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Chemical Structure| 73604-31-6 Chemical Structure| 73604-31-6

Structure of 3-(Aminomethyl)phenol
CAS No.: 73604-31-6

Chemical Structure| 73604-31-6

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Synonyms: m-Hydroxybenzylamine

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Product Citations

Product Citations

O' ; Shea, KE ; Restrepo-Osorio, Rodrigo ;

Abstract: Poly- and perfluoroalkyl substances (PFAS) are pollutants of serious concern due to their adverse health effects, widespread use, and resistance to degradation. β-cyclodextrins (β-CDs) form strong β-CD:PFAS complexes with a wide variety of PFAS. We report herein the incorporation of ionizable functional groups on the primary rim of β-CD, to control the complexation of PFAS as a function of solution pH. The binding constants (KCD:PFAS) of short-chain and long-chain PFAS by amino-β-CDs and thiol-β-CDs decrease by 56 to 98 % with a change in solution pH from neutral to alkaline conditions. The observed reduction in binding constants (KCD:PFAS) with increased pH is assigned to the increased electrostatic repulsion between negatively charged functional group amended to the β-CD (host) and negatively charged PFAS polar head group (guest) under alkaline conditions. The inclusion of two pH-dependent ionizable functional groups to the host was achieved by employing 6-(3-hydroxybenzylamino)-6-deoxy-β- cyclodextrin [(3-OH)BnNHβ-CD]. The phenol functionality is converted from a neutral to an anionic species while the benzyl-amino group is cationic under neutral pH and converted to neutral charge under alkaline conditions, thus the β-CD host can be converted from a positive charge to a negative charge by varying solution pH. The (3-OH)BnNHβ-CD exhibits strong pH-modulated binding with long-chain perfluorocarboxylic acids (PFCAs), evidenced in an 88 % decrease in the association constant with PFOA under alkaline conditions. The association constant for (3-OH)BnNHβ-CD with hexafluoropropylene oxide dimer acid (HFPO-DA), a branched perfluoroether carboxylic acid (PFECA), however, decreases by nearly 50 % under alkaline conditions compared to an 81 % and 98 % decrease observed for mono-thiol and mono-amino β-CDs, respectively. A 95 % decrease in binding in PFOA is observed for mono-thiol-β-CD, while heptakis-(6-mercapto-6-deoxy)-β-cyclodextrin, with seven ionizable thiol groups leads to a modest 23 % decrease for complexation of PFOA with change from neutral to alkaline pH. Steric effects due to chain branching within PFAS in combination with size and number of substituents on the β-CD reduce the impact of pH effects on binding. This study demonstrates derivatization of β-CD with pH ionizable functional groups can be used to control the β-CD binding of PFAS as a possible strategy for the removal and recovery of PFAS from contaminated water streams.

Keywords: Host-guest complexation ; PFAS ; cyclodextrin ; remediation: pH

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Alternative Products

Product Details of [ 73604-31-6 ]

CAS No. :73604-31-6
Formula : C7H9NO
M.W : 123.15
SMILES Code : OC1=CC=CC(CN)=C1
Synonyms :
m-Hydroxybenzylamine
MDL No. :MFCD00798977
InChI Key :JNZYADHPGVZMQK-UHFFFAOYSA-N
Pubchem ID :735894

Safety of [ 73604-31-6 ]

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

Computational Chemistry of [ 73604-31-6 ] 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 2.0
Num. H-bond donors 2.0
Molar Refractivity 36.14
TPSA ?

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

46.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.11
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

0.23
Log Po/w (WLOGP)?

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

0.7
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.

0.88
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

0.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.78

Water Solubility

Log S (ESOL):?

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

-1.18
Solubility 8.22 mg/ml ; 0.0667 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-0.76
Solubility 21.3 mg/ml ; 0.173 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

-1.82
Solubility 1.86 mg/ml ; 0.0151 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

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

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.

-6.89 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<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)

1.0

Application In Synthesis of [ 73604-31-6 ]

* 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.

  • Downstream synthetic route of [ 73604-31-6 ]

[ 73604-31-6 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 73604-31-6 ]
  • [ 4385-76-6 ]
  • N-(3-hydroxybenzyl)-4-(pyridin-4-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
62 mg With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 2h; To a solution of <strong>[4385-76-6]4-(pyridin-4-yl)benzoic acid</strong> (50 mg, 0.25 mmol) and 3- (aminomethyl)phenol (37 mg, 0.3 mmol) in DMF were added diisopropylethylamine (DIEA, 0.13 mL, 0.75 mmol) and FJATU (123 mg, 0.32 mmol). The reaction was stirred at room temperature for 2 hrs and diluted with water. The mixture was concentrated and purified by C-18 column chromatography to give 3 A (62 mg).
 

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