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Chemical Structure| 66-98-8

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Dongyang Zhu ; Zhuqing Zhang ; Lawrence B. Alemany ; Yilin Li ; Njideka Nnorom ; Morgan Barnes , et al.

Abstract: Covalent organic frameworks (COFs) are crystalline, porous organic materials that are promising for applications including catalysis, energy storage, electronics, gas storage, water treatment, and drug delivery. Conventional solvothermal synthesis approaches require elevated temperatures, inert environments, and long reaction times. Herein, we show that transition-metal nitrates can catalyze the rapid synthesis of imine COFs under ambient conditions. We first tested a series of transition metals for the synthesis of a model COF and found that all transition-metal nitrates tested produced crystalline COF products even in the presence of oxygen. Fe(NO3)3·9H2O was found to produce the most crystalline product, and crystalline COFs could be produced within 10 min by optimizing the catalyst loading. Fe(NO3)3·9H2O was further tested as a catalyst for six different COF targets varying in linker lengths, substituents, and stabilities, and it effectively catalyzed the synthesis of all imine COFs tested. This catalyst was also successful in the synthesis of 2D imine COFs with different geometries, 3D COFs, and azine-linked COFs. This work demonstrates a simple, low-cost approach for the synthesis of imine COFs and will significantly lower the barrier for the development of imine COFs for applications.

Purchased from AmBeed: ;

Dongyang Zhu ; Xiaoyi Li ; Yilin Li ; Morgan Barnes ; Chia-Ping Tseng ; Safiya Khalil , et al.

Abstract: Covalent organic frameworks (COFs) are crystalline porous materials linked by dynamic covalent bonds. Dynamic chemistries enable the transformation of an initially amorphous network into a porous and crystalline COF. While dynamic chemistries have been leveraged to realize transformations between different types of COFs, including transformations from two-dimensional (2D) to three-dimensional (3D) COFs and insertion of different linking groups, the transformation of linear polymers into COFs has not yet been reported. Herein, we demonstrate an approach to transform linear imine-linked polymers into ketone-linked COFs through a linker replacement strategy with triformylphloroglucinol (TPG). TPG first reacts through dynamic chemistry to replace linkers in the linear polymers and then undergoes irreversible tautomerism to produce ketone linkages. We have analyzed the time-dependent transformation from the linear polymer into COF through powder X-ray diffraction, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) to understand the transition and substitution mechanisms. This work demonstrates another route to produce COFs through sequential reversible and irreversible chemistries and provides a potential approach to synthesizing COFs through the solution processing of linear polymers followed by transformation into the desired COF structure.

Purchased from AmBeed:

Zhu, Dongyang ;

Abstract: Covalent organic frameworks (COFs) are an emerging class of organic, crystalline macromolecules. Due to their tunable chemistry, tailorable structure, regular pore channels and high surface areas, they have received significant attention for various applications, such as catalysis, energy storage, gas storage and separation, membrane separation and drug delivery. However, developing materials that can be used in these applications requires addressing a number of fundamental challenges in COF synthesis, activation, and transformation. In this thesis, we introduce new catalysts for the rapid synthesis of COFs under ambient conditions, novel strategies for synthesis that increase crystallinity, activation approaches that preserve the porosity even for fragile COFs, and transformation approaches that enable the conversion of linear polymers to COFs. The synthesis of crystalline and porous COFs remains a significant challenge. In Chapter 2, we demonstrate that a series of transition metal nitrates can be used to rapidly produce COFs under ambient conditions. These transition metal nitrates enabled the production of crystalline COFs within 10 minutes at room temperature, and were successfully used to synthesize a wide range of COF targets varying in linker chemistry, linker lengths, substituents, and stabilities In Chapter 3, we demonstrate novel synthetic strategies to produce highly crystalline and porous COFs. We show that in the synthesis of imine COFs, benzaldehyde modulators compete with multi-functional aldehyde monomers to slow down the COF polymerization and growth chemistry. The modulators result in an improved crystallinity of the final COF, and the amount of benzaldehyde modulator added can be optimized for yield and product crystallinity. Activation of COFs generally involves washing and drying to isolate COFs from synthesis solvents and produce dry COF powders. Activation is as important as synthesis since COFs with high crystallinity and porosity can only be produced through proper activation. However, activation processes are usually overlooked, and conventional methods can result in collapse of porous structure and loss of accessible surface areas. In Chapter 4, we present a general approach to COF activation. We demonstrate that the use of an ultralow surface tension solvent perfluorohexane (PFH) enables rapid, simple and effective activation of a range of COFs. This approach avoids the use of supercritical CO2, which is not as widely accessible as PFH. In Chapter 5, we demonstrate a novel route to the synthesis of COFs through the transformation of linear polymers using dynamic and reversible chemistries. Specifically, we demonstrate an approach to transform linear imine-linked polymers into ketone-linked COFs through a linker replacement strategy with triformylphloroglucinol (TPG). TPG first reacts through dynamic chemistry to replace linkers in the linear polymers and then undergoes irreversible tautomerism to produce ketone linkages. This strategy provides an approach to synthesizing COFs through the solution processing of linear polymers followed by transformation to the desired COF structure. Finally, this thesis proposes future research directions based on the topics introduced from Chapter 2 to Chapter 5. We aim to develop more novel catalysts for COF synthesis and broaden their generality. We propose to modify the COF surface chemistry through the introduction of functionalized modulators and design more robust COFs through molecular engineering. We also aim to transform soluble linear polymers into COFs, which might serve as a novel solution processing method for COFs. We anticipate that these investigations provide further insight into the fundamental properties and basic problems in COF areas.

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Alternative Products

Product Details of [ 66-98-8 ]

CAS No. :66-98-8
Formula : C14H10O2
M.W : 210.23
SMILES Code : O=CC1=CC=C(C2=CC=C(C=O)C=C2)C=C1
MDL No. :MFCD00016714
InChI Key :FEHLIYXNTWAEBQ-UHFFFAOYSA-N
Pubchem ID :6200

Safety of [ 66-98-8 ]

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

Computational Chemistry of [ 66-98-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 62.65
TPSA ?

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

34.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.74
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

1.63
Log Po/w (WLOGP)?

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

2.98
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.

2.26
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

3.86
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.49

Water Solubility

Log S (ESOL):?

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

-2.53
Solubility 0.624 mg/ml ; 0.00297 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.

-1.96
Solubility 2.31 mg/ml ; 0.011 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

-4.82
Solubility 0.0032 mg/ml ; 0.0000152 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

Yes
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.

-6.43 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

0.0
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)

1.3

Application In Synthesis of [ 66-98-8 ]

* 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.

  • Downstream synthetic route of [ 66-98-8 ]

[ 66-98-8 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 792-74-5 ]
  • [ 66-98-8 ]
  • 3
  • [ 15862-94-9 ]
  • [ 66-98-8 ]
  • 4'-(2-(4,5-dimethoxy-2-nitrophenyl)-1-hydroxyethyl)[1,1'-biphenyl]-4-carbaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% General procedure: To a glass vessel capable of being sealed with Teflon cap (for microwave vials) were added 1 and benzaldehyde derivative (3 equiv.). The vessel was capped and then, evacuated and backfilled with N2 (process repeated 3X). Anhydrous DMF (3.5mL/mmol) was introduced and the solution was vigorously stirred for 20min at-20C. TDAE was added slowly and the mixture was stirred for 1h. Then, the reaction was stirred at room temperature overnight. After LC-MS analysis clearly showed that the chloride had been totally consumed, the reaction was hydrolysed with distilled water. The mixture was then extracted with dichloromethane. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered off and concentrated under reduced pressure to afford the corresponding crude product 3.
  • 4
  • [ 66-98-8 ]
  • [ 6971-45-5 ]
  • C28H26N4O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With hydrogenchloride; In ethanol; water; at 80℃; for 0.5h;Inert atmosphere; To a solution of [1,1'-biphenyl]-4,4'-dicarboxaldehyde (80 mg, 0.38 mmol) in EtOH (4 mL), <strong>[6971-45-5]2-methoxyphenylhydrazine hydrochloride</strong> (166 mg, 0.95 mmol)and a catalytic amount of concentrated HCl (0.04 mL) wereadded. The reaction mixture was stirred at 80 C for 30 min and the resulting solution was filtered.The residue obtained was washed with hot EtOH (25 mL) to afford compound 9b (118mg, 69%)as a brown solid, which was insoluble.
 

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Technical Information

Categories

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