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Chemical Structure| 58755-57-0 Chemical Structure| 58755-57-0

Structure of 58755-57-0

Chemical Structure| 58755-57-0

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Product Details of [ 58755-57-0 ]

CAS No. :58755-57-0
Formula : C7H4ClNO3
M.W : 185.56
SMILES Code : ClC1=C(C=O)C=CC=C1[N+](=O)[O-]
MDL No. :MFCD08236804
Boiling Point : No data available
InChI Key :WKIVBBWLRIFGHF-UHFFFAOYSA-N
Pubchem ID :12667713

Safety of [ 58755-57-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 58755-57-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 45.66
TPSA ?

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

62.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.04
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.

2.06
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.

0.86
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

0.48
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.26

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 0.717 mg/ml ; 0.00386 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.

-2.82
Solubility 0.279 mg/ml ; 0.0015 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

-2.34
Solubility 0.84 mg/ml ; 0.00453 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.

-6.1 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

3.0 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)

1.65

Application In Synthesis of [ 58755-57-0 ]

* 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 [ 58755-57-0 ]

[ 58755-57-0 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 89639-98-5 ]
  • [ 58755-57-0 ]
YieldReaction ConditionsOperation in experiment
79.7% With pyridinium chlorochromate; In dichloromethane; at 20℃; for 12h; 8.43 g (39.09 mmol) of pyridinium chlorochromate (PCC) were added to a solution of 6.11 g (32.57 mmol) of <strong>[89639-98-5](2-chloro-3-nitrophenyl)methanol</strong> in 120 ml of dichloromethane, and the mixture was stirred at room temperature for 12 hours. After complete conversion, the solvent was evaporated to dryness under reduced pressure. The residue obtained was purified chromatographically on silica gel (mobile phase dichloromethane/methanol 20:1). This gave 4.82 g (25.97 mmol, 79.7% of theory) of the title compound.GC-MS (method 3): Rt=5.09 min; m/z=186 (M+H)+.1H-NMR (400 MHz, DMSO-d6): δ=10.35 (s, 1H), 8.33 (dd, 1H), 8.13 (dd, 1H), 7.77 (t, 1H).
78% A solution of oxalyl chloride in dichloromethane (2.0M, 116 mmol) was chilled to -70 C. (internal temperature) under a nitrogen atmosphere. DMSO (15 mL, 211.3 mmol) was added dropwise maintaining -65 C. and then stirring was continued for 45 min. at -70 C. A solution of the 3-nitro-2-chlorobenzyl alcohol (14.4 g, 76.6 mmol) in dichloromethane (250 mL) was then added and the reaction stirred at -70 C. for 2 h. Triethylamine (54 mL, 387 mmol) was added dropwise and the reaction stirred for 2 h at -70 C. and then 12 h at room temperature. The reaction was quenched by the addition of 500 mL of water. The aqueous phase was extracted twice with dichloromethane. The combined organic layers were washed with brine, dried with MgSO4, filtered, and evaporated to obtain a light brown solid. Column Chromatography (silica gel, 30% dichloromethane/hexanes to 70% dichloromethane/hexanes) produced 11.1 g (78%) of the desired 3-nitro-2-chlorobenzaldehyde as a yellow solid. 3-Nitro-2-chlorobenzaldehyde (11.1 g, 59.5 mmol) was dissolved in DMF (100 mL) and potassium carbonate (9.1 g, 66.2 mmol) was added. By slow addition, methyl thioglycoate (5.4 mL, 60.4 mmol) was added and a slight exotherm was observed. The reaction mixture was stirred 12 h at room temperature. Water (200 mL) was added to the reaction mixture which was then cooled on an ice/water bath. The solid was filtered and washed water until the filtrate was colorless, leaving the 13.3 g (94%) of the desired 7-nitro-benzo[b]thiophene-2-carboxylic acid methyl ester as a white solid.
74% Step 2. 2-Chloro-3-nitrobenzaldehyde; A 250-mL 3-necked round-bottom flask was charged with a solution of oxalyl chloride (5.42 g, 42.70 mmol, 1.10 equiv) in DCM (100 mL). To this was added a solution of DMSO (6.65 g, 85.11 mmol, 2.20 equiv) in DCM (15 mL) drop wise -78 C. 2-Chloro-3-nitrophenyl)methanol (7.23 g, 38.54 mmol, 1.00 equiv) in DCM (35 mL) was added into the solution at -78 C. and allowed to stir for 1 hour. Then, TEA (30 mL) was added at this temperature and allowed to stir for an additional hour. Upon completion, the reaction was quenched with water and extracted with DCM (3×100 mL). Combined organic layers were dried over anhydrous sodium sulfate, filtered off and concentrated on a rotary evaporator. The residue was purified by a silica gel column chromatography eluted with PE:EA (10:1) affording 2-chloro-3-nitrobenzaldehyde as light yellow solid (5.3 g, 74%).
With manganese(IV) oxide; In dichloromethane; at 20℃; General procedure: MnO2 (508 g, 5.84 mol) was added to (2-bromo-4-nitro-phenyl)methanol (135.1 g, 0.582 mol) in DCM (1 L) and the reaction mixture was stirred overnight at rt. The mixture was filtered and the filtrate was evaporated to afford the title compound 18 (110.8 g, 83%) as a yellow solid

  • 2
  • [ 58755-57-0 ]
  • [ 96516-29-9 ]
YieldReaction ConditionsOperation in experiment
77% With potassium fluoride; In N,N-dimethyl-formamide; at 150℃; for 5.0h; To a solution of 2-chloro-3-nitrobenzaldehyde (9.5 g, 51.2 mmol) in DMF (100 mL) was added KF (8.9 g, 154 mmol). The reaction mixture was heated to 150 C and stirred at that temperature for 5 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The crude material was poured into H20 (400 mL) and extracted with DCM (100 mL x 4). The combined organic extracts were concentrated in vacuo and the crude material was purified by silica-gel column chromatography (petroleum ether/EtOAc, 20: 1) to give 2-fluoro-3- nitrobenzaldehyde as a yellow oil (6.7 g, yield: 77%). 1H NMR (400 MHz, CDCI3) d: 10.44 (s, 1H), 8.36-8.30 (m, 1H), 8.22-8.16 (m, 1H), 7.47 (t, J = 8.0 Hz, 1H).
  • 3
  • [ 58755-57-0 ]
  • [ 24629-25-2 ]
  • [ 857040-99-4 ]
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Julia-Kocienski Olefination • Kinetics of Alkyl Halides • Knoevenagel Condensation • Kumada Cross-Coupling Reaction • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nozaki-Hiyama-Kishi Reaction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reformatsky Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Stetter Reaction • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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