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Chemical Structure| 108-75-8 Chemical Structure| 108-75-8

Structure of 108-75-8

Chemical Structure| 108-75-8

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Product Citations

Product Citations

Johansen, Christian M ; Benazzi, Elisabetta ; Peters, Jonas C ;

Abstract: The Hantzsch ester (HEH2) has found considerable utility as a photoreductant in synthesis, with photodriven transfer hydrogenation reactions typically limited to activated substrates. We recently established that the addition of an organic buffer of collidinium triflate [(ColH)OTf] and collidine (Col) allows photodriven transfer hydrogenation from HEH2 to N2 forming NH3 (nitrogen reduction; N2R) in the presence of a Mo catalyst. Given the requirements for Mo-catalyzed thermally driven N2R, this result suggested the generation of a significant driving force for proton-coupled electron transfer (PCET) when irradiating HEH2 in the presence of Col-buffer. In this study, we probe how Col-buffer enables efficient photodriven proton-coupled reductions with HEH2. Wavelength-dependent NH3 yields are consistent with HEH2 photoexcitation, and the combination of HEH2 with Col-buffer is privileged. Data are presented, suggesting that HEH2 is statically quenched via ET to [ColH]OTf through an H-bonded association complex to release ColH and [HEH2]•+. Transient absorbance data and EPR studies establish that the resulting [HEH2]•+ intermediate is rapidly deprotonated by Col to yield HEH, in net furnishing HEH and ColH as potent H-atom donors. Broader utility of this reagent combination is demonstrated in the photoreduction of a range of C=O and N=O π-bonds by HEH2, with a significant boost in rates and yield, and altered reactivity, observed on addition of Col-buffer. ColH is posited as the most potent PCET donor generated (BDFEN−H of 28 kcal mol−1).

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Product Details of [ 108-75-8 ]

CAS No. :108-75-8
Formula : C8H11N
M.W : 121.18
SMILES Code : CC1=CC(C)=CC(C)=N1
MDL No. :MFCD00006338
InChI Key :BWZVCCNYKMEVEX-UHFFFAOYSA-N
Pubchem ID :7953

Safety of [ 108-75-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H226-H302+H332-H311-H315-H319-H335
Precautionary Statements:P210-P233-P240-P241-P242-P243-P261-P264-P270-P271-P280-P301+P312+P330-P303+P361+P353-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501
Class:3(6.1)
UN#:1992
Packing Group:

Computational Chemistry of [ 108-75-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.38
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 39.13
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.

2.08
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

1.88
Log Po/w (WLOGP)?

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

2.01
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.

1.48
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

2.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.03

Water Solubility

Log S (ESOL):?

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

-2.27
Solubility 0.652 mg/ml ; 0.00538 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.

-1.77
Solubility 2.04 mg/ml ; 0.0169 mol/l
Class?

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

Very 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

-3.14
Solubility 0.0882 mg/ml ; 0.000728 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.

-5.7 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<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)

1.14

Application In Synthesis of [ 108-75-8 ]

* 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 [ 108-75-8 ]
  • Downstream synthetic route of [ 108-75-8 ]

[ 108-75-8 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 108-75-8 ]
  • [ 33454-82-9 ]
  • [ 107264-00-6 ]
References: [1] Tetrahedron, 1993, vol. 49, # 11, p. 2151 - 2158.
  • 2
  • [ 108-75-8 ]
  • [ 2926-30-9 ]
  • [ 107264-00-6 ]
  • [ 135182-78-4 ]
References: [1] Bulletin of the Chemical Society of Japan, 1991, vol. 64, # 4, p. 1081 - 1092.
  • 3
  • [ 108-75-8 ]
  • [ 2926-29-6 ]
  • [ 107264-00-6 ]
References: [1] Tetrahedron Letters, 1986, vol. 27, # 28, p. 3271 - 3274.
  • 4
  • [ 108-75-8 ]
  • [ 2926-27-4 ]
  • [ 107264-00-6 ]
  • [ 135182-78-4 ]
References: [1] Bulletin of the Chemical Society of Japan, 1991, vol. 64, # 4, p. 1081 - 1092.
 

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