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Chemical Structure| 121-92-6 Chemical Structure| 121-92-6

Structure of 3-Nitrobenzoic acid
CAS No.: 121-92-6

Chemical Structure| 121-92-6

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Product Details of [ 121-92-6 ]

CAS No. :121-92-6
Formula : C7H5NO4
M.W : 167.12
SMILES Code : O=C(O)C1=CC=CC([N+]([O-])=O)=C1
MDL No. :MFCD00007251
InChI Key :AFPHTEQTJZKQAQ-UHFFFAOYSA-N
Pubchem ID :8497

Safety of [ 121-92-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335-H412
Precautionary Statements:P261-P273-P305+P351+P338

Computational Chemistry of [ 121-92-6 ] 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 4.0
Num. H-bond donors 1.0
Molar Refractivity 42.22
TPSA ?

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

83.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.77
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

1.83
Log Po/w (WLOGP)?

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

1.29
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.

0.51
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

-0.93
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.69

Water Solubility

Log S (ESOL):?

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

-2.27
Solubility 0.904 mg/ml ; 0.00541 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.

-3.2
Solubility 0.106 mg/ml ; 0.000637 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

-1.15
Solubility 12.0 mg/ml ; 0.0716 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.

-6.02 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)

1.62

Application In Synthesis of [ 121-92-6 ]

* 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 [ 121-92-6 ]

[ 121-92-6 ] Synthesis Path-Downstream   1~9

  • 2
  • [ 121-92-6 ]
  • <i>dl</i>(?)-isoborneol [ No CAS ]
  • [ 17408-16-1 ]
  • 3
  • [ 13708-12-8 ]
  • [ 121-92-6 ]
  • [ 1234503-53-7 ]
  • 4
  • [ 121-92-6 ]
  • [ 957061-12-0 ]
  • 5
  • [ 42303-42-4 ]
  • [ 121-92-6 ]
  • [ 1370340-94-5 ]
YieldReaction ConditionsOperation in experiment
76% With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 20℃; for 3h;Inert atmosphere; To the suspension of 3-nitrobenzoic acid ( 1 g, 5.98 mmol) in pyridine ( 10ml) <strong>[42303-42-4]ethyl <strong>[42303-42-4]1-aminocyclopropanecarboxylate hydrochloride</strong></strong> ( 1.090 g, 6.58 mmol) was added followed by EDC.HC1 (1.721 g, 8.98 mmol) under nitrogen. Reaction mixture was stirred at room temperature for 3hrs. Reaction mixture was diluted with cold water ( 100ml) and extracted with ethyl acetate (2X25ml). Separated organic layer was washed with brine and water, dried over sodium sulfate and concentrated under vacuum till dryness to obtain product ( 1.26g, 76%). NMR (400 MHz, CDC13) 8 (ppm): 8.59 (bs, 1H), 8.41-8.38 (m, 1H), 8.20-8. 18(m, 1H), 7.68 (t, 1H, J=8Hz), 6.82 (bs, 1H), 4.19 (q, 2H, J=7.2Hz), 1.70- 1.34 (m, 2H), 1.37- 1.33 (m, 2H), 1.26(t,3H,J=7.2Hz). ESI- MS (m/z): 279.58 (M+l)
  • 6
  • [ 88675-24-5 ]
  • [ 121-92-6 ]
  • [ 1456714-32-1 ]
YieldReaction ConditionsOperation in experiment
240 mg With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 22 - 26℃; for 10h;Inert atmosphere; Step-a: Synthesis of 3-Nitro-N-(tetrahydrofuran-3-yl)benzamide Tetrahydrofuran-3-amine (0.1 g, 1.148 mmol) and 3-nitrobenzoic acid (0.192 g, 1.148 mmol) were taken in pyridine (2 ml), to the mixture EDC.HCl (0.220 g, 1.148 mmol) was added, the reaction mixture was stirred under nitrogen for 10 hrs at room temperature. The reaction mixture was diluted with cold water (15 ml), extracted with ethyl acetate (2*10 ml). Combined organic layer was washed with satd. aq. sod bicarbonate and dil HCl, the organic layer was dried over sodium sulfate and concentrated under vacuum to afford the title product (240 mg). 1HNMR (400 MHz, CDCl3): delta 8.62-8.61 (m, 1H), 8.39-8.36 (m, 1H), 8.19-8.17 (m, 1H), 7.67 (t, 1H, J=8 Hz), 6.62 (d, 1H, J=6 Hz), 4.79-4.75 (m, 1H), 4.08-4.00 (m, 1H), 3.93-3.83 (m, 3H), 2.44-2.37 (m, 1H), 2.01-1.98 (m, 1H).
  • 7
  • [ 42303-42-4 ]
  • [ 121-92-6 ]
  • [ 1456714-42-3 ]
YieldReaction ConditionsOperation in experiment
76% With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 22 - 26℃; for 3h;Inert atmosphere; Step-a: Synthesis of Ethyl 1-(3-nitrobenzamido)cyclopropanecarboxylate To the suspension of 3-nitrobenzoic acid (1 g, 5.98 mmol) in pyridine (10 ml) <strong>[42303-42-4]ethyl <strong>[42303-42-4]1-aminocyclopropanecarboxylate hydrochloride</strong></strong> (1.090 g, 6.58 mmol) was added followed by EDC.HCl (1.721 g, 8.98 mmol) under nitrogen. Reaction mixture was stirred at room temperature for 3 hrs. Reaction mixture was diluted with cold water (100 ml) and extracted with ethyl acetate (2*25 ml). Separated organic layer was washed with brine and water, dried over sodium sulfate and concentrated under vacuum till dryness to obtain product (1.26 g, 76%). 1H NMR (400 MHz, CDCl3) delta (ppm): 8.59 (bs, 1H), 8.41-8.38 (m, 1H), 8.20-8.18 (m, 1H), 7.68 (t, 1H, J=8 Hz), 6.82 (bs, 1H), 4.19 (q, 2H, J=7.2 Hz), 1.70-1.34 (m, 2H), 1.37-1.33 (m, 2H), 1.26 (t, 3H, J=7.2 Hz). ESI-MS (m/z): 279.58 (M+1)
  • 8
  • [ 78287-27-1 ]
  • [ 121-92-6 ]
  • 7-ethylcamptothecin-20(S)-O-m-nitrobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77.1% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 2 - 20℃; for 2.25h; 7-Et-CPT (0.75?g, 2?mmol), EDCI (1.53g, 8?mmol) and DMAP (1.47?g, 12?mmol) were added to a solution of m-nitrobenzoic acid (1.00?g, 6?mmol) in 100?mL of CH2Cl2 with stirring at 2?°C for 15?min. The mixture was stirred at room temperature for 2?h and was poured onto 100?ml ice water. The obtained organic layer was washed with dilute hydrochloric acid and saturated salt water in turn, and concentrated. The crude product was chromatographically separated with CH2Cl2-THF as eluent. The pure product 3g (0.81?g) was obtained as almost white powder, yield 77.1percent, purity 98.97percent (HPLC), mp 272-274?°C. 1H NMR (CDCl3, 500?MHz) delta: 1.11 (t, J?=?7.5?Hz, 3H, 19-H), 1.40 (t, J?=?7.8?Hz, 3H, 30-H), 2.37-2.49 (m, 2H, 18-H), 3.20 (q, 2H, 29-H), 5.25 (d, J?=?18.5?Hz, 1H, 5-H), 5.29 (d, J?=?19.0?Hz, 1H, 5-H), 5.49 (d, J?=?17.0?Hz, 1H, 17-H), 5.79 (d, J?=?17.0?Hz, 1H, 17-H), 7.25 (s, 1H, 14-H), 7.68 (m, 2H, 10, 27-H), 7.77 (t, J?=?7.5?Hz, 1H, 11-H), 8.13 (t, J?=?9.8?Hz, 2H, 9,12-H), 8.40 (d, J?=?7.5?Hz, 1H, 24-H), 8.46 (m, 1H, 26-H), 8.93 (s, 1H, 28-H). ESI-MS m/z: 526.2 (M?+?1)+.
 

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