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Chemical Structure| 603-11-2 Chemical Structure| 603-11-2

Structure of 3-Nitrophthalic acid
CAS No.: 603-11-2

Chemical Structure| 603-11-2

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Product Details of [ 603-11-2 ]

CAS No. :603-11-2
Formula : C8H5NO6
M.W : 211.13
SMILES Code : O=C(O)C1=CC=CC([N+]([O-])=O)=C1C(O)=O
MDL No. :MFCD00007138
InChI Key :KFIRODWJCYBBHY-UHFFFAOYSA-N
Pubchem ID :69043

Safety of [ 603-11-2 ]

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

Computational Chemistry of [ 603-11-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 49.18
TPSA ?

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

120.42 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

-0.09
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

0.75
Log Po/w (WLOGP)?

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

0.99
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.

0.23
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

-1.47
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.08

Water Solubility

Log S (ESOL):?

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

-1.72
Solubility 4.03 mg/ml ; 0.0191 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.

-2.86
Solubility 0.293 mg/ml ; 0.00139 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

-0.53
Solubility 61.9 mg/ml ; 0.293 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.

-7.06 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.

0.56

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)

2.06

Application In Synthesis of [ 603-11-2 ]

* 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 [ 603-11-2 ]

[ 603-11-2 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 67-56-1 ]
  • [ 603-11-2 ]
  • [ 13365-26-9 ]
YieldReaction ConditionsOperation in experiment
100% [0030] The synthesis of mIBX is readily accomplished from commercially available 3-nitrophtalic acid as follows: esterification of 3-nitrophtalic acid via the corresponding acid chloride to give nitrodiester (100%), which upon catalytic hydrogenation provides the aminodiester (100%). Diazotization is then performed, followed by iodination of the aminodiester to provide dimethyl 3-iodophthalate in about 91 % yield. This is followed by saponification, then acidification of dimethyl 3-iodophthalate to give 3-iodophthalic acid in about 93 % yield. 3-iodophthalic acid is then oxidized to form the water-soluble MIBX. This process is carried out using KBrO3 in 0.73H2SO4 at 55-60 C. as follows: KBrO3 (5 g, 30 mmol) is added in portions to a suspension of 3-iodophthalic acid (5 g, 17.1 mmol) in 70 ML of 0.73 M H2SO4 over a period of 20 minutes; The mixture is then maintained at 55-60 C. for 12 hours and the resulting clear orange solution is evaporated to yield an off-white solid, which is triturated with 30 ML of water at 0 C. for 2 hours and filtered to obtain a white solid.This is further triturated with hexane (100 ML) for 6 hours and filtered to give MIBX (3.9 g, 71%) as a white solid with a melting point of 258-260 C. The approximately 70% yield for the conversion of 3-iodophthalic acid to MIBX is the isolated yield of MIBX, with the actual conversion near quantitative as evident from monitoring the oxidation of 3-iodophthalic acid to MIBX by 1H NMR spectroscopy. Water-soluble MIBX is isolated as an analytically pure white solid.The synthesis of MIBX from 3-nitrophthalic acid is illustrated in . The physical properties of MIBX are as follows: mp 258-260 C.; IR (KBr), 3503 3469, 3050, 1708, 1631, 1588, 1369, 730, 700 cm-1; 1H NMR (D2O), 300 MHz): δ 8.35 (dd, J=7.9, 1.0 Hz, 1H), 8.09 (t, J=7.9 Hz, 1H), 7.94 (dd, J=7.9, 1.0 Hz, 1H); 13C NMR (D2O, 75 MHz): δ 125.5, 127.5, 132.5, 134.7, 137.0, 147.1 (ring carbons), 168.9, 172.9 (carbonyl carbons).
With sulfuric acid;Reflux; (1) Put 30 g of 3-nitrophthalic acid into a 500 ml reaction flask and add 300 ml of methanol (1:10, optionally 1:5 to 1:20, preferably 1:10 to 1:15). Sulfuric acid 30g (1:0.5-1:2, preferably 1:1) was warmed at reflux.(2) TLC monitoring, when the formation of the double esterification product exceeds the reduction of the raw material, the refluxing reaction is ended; below 50 C., the methanol is concentrated under reduced pressure to almost no fraction.(3) Add 200ml of water, control the temperature below 25C, add potassium carbonate to neutralize the pH to 7-8, and add 100ml of ethyl acetate to extract.The extract is concentrated and crystallized to obtain dimethyl 3-nitrophthalate, the aqueous layer is acidified to pH 4-5, stirred at room temperature for 2 hours, and the product is filtered to obtain methyl 3-nitro-2-carboxybenzoate (AM1). , Content more than 98%, yield more than 90%,Drying standby.
  • 3
  • [ 83-41-0 ]
  • [ 1975-50-4 ]
  • [ 13506-76-8 ]
  • [ 603-11-2 ]
YieldReaction ConditionsOperation in experiment
With oxygen; nitric acid; at 130 - 140℃; under 16501.7 - 18751.9 Torr; for 7h; (1) 3-Nitro-o-xylene (200 g) and 30% nitric acid (1000 g) are added to the oxidation reactor, the temperature is raised to 130-140 C, the oxygen pressure is 2.2-2.5 MPa, and the reaction is kept for 7 hours while stirring; (2) Cool down to 20-30C and filter to obtain 193 g of crude product (HPLC: 3-nitrophthalic acid 6.63%, 2-methyl-6-nitrobenzoic acid 15.92%, 3-nitro-2-methylbenzoic acid 60.74%, 3-nitro-o-xylene 8.66%); (3) The crude product was washed three times with 200 g of water to obtain 142 g of filter cake (HPLC spectrum shown in Figure 1: 3-nitrophthalic acid 0.52%, 2-methyl-6-nitrobenzoic acid 12.3%, 3-nitro-2-methylbenzoic acid 72.03%, 3-nitro-o-xylene 7.1%).
  • 4
  • [ 603-11-2 ]
  • [ 13365-26-9 ]
YieldReaction ConditionsOperation in experiment
63% With potassium carbonate; dimethyl sulfate; In water; acetone; REFERENCE EXAMPLE 101 Dimethyl 3-nitrophthalate To a suspension of 3-nitrophthalic acid (25.5 g, 0.120 mol) and potassium carbonate (40.1 g, 0.289 mol) in acetone (500 ml), dimethyl sulfate (27.4 ml, 0.289 mmol) was added dropwise, and the reaction mixture was heated under reflux for 21 hours. The solvent was distilled off under reduced pressure, and the residue was combined with water and extracted with ethyl acetate. After the extract was washed with water and dried (MgSO4), the solvent was distilled off under reduced pressure. The residue was subjected to a column chromatography on a silica gel eluding with n-hexane-ethyl acetate (5:1, v/v) to give the title compound (18.0 g, 63%). Recrystallization from ethyl acetate yielded a colorless crystal having a melting point of 66.0 to 67.0 C. IR (KBr): 2955, 1738, 1630, 1613, 1574, 1541 cm-1. 1H-NMR (CDCl3) δ: 3.96 (3H, s), 4.03 (3H, s), 7.69 (1H, t, J=8.2 Hz), 8.32-8.42 (2H, m).
  • 6
  • [ 603-11-2 ]
  • [ 139481-44-0 ]
  • 7
  • [ 603-11-2 ]
  • [ 6946-22-1 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide; acetic acid;PtO2; In water; acetone; 1) Reduction of 3-nitro-1,2-benzene dicarboxylic acid to 3-amino-1,2-benzene dicarboxylic acid. 21.1 g (0.1 moles) of 3-nitro-1,2-benzene dicarboxylic acid dissolved in 75 ml of water containing 8.2 g of NaOH, are placed in a 500 ml glass autoclave. The pH of the mixture is then adjusted to 8-9 by the addition of dilute acetic acid. One gram of PtO2 is then added pressurised under H2 at 4 atm, after flushing 4 times with nitrogen. The autoclave temperature is raised to 50° C. and the mixture is left to react for 24 hours. On completion the platinum oxide is then removed by filtration and 50 ml of conc. HCL are added to the filtrate. An addition of 200 ml of acetone is then made to the resultant opalescent solution to promote precipitation of the inorganic salts, which are then filtered off. The filtrate is finally concentrated until an opalescent solution is obtained, from which after cooling at 4° C., the reaction product is precipitated in the form of hydrochloride. After filtering and drying under vacuum, 19.5 g of 3-amino-1,2-benzene dicarboxylic acid hydrochloride are obtained, representing a 90percent yield.
90% With sodium hydroxide; acetic acid;PtO2; In water; acetone; 1) Reduction of 3-nitro-1,2-benzene dicarboxylic acid to 3-amino-1,2-benzene dicarboxylic acid. 21.1 g (0.1 moles) of 3-nitro-1,2-benzene dicarboxylic acid dissolved in 75 ml of water containing 8.2 g of NaOH, are placed in a 500 ml glass autoclave. The pH of the mixture is then adjusted to 8-9 by the addition of dilute acetic acid. One gramme of PtO2 is then added and the autoclave is pressurised under H2 at 4 atm, after flushing 4 times with nitrogen. The autoclave temperature is raised to 50°C and the mixture is left to react for 24 hours. On completion the platinum oxide is then removed by filtration and 50 ml of conc. HCL are added to the filtrate. An addition of 200 ml of acetone is then made to the resultant opalescent solution to promote precipitation of the inorganic salts, which are then filtered off. The filtrate is finally concentrated until an opalescent solution is obtained, from which after cooling at 4°C, the reaction product is precipitated in the form of hydrochloride. After filtering and drying under vacuum, 19.5 g of 3-amino-1,2-benzene dicarboxylic acid hydrochloride are obtained, representing a 90percent yield. The product structure is confirmed by IR and 1H-NMR spectroscope analysis.
65 g 3-nitrophthalic acid (lOOgm) and 10percent Pd/C (3.2 gm) in ethanol (600ml) was charged in autoclave and hydrogen pressure of 4.0 kg applied for 3.0 hr at 20-25 °C in autoclave. The reaction mass was cooled to 20°C and filtered through hyflo bed. The filtrate was distilled under reduced pressure and to the residue acetone was charged. The reaction mass was cooled to 10°C and followed by addition of conc., hydrochloric acid and stirred. The solvent was removed under reduced pressure and acetonitrile was added. The reaction mass was cooled to 10°C and precipitated solid was filtered. The product was dried at 45-50°C under vacuum for 6 hr to obtain 65.0gm of 3-aminophthalic acid hydrochloride salt.
adding 65kg of purified water into a 200L enamel kettle, stirring and dissolving 3.79kgNaOH, cooling to room temperature (25-35 ° C), adding 3-nitrophthalic acid (10kg), stirring to dissolve, Bucket; About 20L of the above solution was taken and palladium carbon (dry weight 0.5kg) was dispersed therein and evacuated into a 200L hydrogenation reactor. The remaining 3-nitrophthalic acid solution was evacuated into 200L of hydrogenation The kettle, open mixing, replacing the air with nitrogen, then replace the nitrogen with hydrogen, hydrogen pressure is maintained at 0.7-0 .9 Mpa, maintaining the temperature of the reaction liquid at 55-65 ° C for hydrogenation.The reaction takes about 12h; After the reaction, hydrogen was replaced by nitrogen, the palladium carbon was removed by filtration through a sand filter rod filter, and the filtrate was again filtered once with a filter added with diatomaceous earth. The filtrate was pumped into a 200 L enamel kettle with a vacuum; reducing the temperature to -5-0 ° C, dropping 22.3kg (about 18.75L) concentrated hydrochloric acid, keeping the temperature at -5-5 ° C, dropping for about 30min, keeping the temperature for 0.5h after the dropwise addition is completed; Centrifugal filtration, and rinsed twice with ethyl acetate, each 5kg.The solid was transferred to a vacuum oven and dried at 20-45 ° C for 24 h (degree of vacuum ?-0.095 Mpa) to give the final product of 3-aminophthalic acid.

  • 8
  • [ 603-11-2 ]
  • [ 74-88-4 ]
  • [ 13365-26-9 ]
YieldReaction ConditionsOperation in experiment
95% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 20 - 60℃; for 4h; 5.40 2-(2,6-DIOXOPIPERIDIN-3-YL)-4-PHENYLAMINOISOINDOLE-1,3-DIONE 50.40.1 3-Nitrophthalic Acid Dimethyl Ester Methyl iodide (30.2 g, 213 mmol) was added to a stirred mixture of 3-nitrophthalic acid (15.0 g, 71.0 mmol) and sodium bicarbonate (23.9 g, 284 mmol) in DMF (150 mL) at room temperature, and the mixture was then heated in an oil bath set to 60 C. for 4 hours. The mixture was then poured into 700 mL of ice water. After the ice melted, the mixture was extracted with ethyl acetate (3×150 mL) and the organic phases were washed with water (7×500 mL), dried (MgSO4) and evaporated, providing 16.2 g of the product as a pale yellow solid in 95% yield: 1H NMR (CDCl3) δ 3.95 (s, 3H), 4.02 (s, 3H), 7.69 (t, J=8.1 Hz, 1H), 8.36 (m, 2H).
95% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 20 - 60℃; for 4h; Example 1 2-(2,6-Dioxo-piperidin-3-yl)-4-(2-methoxy-phenoxy)-isoindole-l,3-dioneStep 1 : <n="50"/>[162] Methyl iodide (30.2 g, 213 mmol) was added to a stirred mixture of 3- nitrophthalic acid (15.0 g, 71.0 mmol) and sodium bicarbonate (23.9 g, 284 mmol) in DMF (150 mL) at room temperature, and the mixture was then heated in an oil bath set to 60 0C for 4 h. The mixture was then poured into 700 mL of ice water. After the ice melted, the mixture was extracted with ethyl acetate (3 x 150 mL) and the organic phases were washed with water (7 x 500 mL), dried (MgSO4) and evaporated, providing 16.2 g of 3-nitrophthalic acid dimethyl ester as a pale yellow solid, in 95% yield; 1H NMR (CDCl3) δ 3.95 (s, 3H), 4.02 (s, 3H), 7.69 (t, J = 8.1 Hz, IH), 8.36 (m, 2H).
  • 9
  • [ 67-56-1 ]
  • [ 603-11-2 ]
  • [ 75-03-6 ]
  • [ 13365-26-9 ]
  • [ 62351-79-5 ]
YieldReaction ConditionsOperation in experiment
3-Nitrophthalic acid (10.0 g, 0.047 mol) was dissolved in methanol (200 mL), SOCl2 (30 mL) was added dropwise during 1 hour at 0C.The mixture was heated to reflux for 8 hours and concentrated, then treated with DMF (200 mL), K2CO3 (39.0 g, 0.284 mol), and iodoethane (29.0 g, 0.19 mol). Then the mixture was heated to 80C for 8 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate (500 mL) and filtered. The filtrate was washed with water (3x300 ml) and brine (3x300 ml), dried over Na2SO4, filtered, and concentrated to give the mixture as a light brown solid (12.0 g, crude yield about 100%).
  • 10
  • [ 13365-26-9 ]
  • [ 603-11-2 ]
  • 11
  • [ 1004-38-2 ]
  • [ 603-11-2 ]
  • C4H7N5*C8H5NO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% In ethanol; water; for 0.5h; To a 10 ml of ethanol-H2O mixed solution containing H2NPA(0.20 mmol) and <strong>[1004-38-2]TAP</strong>I (0.10 mmol) was stirred for half an hourcontinually. The resulting clear solution was evaporated at20e25 C, and an irregular, colorless bulk crystal was obtained afterseven days. The resulting crystals were filtered and dried afterrinsed with ethanol-H2O mixed solution. Yield: 70%. Analysiscalculated for C12H14N6O7: C, 40.64; H, 3.95; N, 23.71%. Found: C,40.35; H, 4.00; N, 23.51%. Infrared spectrum (KBr disc, cm1):3441s, 3409s, 3208m, 3082m, 2416w, 1679s, 1651s, 1607s, 1569s,1538s, 1454m, 1431m, 1413m, 1351s, 1261m, 1155m, 1133w, 1077w,972w, 912m, 843w, 830m, 810m, 782s, 763m, 705s, 661w, 587m,532s.
  • 12
  • [ 603-11-2 ]
  • [ 150058-27-8 ]
  • 13
  • [ 83-41-0 ]
  • [ 1975-50-4 ]
  • [ 13506-76-8 ]
  • [ 603-11-2 ]
  • C8H7NO5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With oxygen; nitric acid; at 145 - 150℃; under 26252.6 - 30003 Torr; for 8h; (1) 3-Nitro-o-xylene (100 g) and 10% nitric acid (600 g) are added to the oxidation reactor, the temperature is raised to 145-150C, the oxygen pressure is 3.5-4.0 MPa, and the reaction is kept warm and stirred for 8 hours;(2) Cool down to 75-80, filter while hot,Obtain 55 grams of crude 3-nitro-2-methylbenzoic acid, the filtrate weighs 650 g, and the concentration of nitric acid is 4.5%;(3) The filter cake is washed with 11 g of water at 80C, and the washing liquid is combined with the filtrate in step (2) to deoxidize the reactor. After washing with water, the filter cake weighed 46g, added 46 g of anhydrous methanol, heated to 65 to dissolve, filtered out the insoluble matter while it was hot, the filtrate was cooled and crystallized, and kept at 15-20 for 1 hour.Filter and dry to obtain 36 g of 3-nitro-2-methylbenzoic acid product (HPLC: 98.2%, content: 99.0%).
 

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