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Chemical Structure| 616-02-4 Chemical Structure| 616-02-4

Structure of Citraconic anhydride
CAS No.: 616-02-4

Chemical Structure| 616-02-4

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Product Details of [ 616-02-4 ]

CAS No. :616-02-4
Formula : C5H4O3
M.W : 112.08
SMILES Code : CC1=CC(=O)OC1=O
MDL No. :MFCD00005522
InChI Key :AYKYXWQEBUNJCN-UHFFFAOYSA-N
Pubchem ID :12012

Safety of [ 616-02-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H303-H311-H314-H317-H334
Precautionary Statements:P264-P270-P272-P280-P285-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501
Class:8(6.1)
UN#:2922
Packing Group:

Computational Chemistry of [ 616-02-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 0.2
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 25.05
TPSA ?

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

43.37 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.94
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

0.25
Log Po/w (WLOGP)?

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

0.02
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

0.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.48

Water Solubility

Log S (ESOL):?

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

-0.69
Solubility 22.8 mg/ml ; 0.203 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.

-0.72
Solubility 21.3 mg/ml ; 0.19 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

-0.58
Solubility 29.1 mg/ml ; 0.26 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.

-6.81 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

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)

1.96

Application In Synthesis of [ 616-02-4 ]

* 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 [ 616-02-4 ]

[ 616-02-4 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 616-02-4 ]
  • [ 1072-87-3 ]
YieldReaction ConditionsOperation in experiment
70% With 1,1,1,3,3,3-hexamethyl-disilazane; In N,N-dimethyl-formamide; at 100℃; for 1h; To a solution of citraconic anhydride (25) (12.0 g, 107 mmol) in DMF (100 mL) at 100 C hexamethyldisilazane (34.2 mL, 160 mmol) was added. The mixture was stirred at 100 C for 1 h, then it was cooled to room temperature. The solvent was evaporated under reduced pressure. The crude product was recrystallized from a mixture of hexane and ethyl acetate to give the title compound 26 as a white crystalline solid (8.33 g, 70%), mp 104-105 C (lit.: 104-105 C) [3]; Rf (DCM:MeOH 10:1) 0.71; nmax (KBr) 3271, 3098, 2674, 1844, 1778, 1764, 1712, 1634, 1342, 1284, 1175, 1090 cm_1; 1H NMR (500 MHz; DMSO-d6) d (ppm) 1.94 (3H; d; J 1.8 Hz; C(3)-CH3); 6.50 (1H; q; J 1.8 Hz; H-4); 10.72 (1H; br s; NH-1); 13C NMR (126 MHz; DMSO-d6) d (ppm) 10.2 (C(3)-CH3); 128.0 (C-4); 145.9 (C-3); 172.2 (C-5); 173.1 (C-2); HRMS: M 111.0311 (C5H5O2N; delta _8.1 ppm); HR-EI-MS (rel. int. %): 111(100); 83(8); 68(39).
40% With 1,1,1,3,3,3-hexamethyl-disilazane; In methanol; N,N-dimethyl-formamide; at 0 - 20℃; for 20.3333h; Stage 1: 3-methylpyrrole-2,5-dione A solution of hexamethyldisilazane (80.7 g, 104.8 ml, 500 mmol) in methanol was added dropwise to a solution of citraconic anhydride (5.60 g, 4.49 ml, 50 mmol) in N,N-dimethylformamide (170 ml) at 0 C. The reaction solution was stirred at room temperature for 20 h, thereafter methanol (100 ml) was added and the mixture was stirred for a further 20 min. The solvent was concentrated in vacuo and the residue was taken up in a mixture of ethyl acetate/water (150 ml:50 ml). The organic phase was separated off, washed with water (2*50 ml), sodium bicarbonate solution (50 ml) and with water again (50 ml) and then dried with sodium sulfate. The solvent was concentrated and the residue was dried in vacuo. Yield: 2.30 g (40%), white solid Melting point: 100-102 C. [lit. 101-104 C. (K. R. Shah, C. DeWitt Blanton, J. Org. Chem. 1982, 47, 502)].
32% With urea; In sulfolane; at 180℃; for 1h;Product distribution / selectivity; 25 g (0.219 mol) of 2-methyl succinic anhydride were heated in 37.5 g of sulfolane to a reaction temperature of 180 C. After the reaction temperature was achieved 18.95 g (0.32 mol) of urea were spread in and stirring was continued for 1 h at the reaction temperature under flushing with N2. Following cooling, the reaction mixture was first added with 2-propanol and then with MTBE. 6.5 g of 2-methyl succinic imide (32% of the theoretical yield) were obtained
20% With urea; In diethyleneglycol diethylether; at 180℃;Product distribution / selectivity; EXAMPLE 25 In a manner analogous to that of Example 24, diethyleneglycol diethylether was used as the solvent at 180 C. After cooling, first MTBE was added. From the resulting oil 2-methyl succinic imide was obtained in a yield of 20% by recrystallization from ethanol.

  • 2
  • [ 616-02-4 ]
  • [ 135616-40-9 ]
  • [ 147396-58-5 ]
  • [ 357418-52-1 ]
  • 3
  • [ 616-02-4 ]
  • [ 20605-41-8 ]
  • (Z)-4-[N'-(2-Methoxy-acetyl)-hydrazino]-2-methyl-4-oxo-but-2-enoic acid [ No CAS ]
  • 4
  • [ 616-02-4 ]
  • [ 84478-72-8 ]
  • 1-(4-chloro-2-fluoro-5-hydroxy-phenyl)-3-methyl-pyrrole-2,5-dione [ No CAS ]
  • 6
  • [ 616-02-4 ]
  • [ 22259-53-6 ]
  • [ 1217312-35-0 ]
  • 7
  • [ 616-02-4 ]
  • [ 84-67-3 ]
  • C24H20N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With acetic acid; In toluene; for 1h;Inert atmosphere; Reflux; In caseIn a separable flask,50 g (0.234 mol) of <strong>[84-67-3]2,2'-dimethylbiphenyl-4,4'-diamine</strong> (m-TB, manufactured by Wakayama Seika Industry Co., Ltd.)71 g (1.18 mol) of acetic acid and 120 g of toluene were charged and dissolved while heating and stirring at 50 ° C. while introducing nitrogen. 52.8 g (0.472 mol) of citraconic anhydride was added dropwise, and gradually heated while removing generated water outside the system,The reaction was carried out under reflux for 1 hour.After purifying the reaction product by reprecipitation, 90 g of a white crystal bismaleimide compound (e-1) was obtained. Yield 96percent. It was confirmed that the amine equivalent was 100,000 or more and almost all of the amino groups were reacted.
 

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