at ambient temperature (reaction progress was monitored by GCMS), the crude was directly adsorbed onto silica (washing with diethyl ether) and purified by flash column chromatography.
References: [1] Synthesis (Germany), 2018, vol. 50, # 22, p. 4471 - 4475.
 

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