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Chemical Structure| 585-48-8 Chemical Structure| 585-48-8
Chemical Structure| 585-48-8

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2,6-Di-tert-butylpyridine

CAS No.: 585-48-8

4.5 *For Research Use Only !

Cat. No.: A287478 Purity: 98%

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Product Citations

Product Citations

Warring, Levi ;

Abstract: Interest in the chemistry of antimony and bismuth is rapidly growing due to isolation of low coordinate, subvalent or Lewis acidic compounds that can mediate reactivity traditionally reserved for their d block counterparts. Ligand strategies play a key role in the isolation of such species. Anionic ligands with large steric profiles, as well as carbenes, have been widely implemented to stabilize subvalent heavy group 15 element compounds. However, synthetic strategies to prepare Lewis acidic antimony and bismuth complexes remain underexplored. Cationization is one of the most common methods used to enhance the Lewis acidity of heavy group 15 elements by creating a vacant p orbital on the pnictogen atom. Lewis acids are also employed in frustrated Lewis pair (FLP) chemistry to enable intra- and intermolecular reactivity. Carbone ligands, which are neutral, 4 electron donor ligands, offer a unique ability to support highly electrophilic main-group elements. This dissertation investigates the stabilization of heavy pnictenium ions using neutral donor ligands, such as carbodicarbenes and capping arene ligands, and explores their potential in Lewis acid-mediated chemistry. In Chapter Two, the synthesis and characterization of a series carbodicarbene-pnictenium ions is described. The utilization of strongly donating carbodicarbene ligands enables the isolation of mono-, di- and tri-cationic antimony and bismuth cations. These ions have multiple bond character between carbon and antimony/bismuth, representing some of the first examples of stibaalkene and bismaalkene cationic compounds. The Lewis acidity of these ions was assessed using the Gutmann-Beckett method and computationally derived fluoride ion affinities, the latter of which indicates Lewis superacidity for the bis(pyridyl)carbodicarbene-pnictenium trications. In Chapter Three, the reactivity of the bis(pyridyl)-carbodicarbene stibenium trication toward C(sp3)–H and C(sp)–H bonds is demonstrated. The Lewis superacidic antimony cation mimics the chemistry of frustrated Lewis pairs in the presence of the sterically encumbered base 2,6-di-tert-butylpyridine to enable C–H bond breaking of acetonitrile and a set of terminal alkynes.Kinetic analyses, in conjunction with density functional theory, support a mechanism by which acetonitrile coordinates to antimony, acidifying the C–H bonds, which can be subsequently deprotonated by the base in solution. The resulting stiba-methylene nitrile and stiba-alkynyl adducts undergo reactivity with elemental iodine to generate iodoacetonitrile and 1-iodoalkynes while reforming a stibenium trication. In Chapter Four, capping arene ligands are coordinated to antimony and bismuth tribromide to afford a series of κ2-bound complexes. Bromide abstraction from these neutral adducts affords ionic compounds. Both the neutral and ionic species have distinctive Menschutkin interactions, whereby the lone pair on the pnictogen atom is oriented toward the π system of the pendant arene. Shortening of the distances between the pyridyl nitrogen atoms and pnictogen atom are observed upon cationization from the neutral adducts. The Lewis acidity of these complexes was assessed using the Gutmann-Beckett method. Notably, acceptor numbers as high as 111 are observed for these ions.

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Product Details of [ 585-48-8 ]

CAS No. :585-48-8
Formula : C13H21N
Linear Structure Formula :((CH3)3C)2C5H3N
M.W : 191.31
SMILES Code : CC(C)(C)C1=CC=CC(=N1)C(C)(C)C
MDL No. :MFCD00006306
Boiling Point : No data available
InChI Key :UWKQJZCTQGMHKD-UHFFFAOYSA-N
Pubchem ID :68510

Safety of [ 585-48-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319-H335
Precautionary Statements:P210-P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501

Calculated chemistry of [ 585-48-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.62
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 62.78
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.02
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

4.14
Log Po/w (WLOGP)?

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

3.68
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.

2.94
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

3.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.5

Water Solubility

Log S (ESOL):?

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

-3.82
Solubility 0.029 mg/ml ; 0.000152 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.

-4.12
Solubility 0.0146 mg/ml ; 0.0000762 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

-4.45
Solubility 0.00682 mg/ml ; 0.0000356 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.

-4.53 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

2.0
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)

1.8

Application In Synthesis [ 585-48-8 ]

* 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 [ 585-48-8 ]
  • Downstream synthetic route of [ 585-48-8 ]

[ 585-48-8 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 585-48-8 ]
  • [ 85048-76-6 ]
  • [ 935-28-4 ]
  • [ 62907-61-3 ]
References: [1] Journal of the American Chemical Society, 1991, vol. 113, # 3, p. 862 - 869.
 

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