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Chemical Structure| 602-00-6 Chemical Structure| 602-00-6

Structure of 3-Hydroxy-2-nitrobenzoic acid
CAS No.: 602-00-6

Chemical Structure| 602-00-6

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Product Details of [ 602-00-6 ]

CAS No. :602-00-6
Formula : C7H5NO5
M.W : 183.12
SMILES Code : O=C(O)C1=CC=CC(O)=C1[N+]([O-])=O
MDL No. :MFCD00017003
Boiling Point : No data available
InChI Key :KPDBKQKRDJPBRM-UHFFFAOYSA-N
Pubchem ID :293291

Safety of [ 602-00-6 ]

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

Computational Chemistry of [ 602-00-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 44.25
TPSA ?

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

103.35 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.5
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

1.38
Log Po/w (WLOGP)?

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

1.0
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.

-0.04
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

-1.38
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.29

Water Solubility

Log S (ESOL):?

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

-2.05
Solubility 1.62 mg/ml ; 0.00883 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.

-3.15
Solubility 0.129 mg/ml ; 0.000702 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

-0.58
Solubility 48.5 mg/ml ; 0.265 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

No
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

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.44 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.

0.56

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

2.0 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)

1.75

Application In Synthesis of [ 602-00-6 ]

* 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 [ 602-00-6 ]

[ 602-00-6 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 602-00-6 ]
  • [ 89942-77-8 ]
YieldReaction ConditionsOperation in experiment
100% SOCI2 (0.6 mL) was added dropwise to anhydrous MeOH (10 mL) at O0C. The mixture was stirred at this temperature for 0.5 h, then 3-hydroxy-2-nitrobenzoic acid (0.6 g, 3.2 mmol) was added to the mixture. The resulting mixture was heated at reflux for 4 h. TLC (petroleum ether: ethyl acetate = 1 :1) showed the <n="74"/>reaction was complete. The resulting mixture was concentrated in vacuo to give the title compound (0.63 g 100%) as a brown solid.
With thionyl chloride; In methanol; Step 1 To a methanol solution (15 mL) at 0 C. was dropwise added thionyl chloride (6.4 mL, 0.088 mol). After 15 minutes, 3-hydroxy-2-nitrobenzoic acid (4 g, 0.022 mol) was added and the resulting mixture was stirred at room temperature for 72 hours. Volatile was removed under vacuo and the residue was partitioned between water and ethyl acetate. The organic layer was separated, washed with water and saturated sodium chloride, and was dried over sodium sulfate. After concentration, the crude product was recrystallized from dichloromethane and hexane to gave 4.5 g of methyl 3-hydroxy-2-nitrobenzoate.
With hydrogenchloride; sodium chloride; sodium hydrogencarbonate; In methanol; dichloromethane; water; 1st Stage Preparing Methyl (3-Hydroxy-2-nitro)benzoate 3-hydroxy-2-nitrobenzoic acid (5 g; 27.32 mM) was dissolved in anhydrous methanol (200 ml). Anhydrous hydrogen chloride gas was bubbled through the solution until saturated. The mixture was then refluxed for 20 hours (reaction followed by T.L.C.: 10% methanol/90% dichloromethane). Next, the solvent was removed under vacuum to yield a brown solid. The solid was dissolved in water (100 ml) and sodium bicarbonate was added until effervescence stopped. Sodium chloride (15 g) was added to the aqueous solution, and the product was extracted into ethyl acetate (3*50 ml). The pooled aliquots were dried over magnesium sulphate and the solvent removed under vacuum to yield a malty brown solid.
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  • [ 7732-18-5 ]
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  • 3
  • [ 7697-37-2 ]
  • [ 99-06-9 ]
  • [ 610-37-7 ]
  • [ 619-14-7 ]
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  • [ 116779-73-8 ]
  • 4
  • [ 67-56-1 ]
  • [ 602-00-6 ]
  • [ 89942-77-8 ]
YieldReaction ConditionsOperation in experiment
95% Intermediate A-15B: Methyl 3-hydroxy-2-nitrobenzoate To a 100 mL flask containing MeOH (60 mL) at 0 C. was slowly added thionyl chloride (9.96 mL, 137 mmol). The solution was stirred at 0 C. for 30 minutes, and then Intermediate A-15A (10 g, 54.6 mmol) was added. The reaction solution was heated to reflux for 6 hrs. The reaction mixture was concentrated to dryness to give a bright yellow residue. The crude product mixture was purified via silica gel chromatography (0% to 100% of EtOAC/heptane over 15 minutes, 80 g column) giving the desired product (10.2 g, 95% yield). HPLC: RT=1.75 min (H2O/MeOH with TFA, Sunfire C18 3.5 mum, 2.1*30 mm, gradient=4 min, wavelength=220 nm); MS (ES): m/z=220 [M+Na]+; 1H NMR (400 MHz, chloroform-d) delta 7.60 (dd, J=8.5, 7.4Hz, 1H), 7.33-7.22 (m, 5H), 7.10 (dd, J=7.5, 1.3Hz, 1H), 3.96 (s, 3H).
93% With thionyl chloride; at 20℃; for 9h;Heating / reflux; To a stirred mixture of methanol (55 mL) and thionyl chloride (3.19 mL, 43.7 mmol) was added 3-hydroxy-2-nitrobenzoic acid (5.0 g, 27.3 mmol). The reaction mixture was stirred at room temperature for 2 h, refluxed for 7 h then evaporated. Purification by flash chromatography (2.5×10 cm column, 1:3 EtOAc/hexane) gave the title compound as a light yellow solid (5.03 g, 93% yield), mp 114-116 C. LC/MS gave the correct molecular ion [(M-H)-=196] for the desired compound.
64% With hydrogenchloride; In water; for 8h;Reflux; Methyl 3-hydroxy 2-nitrobenzoate (1): Dry HCl was bubbled through the refluxing solution of 3-hydroxy 2-nitro benzoic acid (10 g, 0.055 mol) in 150 ml MeOH for 8 h. The solution was concentrated in high vacuum. Addition of H2O to the concentrated solution precipitated the methyl 3-hydroxy 2-nitro benzoic ester(64% yield, 6.9 g, 0.035 mol). 1H NMR delta = 7.07 (dd, 1H), 7.26 (m,1H), 7.58 (d, 1H), 3.94 (CO2CH3, s, 3H).
With sulfuric acid; for 48h;Reflux; Example 113 Bmethyl 3-hydroxy-2-nitrobenzoate; A solution of 3-hydroxy-2-nitrobenzoic acid (51 g) and con.H2SO4 (5 mL) in anhydrous methanol (450 mL) was heated to reflux for 48 hr. The mixture was concentrated to remove methanol, and the residue was partitioned between water (500 mL) and ethyl acetate (800 mL). The organic layer was washed with brine (300 mL), dried over anhydrous sodium sulfate, and concentrated to give crude compound. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=40:1 to 5:1) to give methyl 3-hydroxy-2-nitrobenzoate (28 g) 1H-NMR (400 MHz, CDCl3) delta 3.8 (s, 3H), 7.32-7.34 (d, J=8.4 Hz, 1H), 7.39-7.41 (d, J=8.0 Hz, 1H), 7.48-7.52 (t, J=8.0 Hz, 1H), 11.37 (s, 1H); LC-MS (m/z) 198 [M+1]+.
With thionyl chloride; at 60℃; General procedure: 3-Hydroxybenzoic acid (10 mmol) and anhydrous methanol (20 mL) were added to a 100 mL dry eggplant-shaped flask. With stirring, thionyl chloride (25 mmol) was added dropwise 5-12 h at 60 C, and the reaction progress was tracked using TLC. After the reaction completion, excess thionyl chloride was removed under reduced pressure, and the system was slowly poured into 100 mL of icewater. The mixture was extracted with ethyl acetate (30 mL 3),the combined organic layer was dried over Na2SO4, concentrated under vaccum. The crude product 1 was used in the next step without further purification.

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  • [ 5121-34-6 ]
 

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